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Machine Learned Cellular Phenotypes Predict Outcome in Ischemic Cardiomyopathy. Circulation research Rogers, A. J., Selvalingam, A., Alhusseini, M. I., Krummen, D. E., Corrado, C., Abuzaid, F., Baykaner, T., Meyer, C., Clopton, P., Giles, W. R., Bailis, P., Niederer, S. A., Wang, P. J., Rappel, W., Zaharia, M., Narayan, S. M. 2020
Abstract

RATIONALE: Susceptibility to ventricular arrhythmias (VT/VF) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside.OBJECTIVE: To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning (ML) of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes.METHODS AND RESULTS: We recorded 5706 ventricular MAPs in 42 patients with coronary disease (CAD) and left ventricular ejection fraction (LVEF) {less than or equal to}40% during steady-state pacing. Patients were randomly allocated to independent training and testing cohorts in a 70:30 ratio, repeated K=10 fold. Support vector machines (SVM) and convolutional neural networks (CNN) were trained to 2 endpoints: (i) sustained VT/VF or (ii) mortality at 3 years. SVM provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each endpoint. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI: 0.76-1.00) and 0.91 for mortality (95% CI: 0.83-1.00) and were the most significant multivariate predictors. Interpreting trained SVM revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium calcium exchanger as predominant phenotypes for VT/VF.CONCLUSIONS: Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.

View details for DOI 10.1161/CIRCRESAHA.120.317345

View details for PubMedID 33167779
Machine Learning to Classify Intracardiac Electrical Patterns during Atrial Fibrillation. Circulation. Arrhythmia and electrophysiology Alhusseini, M. I., Abuzaid, F., Rogers, A. J., Zaman, J. A., Baykaner, T., Clopton, P., Bailis, P., Zaharia, M., Wang, P. J., Rappel, W., Narayan, S. M. 2020
Abstract

Background - Advances in ablation for atrial fibrillation (AF) continue to be hindered by ambiguities in mapping, even between experts. We hypothesized that convolutional neural networks (CNN) may enable objective analysis of intracardiac activation in AF, which could be applied clinically if CNN classifications could also be explained. Methods - We performed panoramic recording of bi-atrial electrical signals in AF. We used the Hilbert-transform to produce 175,000 image grids in 35 patients, labeled for rotational activation by experts who showed consistency but with variability (kappa=0.79). In each patient, ablation terminated AF. A CNN was developed and trained on 100,000 AF image grids, validated on 25,000 grids, then tested on a separate 50,000 grids. Results - In the separate test cohort (50,000 grids), CNN reproducibly classified AF image grids into those with/without rotational sites with 95.0% accuracy (CI 94.8-95.2%). This accuracy exceeded that of support vector machines, traditional linear discriminant and k-nearest neighbor statistical analyses. To probe the CNN, we applied Gradient-weighted Class Activation Mapping which revealed that the decision logic closely mimicked rules used by experts (C-statistic 0.96). Conclusions - Convolutional neural networks improved the classification of intracardiac AF maps compared to other analyses, and agreed with expert evaluation. Novel explainability analyses revealed that the CNN operated using a decision logic similar to rules used by experts, even though these rules were not provided in training. We thus describe a scaleable platform for robust comparisons of complex AF data from multiple systems, which may provide immediate clinical utility to guide ablation.

View details for DOI 10.1161/CIRCEP.119.008160

View details for PubMedID 32631100
Artificial Intelligence and Machine Learning in Arrhythmias and Cardiac Electrophysiology. Circulation. Arrhythmia and electrophysiology Feeny, A. K., Chung, M. K., Madabhushi, A., Attia, Z. I., Cikes, M., Firouznia, M., Friedman, P. A., Kalscheur, M. M., Kapa, S., Narayan, S. M., Noseworthy, P. A., Passman, R. S., Perez, M. V., Peters, N. S., Piccini, J. P., Tarakji, K. G., Thomas, S. A., Trayanova, N. A., Turakhia, M. P., Wang, P. J. 2020
Abstract

Artificial intelligence (AI) and machine learning (ML) in medicine are currently areas of intense exploration, showing potential to automate human tasks and even perform tasks beyond human capabilities. Literacy and understanding of AI/ML methods are becoming increasingly important to researchers and clinicians. The first objective of this review is to provide the novice reader with literacy of AI/ML methods and provide a foundation for how one might conduct an ML study. We provide a technical overview of some of the most commonly used terms, techniques, and challenges in AI/ML studies, with reference to recent studies in cardiac electrophysiology to illustrate key points. The second objective of this review is to use examples from recent literature to discuss how AI and ML are changing clinical practice and research in cardiac electrophysiology, with emphasis on disease detection and diagnosis, prediction of patient outcomes, and novel characterization of disease. The final objective is to highlight important considerations and challenges for appropriate validation, adoption, and deployment of AI technologies into clinical practice.

View details for DOI 10.1161/CIRCEP.119.007952

View details for PubMedID 32628863
The Year in Review in Cardiac Electrophysiology. Circulation. Arrhythmia and electrophysiology Kapa, S., Chung, M. K., Gopinathannair, R., Noseworthy, P. A., Eckhardt, L., Leal, M., Wan, E., Wang, P. J. 2020
Abstract

In the past year there have been numerous advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies. We have seen advances in basic cardiac electrophysiology with data suggesting that secretoneurin may be a biomarker for patients at risk of ventricular arrhythmias and we have learned of the potential role of a natriuretic peptide receptor-C in atrial fibrosis and the role of an atrial specific two-pore potassium channel TASK-1 as a therapeutic target for atrial fibrillation. We have seen studies demonstrating role of sensory neurons in sleep apnea-related atrial fibrillation and the association between bariatric surgery and atrial fibrillation ablation outcomes. Artificial intelligence applied to electrocardiography has yielded estimates of age, gender, and overall health. We have seen new tools for collection of patient-centered outcomes following catheter ablation. There have been significant advances in the ability to identify ventricular tachycardia termination sites through high-density mapping of deceleration zones. We have learned that right ventricular dysfunction may be a predictor of survival benefit after ICD implantation in non-ischemic cardiomyopathy patients. We have seen further insights into the role of His bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advance, we may have new tools to predict arrhythmic event rates in gene carriers. Finally, we have seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease.

View details for DOI 10.1161/CIRCEP.120.008733

View details for PubMedID 32423252
Case Series and Worldwide Surveys: Team Science Meets Clinical Care. Circulation. Arrhythmia and electrophysiology Wang, P. J. 2020; 13 (5): e008742
View details for DOI 10.1161/CIRCEP.120.008742

View details for PubMedID 32421436
Guidance for Cardiac Electrophysiology During the Coronavirus (COVID-19) Pandemic from the Heart Rhythm Society COVID-19 Task Force; Electrophysiology Section of the American College of Cardiology; and the Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, American Heart Association. Circulation Lakkireddy, D. R., Chung, M. K., Gopinathannair, R., Patton, K. K., Gluckman, T. J., Turagam, M., Cheung, J., Patel, P., Sotomonte, J., Lampert, R., Han, J. K., Rajagopalan, B., Eckhardt, L., Joglar, J., Sandau, K., Olshansky, B., Wan, E., Noseworthy, P. A., Leal, M., Kaufman, E., Gutierrez, A., Marine, J. M., Wang, P. J., Russo, A. M. 2020
Abstract

Covid-19 is a global pandemic that is wreaking havoc with the health and economy of much of human civilization. Electrophysiologists have been impacted personally and professionally by this global catastrophe. In this joint document from representatives of the HRS, ACC and AHA we identify the potential risks of exposure to patients, allied health care staff, industry representatives and hospital administrators. We describe the impact of COVID-19 on cardiac arrhythmias and methods of triage based on acuity and patient comorbidities. We provide guidance for managing invasive and non-invasive electrophysiology procedures, clinic visits and cardiac device interrogations. We discuss resource conservation and the role of tele-medicine in remote patient care along with management strategies for affected patients.

View details for DOI 10.1161/CIRCULATIONAHA.120.047063

View details for PubMedID 32228309
PREDICTING SUDDEN CARDIAC DEATH BY MACHINE LEARNING OF VENTRICULAR ACTION POTENTIALS Selvalingam, A., Alhusseini, M., Rogers, A. J., Krummen, D., Abuzaid, F. M., Baykaner, T., Clopton, P., Bailis, P., Zaharia, M., Wang, P., Narayan, S. ELSEVIER SCIENCE INC. 2020: 427
View details for Web of Science ID 000522979100416
LARGER ORGANIZED AREAS IN PERSISTENT ATRIAL FIBRILLATION PREDICTS TERMINATION DURING ABLATION Ravi, N., Rogers, A. J., Bhatia, N., Tung, J. S., Krummen, D., Sauer, W., Alhusseini, M., Baykaner, T., Wang, P., Rappel, W., Narayan, S. ELSEVIER SCIENCE INC. 2020: 279
View details for Web of Science ID 000522979100273
True bipolar or extended bipolar left ventricular pacing is associated with better survival in cardiac resynchronization therapy patients. Pacing and clinical electrophysiology : PACE Kutyifa, V., Jame, S., Wang, P. J., Musat, D., Jones, P., Wehrenberg, S., Stein, K. 2020
Abstract

BACKGROUND: Limited studies are available on the clinical significance of left ventricular lead polarity in patients undergoing cardiac resynchronization (CRT), with a recent study suggesting better outcomes with LV true bipolar pacing.OBJECTIVES: We aimed to determine whether True-Bipolar LV pacing is associated with reduced mortality in a large, real-life CRT cohort, followed by remote monitoring.METHODS: We analyzed de-identified device data from CRT patients followed by the Boston Scientific LATITUDE remote monitoring database system. Patients with LV bipolar leads paced between the LV ring and LV tip were identified as True-Bipolar and those with LV bipolar leads paced between LV tip or LV ring to RV coil were identified as Extended Bipolar. Patients with unipolar leads were identified as Unipolar.RESULTS: Of the 59,046 patients included in the study, 2,927 had Unipolar pacing, 34,390 had Extended Bipolar pacing, and 21,729 had True-Bipolar pacing. LV True-Bipolar pacing was associated with a significant 30% lower risk of all-cause mortality as compared to unipolar pacing (HR = 0.70, 95% CI: 0.62-0.79, p<0.001), after adjustment for age, gender, LV lead impedance, LV pacing threshold, and BIV pacing percentage<95%. Extended-Bipolar LV pacing was also associated with 24% lower risk of all-cause mortality when compared to Unipolar LV pacing (HR = 0.76, 95% CI: 0.68-0.85; p<0.001). However, there were no differences in outcomes between True-Bipolar or Extended-Bipolar LV pacing (HR = 0.97, 95% CI: 0.93-1.01; p = 0.198).CONCLUSION: True-Bipolar and Extended-Bipolar LV pacing is associated with a lower risk of mortality in cardiac resynchronization therapy patients as compared to Unipolar LV pacing. This article is protected by copyright. All rights reserved.

View details for DOI 10.1111/pace.13889

View details for PubMedID 32067233
Electrical Storm in COVID-19. JACC. Case reports O'Brien, C., Ning, N., McAvoy, J., Mitchell, J. E., Kalwani, N., Wang, P., Nguyen, D., Reejhsinghani, R., Rogers, A., Lorenzo, J. 2020; 2 (9): 1256?60
Abstract

COVID-19 is a global pandemic caused by SARS-CoV-2. Infection is associated with significant morbidity and mortality. Individuals with pre-existing cardiovascular disease or evidence of myocardial injury are at risk for severe disease and death. Little is understood about the mechanisms of myocardial injury or life-threatening cardiovascular sequelae. (Level�of Difficulty: Intermediate.).

View details for DOI 10.1016/j.jaccas.2020.05.032

View details for PubMedID 32835266

View details for PubMedCentralID PMC7259914
Guidance for Rebooting Electrophysiology Through the COVID-19 Pandemic From the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology: Endorsed by the American College of Cardiology. JACC. Clinical electrophysiology Lakkireddy, D. R., Chung, M. K., Deering, T. F., Gopinathannair, R., Albert, C. M., Epstein, L. M., Harding, C. V., Hurwitz, J. L., Jeffery, C. C., Krahn, A. D., Kusumoto, F. M., Lampert, R., Mansour, M., Natale, A., Patton, K. K., Seiler, A., Shah, M. J., Wang, P. J., Russo, A. M. 2020; 6 (8): 1053?66
Abstract

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of�outpatient and periprocedural care pathways.

View details for DOI 10.1016/j.jacep.2020.06.004

View details for PubMedID 32819525
Termination of persistent atrial fibrillation by ablating sites that control large atrial areas. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Bhatia, N. K., Rogers, A. J., Krummen, D. E., Hossainy, S., Sauer, W., Miller, J. M., Alhusseini, M. I., Peszek, A., Armenia, E., Baykaner, T., Brachmann, J., Turakhia, M. P., Clopton, P., Wang, P. J., Rappel, W. J., Narayan, S. M. 2020
Abstract

Persistent atrial fibrillation (AF) has been explained by multiple mechanisms which, while they conflict, all agree that more disorganized AF is more difficult to treat than organized AF. We hypothesized that persistent AF consists of interacting organized areas which may enlarge, shrink or coalesce, and that patients whose AF areas enlarge by ablation are more likely to respond to therapy.We mapped vectorial propagation in persistent AF using wavefront fields (WFF), constructed from raw unipolar electrograms at 64-pole basket catheters, during ablation until termination (Group 1, N?=?20 patients) or cardioversion (Group 2, N?=?20 patients). Wavefront field mapping of patients (age 61.1?�?13.2 years, left atrium 47.1?�?6.9?mm) at baseline showed 4.6?�?1.0 organized areas, each separated by disorganization. Ablation of sites that led to termination controlled larger organized area than competing sites (44.1?�?11.1% vs. 22.4?�?7.0%, P?
View details for DOI 10.1093/europace/euaa018

View details for PubMedID 32243508
Guidance for Cardiac Electrophysiology During the Coronavirus (COVID-19) Pandemic from the Heart Rhythm Society COVID-19 Task Force; Electrophysiology Section of the American College of Cardiology; and the Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, American Heart Association. Heart rhythm Lakkireddy, D. R., Chung, M. K., Gopinathannair, R., Patton, K. K., Gluckman, T. J., Turagam, M., Cheung, J., Patel, P., Sotomonte, J., Lampert, R., Han, J. K., Rajagopalan, B., Eckhardt, L., Joglar, J., Sandau, K., Olshansky, B., Wan, E., Noseworthy, P. A., Leal, M., Kaufman, E., Gutierrez, A., Marine, J. M., Wang, P. J., Russo, A. M. 2020
Abstract

Covid-19 is a global pandemic that is wreaking havoc with the health and economy of much of human civilization. Electrophysiologists have been impacted personally and professionally by this global catastrophe. In this joint document from representatives of the HRS, ACC and AHA we identify the potential risks of exposure to patients, allied health care staff, industry representatives and hospital administrators. We describe the impact of COVID-19 on cardiac arrhythmias and methods of triage based on acuity and patient comorbidities. We provide guidance for managing invasive and non-invasive electrophysiology procedures, clinic visits and cardiac device interrogations. We discuss resource conservation and the role of tele-medicine in remote patient care along with management strategies for affected patients.

View details for DOI 10.1016/j.hrthm.2020.03.028

View details for PubMedID 32247013
Guidance for rebooting electrophysiology through the COVID-19 pandemic from the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology. Heart rhythm Lakkireddy, D. R., Chung, M. K., Deering, T. F., Gopinathannair, R., Albert, C. M., Epstein, L. M., Harding, C. V., Hurwitz, J. L., Jeffery, C. C., Krahn, A. D., Kusumoto, F. M., Lampert, R., Mansour, M., Natale, A., Patton, K. K., Seiler, A., Shah, M. J., Wang, P. J., Russo, A. M. 2020
Abstract

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.

View details for DOI 10.1016/j.hrthm.2020.06.012

View details for PubMedID 32540298
Intrinsically stretchable electrode array enabled in vivo electrophysiological mapping of atrial fibrillation at cellular resolution. Proceedings of the National Academy of Sciences of the United States of America Liu, J., Zhang, X., Liu, Y., Rodrigo, M., Loftus, P. D., Aparicio-Valenzuela, J., Zheng, J., Pong, T., Cyr, K. J., Babakhanian, M., Hasi, J., Li, J., Jiang, Y., Kenney, C. J., Wang, P. J., Lee, A. M., Bao, Z. 2020
Abstract

Electrophysiological mapping of chronic atrial fibrillation (AF) at high throughput and high resolution is critical for understanding its underlying mechanism and guiding definitive treatment such as cardiac ablation, but current electrophysiological tools are limited by either low spatial resolution or electromechanical uncoupling of the beating heart. To overcome this limitation, we herein introduce a scalable method for fabricating a tissue-like, high-density, fully elastic electrode (elastrode) array capable of achieving real-time, stable, cellular level-resolution electrophysiological mapping in vivo. Testing with acute rabbit and porcine models, the device is proven to have robust and intimate tissue coupling while maintaining its chemical, mechanical, and electrical properties during the cardiac cycle. The elastrode array records epicardial atrial signals with comparable efficacy to currently available endocardial-mapping techniques but with 2 times higher atrial-to-ventricular signal ratio and >100 times higher spatial resolution and can reliably identify electrical local heterogeneity within an area of simultaneously identified rotor-like electrical patterns in a porcine model of chronic AF.

View details for DOI 10.1073/pnas.2000207117

View details for PubMedID 32541030
Continuous Ablation Improves Lesion Maturation Compared with Intermittent Ablation Strategies. Journal of cardiovascular electrophysiology Rogers, A. J., Borne, R. T., Ho, G., Sauer, W. H., Wang, P. J., Narayan, S. M., Zheng, L., Nguyen, D. T. 2020
Abstract

Interrupted ablation is increasingly proposed as part of high-power short duration radiofrequency ablation (RFA) strategies and may also result from loss of contact from respiratory patterns or cardiac motion.To study the extent that ablation interruption affects lesions.In ex vivo and in vivo experiments, lesion characteristics and tissue temperatures were compared between continuous (Group 1) and interrupted (Groups 2,3) RFA with equal total ablation duration and contact force. Extended duration ablation lesions were also characterized from 1 to 5 minutes.In the ex vivo study, continuous RFA (Group 1) produced larger total lesion volumes compared with each interrupted ablation lesion group (273.8�36.5 mm3 vs. 205.1�34.2 and vs. 174.3�32.3, all p<0.001). Peak temperatures for Group 1 were higher at 3mm and 5mm than Groups 2 and 3. In vivo, continuous ablation resulted in larger lesions, greater lesion depths, and higher tissue temperatures. Longer ablation durations created larger lesion volumes and increased lesion depths. However, after 3 min of ablation, the rate of lesion volume and depth formation decreased.Continuous RFA delivery resulted in larger and deeper lesions with higher tissue temperatures compared to interrupted ablation. This work may have implications for high-power short duration ablation strategies, motivates strategies to reduce variations in ablation delivery, and provides an upper limit for ablation duration beyond which power delivery has diminishing returns. This article is protected by copyright. All rights reserved.

View details for DOI 10.1111/jce.14510

View details for PubMedID 32323395
Non-Invasive Assessment of Complexity of Atrial Fibrillation: Correlation with Contact Mapping and Impact of Ablation. Circulation. Arrhythmia and electrophysiology Rodrigo, M., Climent, A. M., Hern�ndez-Romero, I., Liberos, A., Baykaner, T., Rogers, A. J., Alhusseini, M., Wang, P. J., Fern�ndez-Avil�s, F., Guillem, M. S., Narayan, S. M., Atienza, F. 2020
Abstract

Background - It is difficult to non-invasively phenotype atrial fibrillation (AF) in a way that reflects clinical endpoints such as response to therapy. We set out to map electrical patterns of disorganization and regions of reentrant activity in AF from the body surface using electrocardiographic imaging (ECGI), calibrated to panoramic intracardiac recordings and referenced to AF termination by ablation. Methods - Bi-atrial intracardiac electrograms of 47 AF patients at ablation (30 persistent, 29 male, 63�9 years) were recorded with 64-pole basket catheters and simultaneous 57-lead body surface ECGs. Atrial epicardial electrical activity was reconstructed and organized sites were invasively and non-invasively tracked in 3D using phase singularity (PS). In a subset of 17 patients, sites of AF organization were targeted for ablation. Results - Body surface mapping showed greater AF organization near intracardially-detected drivers than elsewhere, both in PS density (2.3�2.1 vs 1.9�1.6, p=0.02) and number of drivers (3.2�2.3 vs 2.7�1.7, p=0.02). Complexity, defined as the number of stable AF reentrant sites, was concordant between non-invasive and invasive methods (r2 =0.5, CC=0.71). In the subset receiving targeted ablation, AF complexity showed lower values in those in whom AF terminated than those in whom AF did not terminate (p<0.01). Conclusions - AF complexity tracked non-invasively correlates well with organized and disorganized regions detected by panoramic intracardiac mapping, and correlates with the acute outcome by ablation. This approach may assist in bedside monitoring of therapy or in improving the efficacy of ongoing ablation procedures.

View details for DOI 10.1161/CIRCEP.119.007700

View details for PubMedID 32078374
Cardiac Procedural Deferral during the Coronavirus (COVID-19) Pandemic. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Yong, C. M., Ang, L., Welt, F. G., Gummidipundi, S., Henry, T. D., Pinto, D. S., Cox, D., Wang, P., Asch, S., Mahmud, E., Fearon, W. F. 2020
Abstract

We aimed to examine factors impacting variability in cardiac procedural deferral during the COVID-19 pandemic and assess cardiologists' perspectives regarding its implications.Unprecedented cardiac procedural deferral was implemented nationwide during the COVID-19 pandemic.A web-based survey was administered by SCAI and the ACC Interventional Council to cardiac catheterization laboratory (CCL) directors and interventional cardiologists across the United States during the COVID-19 pandemic.Among 414 total responses, 48 states and 360 unique cardiac catheterization laboratories were represented, with mean inpatient COVID-19 burden 16.4+21.9%. There was a spectrum of deferral by procedure type, varying by both severity of COVID-19 burden and procedural urgency (p<0.001). Percutaneous coronary intervention volumes dropped by 55% (p<0.0001) and transcatheter aortic valve replacement volumes dropped by 64%, (p=0.004), with cardiologists reporting an increase in late presenting ST-Elevation Myocardial Infarctions and deaths among patients waiting for transcatheter aortic valve replacement. Almost 1/3 of catheterization laboratories had at least one interventionalist testing positive for COVID-19. Salary reductions did not influence procedural deferral or speed of reinstituting normal volumes. Pandemic preparedness improved significantly over time, with the most pressing current problems focused on inadequate testing and staff health risks.During the COVID-19 pandemic, cardiac procedural deferrals were associated with procedural urgency and severity of hospital COVID-19 burden. Yet patients did not appear to be similarly influenced, with cardiologists reporting increases in late presenting ST-Elevation Myocardial Infarctions independent of local COVID-19 burden. The safety and importance of seeking healthcare during this pandemic deserves emphasis. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/ccd.29262

View details for PubMedID 32882075
Guidance for rebooting electrophysiology through the COVID-19 pandemic from the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology. Circulation. Arrhythmia and electrophysiology Lakkireddy, D. R., Chung, M. K., Deering, T. F., Gopinathannair, R., Albert, C. M., Epstein, L. M., Harding, C. V., Hurwitz, J. L., Jeffery, C. C., Krahn, A. D., Kusumoto, F. M., Lampert, R., Mansour, M., Natale, A., Patton, K. K., Seiler, A., Shah, M. J., Wang, P. J., Russo, A. M. 2020
Abstract

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.

View details for DOI 10.1161/CIRCEP.120.008999

View details for PubMedID 32530306
Novel Three-Dimensional Imaging Approach for Cryoballoon Navigation and Confirmation of Pulmonary Vein Occlusion. Pacing and clinical electrophysiology : PACE Kowalewski, C. A., Rodrigo, M., Brodt, C., Haddad, F., Wang, P. J., Narayan, S. M. 2019
Abstract

BACKGROUND: Cryoballoon apposition is crucial for durable pulmonary vein isolation (PVI) in atrial fibrillation, yet the balloon is difficult to visualize by conventional mapping systems, and pulmonary venography may miss small or out-of-plane leaks. We report a novel imaging system that offers real-time 3-D navigation of the cryoballoon within atrial anatomy that may circumvent these issues.METHODS AND RESULTS: A novel overlay guidance system(OGS) (Siemens Healthcare, Forchheim, Germany) registers already-acquired segmented atrial cardiac tomography (CT) with fluoroscopy, enabling real-time visualization of the cryoballoon within tomographic left atrial imaging during PVI. Phantom experiments in a patient-specific 3D printed left atrium showed feasibility for confirming PV apposition and leaks. We applied OGS prospectively to 68 PVs during PVI in 17 patients. The cryoballoon was successfully reconstructed in all cases, and its apposition was compared to concurrent PV venography. The OGS uncovered leaks undetected by venography in 9 veins (8 cases) which enabled repositioning, confirming apposition in remaining 68 veins. Concordance of OGS to venography was 83.8% (chi2 , p<0.01) CONCLUSIONS: We report a new system for real-time imaging of cryoballoon catheters to ensure PV apposition within the tomography of the left atrium. While providing high concordance with other imaging modalities for confirming balloon apposition or leak, the system also identified leaks missed by venography. Future studies should determine if this tool can provide a new reference for cryoballoon positioning. This article is protected by copyright. All rights reserved Cryoballoon ablation is increasingly used for pulmonary vein isolation (PVI), but it may be difficult to track cryoballoon position relative to the PV for complete occlusion. We describe a novel overlay guidance system (OGS) for real-time 3D visualization of the cryoballoon within atrial anatomy, by registering atrial computed tomography in 2 fluoroscopic planes. Phantom experiments with a custom 3D printed left atrium showed feasibility for visualizing balloon apposition within PVs. In 68 PVs in 17 patients, the OGS prospectively identified cryoballoon position relative to PVs, and uncovered leaks undetected by venography. Future studies should test if the OGS can serve as a new reference for cryoballoon positioning.

View details for DOI 10.1111/pace.13858

View details for PubMedID 31868241
Comparison of Long-Term Adverse Outcomes in Patients With Atrial Fibrillation Having Ablation Versus Antiarrhythmic Medications. The American journal of cardiology Freeman, J. V., Tabada, G. H., Reynolds, K., Sung, S. H., Singer, D. E., Wang, P. J., Liu, T. I., Gupta, N., Hlatky, M. A., Go, A. S. 2019
Abstract

The impact of atrial fibrillation (AF) catheter ablation versus chronic antiarrhythmic therapy alone on clinical outcomes such as death and stroke remains unclear. We compared adverse outcomes for AF ablation versus chronic antiarrhythmic therapy in 1,070 adults with AF treated between 2010 and 2014 in the Kaiser Permanente Northern California and Southern California healthcare delivery systems. Patients who underwent AF catheter ablation were matched to patients treated with only antiarrhythmic medications, based on age, gender, history of heart failure, history of coronary heart disease, history of hypertension, history of diabetes, and high-dimensional propensity score. We compared crude and adjusted rates of death, ischemic stroke or transient ischemic attack, intracranial hemorrhage, and hospitalization. The matched cohort of 535 patients treated with AF ablation and 535 treated with antiarrhythmic therapy had a median follow-up of 2.0 (interquartile range 1.1 to 3.5) years. There was no significant difference in adjusted rates of death (adjusted hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.03 to 1.95), intracranial hemorrhage (adjusted HR 0.17, CI 0.02 to 1.71), ischemic stroke or transient ischemic attack (adjusted HR 0.53, CI 0.18 to 1.60), and heart failure hospitalization (adjusted HR 0.85, CI 0.34 to 2.12), although there was a trend toward improvement in these outcomes with ablation. However, there was a significantly increased risk of all-cause hospitalization following ablation (adjusted HR 1.60, CI 1.25 to 2.05). In a contemporary, multicenter, propensity-matched observational cohort, AF ablation was not significantly associated with death, intracranial hemorrhage, ischemic stroke or transient ischemic attack, or heart failure hospitalization, but was associated with a higher rate of all cause-hospitalization.

View details for DOI 10.1016/j.amjcard.2019.11.004

View details for PubMedID 31843233
Wavefront Field Mapping Reveals a Physiologic Network Between Drivers Where Ablation Terminates Atrial Fibrillation. Circulation. Arrhythmia and electrophysiology Leef, G., Shenasa, F., Bhatia, N. K., Rogers, A. J., Sauer, W., Miller, J. M., Swerdlow, M., Tamboli, M., Alhusseini, M. I., Armenia, E., Baykaner, T., Brachmann, J., Turakhia, M. P., Atienza, F., Rappel, W., Wang, P. J., Narayan, S. M. 2019; 12 (8): e006835
Abstract

BACKGROUND: Localized drivers are proposed mechanisms for persistent atrial fibrillation (AF) from optical mapping of human atria and clinical studies of AF, yet are controversial because drivers fluctuate and ablating them may not terminate AF. We used wavefront field mapping to test the hypothesis that AF drivers, if concurrent, may interact to produce fluctuating areas of control to explain their appearance/disappearance and acute impact of ablation.METHODS: We recruited 54 patients from an international registry in whom persistent AF terminated by targeted ablation. Unipolar AF electrograms were analyzed from 64-pole baskets to reconstruct activation times, map propagation vectors each 20 ms, and create nonproprietary phase maps.RESULTS: Each patient (63.6�8.5 years, 29.6% women) showed 4.0�2.1 spatially anchored rotational or focal sites in AF in 3 patterns. First, a single (type I; n=7) or, second, paired chiral-antichiral (type II; n=5) rotational drivers controlled most of the atrial area. Ablation of 1 to 2 large drivers terminated all cases of types I or II AF. Third, interaction of 3 to 5 drivers (type III; n=42) with changing areas of control. Targeted ablation at driver centers terminated AF and required more ablation in types III versus I (P=0.02 in left atrium).CONCLUSIONS: Wavefront field mapping of persistent AF reveals a pathophysiologic network of a small number of spatially anchored rotational and focal sites, which interact, fluctuate, and control varying areas. Future work should define whether AF drivers that control larger atrial areas are attractive targets for ablation.

View details for DOI 10.1161/CIRCEP.118.006835

View details for PubMedID 31352796
Comparison of QT Interval Measurement Methods and Correction Formulas in Atrial Fibrillation AMERICAN JOURNAL OF CARDIOLOGY Tooley, J., Ouyang, D., Hadley, D., Turakhia, M., Wang, P., Ashley, E., Froelicher, V., Perez, M. 2019; 123 (11): 1822?27
View details for DOI 10.1016/j.amjcard.2019.02.057

View details for Web of Science ID 000470339900014
Comparison of QT Interval Measurement Methods and Correction Formulas in Atrial Fibrillation. The American journal of cardiology Tooley, J., Ouyang, D., Hadley, D., Turakhia, M., Wang, P., Ashley, E., Froelicher, V., Perez, M. 2019
Abstract

Antiarrhythmic drugs used in atrial fibrillation (AF) cause QT prolongation and are associated with torsades de pointes, a deadly ventricular arrhythmia. No consensus exists on the optimal method of QT measurement or correction in AF. Therefore, we compared common methods to measure and correct QT in AF to identify the most accurate approach. We identified patients who had electrocardiograms done at Stanford Hospital (Stanford, California) between January 2014 and October 2016 with conversion from AF to sinus rhythm (SR) within a 24-hour period. QT intervals were determined using different measurement methods and corrected using the Bazett's, Framingham, Fridericia, or Hodges formulas for heart rate (HR). Comparisons were made between QT in a patient's last instance of AF to SR. Computerized measurements were taken from 715 patients. Manual measurements were taken from a 50-patient subset. Bazett's formula produced the longest corrected QT in AF compared with other formulas (p <0.005). Measuring QT as an average over multiple beats resulted in a smaller difference between AF and SR than choosing a single beat. Determining QT from a 5-beat average resulted in a QTc that was 19.0ms higher (interquartile range 0.30 to 43.7) in AF than SR. After correcting for residual effect of HR on QTc, there was not a significant difference between QTc in AF to SR. In conclusion, measuring QT over multiple beats produces a more accurate measurement of QT in AF. Differences between QTc in AF and SR exist because of imperfect HR correction formula and not due to an independent effect of AF.

View details for PubMedID 30961909
MACHINE LEARNING IDENTIFIES SITES WHERE ABLATION TERMINATES PERSISTENT ATRIAL FIBRILLATION Alhusseini, M., Abuzaid, F., Clopton, P., Rogers, A., Rodrigo, M., Baykaner, T., Wang, P., Rappel, W., Narayan, S. ELSEVIER SCIENCE INC. 2019: 301
View details for Web of Science ID 000460565900301
SITES THAT CONTROL LARGER AREAS DURING ATRIAL FIBRILLATION MAY DETERMINE TERMINATION DURING ABLATION Bhatia, N. K., Hossainy, S., Rogers, A., Alhusseini, M., Brodt, C., Moosvi, N., Baykaner, T., Wang, P., Rappel, W., Narayan, S. ELSEVIER SCIENCE INC. 2019: 400
View details for Web of Science ID 000460565900400
INTRACLASS CORRELATIONS OF VOLTAGE, FRACTIONATED ELECTROGRAMS, AND DOMINANT FREQUENCY IN PATIENTS WHERE LOCALIZED ABLATION TERMINATED PERSISTENT ATRIAL FIBRILLATION Rogers, A. J., Moosvi, N., Singh, A., Alhusseini, M., Baykaner, T., Clopton, P., Rappel, W., Wang, P., Narayan, S. ELSEVIER SCIENCE INC. 2019: 521
View details for Web of Science ID 000460565900521
Year in Review in Cardiac Electrophysiology. Circulation. Arrhythmia and electrophysiology Tzou, W. S., Hussein, A. A., Madhavan, M., Viswanathan, M. N., Steinberg, B. A., Ceresnak, S. R., Davis, D. R., Park, D. S., Wang, P. J., Kapa, S. 2019; 12 (2): e007142
View details for PubMedID 30744401
Year in Review in Cardiac Electrophysiology CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Tzou, W. S., Hussein, A. A., Madhavan, M., Viswanathan, M. N., Steinberg, B. A., Ceresnak, S. R., Davis, D. R., Park, D. S., Wang, P. J., Kapa, S. 2019; 12 (2)
View details for DOI 10.1161/CIRCEP.118.007142

View details for Web of Science ID 000459028300007
Secular trends in success rate of catheter ablation for atrial fibrillation: The SMASH-AF cohort AMERICAN HEART JOURNAL Perino, A. C., Leef, G. C., Cluckey, A., Yunus, F. N., Askari, M., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2019; 208: 110?19
View details for DOI 10.1016/j.ahj.2018.10.006

View details for Web of Science ID 000459125900013
New Concepts in Sudden Cardiac Arrest to Addressan Intractable Epidemic: JACC State-of-the-Art Review. Journal of the American College of Cardiology Narayan, S. M., Wang, P. J., Daubert, J. P. 2019; 73 (1): 70?88
Abstract

Sudden cardiac arrest (SCA) is one of the largest causes of mortality globally, with an out-of-hospital survival below 10% despite intense research. This document outlines challenges in addressing the epidemic of SCA, along the framework of respond, understand and predict, and prevent. Response could be improved by technology-assisted orchestration of community responder systems, access to automated external defibrillators, and innovations to match resuscitation resources to victims in place and time. Efforts to understand and predict SCA may be enhanced by refining taxonomy along phenotypical and pathophysiological "axes of risk," extending beyond cardiovascular pathology to identify less heterogeneous cohorts, facilitated by open-data platforms and analytics including machine learning to integrate discoveries across disciplines. Prevention of SCA must integrate these concepts, recognizing that all members of society are stakeholders. Ultimately, solutions to the public health challenge of SCA will require greater awareness, societal debate and focused public policy.

View details for PubMedID 30621954
New Concepts in Sudden Cardiac Arrest to Address an Intractable Epidemic JACC State-of-the-Art Review JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Narayan, S. M., Wang, P. J., Daubert, J. P. 2019; 73 (1): 70?88
View details for DOI 10.1016/j.jacc.2018.09.083

View details for Web of Science ID 000455014900021
Efficacy of Ablation Lesion Sets in Addition to Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation: Findings From the SMASH-AF Meta-Analysis Study Cohort JOURNAL OF THE AMERICAN HEART ASSOCIATION Cluckey, A., Perino, A. C., Yunus, F. N., Leef, G. C., Askari, M., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2019; 8 (1)
View details for DOI 10.1161/JAHA.118.009976

View details for Web of Science ID 000455185000012
Efficacy of Ablation Lesion Sets in Addition to Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation: Findings From the SMASH - AF Meta-Analysis Study Cohort. Journal of the American Heart Association Cluckey, A., Perino, A. C., Yunus, F. N., Leef, G. C., Askari, M., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2019; 8 (1): e009976
Abstract

Background The objective was to explore the efficacy of ablation lesion sets in addition to pulmonary vein isolation ( PVI ) for paroxysmal atrial fibrillation. The optimal strategy for catheter ablation of paroxysmal atrial fibrillation is debated. Methods and Results The SMASH-AF (Systematic Review and Meta-analysis of Ablation Strategy Heterogeneity in Atrial Fibrillation) study cohort includes trials and observational studies identified in PubMed, Scopus, and Cochrane databases from January 1 1990, to August 1, 2016. We included studies reporting single procedure paroxysmal atrial fibrillation ablation success rates. Exclusion criteria included insufficient reporting of outcomes, ablation strategies that were not prespecified and uniform, and a sample size of fewer than 40 patients. We analyzed lesion sets performed in addition to PVI ( PVI plus) using multivariable random-effects meta-regression to control for patient, study, and procedure characteristics. The analysis included 145 total studies with 23263 patients ( PVI- only cohort: 115 studies, 148 treatment arms, 16500 patients; PVI plus cohort: 39 studies; 46 treatment arms, 6763 patients). PVI plus studies, as compared with PVI -only studies, included younger patients (56.7years versus 58.8years, P=0.001), fewer women (27.2% versus 32.0% women, P=0.002), and were more methodologically rigorous with longer follow-up (29.5 versus 17.1months, P 0.004) and more randomization (19.4% versus 11.8%, P<0.001). In multivariable meta-regression, PVI plus studies were associated with improved success (7.6% absolute improvement [95% CI, 2.6-12.5%]; P<0.01, I2=88%), specifically superior vena cava isolation (4 studies, 4 treatment arms, 1392 patients; 15.1% absolute improvement [95%CI, 2.3-27.9%]; P 0.02, I2=87%). However, residual heterogeneity was large. Conclusions Across the paroxysmal atrial fibrillation ablation literature, PVI plus ablation strategies were associated with incremental improvements in success rate. However, large residual heterogeneity complicates evidence synthesis.

View details for PubMedID 30587059
Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy. Nature Lee, J., Termglinchan, V., Diecke, S., Itzhaki, I., Lam, C. K., Garg, P., Lau, E., Greenhaw, M., Seeger, T., Wu, H., Zhang, J. Z., Chen, X., Gil, I. P., Ameen, M., Sallam, K., Rhee, J. W., Churko, J. M., Chaudhary, R., Chour, T., Wang, P. J., Snyder, M. P., Chang, H. Y., Karakikes, I., Wu, J. C. 2019
Abstract

Lamin A/C (LMNA) is one of the most frequently mutated genes associated with dilated cardiomyopathy (DCM). DCM related to mutations in LMNA is a common inherited cardiomyopathy that is associated with systolic dysfunction and cardiac arrhythmias. Here we modelled the LMNA-related DCM in vitro using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Electrophysiological studies showed that the mutant iPSC-CMs displayed aberrant calcium homeostasis that led to arrhythmias at the single-cell level. Mechanistically, we show that the platelet-derived growth factor (PDGF) signalling pathway is activated in mutant iPSC-CMs compared to isogenic control iPSC-CMs. Conversely, pharmacological and molecular inhibition of the PDGF signalling pathway ameliorated the arrhythmic phenotypes of mutant iPSC-CMs in vitro. Taken together, our findings suggest that the activation of the PDGF pathway contributes to the pathogenesis of LMNA-related DCM and point to PDGF receptor-? (PDGFRB) as a potential therapeutic target.

View details for DOI 10.1038/s41586-019-1406-x

View details for PubMedID 31316208
Research Needs and Priorities for Catheter Ablation of Atrial Fibrillation: A Report from a National Heart, Lung, and Blood Institute Virtual Workshop. Circulation Al-Khatib, S. M., Benjamin, E. J., Buxton, A. E., Calkins, H., Chung, M. K., Curtis, A. B., Desvigne-Nickens, P., Jais, P., Packer, D. L., Piccini, J. P., Rosenberg, Y., Russo, A. M., Wang, P. J., Cooper, L. S., Go, A. S. 2019
Abstract

Catheter ablation has brought major advances in the management of patients with atrial fibrillation (AF). As evidenced by multiple randomized trials, AF catheter ablation can reduce the risk of recurrent AF and improve quality of life. In some studies, AF ablation significantly reduced cardiovascular hospitalizations. Despite the existing data on AF catheter ablation, numerous knowledge gaps remain in relation to this intervention. This report is based on a recent virtual workshop convened by the National Heart, Lung, and Blood Institute to identify key research opportunities in AF ablation. We outline knowledge gaps related to emerging technologies, the relationship between cardiac structure and function and the success of AF ablation, patient subgroups in whom clinical benefit from ablation varies, and potential platforms to advance clinical research in this area. This report also considers the potential value and challenges of a sham ablation randomized trial. Prioritized research opportunities are identified and highlighted to empower relevant stakeholders to collaborate in designing and conducting effective, cost-efficient, and transformative research to optimize the use and outcomes of AF ablation.

View details for DOI 10.1161/CIRCULATIONAHA.119.042706

View details for PubMedID 31744331
Urinary tract infection after catheter ablation of atrial fibrillation. Pacing and clinical electrophysiology : PACE Cluckey, A., Perino, A. C., Fan, J., Askari, M., Nasir, J., Marcus, G. M., Baykaner, T., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2019
Abstract

Urinary tract infection (UTI) is common after surgical procedures and a quality improvement target. For non-surgical procedures such as catheter ablation of atrial fibrillation (AF), UTI risk has not been characterized. We sought to determine incidence and risk factors of UTI after AF ablation and risk variation across sites.Using Marketscan commercial claims databases, we performed a retrospective cohort study of patients that underwent AF ablation from 2007 to 2011. The primary outcome was UTI diagnosis within 30 days after ablation. We performed multivariate analyses to determine risk factors for UTI and risk of sepsis within 30 days after ablation with UTI as the predictor variable. Median odds ratio was used to quantify UTI site variation.Among 21,091 patients (age 59.2�10.9; 29.1% female; CHA2 DS2 -VASc 2.0�1.6), 622 (2.9%) were diagnosed with UTI within 30 days. In multivariate analyses, UTI was independently associated with age, female sex, prior UTI, and general anesthesia (all p < 0.01). UTI diagnosis was associated with a substantial increased risk of sepsis within 30 days (5.0% vs. 0.3%; OR 17.5; 95% CI 10.8 - 28.2; p < 0.0001). Among 416 sites, 211 had at least one UTI. Among these 211 sites, the incidence of post-ablation UTI ranged from 0.7%-26.7% (median: 5.4%; IQR: 3.0%-7.1%; 95th percentile: 14.3%; median odds ratio: 1.45; 95% CI 1.41-1.50).UTI after AF ablation is not uncommon and varies substantially across sites. Consideration of UTI as a quality measure and interventions targeted at high-risk patients or sites warrant consideration. This article is protected by copyright. All rights reserved.

View details for DOI 10.1111/pace.13738

View details for PubMedID 31168821
AF Drivers Where Ablation Terminates Persistent AF Fluctuate Due to Competing Drivers but Remain Anchored in Specific Locations Meckler, G. L., Kowalewski, C. A., Rogers, A. J., Rodrigo, M., Clopton, P., Shenasa, F., Alhusseini, M., Swerdlow, M., Joshi, V., Hossainy, S., Zaman, J., Baykaner, T., Brachmann, J., Miller, J., Krummen, D. E., Sauer, W., Viswanathan, M., Wang, P., Narayan, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619407352
Electrode Density is Greater at Sites Where Ablation Acutely Terminates Atrial Fibrillation Rogers, A. J., Juan, R. C., Collart, O., Swerdlow, M., Alhusseini, M., Rodrigo, M., Kowalewski, C., Baykaner, T., Zaman, J., Wang, P. J., Rappel, W., Narayan, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619405137
Preserved Apical Myocardial Deformation Identifies Responders of Cardiac Resynchronization Therapy Biering-Sorensen, T., Kutyifa, V., Knappe, D., Pouleur, A., Claggett, B., Wang, P. J., Solomon, S. D. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619406320
Esophageal Re-Warming Profile During Cryoballoon Ablation Why We Should Avoid the Freeze Thaw Refreeze Technique Tomaiko, E. D., Orme, J., Habib, A., Su, W., Wang, P. J., Jaskanawal, B., Su, S. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619407341
Comparing Multiple Mapping Methods at Sites of AF Termination: The COMPARE-AF Registry. Zaman, J. A., Baykaner, T., Meckler, G., Clopton, P., Alhusseini, M., Shenasa, F., Kowalewski, C., Rogers, A., Vidmar, D., Krummen, D., Viswanathan, M., Rappel, W., Brachmann, J., Peters, N., Miller, J., Wang, P., Sauer, W., Atienza, F., Narayan, S. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619405012
Sites Where Ablation Terminated Atrial Fibrillation Identified by Machine Learning Models Alhusseini, M., Abuzaid, F., Swerdlow, M., Meckler, G., Clopton, P., Rogers, A., Rodrigo, M., Baykaner, T., Zaman, J., Kowalewski, C., Shenasa, F., Atienza, F., Mohan, N., Wang, P. J., Rappel, W. J., Bailis, P., Zaharia, M., Narayan, S. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619403044
Machine Learning Reveals That Drivers for Persistent Atrial Fibrillation at Termination Sites Show Irregular Rotational Cycles and Domain Size Alhusseini, M., Abuzaid, F., Swerdlow, M., Clopton, P., Meckler, G. L., Maniar, N. M., Rogers, A., Rodrigo, M., Baykaner, T., Zaman, J., Kowalewski, C., Shenasa, F., Tamboli, M., Viswanathan, M., Wang, P., Atienza, F., Rappel, W. J., Bailis, P., Zaharia, M., Narayan, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619404020
Vector Propagation Automatically Identifies Sites of Termination of Persistent Atrial Fibrillation by Ablation Leef, G., Shenasa, F., Rogers, A. J., Baykaner, T., Atienza, F., Wang, P. J., Rappel, W., Narayan, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619402355
Procedural and Clinical Determinants of Acute Success of Driver Ablation for Persistent Atrial Fibrillation Baykaner, T., Rogers, A. J., Rodrigo, M., Alhusseini, M., Zaman, J. A., Wang, P. J., Narayan, S. M., Spitzer, S., Szili-Torok, T. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619404248
Localized Driver Regions That Control Larger Regions of the Atria May Be Critical to Sustaining Atrial Fibrillation: Analyses From Novel Vector Mapping Leef, G., Shenasa, F., Sauer, W., Miller, J. M., Vidmar, D., Swerdlow, M. A., Tomboli, M., Rogers, A. J., Alhusseini, M., Armenia, E., Baykaner, T., Brachmann, J., Atienza, F., Wang, P. J., Rappel, W., Narayan, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619402146
Rotor Substrate Ablation for Antiarrhythmic-Refractory Ventricular Fibrillation With Infrequent, Multifocal Triggers Krummen, D. E., Ho, G., Hoffmayer, K. S., Schweis, F., Bradshaw, A., Baykaner, T., Wang, P. J., Viswanathan, M. N., Rappel, W., Narayan, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619404256
Secular trends in success rate of catheter ablation for atrial fibrillation: The SMASH-AF cohort. American heart journal Perino, A. C., Leef, G. C., Cluckey, A., Yunus, F. N., Askari, M., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2018
Abstract

BACKGROUND: Approaches, tools, and technologies for atrial fibrillation (AF) ablation have evolved significantly since its inception. We sought to characterize secular trends in AF ablation success rates.METHODS: We performed a systematic review and meta-analysis of AF ablation from January 1, 1990, to August 1, 2016, searching PubMed, Scopus, and Cochrane databases. Major exclusion criteria were insufficient outcome reporting and ablation strategies that were not prespecified and uniform. We stratified treatment arms by AF type (paroxysmal AF; nonparoxysmal AF) and analyzed single-procedure outcomes. Multivariate meta-regressions analyzed effects of study, patient, and procedure characteristics on success rate trends. Registered in PROSPERO (CRD42016036549).RESULTS: A total of 180 trials and observational studies with 28,118 patients met inclusion. For paroxysmal AF ablation studies, unadjusted success rate summary estimates ranged from 73.1% in 2003 to 77.1% in 2016, increasing by 0.9%/year (95% CI 0.4%-1.4%; P = .001; I2 = 90%). After controlling for study design and patient demographics, rate of improvement in success rate summary estimate increased (1.6%/year; 95% CI 0.9%-2.2%; P = .001; I2 = 87%). For nonparoxysmal AF ablation studies, unadjusted success rate summary estimates ranged from 70.0% in 2010 to 64.3% in 2016 (1.1%/year; 95% CI -1.3% to 3.5%; P = .37; I2 = 85%), with no improvement in multivariate analyses.CONCLUSIONS: Despite substantial research investment and health care expenditure, improvements in AF ablation success rates have been incremental. Meaningful improvements may require major paradigm or technology changes, and evaluation of clinical outcomes such as mortality and quality of life may prove to be important going forward.

View details for PubMedID 30502925
Year in Review in Cardiac Electrophysiology. Circulation. Arrhythmia and electrophysiology Kapa, S., Davis, D. R., Park, D. S., Steinberg, B. A., Viswanathan, M. N., Tzou, W., Madhavan, M., Ceresnak, S. R., Wang, P. J. 2018; 11 (7): e006648
View details for PubMedID 30012874
Year in Review in Cardiac Electrophysiology CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Kapa, S., Davis, D. R., Park, D. S., Steinberg, B. A., Viswanathan, M. N., Tzou, W., Madhavan, M., Ceresnak, S. R., Wang, P. J. 2018; 11 (7)
View details for DOI 10.1161/CIRCEP.118.006648

View details for Web of Science ID 000438922000016
Interaction of Localized Drivers and Disorganized Activation in Persistent Atrial Fibrillation: Reconciling Putative Mechanisms Using Multiple Mapping Techniques CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Kowalewski, C. B., Shenasa, F., Rodrigo, M., Clopton, P., Meckler, G., Alhusseini, M. I., Swerdlow, M. A., Joshi, V., Hossainy, S., Zaman, J. B., Baykaner, T., Rogers, A. J., Brachmann, J., Miller, J. M., Krummen, D. E., Sauer, W. H., Peters, N. S., Wang, P. J., Narayan, S. M. 2018; 11 (6): e005846
Abstract

Mechanisms for persistent atrial fibrillation (AF) are unclear. We hypothesized that putative AF drivers and disorganized zones may interact dynamically over short time scales. We studied this interaction over prolonged durations, focusing on regions where ablation terminates persistent AF using 2 mapping methods.We recruited 55 patients with persistent AF in whom ablation terminated AF prior to pulmonary vein isolation from a multicenter registry. AF was mapped globally using electrograms for 360�45 cycles using (1) a published phase method and (2) a commercial activation/phase method.Patients were 62.2�9.7 years, 76% male. Sites of AF termination showed rotational/focal patterns by methods 1 and 2 (51/55 vs 55/55; P=0.13) in spatially conserved regions, yet fluctuated over time. Time points with no AF driver showed competing drivers elsewhere or disordered waves. Organized regions were detected for 61.6�23.9% and 70.6�20.6% of 1 minute per method (P=nonsignificant), confirmed by automatic phase tracking (P<0.05). To detect AF drivers with >90% sensitivity, 8 to 32 s of AF recordings were required depending on driver definition.Sites at which persistent AF terminated by ablation show organized activation that fluctuate over time, because of collision from concurrent organized zones or fibrillatory waves, yet recur in conserved spatial regions. Results were similar by 2 mapping methods. This network of competing mechanisms should be reconciled with existing disorganized or driver mechanisms for AF, to improve clinical mapping and ablation of persistent AF.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02997254.

View details for PubMedID 29884620
The prognostic benefit of cardiac resynchronization therapy is greater in concordant vs. discordant left bundle branch block in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) EUROPACE Padeletti, L., Aimo, A., Vishenvsky, B., Schwartz, A., McNitt, S., Wang, P. J., Moss, A. J., Emdin, M., Zareba, W. 2018; 20 (5): 794?800
Abstract

Discordant and concordant left bundle branch block (dLBBB/cLBBB) are characterized by negative or positive T waves, respectively, in lateral leads. We assessed if the two morphologies are associated with different clinical status and prognosis in patients with heart failure (HF) and current indication to Cardiac Resynchronization Therapy (CRT)/CRT-Defibrillator (CRT-D).Baseline electrocardiograms of 1270 patients with LBBB in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy cohort were analysed to identify dLBBB and cLBBB. The two groups were compared with respect to baseline clinical characteristics, primary endpoint (HF event or death), and secondary endpoint (ventricular tachycardia, ventricular fibrillation, or death) over a 3.5-year period, and benefit of CRT-D over implantable cardioverter defibrillator (ICD). dLBBB was identified in 909 (72%) patients, and cLBBB in 361 (28%). Patients with dLBBB were older, had more severe symptoms and systolic dysfunction, as well as higher brain natriuretic peptide. CRT-D was superior to ICD in patients with both LBBB morphologies. The occurrence of the primary outcome was significantly more frequent in patients with dLBBB than in those with cLBBB, both in the entire cohort (P = 0.005), and in the CRT-D arm (P = 0.002). There was a trend towards more frequent occurrence of the secondary endpoint in patients with dLBBB than in those with cLBBB, but statistical significance was not reached in the whole population or in the subgroup undergoing CRT-D. Among patients receiving CRT-D, dLBBB was an independent predictor of the primary endpoint.dLBBB morphology is associated with more severe HF clinical status and worse prognosis, even in patients receiving CRT-D, compared with cLBBB morphology.

View details for PubMedID 28398490
Clinical Implications of Ablation of Drivers for Atrial Fibrillation A Systematic Review and Meta-Analysis CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Baykaner, T., Rogers, A. J., Meckler, G. L., Zaman, J., Navara, R., Rodrigo, M., Alhusseini, M., Kowalewski, C. B., Viswanathan, M. N., Narayan, S. M., Clopton, P., Wang, P. J., Heidenreich, P. A. 2018; 11 (5)
View details for DOI 10.1161/CIRCEP.117.006119

View details for Web of Science ID 000439150300011
Geographic and racial representation and reported success rates of studies of catheter ablation for atrial fibrillation: Findings from the SMASH-AF meta-analysis study cohort JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Leef, G. C., Perino, A. C., Cluckey, A., Yunus, F. N., Askari, M., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2018; 29 (5): 747?55
View details for DOI 10.1111/jce.13439

View details for Web of Science ID 000433580000013
Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Navara, R., Leef, G., Shenasa, F., Kowalewski, C., Rogers, A. J., Meckler, G., Zaman, J. B., Baykaner, T., Park, S., Turakhia, M. P., Zei, P., Viswanathan, M., Wang, P. J., Narayan, S. M. 2018; 29 (5): 687?95
View details for DOI 10.1111/jce.13446

View details for Web of Science ID 000433580000005
Retrospective review of Arctic Front Advance Cryoballoon Ablation: a multicenter examination of second-generation cryoballoon (RADICOOL trial) JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Su, W., Orme, G., Hoyt, R., Baker, J., Compton, S., Fellows, C., Harding, J., Svinarich, J., Kowalski, M., Piedad, B., Kenigsberg, D., Seger, J., Ahmad, Z. K., Wang, P. 2018; 51 (3): 199?204
Abstract

Pulmonary vein isolation (PVI) via catheter ablation is an approved therapy for patients with drug-refractory and symptomatic atrial fibrillation (AF). Furthermore, cryoballoon is now considered to be as effective as focal radiofrequency catheter ablation. This study examines the second-generation cryoballoon performance in a US multicenter review of real-world practices.By retrospective chart collections, the long-term efficacy and safety of the cryoballoon procedure were assessed in 15 US centers. All patients had a history of drug-refractory symptomatic paroxysmal AF and were treated with a cryoballoon PVI strategy at the index ablation.Four hundred fifty-two patients were evaluated, and acute PVI was achieved in 99% of patients by cryoballoon catheter ablation. In 0.88% of patients (4/452), an additional focal ablation catheter was used to achieve acute PVI during the ablation procedure. Average procedure time was 128 (range 82 to 260)�min, using an average of 17 (range 1 to 19)�min of fluoroscopy. The most frequent adverse event was transient phrenic nerve injury (1.5%; 7/452 patients) which all resolved by the end of the procedure with no diaphragmatic dysfunction at discharge. There were no strokes, transient ischemic attacks, cardiac tamponade, atrioesophageal fistulas, or deaths during the study. At the 12-month efficacy endpoint, single-procedure success of freedom from atrial arrhythmia was 87% (393/452 patients).This real-world examination of the US practice demonstrates that second-generation cryoballoon ablation by PVI strategy is safe and effective among patients with paroxysmal AF.

View details for PubMedID 29478173
Cryoballoon Ablation for Atrial Fibrillation: a Comprehensive Review and Practice Guide KOREAN CIRCULATION JOURNAL Jin, E., Wang, P. J. 2018; 48 (2): 114?23
Abstract

The cryoballoon was invented to achieve circumferential pulmonary vein isolation more efficiently to compliment the shortcomings of point-by-point ablation by radiofrequency ablation (RFA). Its efficacy and safety were shown to be comparable to those of RFA, and the clinical outcomes have improved with the second-generation cryoballoon. The basic biophysics, implemental techniques, procedural recommendations, clinical outcomes, and complications of the cryoballoon are presented in this practical and systematic review.

View details for PubMedID 29441744

View details for PubMedCentralID PMC5861002
Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation. Journal of cardiovascular electrophysiology Navara, R., Leef, G., Shenasa, F., Kowalewski, C., Rogers, A. J., Meckler, G., Zaman, J. A., Baykaner, T., Park, S., Turakhia, M. P., Zei, P., Viswanathan, M., Wang, P. J., Narayan, S. M. 2018
Abstract

OBJECTIVE: To investigate mechanisms by which atrial fibrillation (AF) may terminate during ablation near the pulmonary veins before the veins are isolated (PVI).INTRODUCTION: It remains unstudied how AF may terminate during ablation before PVs are isolated, or how patients with PV reconnection can be arrhythmia-free. We studied patients in whom PV antral ablation terminated AF before PVI, using two independent mapping methods.METHODS: We studied patients with AF referred for ablation, in whom biatrial contact basket electrograms were studied by both an activation/phase mapping method and by a second validated mapping method reported not to create false rotational activity.RESULTS: In 22 patients (age 60.1 � 10.4, 36% persistent AF), ablation at sites near the PVs terminated AF (77% to sinus rhythm) prior to PVI. AF propagation revealed rotational (n=20) and focal (n=2) patterns at sites of termination by mapping method 1 and method 2. Both methods showed organized sites that were spatially concordant (P<0.001) with similar stability (P<0.001). Vagal slowing was not observed at sites of AF termination.DISCUSSION: PV antral regions where ablation terminated AF before PVI exhibited rotational and focal activation by two independent mapping methods. These data provide an alternative mechanism for the success of PVI, and may explain AF termination before PVI or lack of arrhythmias despite PV reconnection. Mapping such sites may enable targeted PV lesion sets and improved freedom from AF.

View details for PubMedID 29377478
Geographic and racial representation and reported success rates of studies of catheter ablation for atrial fibrillation: Findings from the SMASH-AF meta-analysis study cohort. Journal of cardiovascular electrophysiology Leef, G. C., Perino, A. C., Cluckey, A., Yunus, F. N., Askari, M., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2018
Abstract

INTRODUCTION: We performed a systematic review and meta-analysis of geographic and racial representation and reported success rates of studies of catheter ablation for atrial fibrillation (AF).METHODS AND RESULTS: We searched PubMed, Scopus, and Cochrane databases from 1/1/1990 to 8/1/2016 for trials and observational studies reporting AF ablation outcomes. Major exclusion criteria were insufficient reporting of outcomes, non-English language articles, and ablation strategies that were not prespecified and uniform. We described geographic and racial representation and single-procedure ablation success rates by country, controlling for patient demographics and study design characteristics. The analysis cohort included 306 studies (49,227 patients) from 28 countries. Over half of the paroxysmal (PAF) and nonparoxysmal AF (NPAF) treatment arms were conducted in 5 and 3 countries, respectively. Reporting of race or ethnicity demographics and outcomes were rare (1 study, 0.3%) and nonexistent, respectively. Unadjusted success rates by country ranged from 63.5% to 83.0% for PAF studies and 52.7% to 71.6% for NPAF studies, with substantial variation in patient demographics and study design. After controlling for covariates, South Korea and the United States had higher PAF ablation success rates, with large residual heterogeneity. NPAF ablation success rates were statistically similar by country.CONCLUSIONS: Studies of AF ablation have substantial variation in patient demographics, study design, and reported outcomes by country. There is limited geographic representation of trials and observational studies of AF ablation and a paucity of race- or ethnicity-stratified results. Future AF ablation studies and registries should aim to have broad representation by race, geography, and ethnicity to ensure generalizability.

View details for PubMedID 29364570
Clinical Implications of Ablation of Drivers for Atrial Fibrillation: A Systematic Review and Meta-Analysis. Circulation. Arrhythmia and electrophysiology Baykaner, T., Rogers, A. J., Meckler, G. L., Zaman, J., Navara, R., Rodrigo, M., Alhusseini, M., Kowalewski, C. A., Viswanathan, M. N., Narayan, S. M., Clopton, P., Wang, P. J., Heidenreich, P. A. 2018; 11 (5): e006119
Abstract

The outcomes from pulmonary vein isolation (PVI) for atrial fibrillation (AF) are suboptimal, but the benefits of additional lesion sets remain unproven. Recent studies propose ablation of AF drivers improves outcomes over PVI, yet with conflicting reports in the literature. We undertook a systematic literature review and meta-analysis to determine outcomes from ablation of AF drivers in addition to PVI or as a stand-alone procedure.Database search was done using the terms atrial fibrillation and ablation or catheter ablation and driver or rotor or focal impulse or FIRM (Focal Impulse and Rotor Modulation). We pooled data using random effects model and assessed heterogeneity with I2 statistic.Seventeen studies met inclusion criteria, in a cohort size of 3294 patients. Adding AF driver ablation to PVI reported freedom from AF of 72.5% (confidence interval [CI], 62.1%-81.8%; P<0.01) and from all arrhythmias of 57.8% (CI, 47.5%-67.7%; P<0.01). AF driver ablation when added to PVI or as stand-alone procedure compared with controls produced an odds ratio of 3.1 (CI, 1.3-7.7; P=0.02) for freedom from AF and an odds ratio of 1.8 (CI, 1.2-2.7; P<0.01) for freedom from all arrhythmias in 4 controlled studies. AF termination rate was 40.5% (CI, 30.6%-50.9%) and predicted favorable outcome from ablation(P<0.05).In controlled studies, the addition of AF driver ablation to PVI supports the possible benefit of a combined approach of AF driver ablation and PVI in improving single-procedure freedom from all arrhythmias. However, most studies are uncontrolled and are limited by substantial heterogeneity in outcomes. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to PVI.

View details for PubMedID 29743170
Patient and facility variation in costs of catheter ablation for atrial fibrillation. Journal of cardiovascular electrophysiology Perino, A. C., Fan, J., Schmitt, S., Kaiser, D. W., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Chang, A. Y., Turakhia, M. P. 2018
Abstract

Cost-effectiveness or value of cardiovascular therapies may be undermined by unwarranted cost variation, particularly for heterogeneous procedures such as catheter ablation for atrial fibrillation (AF). We sought to characterize cost variation of AF ablation in the U.S. health care system and the relationship between cost and outcomes.We performed a retrospective cohort study using data from the MarketScan� commercial claims and Medicare supplemental databases including patients who received an AF ablation from 2007 through 2011. We aggregated encounter cost, reflecting total payments received for the encounter, to the facility level to calculate median facility cost. We classified procedures as outpatient or inpatient and assessed for association between cost and 30-day and one-year outcomes. The analysis cohort included 9,415 AF ablations (59�11 years; 28% female; 52% outpatient) occurring at 327 facilities, with large cost variation across facilities (median: $25,100; 25th percentile: $18,900, 75th percentile: $35,600, 95th percentile: $57,800). Among outpatient procedures, there was reduced health care utilization in higher cost quintiles with reductions in rehospitalization at 30-days (Quintile 1: 16.1%, Quintile 5: 8.8%, p�<�0.001) and one-year (Quintile 1: 34.8%, Quintile 5: 25.6%, p�<�0.001), which remained significant in multivariate analysis.Although median costs of AF ablation are below amounts used in prior cost-effectiveness studies that demonstrated good value, large facility variation in cost suggests opportunities for cost reduction. However, for outpatient encounters, association of cost to modestly improved outcomes suggests cost containment strategies could have variable effects. This article is protected by copyright. All rights reserved.

View details for PubMedID 29864193
Identification and Characterization of Sites Where Persistent Atrial Fibrillation Is Terminated by Localized Ablation CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Zaman, J. B., Sauer, W. H., Alhusseini, M. I., Baykaner, T., Borne, R. T., Kowalewski, C. B., Busch, S., Zei, P. C., Park, S., Viswanathan, M. N., Wang, P. J., Brachmann, J., Krummen, D. E., Miller, J. M., Rappel, W., Narayan, S. M., Peters, N. S. 2018; 11 (1): e005258
Abstract

The mechanisms by which persistent atrial fibrillation (AF) terminates via localized ablation are not well understood. To address the hypothesis that sites where localized ablation terminates persistent AF have characteristics identifiable with activation mapping during AF, we systematically examined activation patterns acquired only in cases of unequivocal termination by ablation.We recruited 57 patients with persistent AF undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or organized tachycardia. For each site, we performed an offline analysis of unprocessed unipolar electrograms collected during AF from multipolar basket catheters using the maximum -dV/dt assignment to construct isochronal activation maps for multiple cycles. Additional computational modeling and phase analysis were used to study mechanisms of map variability. At all sites of AF termination, localized repetitive activation patterns were observed. Partial rotational circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%), and complete rotational activity in 12 of 57 (21%) cases. In computer simulations, incomplete segments of partial rotations coincided with areas of slow conduction characterized by complex, multicomponent electrograms, and variations in assigning activation times at such sites substantially altered mapped mechanisms.Local activation mapping at sites of termination of persistent AF showed repetitive patterns of rotational or focal activity. In computer simulations, complete rotational activation sequence was observed but was sensitive to assignment of activation timing particularly in segments of slow conduction. The observed phenomena of repetitive localized activation and the mechanism by which local ablation terminates putative AF drivers require further investigation.

View details for PubMedID 29330332

View details for PubMedCentralID PMC5769709
Ablation of Atrial Fibrillation Drivers ARRHYTHMIA & ELECTROPHYSIOLOGY REVIEW Baykaner, T., Zaman, J. B., Wang, P. J., Narayan, S. M. 2017; 6 (4): 195?201
Abstract

Pulmonary vein isolation (PVI) is central to ablation approaches for atrial fibrillation (AF), yet many patients still have arrhythmia recurrence after one or more procedures, despite evolving technologies for PVI. Ablation of localised AF drivers, which lie outside the pulmonary veins in many patients, is a practical approach that has been shown to improve success by many groups. Such localised drivers lie in atrial regions shown mechanistically to sustain AF in optical mapping and clinical studies of human AF, as well as computational and animal studies. Clinical studies now verify rotational activation by multiple mapping approaches in the same patients, at sites where ablation terminates persistent AF. This review article provides a mechanistic and clinical rationale to ablate localised drivers, and describes successful techniques for their ablation as well as pitfalls to avoid, which may explain discrepancies between results from some centres. We hope that this review will serve as a platform for future improvements in the patient-tailored ablation for complex arrhythmias.

View details for PubMedID 29326835

View details for PubMedCentralID PMC5739904
Update to Practice Standards for Electrocardiographic Monitoring in Hospital Settings: A Scientific Statement From the American Heart Association CIRCULATION Sandau, K. E., Funk, M., Auerbach, A., Barsness, G. W., Blum, K., Cvach, M., Lampert, R., May, J. L., McDaniel, G. M., Perez, M. V., Sendelbach, S., Sommargren, C. E., Wang, P. J. 2017; 136 (19): E273?E344
Abstract

This scientific statement provides an interprofessional, comprehensive review of evidence and recommendations for indications, duration, and implementation of continuous electro cardiographic monitoring of hospitalized patients. Since the original practice standards were published in 2004, new issues have emerged that need to be addressed: overuse of arrhythmia monitoring among a variety of patient populations, appropriate use of ischemia and QT-interval monitoring among select populations, alarm management, and documentation in electronic health records.Authors were commissioned by the American Heart Association and included experts from general cardiology, electrophysiology (adult and pediatric), and interventional cardiology, as well as a hospitalist and experts in alarm management. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Authors were assigned topics relevant to their areas of expertise, reviewed the literature with an emphasis on publications since the prior practice standards, and drafted recommendations on indications and duration for electrocardiographic monitoring in accordance with the American Heart Association Level of Evidence grading algorithm that was in place at the time of commissioning.The comprehensive document is grouped into 5 sections: (1) Overview of Arrhythmia, Ischemia, and QTc Monitoring; (2) Recommendations for Indication and Duration of Electrocardiographic Monitoring presented by patient population; (3) Organizational Aspects: Alarm Management, Education of Staff, and Documentation; (4) Implementation of Practice Standards; and (5) Call for Research.Many of the recommendations are based on limited data, so authors conclude with specific questions for further research.

View details for DOI 10.1161/CIR.0000000000000527

View details for Web of Science ID 000414615600001

View details for PubMedID 28974521
The continuous challenge of AF ablation: From foci to rotational activity. Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology Narayan, S. M., Vishwanathan, M. N., Kowalewski, C. A., Baykaner, T., Rodrigo, M., Zaman, J. A., Wang, P. J. 2017; 36 Suppl 1: 9?17
Abstract

Pulmonary vein isolation (PVI) is central to ablation approaches for atrial fibrillation (AF), yet many patients still have arrhythmia recurrence after one or more procedures despite the latest technology for PVI. Ablation of rotational or focal sources for AF, which lie outside the pulmonary veins in many patients, is a practical approach that has been shown to improve success by many groups. Localized sources lie in atrial regions shown mechanistically to sustain AF in optical mapping and clinical studies of human AF, as well as computational and animal studies. Because they arise in localized atrial regions, AF sources may explain central paradoxes in clinical practice - such as how limited ablation in patient specific sites can terminate persistent AF yet extensive anatomical ablation at stereotypical locations, which should extinguish disordered waves, does not improve success in clinical trials. Ongoing studies may help to resolve many controversies in the field of rotational sources for AF. Studies now verify rotational activation by multiple mapping approaches in the same patients, at sites where ablation terminates persistent AF. However, these studies also show that certain mapping methods are less effective for detecting AF sources than others. It is also recognized that the success of AF source ablation is technique dependent. This review article provides a mechanistic and clinical rationale to ablate localized sources (rotational and focal), and describes successful techniques for their ablation as well as pitfalls to avoid. We hope that this review will serve as a platform for future improvements in the patient-tailored ablation for complex arrhythmias.

View details for PubMedID 29126896
Hybrid Atrial Fibrillation Ablation: Current Status and a Look Ahead. Circulation. Arrhythmia and electrophysiology Khoynezhad, A., Ellenbogen, K. A., Al-Atassi, T., Wang, P. J., Kasirajan, V., Wang, X., Edgerton, J. R. 2017; 10 (10)
View details for PubMedID 29018166
Hybrid Atrial Fibrillation Ablation Current Status and a Look Ahead CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Khoynezhad, A., Ellenbogen, K. A., Al-Atassi, T., Wang, P. J., Kasirajan, V., Wang, X., Edgerton, J. R. 2017; 10 (10)
View details for DOI 10.1161/CIRCEP.117.005263

View details for Web of Science ID 000413093000006
Ablation of Focal Impulses and Rotational Sources: What Can Be Learned from Differing Procedural Outcomes? CURRENT CARDIOVASCULAR RISK REPORTS Narayan, S. M., Rodrigo, M., Kowalewski, C. B., Shenasa, F., Meckler, G. L., Vishwanathan, M. N., Baykaner, T., Zaman, J. B., Wang, P. J. 2017; 11 (9)
View details for DOI 10.1007/s12170-017-0552-7

View details for Web of Science ID 000408062700004
Treating Specialty and Outcomes in Newly Diagnosed Atrial Fibrillation From the TREAT-AF Study JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Perino, A. C., Fan, J., Schmitt, S. K., Askari, M., Kaiser, D. W., Deshmukh, A., Heidenreich, P. A., Swan, C., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2017; 70 (1): 78?86
Abstract

Atrial fibrillation (AF) occurs in many clinical contexts and is diagnosed and treated by clinicians across�many specialties. This approach has resulted in treatment variations.The goal of this study was to evaluate the association between treating specialty and AF outcomes among�patients newly diagnosed with AF.Using data from the TREAT-AF (Retrospective Evaluation and Assessment of Therapies in AF) study from�the Veterans Health Administration, patients with newly diagnosed, nonvalvular AF between 2004 and 2012�were identified who had at least 1 outpatient encounter with primary care or cardiology within 90 days of the AF diagnosis. Cox proportional hazards regression was used to evaluate the association between treating specialty and AF outcomes.Among 184,161 patients with newly diagnosed AF (age 70 � 11 years; 1.7% women; CHA2DS2-VASc score 2.6�� 1.7), 40% received cardiology care and 60% received primary care only. After adjustment for covariates, cardiology�care was associated with reductions in stroke (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.86 to 0.96; p�<�0.001) and death (HR: 0.89; 95% CI: 0.88 to 0.91; p�< 0.0001) and increases in hospitalizations for AF/supraventricular�tachycardia (HR: 1.38; 95% CI: 1.35 to 1.42; p�< 0.0001) and myocardial infarction (HR: 1.03; 95% CI: 1.00 to 1.05; p�< 0.04). The propensity-matched cohort had similar results. In mediation analysis, oral anticoagulation prescription within 90 days of diagnosis may have mediated reductions in stroke but did not mediate reductions in�survival.In patients with newly diagnosed AF, cardiology care was associated with improved outcomes, potentially mediated by early prescription of oral anticoagulation therapy. Although hypothesis-generating, these data�warrant serious consideration and study of health care system interventions at the time of new AF diagnosis.

View details for PubMedID 28662810
Predictive value of device-derived activity level for short-term outcomes in MADIT-CRT HEART RHYTHM Jame, S., Kutyifa, V., Polonsky, B., McNitt, S., Al-Ahmad, A., Moss, A. J., Zareba, W., Wang, P. J. 2017; 14 (7): 1081?86
Abstract

There are limited data on the prognostic importance of declining activity level in patients with heart failure.We aimed to assess the association of reduced activity level with adverse cardiovascular outcomes in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT).Final device interrogations from patients enrolled in the MADIT-CRT with cardiac resynchronization devices capable of recording percent daily activity level were assessed. To determine temporal change, standardized activity levels (SALs) comparing each week to the monthly activity 3 months prior were obtained. Death, heart failure events (HFEs)/death, and ventricular tachyarrhythmias (VTAs)/death were the primary end points of this study.The average absolute activity level and SAL of the final week prior to death or end of study were significantly lower in patients who died compared with those in patients who did not. The total cohort (N = 1008) was further randomized into 2 subgroups to identify (group 1) and validate an optimal threshold (group 2). Patients with >40% reduced SAL had a significantly increased 77-day short-term cumulative incidence of death (P = .0006), HFE/death (P < .0001), or VTA/death (P = .0248). After adjustment for clinical covariates, these patients remained at an increased risk for death (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5-4.9; P = .001), HFE/death (HR, 2.7; 95% CI, 1.8-3.9; P�? .001) and VTA/death (HR, 1.9; 95% CI, 1.31-2.6; P = .001). A decline in SAL following a nonfatal VTA and HFE was also associated with an increased probability of death.Decline in activity level is a short-term predictor for adverse cardiovascular events in patients with mild to moderate heart failure undergoing cardiac resynchronization.

View details for PubMedID 28347835
Multicentre safety of adding Focal Impulse and Rotor Modulation (FIRM) to conventional ablation for atrial fibrillation. Europace Krummen, D. E., Baykaner, T., Schricker, A. A., Kowalewski, C. A., Swarup, V., Miller, J. M., Tomassoni, G. F., Park, S., Viswanathan, M. N., Wang, P. J., Narayan, S. M. 2017; 19 (5): 769-774
Abstract

Focal Impulse and Rotor Modulation (FIRM) uses 64-electrode basket catheters to identify atrial fibrillation (AF)-sustaining sites for ablation, with promising results in many studies. Accordingly, new basket designs are being tested by several groups. We set out to determine the procedural safety of adding basket mapping and map-guided ablation to conventional pulmonary vein isolation (PVI).We collected 30?day procedural safety data in five US centres for consecutive patients undergoing FIRM plus PVI (FIRM-PVI) compared with contemporaneous controls undergoing PVI without FIRM. A total of 625 cases were included in this analysis: 325 FIRM-PVI and 300 PVI-controls. FIRM-PVI patients were more likely than PVI-controls to be male (83% vs. 66%, P?
View details for DOI 10.1093/europace/euw377

View details for PubMedID 28339546
Drivers of Persistent Atrial Fibrillation: Are Focal and Rotational Sites Transient or Stable Over Time? Navara, R., Leef, G., Shenasa, F., Kowalewski, C., Baykaner, T., Rogers, A., Zaman, J., Park, H., Zei, P., Wang, P. J., Narayan, S. M. WILEY. 2017: 606?7
View details for Web of Science ID 000403296100062
What Explains Atrial Fibrillation Mechanisms at Sites Where Ablation Terminates Persistent Atrial Fibrillation Prior to Pulmonary Vein Isolation? Navara, R., Meckler, G. L., Kowalewski, C. B., Shenasa, F., Baykaner, T., Zaman, U. B., Al-Husseini, M., Hossainy, S., Krummen, D., Brachmann, J., Viswanathan, M., Park, S., Turakhia, M., Wang, P. J., Narayan, S. M. WILEY. 2017: 607
View details for Web of Science ID 000403296100063
Effect of cardiac resynchronization therapy on the risk of ventricular tachyarrhythmias in patients with chronic kidney disease ANNALS OF NONINVASIVE ELECTROCARDIOLOGY Daimee, U. A., Biton, Y., Moss, A. J., Zareba, W., Cannom, D., Klein, H., Solomon, S., Ruwald, M. H., McNitt, S., Polonsky, B., Wang, P. J., Goldenberg, I., Kutyifa, V. 2017; 22 (3)
View details for DOI 10.1111/anec.12404

View details for Web of Science ID 000404596800003
Two Independent Mapping Techniques Identify Rotational Activity Patterns at Sites of Local Termination during Persistent Atrial Fibrillation. Journal of cardiovascular electrophysiology Alhusseini, M., Vidmar, D., Meckler, G. L., Kowalewski, C., Shenasa, F., Wang, P. J., Narayan, S. M., Rappel, W. 2017
Abstract

The mechanisms for atrial fibrillation (AF) are unclear in part because diverse mapping techniques yield diverse maps, ranging from stable organized sources to highly disordered waves. We hypothesized that AF mechanisms may be clarified if mapping techniques were compared in the same patients, and referenced to a clinical endpoint. We compared two independent AF mapping techniques in patients in whom ablation terminated persistent AF before pulmonary vein isolation (PVI).We identified 12 patients with persistent AF (61.2 � 10.8 years, four female) in whom mapping with 64 pole baskets and technique 1 (activation/phase mapping, FIRM) identified rotational activation patterns during at least 50% of the 4-second mapping interval and targeted ablation at these rotational sites terminated AF to sinus rhythm (n = 10) or atrial tachycardia. We analyzed the unipolar electrograms of these patients to determine phase maps of activation by an independent technique 2 (Kuklik, Schotten et�al., IEEE Trans Biomed Eng 2015). Compared to technique 1, technique 2 revealed a source in 12 of 12 (100%) cases with spatial concordance in all cases (P <0.05) and similar rotational characteristics.At sites where ablation terminated persistent AF, two independent mapping techniques identified stable rotational activation for multiple cycles that drove peripheral disorder. Future comparative studies referenced to a clinical endpoint may help reconcile if discrepancies between AF mapping studies reports represent techniques, patient populations or models of AF, and improve mapping to better guide ablation.

View details for DOI 10.1111/jce.13177

View details for PubMedID 28185348
Electrocardiographic spatial loops indicate organization of atrial fibrillation minutes before ablation-related transitions to atrial tachycardia. Journal of electrocardiology Baykaner, T., Trikha, R., Zaman, J. A., Krummen, D. E., Wang, P. J., Narayan, S. M. 2017
Abstract

During ablation for atrial fibrillation (AF), it is challenging to anticipate transitions to organized tachycardia (AT). Defining indices of this transition may help to understand fibrillatory conduction and help track therapy.To determine the timescale over which atrial fibrillation (AF) organizes en route to atrial tachycardia (AT) using the ECG referenced to intracardiac electrograms.In 17 AF patients at ablation (58.7�9.6years; 53% persistent AF) we analyzed spatial loops of atrial activity on the ECG and intracardiac electrograms over successive timepoints. Loops were tracked at precisely 15, 10, 5, 3 and 1min prior to defined transitions of AF to AT.Organizational indices reliably quantified changes from AF to AT. Spatiotemporal AF organization on the ECG was identifiable at least 15min before AT was established (p=0.02).AF shows anticipatory global organization on the ECG minutes before AT is clinically evident. These results offer a foundation to establish when AF therapy is on an effective path, and for a quantitative classification separating AT from AF.

View details for DOI 10.1016/j.jelectrocard.2017.01.007

View details for PubMedID 28108014
Sex Differences in Inappropriate ICD Device Therapies: MADIT-II and MADIT-CRT. Journal of cardiovascular electrophysiology Tompkins, C. M., McNitt, S., Polonsky, B., Daubert, J. P., Wang, P. J., Moss, A. J., Zareba, W., Kutyifa, V. 2017; 28 (1): 94?102
Abstract

Approximately 10-20% of ICD recipients receive inappropriate device therapies. The purpose of this study was to compare the frequency of inappropriate therapies (IT) between men and women enrolled in MADIT II and MADIT-CRT, and assess for potential adverse outcomes.The electrograms for each ICD or CRT-D therapy, defined as either ATP or shock, were reviewed by adjudication committees for both studies. ICD therapy was considered inappropriate if it was delivered for reasons other than VT/VF. The rhythm triggering IT was categorized as atrial fibrillation/flutter, SVT, or inappropriate sensing when possible.One thousand nine hundred and fifty-four men and 556 women received ICD or CRT-D devices. The risk of IT was significantly lower in women than men (9.2% vs. 13.5%, P = 0.006). The most common cause of IT in men was atrial fibrillation (38%) and SVT in women (43%). Inappropriate shock was not associated with increased mortality in either women (HR 0.82 [95% CI 0.11-6.08]; P = NS) or men (HR 1.37 [95% CI 0.75-2.48]; P = NS) by multivariate analysis. Conversely, appropriate shock therapy strongly correlated with increased risk of death during subsequent post-shock follow-up in women (HR 5.99 [95% CI 2.75-13.02]; P < 0.0001) and men (HR 2.61 [95% CI 1.82-3.74]; P < 0.0001).Women experience significantly less IT than men, partially explained by the increased frequency of atrial fibrillation in men. IT was not associated with increased mortality in either sex. Appropriate shock therapy was a strong predictor of death in both, with women showing a 2-fold higher risk than men during post-shock long-term follow-up.

View details for PubMedID 27696593
Myocardial bridging is associated with exercise-induced ventricular arrhythmia and increases in QT dispersion. Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc Nishikii-Tachibana, M., Pargaonkar, V. S., Schnittger, I., Haddad, F., Rogers, I. S., Tremmel, J. A., Wang, P. J. 2017
Abstract

A myocardial bridge (MB) has been associated with ventricular arrhythmia and sudden death during exercise. QT dispersion (QTd) is a measure of abnormal repolarization and may predict ventricular arrhythmia. We investigated the frequency of ventricular arrhythmias during exercise and the QTd at rest and after exercise, in patients with an MB compared to a normal cohort.We studied the rest and stress ECG tracings of patients with an MB suspected by focal septal buckling on exercise echocardiography (EE) (Echo-MB group, N�=�510), those with an MB confirmed by another examination (MB group, N�=�110), and healthy controls (Control group, N�=�198).The frequency of exercise-induced premature ventricular contractions (PVCs) was significantly higher in the Echo-MB and MB groups compared with the Control group (both p�<�.001). In all, 25 patients (4.9%) in the Echo-MB group, seven patients (6.4%) in the MB group and no patients in the Control group had exercise-induced non-sustained ventricular tachycardia (NSVT). There was no difference in the baseline QTd between the groups. In the Echo-MB and MB groups, QTd postexercise increased significantly when compared with baseline (both p�<�.001). Patients with NSVT had a higher frequency of male gender and an even greater increase in QTd with exercise compared with the non-NSVT group.There is an increased frequency of exercise-induced PVCs and NSVT in patients with MBs. Exercise significantly increases QTd in MB patients, with an even greater increase in QTd in MB patients with NSVT. Exercise in MB patients results in ventricular arrhythmias and abnormalities in repolarization.

View details for PubMedID 28921787
Spatial relationship of sites for atrial fibrillation drivers and atrial tachycardia in patients with both arrhythmias. International journal of cardiology Baykaner, T., Zaman, J. A., Rogers, A. J., Navara, R., AlHusseini, M., Borne, R. T., Park, S., Wang, P. J., Krummen, D. E., Sauer, W. H., Narayan, S. M. 2017; 248: 188?95
Abstract

Atrial fibrillation (AF) often converts to and from atrial tachycardia (AT), but it is undefined if these rhythms are mechanistically related in such patients. We tested the hypothesis that critical sites for AT may be related to regional AF sources in patients with both rhythms, by mapping their locations and response to ablation on transitions to and from AF.From 219 patients undergoing spatial mapping of AF prior to ablation at 3 centers, we enrolled 26 patients in whom AF converted to AT by ablation (n=19) or spontaneously (n=7; left atrial size 42�6cm, 38% persistent AF). Both atria were mapped in both rhythms by 64-electrode baskets, traditional activation maps and entrainment.Each patient had a single mapped AT (17 reentrant, 9 focal) and 3.7�1.7 AF sources. The mapped AT spatially overlapped one AF source in 88% (23/26) of patients, in left (15/23) or right (8/23) atria. AF transitioned to AT by 3 mechanisms: (a) ablation anchoring AF rotor to AT (n=13); (b) residual, unablated AF source producing AT (n=6); (c) spontaneous slowing of AF rotor leaving reentrant AT at this site without any ablation (n=7). Electrogram analysis revealed a lower peak-to-peak voltage at overlapping sites (0.36�0.2mV vs 0.49�0.2mV p=0.03).Mechanisms responsible for AT and AF may arise in overlapping atrial regions. This mechanistic inter-relationship may reflect structural and/or functional properties in either atrium. Future work should delineate how acceleration of an organized AT may produce AF, and whether such regions can be targeted a priori to prevent AT recurrence post AF ablation.

View details for PubMedID 28733070
Effect of Significant Weight Change on Inappropriate Implantable Cardioverter-Defibrillator Therapy PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Daimee, U. A., Biton, Y., Aktas, M. K., Zannad, F., Klein, H., Szepietowska, B., Mcnitt, S., Polonsky, B., Wang, P. J., Zareba, W., Moss, A. J., Kutyifa, V. 2017; 40 (1): 9?16
Abstract

Weight loss has been associated with adverse outcomes among heart failure (HF) patients, including those receiving cardiac resynchronization therapy with defibrillator (CRT-D). The effect of significant weight change on inappropriate implantable cardioverter-defibrillator (ICD) therapy among CRT-D patients is not well understood.We evaluated the impact of significant weight change at 1 year on subsequent inappropriate ICD therapy during follow-up among 993 CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. Patients were divided into three subgroups based on weight change at 1 year after enrollment: weight loss (weight loss ? 5%), weight gain (weight gain ? 5%), and stable weight (weight loss and weight gain < 5%). The primary end point was inappropriate ICD therapy. Secondary end point included inappropriate ICD therapy related to supraventricular arrhythmias (SVAs).There were 102 (10.3%) patients who experienced weight loss, 689 (69.4%) whose weight was stable, and 202 (20.3%) who gained weight at 1 year. Patients with weight loss had increased risk of subsequent inappropriate ICD therapy relative to patients with stable weight (hazard ratio [HR] = 2.35, 95% confidence interval [CI]: 1.39-3.98, P = 0.001) or weight gain (HR = 2.27, 95% CI: 1.18-4.38, P = 0.014). Furthermore, patients losing weight were at greater risk of subsequent inappropriate ICD therapy related to SVAs when compared to patients with stable weight (HR = 2.16, 95% CI: 1.18-3.95, P = 0.013) or weight gain (HR = 2.02, 95% CI: 0.95-4.29, P = 0.068).In mild HF patients receiving CRT-D, significant weight loss at 1 year is associated with increased risk of subsequent inappropriate ICD therapy, including risk related to SVAs.

View details for PubMedID 27808410
Recurrent Post-Ablation Paroxysmal Atrial Fibrillation Shares Substrates With Persistent Atrial Fibrillation : An 11-Center Study. JACC. Clinical electrophysiology Zaman, J. A., Baykaner, T., Clopton, P., Swarup, V., Kowal, R. C., Daubert, J. P., Day, J. D., Hummel, J., Schricker, A. A., Krummen, D. E., Mansour, M., Tomassoni, G. F., Wheelan, K. R., Vishwanathan, M., Park, S., Wang, P. J., Narayan, S. M., Miller, J. M. 2017; 3 (4): 393?402
Abstract

The role of atrial fibrillation (AF) substrates is unclear in patients with paroxysmal AF (PAF) that recurs after pulmonary vein isolation (PVI). We hypothesized that patients with recurrent post-ablation (redo) PAF despite PVI have electrical substrates marked by rotors and focal sources, and structural substrates that resemble persistent AF more than patients with (de novo) PAF at first ablation.In 175 patients at 11 centers, we compared AF substrates in both atria using 64 pole-basket catheters and phase mapping, and indices of anatomical remodeling between patients with de novo or redo PAF and first ablation for persistent AF.Sources were seen in all patients. More patients with de novo PAF (78.0%) had sources near PVs than patients with redo PAF (47.4%, p=0.005) or persistent AF (46.9%, p=0.001). The total number of sources per patient (p=0.444), and number of non-PV sources (p=0.701) were similar between groups, indicating that redo PAF patients had residual non-PV sources after elimination of PV sources by prior PVI. Structurally, left atrial size did not separate de novo from redo PAF (49.5�9.5 vs. 49.0�7.1mm, p=0.956) but was larger in patients with persistent AF (55.2�8.4mm, p=0.001).Patients with paroxysmal AF despite prior PVI show electrical substrates that resemble persistent AF more closely than patients with paroxysmal AF at first ablation. Notably, these subgroups of paroxysmal AF are indistinguishable by structural indices. These data motivate studies of trigger versus substrate mechanisms for patients with recurrent paroxysmal AF after PVI.

View details for PubMedID 28596994
Safety and Clinical Outcomes of Catheter Ablation of Atrial Fibrillation in Patients With Chronic Kidney Disease JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Ullal, A. J., Kaiser, D. W., Fan, J., Schmitt, S. K., Than, C. T., Winkelmayer, W. C., Heidenreich, P. A., Piccini, J. P., Perez, M. V., Wang, P. J., Turakhia, M. P. 2017; 28 (1): 39-48
Abstract

Data regarding catheter ablation of atrial fibrillation (AF) in patients with chronic kidney disease (CKD) is limited. We therefore assessed the association of CKD with common safety and clinical outcomes in a nationwide sample of ablation recipients.Using MarketScan(�) Commercial Claims and Medicare Supplemental Databases, we evaluated 30-day safety and 1-year clinical outcomes in patients who underwent a first AF ablation procedure between 2007 and 2011. We calculated frequency of common 30-day complications and calculated frequencies, incidence rates, and Cox proportional hazards for outcomes at 1-year postablation.Of 21,091 patients included, 1,593 (7.6%) had CKD. Patients with CKD were older (64 years vs. 59 years, P < 0.001) with higher CHA2 DS2 -VASc scores (3.2 vs. 1.8, P < 0.001). At 30 days postablation, patients with CKD had similar rates of stroke/TIA (0.13% vs. 0.13%, P = 0.99), perforation/tamponade (3.2% vs. 3.1%, P = 0.83), and vascular complications (2.4% vs. 2.2%, P = 0.59) as patients without CKD, but were more likely to be hospitalized for heart failure (2.1% vs. 0.4%, P < 0.001). In multivariate analysis, there were no significant differences in hazards of AF hospitalization (adjusted HR: 1.02, 95%CI: 0.87-1.20), cardioversion (adjusted HR: 0.99, 95%CI: 0.87-1.12), or repeat AF ablation (adjusted HR: 0.89, 95%CI: 0.76-1.06) at 1 year.Among patients selected for AF ablation, those with and without CKD had similar rates of postprocedural complications although they were more likely to be re-admitted for heart failure. CKD was not independently associated with AF hospitalization, cardioversion, and repeat ablation. These findings can inform clinical decision-making in patients with AF and CKD.

View details for DOI 10.1111/jce.13118

View details for Web of Science ID 000393901900004
Sex Differences in Inappropriate ICD Device Therapies: MADIT-II and MADIT-CRT JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Tompkins, C. M., McNitt, S., Polonsky, B., Daubert, J. P., Wang, P. J., Moss, A. J., Zareba, W., Kutyifa, V. 2017; 28 (1): 94-102
Abstract

Approximately 10-20% of ICD recipients receive inappropriate device therapies. The purpose of this study was to compare the frequency of inappropriate therapies (IT) between men and women enrolled in MADIT II and MADIT-CRT, and assess for potential adverse outcomes.The electrograms for each ICD or CRT-D therapy, defined as either ATP or shock, were reviewed by adjudication committees for both studies. ICD therapy was considered inappropriate if it was delivered for reasons other than VT/VF. The rhythm triggering IT was categorized as atrial fibrillation/flutter, SVT, or inappropriate sensing when possible.One thousand nine hundred and fifty-four men and 556 women received ICD or CRT-D devices. The risk of IT was significantly lower in women than men (9.2% vs. 13.5%, P = 0.006). The most common cause of IT in men was atrial fibrillation (38%) and SVT in women (43%). Inappropriate shock was not associated with increased mortality in either women (HR 0.82 [95% CI 0.11-6.08]; P = NS) or men (HR 1.37 [95% CI 0.75-2.48]; P = NS) by multivariate analysis. Conversely, appropriate shock therapy strongly correlated with increased risk of death during subsequent post-shock follow-up in women (HR 5.99 [95% CI 2.75-13.02]; P < 0.0001) and men (HR 2.61 [95% CI 1.82-3.74]; P < 0.0001).Women experience significantly less IT than men, partially explained by the increased frequency of atrial fibrillation in men. IT was not associated with increased mortality in either sex. Appropriate shock therapy was a strong predictor of death in both, with women showing a 2-fold higher risk than men during post-shock long-term follow-up.

View details for DOI 10.1111/jce.13102

View details for Web of Science ID 000393901900011
Regional Longitudinal Deformation Improves Prediction of Ventricular Tachyarrhythmias in Patients With Heart Failure With Reduced Ejection Fraction: A MADIT-CRT Substudy (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) CIRCULATION-CARDIOVASCULAR IMAGING Biering-Sorensen, T., Knappe, D., Pouleur, A., Claggett, B., Wang, P. J., Moss, A. J., Solomon, S. D., Kutyifa, V. 2017; 10 (1)
Abstract

Left ventricular dysfunction is a known predictor of ventricular arrhythmias. We hypothesized that measures of regional longitudinal deformation by speckle-tracking echocardiography predict ventricular tachyarrhythmias and provide incremental prognostic information over clinical and conventional echocardiographic characteristics.We studied 1064 patients enrolled in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) with speckle-tracking data available. Peak longitudinal strain was obtained for the septal, lateral, anterior, and inferior myocardial walls at baseline. The end point was the first event of ventricular tachycardia (VT) or fibrillation (VF). During the median follow-up of 2.9 years, 254 (24%) patients developed VT/VF. Patients with VT/VF had significantly lower left ventricular ejection fraction (28.3% versus 29.5%; P<0.001) and longitudinal strain in all myocardial walls compared with patients without VT/VF (anterior-strain, -7.7% versus -8.8%; P<0.001; lateral-strain, -7.3% versus -7.9%; P=0.022; inferior-strain, -8.3% versus -9.9%; P<0.001; septal-strain, -9.1% versus -10.0%; P<0.001). After multivariate adjustment, only anterior and inferior longitudinal strain remained independent predictors of VT/VF (anterior: hazard ratio, 1.08 [1.03-1.13]; P=0.001; inferior: hazard ratio, 1.08 [1.04-1.12]; P<0.001; per 1% absolute decrease for both). When including B-type natriuretic peptide in the model, only a decreasing myocardial function in the inferior myocardial wall predicted VT/VF (hazard ratio, 1.05 [1.00-1.11]; P=0.039). Only strain obtained from the inferior myocardial wall provided incremental prognostic information for VT/VF over clinical and echocardiographic parameters (C statistic 0.71 versus 0.69; P=0.005).Assessment of regional longitudinal myocardial deformation in the inferior region provided incremental prognostic information over clinical and echocardiographic risk factors in predicting ventricular tachyarrhythmias.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

View details for DOI 10.1161/CIRCIMAGING.116.005096

View details for Web of Science ID 000394390100004

View details for PubMedID 28003221
Effect of cardiac resynchronization therapy on the risk of ventricular tachyarrhythmias in patients with chronic kidney disease. Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc Daimee, U. A., Biton, Y., Moss, A. J., Zareba, W., Cannom, D., Klein, H., Solomon, S., Ruwald, M. H., McNitt, S., Polonsky, B., Wang, P. J., Goldenberg, I., Kutyifa, V. 2017; 22 (3)
Abstract

The effect of chronic kidney disease (CKD) on benefit from cardiac resynchronization therapy with defibrillator (CRT-D) in reducing ventricular tachyarrhythmia (VTA) risk among mild heart failure (HF) patients is not well understood.We evaluated the impact of baseline renal function on VTAs in 1274 left bundle branch block (LBBB) patients enrolled in MADIT-CRT. Two prespecified subgroups were created based on estimated glomerular filtration rate (GFR): GFR <60 (n�=�413) and GFR ?60�ml/min/1.73�m2 (n�=�861). Primary end point was ventricular tachycardia/ventricular fibrillation/death (VT/VF/death). Secondary end points were any VT/VF and ventricular tachycardia ? 200�bpm or VF (fast VT/VF).There were 413 (32%) LBBB patients presenting with CKD, primarily of moderate severity (GFR mean 48.1��8.3). For patients with and without CKD, CRT-D was associated with lower risk of the primary end point (GFR<60: HR�=�0.61, 95% CI: 0.41-0.89, p�=�.010; GFR?60: HR�=�0.58, 95% CI: 0.52-0.89, p�=�.005), relative to ICD-only treatment. For patients in both renal function categories, CRT-D in comparison to ICD alone was associated with lower risk of VT/VF (GFR<60: HR�=�0.68, 95% CI: 0.42-1.10, p�=�.113; GFR?60: HR�=�0.65, 95% CI: 0.48-0.88, p�=�.005) and fast VT/VF (GFR<60: HR�=�0.49, 95% CI: 0.25-0.96, p�=�.038; GFR?60: HR�=�0.55, 95% CI: 0.39-0.80, p�=�.001), when accounting for competing mortality risk. This effect was independent of CRT-induced reverse remodeling.Among mild HF patients with LBBB, those with and without CKD both derived benefit from CRT-D in risk reduction in VTAs, independent of cardiac reverse remodeling.

View details for PubMedID 27629147
Overview of Balloon Approaches to AF Ablation Some Like it Hot? JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Wang, P. J. 2016; 68 (25): 2758?60
View details for PubMedID 28007138
Effectiveness and Safety of an Independently Run Nurse Practitioner Outpatient Cardioversion Program (2009 to 2014) AMERICAN JOURNAL OF CARDIOLOGY Norton, L., Tsiperfal, A., Cook, K., Bagdasarian, A., Varady, J., Shah, M., Wang, P. 2016; 118 (12): 1842-1846
Abstract

Sustained growth in the arrhythmia population at Stanford Health Care led to an independent nurse practitioner-run outpatient direct current cardioversion (DCCV) program in 2012. DCCVs performed by a medical doctor, a nurse practitioner under supervision, or nurse practitioners from 2009 to 2014 were compared for safety and efficacy. A retrospective review of the electronic medical records system (Epic) was performed on biodemographic data, cardiovascular risk factors, medication history, procedural data, and DCCV outcomes. A total of 869 DCCVs were performed on 557 outpatients. Subjects were largely men with an average age of 65�years; 1/3 were obese; most had atrial fibrillation; and majority of subjects were on warfarin. The success rate of the DCCVs was 93.4% (812 of 869) with no differences among the groups. There were no short-term complications: stroke, myocardial infarction, or death. The length of stay was shortest in the NP group compared to the other groups (p <0.001). In conclusion, the success rate of DCCV in all groups was extremely high, and there were no complications in any of the DCCV groups.

View details for DOI 10.1016/j.amjcard.2016.08.074

View details for Web of Science ID 000389868400011

View details for PubMedID 27771002
Safety and Clinical Outcomes of Catheter Ablation of Atrial Fibrillation in Patients with Chronic Kidney Disease. Journal of cardiovascular electrophysiology Ullal, A. J., Kaiser, D. W., Fan, J., Schmitt, S., Than, C. T., Winkelmayer, W. C., Heidenreich, P. A., Piccini, J. P., Perez, M. V., Wang, P. J., Turakhia, M. P. 2016
Abstract

Data regarding catheter ablation of atrial fibrillation (AF) in patients with chronic kidney disease (CKD) is limited. We therefore assessed the association of CKD with common safety and clinical outcomes in a nationwide sample of ablation recipients.Using MarketScan(�) Commercial Claims and Medicare Supplemental Databases, we evaluated 30-day safety and 1-year clinical outcomes in patients who underwent a first AF ablation procedure between 2007 and 2011. We calculated frequency of common 30-day complications and calculated frequencies, incidence rates, and Cox proportional hazards for outcomes at 1-year postablation.Of 21,091 patients included, 1,593 (7.6%) had CKD. Patients with CKD were older (64 years vs. 59 years, P < 0.001) with higher CHA2 DS2 -VASc scores (3.2 vs. 1.8, P < 0.001). At 30 days postablation, patients with CKD had similar rates of stroke/TIA (0.13% vs. 0.13%, P = 0.99), perforation/tamponade (3.2% vs. 3.1%, P = 0.83), and vascular complications (2.4% vs. 2.2%, P = 0.59) as patients without CKD, but were more likely to be hospitalized for heart failure (2.1% vs. 0.4%, P < 0.001). In multivariate analysis, there were no significant differences in hazards of AF hospitalization (adjusted HR: 1.02, 95%CI: 0.87-1.20), cardioversion (adjusted HR: 0.99, 95%CI: 0.87-1.12), or repeat AF ablation (adjusted HR: 0.89, 95%CI: 0.76-1.06) at 1 year.Among patients selected for AF ablation, those with and without CKD had similar rates of postprocedural complications although they were more likely to be re-admitted for heart failure. CKD was not independently associated with AF hospitalization, cardioversion, and repeat ablation. These findings can inform clinical decision-making in patients with AF and CKD.

View details for DOI 10.1111/jce.13118

View details for PubMedID 27782345
Novel usage of the cryoballoon catheter to achieve large area atrial substrate modification in persistent and long-standing persistent atrial fibrillation JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Su, W. W., Alzubaidi, M., Tseng, R., Jebaily, N., Lin, Y., Wang, P. J. 2016; 46 (3): 275-285
Abstract

The cryoballoon catheter has proven to be both safe and effective when used for pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). More recently, the cryoballoon catheter has demonstrated the ability to create durable, transmural, and large areas of PV ablation. However, persistent and long-standing persistent AF can require additional cardiac substrate modification(s) before a patient is returned to normal sinus rhythm. Yet, no study has reported the techniques necessary to achieve extra-PV lesion sets using the cryoballoon catheter.Cryoballoon ablation was completed in 225 patients with varying degrees of AF disease. In several cases, the balloon was used for more than PV isolation. This study examines the 11 anatomical cardiac locations where extra-PV lesion sets were utilized.This study demonstrates that these extra-PV ablations can be done safely with the balloon catheter (3.6�% total complication rate). The 12-month efficacy (freedom from all atrial arrhythmia) using these techniques was 88�% in 88 patients with paroxysmal AF, 71�% in 75 patients with persistent AF, and 55�% in 62 patients with long-standing persistent AF. While using this protocol, mean procedure time was 2.2?�?0.6�h, and average fluoroscopy time was 4.2?�?2.2�min.The cryoballoon catheter can be used to make effective and safe extra-PV lesions. However, these techniques will need to be validated in more multi-center studies with review of complication rates and long-term freedom from AF.

View details for DOI 10.1007/s10840-016-0120-y

View details for Web of Science ID 000387109800010

View details for PubMedID 26936265
Bipolar left ventricular pacing is associated with significant reduction in heart failure or death in CRT-D patients with LBBB HEART RHYTHM Jame, S., Kutyifa, V., Aktas, M. K., McNitt, S., Polonsky, B., Al-Ahmad, A., Zareba, W., Moss, A., Wang, P. J. 2016; 13 (7): 1468-1474
Abstract

There are limited data on the significance of left ventricular (LV) lead pacing polarity to predict clinical outcomes.We aimed to determine the association between the LV lead pacing polarity for heart failure (HF) or death and ventricular tachyarrhythmias (VTA) in patients enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy), receiving a cardiac resynchronization therapy device with implanted cardioverter-defibrillator (CRT-D).We retrospectively analyzed LV pacing polarity. Patients with LV bipolar leads paced between LV ring and LV tip were identified as True Bipolar, while those with LV bipolar leads paced between LV tip or LV ring and right ventricular coil or unipolar leads were identified as Unipolar/Extended Bipolar. Kaplan-Meier survival analyses and multivariate Cox proportional hazards regression models were used.Of the 969 patients, 421 had True Bipolar pacing while the remainder (n = 548) had Unipolar/Extended Bipolar pacing. Among patients with left bundle branch block (LBBB), True Bipolar pacing was associated with lower cumulative incidence of death (P = .022) and HF/death (P = .046) compared to those with Unipolar/Extended Bipolar LV pacing. After adjustment for clinical covariates, bipolar LV pacing in LBBB patients was associated with 54% lower risk for death (HR: 0.46; 95% CI: 0.24-0.88; P = .020) and 32% lower risk for HF/death (HR: 0.68; 95% CI: 0.46-1.00; P = .048) compared to Unipolar/Extended Bipolar LV pacing, but not in those with non-LBBB. No association was seen with risk of ventricular tachyarrhythmia.True Bipolar LV pacing configuration is associated with a significantly lower risk of HF/death and all-cause mortality in CRT-D patients with LBBB.

View details for DOI 10.1016/j.hrthm.2016.03.009

View details for Web of Science ID 000378090000014

View details for PubMedID 26961303
Cost-Effectiveness of Percutaneous Closure of the Left Atrial Appendage in Atrial Fibrillation Based on Results From PROTECT AF Versus PREVAIL CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Freeman, J. V., Hutton, D. W., Barnes, G. D., Zhu, R. P., Owens, D. K., Garber, A. M., Go, A. S., Hlatky, M. A., Heidenreich, P. A., Wang, P. J., Al-Ahmad, A., Turakhia, M. P. 2016; 9 (6)
Abstract

Randomized trials of left atrial appendage (LAA) closure with the Watchman device have shown varying results, and its cost effectiveness compared with anticoagulation has not been evaluated using all available contemporary trial data.We used a Markov decision model to estimate lifetime quality-adjusted survival, costs, and cost effectiveness of LAA closure with Watchman, compared directly with warfarin and indirectly with dabigatran, using data from the long-term (mean 3.8 year) follow-up of Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation (PROTECT AF) and Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation (PREVAIL) randomized trials. Using data from PROTECT AF, the incremental cost-effectiveness ratios compared with warfarin and dabigatran were $20?486 and $23?422 per quality-adjusted life year, respectively. Using data from PREVAIL, LAA closure was dominated by warfarin and dabigatran, meaning that it was less effective (8.44, 8.54, and 8.59 quality-adjusted life years, respectively) and more costly. At a willingness-to-pay threshold of $50?000 per quality-adjusted life year, LAA closure was cost effective 90% and 9% of the time under PROTECT AF and PREVAIL assumptions, respectively. These results were sensitive to the rates of ischemic stroke and intracranial hemorrhage for LAA closure and medical anticoagulation.Using data from the PROTECT AF trial, LAA closure with the Watchman device was cost effective; using PREVAIL trial data, Watchman was more costly and less effective than warfarin and dabigatran. PROTECT AF enrolled more patients and has substantially longer follow-up time, allowing greater statistical certainty with the cost-effectiveness results. However, longer-term trial results and postmarketing surveillance of major adverse events will be vital to determining the value of the Watchman in clinical practice.

View details for DOI 10.1161/CIRCEP.115.003407

View details for PubMedID 27307517
Cost-Effectiveness of Percutaneous Closure of the Left Atrial Appendage in Atrial Fibrillation Based on Results From PROTECT AF Versus PREVAIL CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Freeman, J. V., Hutton, D. W., Barnes, G. D., Zhu, R. P., Owens, D. K., Garber, A. M., Go, A. S., Hlatky, M. A., Heidenreich, P. A., Wang, P. J., Al-Ahmad, A., Turakhia, M. P. 2016; 9 (6)
View details for DOI 10.1161/CIRCEP.115.003407

View details for Web of Science ID 000378143300006
Experiences and Perceived Needs of Patients Living with Atrial Fibrillation Ottoboni, L. K., Wang, P. J., Rehm, R. WILEY-BLACKWELL. 2016: 654
View details for Web of Science ID 000378397900059
Electrocardiographic Early Repolarization A Scientific Statement From the American Heart Association CIRCULATION Patton, K. K., Ellinor, P. T., Ezekowitz, M., Kowey, P., Lubitz, S. A., Perez, M., Piccini, J., Turakhia, M., Wang, P., Viskin, S., Amer Heart Assoc Electrocardiograp, Council Clinical Cardiology, Council Functional Genomics Transl 2016; 133 (15): 1520?29
View details for DOI 10.1161/CIR.0000000000000388

View details for Web of Science ID 000373933400012

View details for PubMedID 27067089
Brain natriuretic peptide and the risk of ventricular tachyarrhythmias in mildly symptomatic heart failure patients enrolled in MADIT-CRT. Heart rhythm Medina, A., Moss, A. J., McNitt, S., Zareba, W., Wang, P. J., Goldenberg, I. 2016; 13 (4): 852-859
Abstract

There are limited data about the correlation between brain natriuretic peptide (BNP) levels and arrhythmic risk assessment in patients who receive device therapy for the treatment of heart failure (HF) or for the prevention of sudden cardiac death.We aimed to investigate the association between BNP levels and the risk of ventricular tachyarrhythmias among mildly symptomatic HF patients who receive an intracardiac defibrillator (ICD) with or without cardiac resynchronization therapy (respectively, CRT-D or CRT).The study population involved 1197 patients enrolled in MADIT-CRT. Plasma BNP was measured in a core laboratory at baseline and after 1-year follow-up. Ventricular tachycardia/fibrillation (VT/VF) events were identified from ICD/CRT-D interrogations.Multivariate Cox hazards regression modeling showed that elevated baseline (> median = 72 ng/L) and 1-year BNP were associated with a significant increase in the risk of VT/VF (HR = 1.36, P = .026; and HR = 1.79, P < .001, respectively); and VT/VF or death (HR = 1.37, P = .008; and HR = 1.84, P < .0001, respectively) during follow-up. At 1 year post device implantation, BNP levels were significantly lower among study patients treated with CRT-D as compared with those who received ICD only (P = .014). CRT-D patients who had greater than median reductions in BNP levels (greater than one-third reduction of initial value) experienced a significantly lower risk of subsequent VT/VF (HR = 0.61, P = .021) and VT/VF or death (HR = 0.45, P < .0001) as compared to patients without such reductions.In MADIT-CRT, elevated baseline and follow-up BNP levels were independent predictors of increased risk for subsequent ventricular tachyarrhythmias, whereas BNP reductions following CRT-D implantation identified patients with a lower incidence of VT/VF during follow-up.

View details for DOI 10.1016/j.hrthm.2015.12.024

View details for PubMedID 26724489
Brain natriuretic peptide and the risk of ventricular tachyarrhythmias in mildly symptomatic heart failure patients enrolled in MADIT-CRT HEART RHYTHM Medina, A., Moss, A. J., McNitt, S., Zareba, W., Wang, P. J., Goldenberg, I. 2016; 13 (4): 852-859
Abstract

There are limited data about the correlation between brain natriuretic peptide (BNP) levels and arrhythmic risk assessment in patients who receive device therapy for the treatment of heart failure (HF) or for the prevention of sudden cardiac death.We aimed to investigate the association between BNP levels and the risk of ventricular tachyarrhythmias among mildly symptomatic HF patients who receive an intracardiac defibrillator (ICD) with or without cardiac resynchronization therapy (respectively, CRT-D or CRT).The study population involved 1197 patients enrolled in MADIT-CRT. Plasma BNP was measured in a core laboratory at baseline and after 1-year follow-up. Ventricular tachycardia/fibrillation (VT/VF) events were identified from ICD/CRT-D interrogations.Multivariate Cox hazards regression modeling showed that elevated baseline (> median = 72 ng/L) and 1-year BNP were associated with a significant increase in the risk of VT/VF (HR = 1.36, P = .026; and HR = 1.79, P < .001, respectively); and VT/VF or death (HR = 1.37, P = .008; and HR = 1.84, P < .0001, respectively) during follow-up. At 1 year post device implantation, BNP levels were significantly lower among study patients treated with CRT-D as compared with those who received ICD only (P = .014). CRT-D patients who had greater than median reductions in BNP levels (greater than one-third reduction of initial value) experienced a significantly lower risk of subsequent VT/VF (HR = 0.61, P = .021) and VT/VF or death (HR = 0.45, P < .0001) as compared to patients without such reductions.In MADIT-CRT, elevated baseline and follow-up BNP levels were independent predictors of increased risk for subsequent ventricular tachyarrhythmias, whereas BNP reductions following CRT-D implantation identified patients with a lower incidence of VT/VF during follow-up.

View details for DOI 10.1016/j.hrthm.2015.12.024

View details for Web of Science ID 000372369100013
The precise timing of tachycardia entrainment is determined by the postpacing interval, the tachycardia cycle length, and the pacing rate: Theoretical insights and practical applications HEART RHYTHM Kaiser, D. W., Hsia, H. H., Dubin, A. M., Liem, L. B., Viswanathan, M. N., Zei, P. C., Wang, P. J., Narayan, S. M., Turakhia, M. P. 2016; 13 (3): 695-703
Abstract

Previous observations have reported that the number of pacing stimuli required to entrain a tachycardia varies on the basis of arrhythmia type and location, but a quantitative formulation of the number needed to entrain (NNE) that unifies these observations has not been characterized.We sought to investigate the relationship between the number of pacing stimulations, the tachycardia cycle length (TCL), the overdrive pacing cycle length (PCL), and the postpacing interval (PPI) to accurately estimate the timing of tachycardia entrainment.First, we detailed a mathematical derivation unifying electrophysiological parameters with empirical confirmation in 2 patients undergoing catheter ablation of typical atrial flutter. Second, we validated our formula in 44 patients who underwent various catheter ablation procedures. For accuracy, we corrected for rate-related changes in conduction velocity.We derived the equations NNE = |(PPI - TCL)/(TCL - PCL)| + 1 and Tachycardia advancement = (NNE - 1) � (TCL - PCL) - (PPI - TCL), which state that the NNE and the amount of tachycardia advancement on the first resetting stimulation are determined using regularly measured intracardiac parameters. In the retrospective cohort, the observed PPI - TCL highly correlated with the predicted PPI - TCL (mean difference 5.8 ms; r = 0.97; P < .001), calculated as PPI - TCL = (NNE - 1) � (TCL - PCL) - tachycardia advancement.The number of pacing stimulations required to entrain a reentrant tachycardia is predictable at any PCL after correcting for cycle length-dependent changes in conduction velocity. This relationship unifies established empirically derived diagnostic and mapping criteria for supraventricular tachycardia and ventricular tachycardia. This relationship may help elucidate when antitachycardia pacing episodes are ineffective or proarrhythmic and could potentially serve as a theoretical basis to customize antitachycardia pacing settings for improved safety and effectiveness.

View details for DOI 10.1016/j.hrthm.2015.11.032

View details for Web of Science ID 000372367800012

View details for PubMedCentralID PMC4770895
The precise timing of tachycardia entrainment is determined by the postpacing interval, the tachycardia cycle length, and the pacing rate: Theoretical insights and practical applications. Heart rhythm Kaiser, D. W., Hsia, H. H., Dubin, A. M., Liem, L. B., Viswanathan, M. N., Zei, P. C., Wang, P. J., Narayan, S. M., Turakhia, M. P. 2016; 13 (3): 695-703
Abstract

Previous observations have reported that the number of pacing stimuli required to entrain a tachycardia varies on the basis of arrhythmia type and location, but a quantitative formulation of the number needed to entrain (NNE) that unifies these observations has not been characterized.We sought to investigate the relationship between the number of pacing stimulations, the tachycardia cycle length (TCL), the overdrive pacing cycle length (PCL), and the postpacing interval (PPI) to accurately estimate the timing of tachycardia entrainment.First, we detailed a mathematical derivation unifying electrophysiological parameters with empirical confirmation in 2 patients undergoing catheter ablation of typical atrial flutter. Second, we validated our formula in 44 patients who underwent various catheter ablation procedures. For accuracy, we corrected for rate-related changes in conduction velocity.We derived the equations NNE = |(PPI - TCL)/(TCL - PCL)| + 1 and Tachycardia advancement = (NNE - 1) � (TCL - PCL) - (PPI - TCL), which state that the NNE and the amount of tachycardia advancement on the first resetting stimulation are determined using regularly measured intracardiac parameters. In the retrospective cohort, the observed PPI - TCL highly correlated with the predicted PPI - TCL (mean difference 5.8 ms; r = 0.97; P < .001), calculated as PPI - TCL = (NNE - 1) � (TCL - PCL) - tachycardia advancement.The number of pacing stimulations required to entrain a reentrant tachycardia is predictable at any PCL after correcting for cycle length-dependent changes in conduction velocity. This relationship unifies established empirically derived diagnostic and mapping criteria for supraventricular tachycardia and ventricular tachycardia. This relationship may help elucidate when antitachycardia pacing episodes are ineffective or proarrhythmic and could potentially serve as a theoretical basis to customize antitachycardia pacing settings for improved safety and effectiveness.

View details for DOI 10.1016/j.hrthm.2015.11.032

View details for PubMedID 26611239
MULTISPECTRAL IMAGING OF TISSUE ABLATION Blasinski, H., Caves, J., Farrell, J., Wandell, B., Wang, P., IEEE IEEE. 2016: 360?63
View details for DOI 10.1109/ISBI.2016.7493283

View details for Web of Science ID 000386377400087
Sex Differences in Device Therapies for Ventricular Arrhythmias or Death in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) Trial JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Tompkins, C. M., Kutyifa, V., Arshad, A., McNitt, S., Polonsky, B., Wang, P. J., Moss, A. J., Zareba, W. 2015; 26 (8): 862-871
Abstract

Studies suggest that women with ischemic heart disease are less likely to experience appropriate ICD therapies for ventricular arrhythmias (VT/VF). We evaluated the influence of sex on arrhythmic events or death in subjects enrolled in MADIT-CRT.Arrhythmic event rates, defined as VT/VF treated with defibrillator therapy or all-cause death, were determined among 1,790 subjects enrolled in MADIT-CRT with documented 3-year follow-up. Predictors of VT/VF/death were identified using multivariate analysis. Ninety-one (21%) women and 466 (35%) men experienced VT/VF/death over the follow-up period. The overall probability of VT/VF/death was significantly lower in women versus men (HR 0.62; P < 0.001). The probability of VT/VF/death was the lowest in women with ischemic heart disease (HR 0.51; P = 0.003). In ICD subjects, the 3-year risk of VT/VF was lower in ischemic women versus men (P = 0.021), and in nonischemic women versus men (P = 0.049). The probability of VT/VF/death was significantly lower in women (HR 0.52; P = 0.007) and men (HR 0.74; P = 0.018) with LBBB who received CRT-D. Appropriate shock therapy strongly correlated with increased risk of death during postshock follow-up in women (HR 5.18; P = 0.001) and men (HR 1.63; P = 0.033); interaction P value of 0.034.In this substudy of MADIT-CRT, sex, etiology of heart disease and type of device implanted significantly influenced subsequent risk for VT/VF or death. Women with ischemic heart disease and women with LBBB who received CRT-D had the lowest incidence of VT/VF or death when compared to men. Appropriate shock therapy was a strong predictor of death, particularly in women.

View details for DOI 10.1111/jce.12701

View details for Web of Science ID 000358686300008

View details for PubMedID 25929699
Best practice guide for cryoballoon ablation in atrial fibrillation: The compilation experience of more than 3000 procedures HEART RHYTHM Su, W., Kowal, R., Kowalski, M., Metzner, A., Svinarich, J. T., Wheelan, K., Wang, P. 2015; 12 (7): 1658-1666
Abstract

Since the release of the second-generation cryoballoon (CB2; Arctic Front Advance(TM), Medtronic Inc) and its design modifications with improved cooling characteristics, the technique, dosing, and complication profile is significantly different from that of the first-generation cryoballoon. A comprehensive report of CB2 procedural recommendations has not been reported.The purpose of this study was to review the current best practices from a group of experienced centers to create a user's consensus guide for CB2 ablation.High-volume operators with a combined experience of more than 3000 CB2 cases were interviewed, and consensus for technical and procedural best practice was established.Comprehensive review of the CB2 ablation best practice guide will provide a detailed technique for achieving safer and more effective outcomes for CB2 atrial fibrillation ablation.

View details for DOI 10.1016/j.hrthm.2015.03.021

View details for Web of Science ID 000356766500043

View details for PubMedID 25778428
Feasibility of Extended Ambulatory Electrocardiogram Monitoring to Identify Silent Atrial Fibrillation in High-risk Patients: The Screening Study for Undiagnosed Atrial Fibrillation (STUDY-AF) CLINICAL CARDIOLOGY Turakhia, M. P., Ullal, A. J., Hoang, D. D., Than, C. T., Miller, J. D., Friday, K. J., Perez, M. V., Freeman, J. V., Wang, P. J., Heidenreich, P. A. 2015; 38 (5): 285-292
Abstract

Identification of silent atrial fibrillation (AF) could prevent stroke and other sequelae.Screening for AF using continuous ambulatory electrocardiographic (ECG) monitoring can detect silent AF in asymptomatic in patients with known risk factors.We performed a single-center prospective screening study using a wearable patch-based device that provides up to 2 weeks of continuous ambulatory ECG monitoring (iRhythm Technologies, Inc.). Inclusion criteria were age ?55 years and ?2 of the following risk factors: coronary disease, heart failure, hypertension, diabetes, sleep apnea. We excluded patients with prior AF, stroke, transient ischemic attack, implantable pacemaker or defibrillator, or with palpitations or syncope in the prior year.Out of 75 subjects (all male, age 69 � 8.0 years; ejection fraction 57% � 8.7%), AF was detected in 4 subjects (5.3%; AF burden 28% � 48%). Atrial tachycardia (AT) was present in 67% (?4 beats), 44% (?8 beats), and 6.7% (?60 seconds) of subjects. The combined diagnostic yield of sustained AT/AF was 11%. In subjects without sustained AT/AF, 11 (16%) had ?30 supraventricular ectopic complexes per hour.Outpatient extended ECG screening for asymptomatic AF is feasible, with AF identified in 1 in 20 subjects and sustained AT/AF identified in 1 in 9 subjects, respectively. We also found a high prevalence of asymptomatic AT and frequent supraventricular ectopic complexes, which may be relevant to development of AF or stroke. If confirmed in a larger study, primary screening for AF could have a significant impact on public health.

View details for DOI 10.1002/clc.22387

View details for PubMedID 25873476
COST VARIATION AND ASSOCIATED OUTCOMES OF CATHETER ABLATION FOR ATRIAL FIBRILLATION Perino, A., Fan, J., Schmitt, S., Chang, A. Y., Kaiser, D., Heidenreich, P., Swan, C., Narayan, S., Wang, P., Turakhia, M. ELSEVIER SCIENCE INC. 2015: A277
View details for DOI 10.1016/S0735-1097(15)60277-7

View details for Web of Science ID 000375328800278
Hybrid Epicardial and Endocardial Ablation of Atrial Fibrillation: Is Ablation on Two Sides of the Atrial Wall Better Than One? JOURNAL OF THE AMERICAN HEART ASSOCIATION Wang, P. J. 2015; 4 (3): e001893
View details for PubMedID 25809549
The association between biventricular pacing and cardiac resynchronization therapy-defibrillator efficacy when compared with implantable cardioverter defibrillator on outcomes and reverse remodelling EUROPEAN HEART JOURNAL Ruwald, A., Kutyifa, V., Ruwald, M. H., Solomon, S., Daubert, J. P., Jons, C., Brenyo, A., McNitt, S., Duc Do, D., Tanabe, K., Al-Ahmad, A., Wang, P., Moss, A. J., Zareba, W. 2015; 36 (7): 440-448
Abstract

Previous studies on biventricular (BIV) pacing and cardiac resynchronization therapy-defibrillator (CRT-D) efficacy have used arbitrarily chosen BIV pacing percentages, and no study has employed implantable cardioverter defibrillator (ICD) patients as a control group.Using Kaplan-Meier plots, we estimated the threshold of BIV pacing percentage needed for CRT-D to be superior to ICD on the end-point of heart failure (HF) or death in 1219 left bundle branch block (LBBB) patients in the MADIT-CRT trial. Patients were censored at the time of crossover. In multivariable Cox analyses, no difference was seen in the risk of HF/death between ICD and CRT-D patients with BIV pacing ?90% [HR = 0.78 (0.47-1.30), P = 0.344], and with increasing BIV pacing the risk of HF/death was decreased [CRT-D BIV 91-96% vs. ICD: HR = 0.63 (0.42-0.94), P = 0.024 and CRT-D BIV ?97% vs. ICD: HR = 0.32 (0.23-0.44), P < 0.001]. The risk of death alone was reduced by 52% in CRT-D patients with BIV ?97% (HR = 0.48, P < 0.016), when compared with ICD patients. Within the CRT-D group, for every 1 percentage point increase in BIV pacing, the risk of HF/death and death alone significantly decreased by 6 and 10%, respectively. Increasing BIV pacing percentage was associated with significant reductions in left ventricular volume.In patients with LBBB, who were in sinus rhythm at enrolment, BIV pacing exceeding 90% was associated with a benefit of CRT-D in HF/death when compared with ICD patients. Furthermore, BIV pacing ?97% was associated with an even further reduction in HF/death, a significant 52% reduction in death alone, and increased reverse remodelling. Clinical trials.gov identifier: NCT00180271.

View details for DOI 10.1093/eurheartj/ehu294

View details for Web of Science ID 000351589000016
Highly skin-conformal microhairy sensor for pulse signal amplification. Advanced materials Pang, C., Koo, J. H., Nguyen, A., Caves, J. M., Kim, M., Chortos, A., Kim, K., Wang, P. J., Tok, J. B., Bao, Z. 2015; 27 (4): 634-640
Abstract

A bioinspired microhairy sensor is developed to enable ultraconformability on nonflat surfaces and significant enhancement in the signal-to-noise ratio of the retrieved signals. The device shows ?12 times increase in the signal-to-noise ratio in the generated capacitive signals, allowing the ultraconformal microhair pressure sensors to be capable of measuring weak pulsations of internal jugular venous pulses stemming from a human neck.

View details for DOI 10.1002/adma.201403807

View details for PubMedID 25358966
The association between biventricular pacing and cardiac resynchronization therapy-defibrillator efficacy when compared with implantable cardioverter defibrillator on outcomes and reverse remodelling. European heart journal Ruwald, A. C., Kutyifa, V., Ruwald, M. H., Solomon, S., Daubert, J. P., Jons, C., Brenyo, A., McNitt, S., Do, D., Tanabe, K., Al-Ahmad, A., Wang, P., Moss, A. J., Zareba, W. 2015; 36 (7): 440?48
Abstract

Previous studies on biventricular (BIV) pacing and cardiac resynchronization therapy-defibrillator (CRT-D) efficacy have used arbitrarily chosen BIV pacing percentages, and no study has employed implantable cardioverter defibrillator (ICD) patients as a control group.Using Kaplan-Meier plots, we estimated the threshold of BIV pacing percentage needed for CRT-D to be superior to ICD on the end-point of heart failure (HF) or death in 1219 left bundle branch block (LBBB) patients in the MADIT-CRT trial. Patients were censored at the time of crossover. In multivariable Cox analyses, no difference was seen in the risk of HF/death between ICD and CRT-D patients with BIV pacing ?90% [HR = 0.78 (0.47-1.30), P = 0.344], and with increasing BIV pacing the risk of HF/death was decreased [CRT-D BIV 91-96% vs. ICD: HR = 0.63 (0.42-0.94), P = 0.024 and CRT-D BIV ?97% vs. ICD: HR = 0.32 (0.23-0.44), P < 0.001]. The risk of death alone was reduced by 52% in CRT-D patients with BIV ?97% (HR = 0.48, P < 0.016), when compared with ICD patients. Within the CRT-D group, for every 1 percentage point increase in BIV pacing, the risk of HF/death and death alone significantly decreased by 6 and 10%, respectively. Increasing BIV pacing percentage was associated with significant reductions in left ventricular volume.In patients with LBBB, who were in sinus rhythm at enrolment, BIV pacing exceeding 90% was associated with a benefit of CRT-D in HF/death when compared with ICD patients. Furthermore, BIV pacing ?97% was associated with an even further reduction in HF/death, a significant 52% reduction in death alone, and increased reverse remodelling. Clinical trials.gov identifier: NCT00180271.

View details for PubMedID 25112662
Reduction of Iatrogenic Atrial Septal Defects with an Anterior and Inferior Transseptal Puncture Site when Operating the Cryoballoon Ablation Catheter. Journal of visualized experiments : JoVE Rich, M. E., Tseng, A., Lim, H. W., Wang, P. J., Su, W. W. 2015
Abstract

The cryoballoon catheter ablates atrial fibrillation (AF) triggers in the left atrium (LA) and pulmonary veins (PVs) via transseptal access. The typical transseptal puncture site is the fossa ovalis (FO) - the atrial septum's thinnest section. A potentially beneficial transseptal site, for the cryoballoon, is near the inferior limbus (IL). This study examines an alternative transseptal site near the IL, which may decrease the frequency of acute iatrogenic atrial septal defect (IASD). Also, the study evaluates the acute pulmonary vein isolation (PVI) success rate utilizing the IL location. 200 patients were evaluated by retrospective chart review for acute PVI success rate with an IL transseptal site. An additional 128 IL transseptal patients were compared to 45 FO transseptal patients by performing Doppler intracardiac echocardiography (ICE) post-ablation to assess transseptal flow after removal of the transseptal sheath. After sheath removal and by Doppler ICE imaging, 42 of 128 (33%) IL transseptal patients demonstrated acute transseptal flow, while 45 of 45 (100%) FO transseptal puncture patients had acute transseptal flow. The difference in acute transseptal flow detection between FO and IL sites was statistically significant (P <0.0001). Furthermore, 186 of 200 patients (with an IL transseptal puncture) did not need additional ablation(s) and had achieved an acute PVI by a "cryoballoon only" technique. An IL transseptal puncture site for cryoballoon AF ablations is an effective location to mediate PVI at all four PVs. Additionally, an IL transseptal location can lower the incidence of acute transseptal flow by Doppler ICE when compared to the FO. Potentially, the IL transseptal site may reduce later IASD complications post-cryoballoon procedures.

View details for DOI 10.3791/52811

View details for PubMedID 26132435
Comparison of Age (<75 Years Versus >= 75 Years) to Risk of Ventricular Tachyarrhythmias and Implantable Cardioverter Defibrillator Shocks (from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) AMERICAN JOURNAL OF CARDIOLOGY Aktas, M. K., Goldenberg, I., Moss, A. J., Huang, D. T., Kutyifa, V., Wang, P. J., Brenyo, A., McNitt, S., Zareba, W., Barsheshet, A. 2014; 114 (12): 1855-1860
Abstract

There are limited data regarding the effect of age on the risk of ventricular tachyarrhythmias (VTAs). The present study was designed to compare the risk for VTAs in young and older patients with left bundle branch block (LBBB) and mildly symptomatic heart failure who receive device therapy. The risk of the first ventricular tachycardia (VT) or ventricular fibrillation (VF) event and the risk of first appropriate implantable cardioverter defibrillator (ICD) shock was compared between young (<75�years, n�= 1,037) and older (?75�years, n�= 227) patients with LBBB enrolled in Multicenter Automatic Implantation Trial with Cardiac Resynchronization Therapy. The cumulative incidence of a first VTA through 2�years of follow-up was significantly lower in older patients than in younger patients. Multivariate analysis showed that older patients experienced a significantly lower risk of VT/VF (hazard ratio 0.38, 95% confidence interval 0.22 to 0.64, p <0.001) and a�significantly lower risk of appropriate ICD shocks (hazard ratio 0.37, 95% confidence interval 0.17 to 0.82, p�= 0.014) compared with younger patients. Each increasing decade of life was associated with a 19% (p�= 0.002) and 22% (p�= 0.018) reduction in the risk of VT/VF and appropriate ICD shocks, respectively. The lower risk of VT/VF and appropriate ICD shocks in older patients was evident in patients implanted with an ICD only�and�in those implanted with a cardiac resynchronization therapy with defibrillator. In conclusion, in patients with LBBB and mild symptoms of heart failure, aging is associated with a significant decrease in the incidence of VT/VF and ICD shocks.

View details for DOI 10.1016/j.amjcard.2014.09.026

View details for Web of Science ID 000346887300012

View details for PubMedID 25438913
Association Between Frequency of Atrial and Ventricular Ectopic Beats and Biventricular Pacing Percentage and Outcomes in Patients With Cardiac Resynchronization Therapy JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Ruwald, M. H., Mittal, S., Ruwald, A., Aktas, M. K., Daubert, J. P., McNitt, S., Al-Ahmad, A., Jons, C., Kutyifa, V., Steinberg, J. S., Wang, P., Moss, A. J., Zareba, W. 2014; 64 (10): 971-981
Abstract

A high percentage of biventricular pacing is required for optimal outcome in patients treated with cardiac resynchronization therapy (CRT), but the influence of ectopic beats on the success of biventricular pacing has not been well established.This study sought to determine if increased ectopic beats reduce the chance of high biventricular pacing percentage and are associated with subsequent adverse outcomes.From the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy), 801 patients with an implanted CRT-defibrillator device with data available on biventricular pacing percentage and pre-implantation 24-h Holter recordings were included. Using logistic regression, we estimated the influence of ectopic beats on the percentage of biventricular pacing. Reverse remodeling was measured as reductions in atrial and left ventricular end-systolic volumes (LVESV) at 1 year. Cox models were used to assess the influence of ectopic beats on the outcomes of heart failure (HF) or death, ventricular tachyarrhythmias (VTAs), and death.In the pre-implantation Holter recording, ectopic beats accounted for a mean 3.2 � 5.5% of all beats. The probability of subsequent low biventricular pacing percentage (<97%) was increased 3-fold (odds ratio: 3.37; 95% confidence interval: 1.74 to 6.50; p < 0.001) in patients with 0.1% to 1.5% ectopic beats and 13-fold (odds ratio: 13.42; 95% confidence interval: 7.02 to 25.66; p < 0.001) in patients with >1.5% ectopic beats compared with those with <0.1% ectopic beats. Patients with ?0.1% ectopic beats had significantly less reverse remodeling (percent reduction in LVESV 31 � 15%) than patients with <0.1% ectopic beats (percent reduction in LVESV 39 � 14%; p < 0.001). The risk of HF/death and VTA was increased significantly in those with 0.1% to 1.5% ectopic beats (hazard ratio: 3.13 and 1.84, respectively) and for >1.5% ectopic beats (hazard ratio: 2.38 and 2.74, respectively).Relatively low frequencies of ectopic beats (?0.1%) dramatically increase the probability of low biventricular pacing (<97%), with reduced CRT efficacy by less reverse remodeling and higher risk of HF/death and VTA. This supports pre-implantation Holter monitoring of patients selected for CRT for optimal outcome. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271).

View details for DOI 10.1016/j.jacc.2014.06.1177

View details for Web of Science ID 000341085900003

View details for PubMedID 25190230
Association Between Success Rate and Citation Count of Studies of Radiofrequency Catheter Ablation for Atrial Fibrillation Possible Evidence of Citation Bias CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Perino, A. C., Hoang, D. D., Holmes, T. H., Santangeli, P., Heidenreich, P. A., Perez, M. V., Wang, P. J., Turakhia, M. P. 2014; 7 (5): 687-692
Abstract

The preferential citation of studies with the highest success rates could exaggerate perceived effectiveness, particularly for treatments with widely varying published success rates such as radiofrequency catheter ablation for atrial fibrillation.We systematically identified observational studies and clinical trials of radiofrequency catheter ablation of atrial fibrillation between 1990 and 2012. Generalized Poisson regression was used to estimate association between study success rate and total citation count, adjusting for sample size, journal impact factor, time since publication, study design, and whether first or last author was a consensus-defined pre-eminent expert. We identified 174 articles meeting our inclusion criteria (36 289 subjects). After adjustment only for time since publication, a 10-point increase above the mean in pooled reported success rates was associated with a 17.8% increase in citation count at 5 years postpublication (95% confidence interval, 7.1-28.4%; P<0.001). After additional adjustment for impact factor, sample size, randomized trial design, and pre-eminent expert authorship, the association remained significant (18.6% increase in citation count; 95% confidence interval, 7.6-29.6%; P<0.0001). In this full model, time since publication, impact factor, and pre-eminent expert authorship were significant covariates, whereas randomized control trial design and study sample size were not.Among studies of radiofrequency catheter ablation of atrial fibrillation, high success rate was independently associated with citation count, which may indicate citation bias. To readers of the literature, radiofrequency catheter ablation of atrial fibrillation could be perceived to be more effective than the data supports. These findings may have implications for a wide variety of novel cardiovascular therapies.

View details for DOI 10.1161/CIRCOUTCOMES.114.000912

View details for Web of Science ID 000342365200011
Association between success rate and citation count of studies of radiofrequency catheter ablation for atrial fibrillation: possible evidence of citation bias. Circulation. Cardiovascular quality and outcomes Perino, A. C., Hoang, D. D., Holmes, T. H., Santangeli, P., Heidenreich, P. A., Perez, M. V., Wang, P. J., Turakhia, M. P. 2014; 7 (5): 687-692
Abstract

The preferential citation of studies with the highest success rates could exaggerate perceived effectiveness, particularly for treatments with widely varying published success rates such as radiofrequency catheter ablation for atrial fibrillation.We systematically identified observational studies and clinical trials of radiofrequency catheter ablation of atrial fibrillation between 1990 and 2012. Generalized Poisson regression was used to estimate association between study success rate and total citation count, adjusting for sample size, journal impact factor, time since publication, study design, and whether first or last author was a consensus-defined pre-eminent expert. We identified 174 articles meeting our inclusion criteria (36 289 subjects). After adjustment only for time since publication, a 10-point increase above the mean in pooled reported success rates was associated with a 17.8% increase in citation count at 5 years postpublication (95% confidence interval, 7.1-28.4%; P<0.001). After additional adjustment for impact factor, sample size, randomized trial design, and pre-eminent expert authorship, the association remained significant (18.6% increase in citation count; 95% confidence interval, 7.6-29.6%; P<0.0001). In this full model, time since publication, impact factor, and pre-eminent expert authorship were significant covariates, whereas randomized control trial design and study sample size were not.Among studies of radiofrequency catheter ablation of atrial fibrillation, high success rate was independently associated with citation count, which may indicate citation bias. To readers of the literature, radiofrequency catheter ablation of atrial fibrillation could be perceived to be more effective than the data supports. These findings may have implications for a wide variety of novel cardiovascular therapies.

View details for DOI 10.1161/CIRCOUTCOMES.114.000912

View details for PubMedID 25205786
Cardiac resynchronization therapy is associated with reductions in left atrial volume and inappropriate implantable cardioverter-defibrillator therapy in MADIT-CRT HEART RHYTHM Slyngstad, T., Ruwald, A. H., Kutyifa, V., McNitt, S., Polonsky, B., Solomon, S. D., Foster, E., Goldenberg, I., Wang, P. J., Klein, H., Zareba, W., Moss, A. J. 2014; 11 (6): 1001-1007
Abstract

There are no prior studies assessing the relationship between left atrial volume (LAV) and inappropriate implantable cardioverter-defibrillator (ICD) therapy following treatment with cardiac resynchronization therapy.The purpose of this study was to investigate the hypothesis that patients randomized to cardiac resynchronization therapy with defibrillator (CRT-D) in the Multicenter Automatic Defibrillator Trial-Cardiac Resynchronization Therapy (MADIT-CRT) who had significant LAV reductions would have reduced risks of inappropriate ICD therapy.Cardiac resynchronization remodeling was assessed by measuring LAV change between baseline and 12-month echocardiograms in 751 CRT-D treated patients. Patients were stratified into quartiles based on percent reduction of LAV change. High LAV responders were those in the highest 3 quartiles of LAV reduction (LAV reduction ?21%). Low LAV responders were those in the lowest quartile of LAV reduction (LAV reduction <21%). Clinical factors associated with ?21% reduction in LAV were evaluated by linear regression analysis.In Cox proportional hazards regression analyses, high LAV responders had a 39% reduction in the risk of inappropriate therapy (hazard ratio 0.61, P = .04) and left bundle branch block patients exhibited an even greater risk reduction in inappropriate therapy (hazard ratio 0.51, P = .02) compared to low LAV responders during follow-up extending up to 3 years after the 12-month echocardiogram. High LAV responders also had a significantly lower risk of heart failure or death during follow-up than did low LAV responders.A ?21% reduction in LAV with cardiac resynchronization therapy is associated with significant reductions in inappropriate ICD therapy and in heart failure or death during a 3-year follow-up.

View details for DOI 10.1016/j.hrthm.2014.01.033

View details for Web of Science ID 000336395600014

View details for PubMedID 24502968
A histological and mechanical analysis of the cardiac lead-tissue interface: implications for lead extraction. Acta biomaterialia Rennert, R. C., Rustad, K., Levi, K., Harwood, M., Sorkin, M., Wong, V. W., Al-Ahmad, A., Zei, P., Hsia, H., Beygui, R. E., Norton, L., Wang, P., Gurtner, G. C. 2014; 10 (5): 2200-2208
Abstract

The major risks of pacemaker and implantable cardioverter defibrillator extraction are attributable to the fibrotic tissue that encases them in situ, yet little is known about the cellular and functional properties of this response. In the present research, we performed a histological and mechanical analysis of human tissue collected from the lead-tissue interface to better understand this process and provide insights for the improvement of lead design and extraction. The lead-tissue interface consisted of a thin cellular layer underlying a smooth, acellular surface, followed by a circumferentially organized collagen-rich matrix. 51.8�4.9% of cells were myofibroblasts via immunohistochemistry, with these cells displaying a similar circumferential organization. Upon mechanical testing, samples exhibited a triphasic force-displacement response consisting of a toe region during initial tensioning, a linear elastic region and a yield and failure region. Mean fracture load was 5.6�2.1N, and mean circumferential stress at failure was 9.5�4.1MPa. While the low cellularity and fibrotic composition of tissue observed herein is consistent with a foreign body reaction to an implanted material, the significant myofibroblast response provides a mechanical explanation for the contractile forces complicating extractions. Moreover, the tensile properties of this tissue suggest the feasibility of circumferential mechanical tissue disruption, similar to balloon angioplasty devices, as a novel approach to assist with lead extraction.

View details for DOI 10.1016/j.actbio.2014.01.008

View details for PubMedID 24434537
Shock-induced ventricular tachycardia: what is the mechanism? Pacing and clinical electrophysiology : PACE Santangeli, P., Hsia, H. H., Wang, P. J., Al-Ahmad, A. 2014; 37 (4): 516-519
View details for DOI 10.1111/pace.12244

View details for PubMedID 23980924
The Effect of Intermittent Atrial Tachyarrhythmia on Heart Failure or Death in Cardiac Resynchronization Therapy With Defibrillator Versus Implantable Cardioverter-Defibrillator Patients A MADIT-CRT Substudy (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Ruwald, A., Pietrasik, G., Goldenberg, I., Kutyifa, V., Daubert, J. P., Ruwald, M. H., Jons, C., McNitt, S., Wang, P., Zareba, W., Moss, A. J. 2014; 63 (12): 1190-1197
Abstract

This study aimed to investigate the effect of both history of intermittent atrial tachyarrhythmias (IAT) and in-trial IAT on the risk of heart failure (HF) or death comparing cardiac resynchronization therapy with defibrillator (CRT-D) to implantable cardioverter-defibrillator (ICD) treatment in mildly symptomatic HF patients with left bundle branch block (LBBB).Limited data exist regarding the benefit of CRT-D in patients with IAT.The benefit of CRT-D in reducing the risk of HF/death was evaluated using multivariate Cox models incorporating the presence of, respectively, a history of IAT at baseline and time-dependent development of in-trial IAT during follow-up in 1,264 patients with LBBB enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study.The overall beneficial effect of CRT-D versus ICD on the risk of HF/death was not significantly different between LBBB patients with or without history of IAT (HR: 0.50, p = 0.028, and HR: 0.46, p < 0.001, respectively; p for interaction = 0.79). Among patients who had in-trial IAT, CRT-D was associated with a significant 57% reduction in the risk of HF/death compared with ICD-only therapy (HR: 0.43, p = 0.047), similar to the effect of the device among patients who did not have IAT (HR: 0.47, p < 0.001; p for interaction = 0.85). The percentage of patients with biventricular pacing ?92% was similar in both groups (p = 0.43). Consistent results were shown for the benefit of CRT-D among patients who had in-trial atrial fibrillation/flutter (HR: 0.30, p = 0.027; p for interaction = 0.41).In the MADIT-CRT study, the clinical benefit of CRT-D in LBBB patients was not attenuated by prior history of IAT or by the development of in-trial atrial tachyarrhythmias. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy; NCT00180271).

View details for DOI 10.1016/j.jacc.2013.10.074

View details for Web of Science ID 000333256100012

View details for PubMedID 24333490
Exercise capacity and paroxysmal atrial fibrillation in patients with hypertrophic cardiomyopathy. Heart Azarbal, F., Singh, M., Finocchiaro, G., Le, V., Schnittger, I., Wang, P., Myers, J., Ashley, E., Perez, M. 2014; 100 (8): 624-630
Abstract

Atrial fibrillation (AF) is the most common arrhythmia among patients with hypertrophic cardiomyopathy (HCM). The relationship between paroxysmal AF and exercise capacity in this population is incompletely understood.Patients with HCM underwent symptom-limited cardiopulmonary testing with expired gas analysis at Stanford Hospital between October 2006 and October 2012. Baseline demographics, medical histories and resting echocardiograms were obtained for all subjects. Diagnosis of AF was established by review of medical records and baseline ECG. Those with paroxysmal AF were in sinus rhythm at the time of cardiopulmonary testing with expired gas analysis. Exercise intolerance was defined as peak VO2<20 mL/kg/min. We used multivariate logistic regression to evaluate the association between exercise intolerance and paroxysmal AF.Among the 265 patients recruited, 55 had AF (28 paroxysmal and 27 permanent). Compared with those without AF, subjects with paroxysmal AF were older, more likely to use antiarrhythmic and anticoagulant medications, and had larger left atria. Patients with paroxysmal AF achieved lower peak VO2 (21.9�9.2 mL/kg/min vs 26.9�10.8 mL/kg/min, p=0.02) and were more likely to have exercise intolerance (61% vs 28%, p<0.001) compared with those without AF. After adjustment for age, sex and body mass index (BMI) exercise intolerance remained significantly associated with paroxysmal AF (OR 4.65, 95% CI 1.83 to 11.83, p=0.001).Patients with HCM and paroxysmal AF demonstrate exercise intolerance despite being in sinus rhythm at the time of exercise testing.

View details for DOI 10.1136/heartjnl-2013-304908

View details for PubMedID 24326897
Accuracy Assessment of Catheter Guidance Technology in Electrophysiology Procedures: A Comparison of a New 3D-Based Fluoroscopy Navigation System to Current Electroanatomic Mapping Systems JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Bourier, F., Fahrig, R., Wang, P., Santangeli, P., Kurzidim, K., Strobel, N., Moore, T., Hinkel, C., Al-Ahmad, A. 2014; 25 (1): 74-83
Abstract

With increasing complexity in electrophysiology (EP) procedures, the use of electroanatomic mapping systems (EAMS) as a supplement to fluoroscopy has become common practice. This is the first study that evaluates spatial and point localization accuracy for 2 current EAMS, CARTO3(�) (Biosense Webster, Diamond Bar, CA, USA) and EnSite Velocity(�) (St. Jude Medical Inc., St. Paul, MN, USA), and for a novel overlay guidance (OG) software (Siemens AG, Forchheim, Germany) in a phantom experiment.A C-arm CT scan was performed on an acrylic phantom containing holes and location markers. Spatial accuracy was assessed for each system using distance measurements involving known markers inside the phantom and properly placed catheters. Anatomical maps of the phantom were acquired by each EAMS, whereas the 3D-based OG software superimposed an overlay image of the phantom, segmented from the C-arm CT data set, onto biplane fluoroscopy. Registration processes and landmark measurements quantitatively assessed the spatial accuracy of each technology with respect to the ground truth phantom. Point localization performance was 0.49 � 0.25 mm in OG, 0.46 � 0.17 mm in CARTO3(�) and 0.79 � 0.83 mm in EnSite(�) . The registration offset between virtual visualization and reality was 1.10 � 0.52 mm in OG, 1.62 � 0.77 mm in CARTO3(�) and 2.02 � 1.21 mm in EnSite(�) . The offset to phantom C-arm CT landmark measurements was 0.30 � 0.26 mm in OG, 0.24 � 0.21 mm in CARTO3(�) and 1.32 � 0.98 mm in EnSite(�) .Each of the evaluated EP guidance systems showed a high level of accuracy; the observed offsets between the virtual 3D visualization and the real phantom were below a clinically relevant threshold of 3 mm.

View details for Web of Science ID 000334516800019

View details for PubMedID 24102965
Decisional Balance among Potential Implantable Cardioverter Defibrillator Recipients: Development of the ICD-Decision Analysis Scale (ICD-DAS) PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Hazelton, A. G., Sears, S. F., Ford, J., Cahill, J., Nekkanti, R., DeAntonio, H., Ottoboni, L., Norton, L., Wang, P. 2014; 37 (1): 63-72
Abstract

Sudden cardiac death is a well-documented public health problem and the implantable cardioverter defibrillator (ICD) has demonstrated benefit in reducing mortality. Prospective patients must identify and evaluate the ICD's pros and cons and produce a personal decision. The purpose of this study was to create and evaluate a measure of patient-evaluated pros and cons of the ICD, and its relationship to patient decision regarding ICD implantation.The ICD-decision analysis scale (ICD-DAS) was created and tested in prospective ICD recipients (N�= 104). Factor analysis was performed to evaluate interitem relationships, and subsequently, identified subscales; additional psychosocial measures were used to predict the ICD decision. A two-factor measure for ICD decision making was established with two subscales: ICD Pros and ICD Cons. The subscales have high internal consistency and were strong predictors of intent to choose an ICD. Other psychosocial measures were not significantly predictive of ICD Choice, yet simultaneous entry of ICD Pros and Cons subscales resulted in a significant increase in R(2) , F(2, 59)�= 19.36, P�< 0.001. The full model was significantly greater than zero, F(11, 70)�= 5.017, P�< 0.001, R(2) �= 0.48.The ICD-DAS provides the first empirically tested and clinically useful approach to understanding the specific pros and cons for prospective ICD patients. The measure can assist clinicians with patient-centered discussions regarding sudden cardiac arrest treatments. The ICD-DAS will allow for the provision of tailored education or counseling and may be used to predict postdecision outcomes.

View details for DOI 10.1111/pace.12253

View details for Web of Science ID 000329258600008

View details for PubMedID 24219117
Palpitations in a patient with a dual-chamber pacemaker: what is the mechanism? Heart rhythm Santangeli, P., Tsiperfal, A., Wang, P. J., Al-Ahmad, A. 2013; 10 (12): 1824-1825
View details for DOI 10.1016/j.hrthm.2013.07.036

View details for PubMedID 23891958
The Relation Between Atrial and Ventricular Ectopic Beats, Biventricular Pacing Percentage, and Reverse Remodeling Ruwald, M. H., Moss, A. J., Ruwald, A. H., Tanabe, K., Kutyifa, V., Jons, C., McNitt, S., Al-Ahmad, A., Daubert, J. P., Wang, P. J., Zareba, W. LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000332162903272
Novel Utilization of Cryoballoon for Ablation of Coumadin Ridge, Left and Right Atrial Appendage for Atrial Fibrillation Whittington, W. W., Al-Zubaidi, M., Tseng, R., Wang, P., Su, W. LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000332162906304
Second Generation Cryoballoon Ablation With Improved Freezing Results in Pulmonary Injury and Unexpected Late Adhesion Whittington, W. W., Al-Zubaidi, M., Tseng, R., Wang, P., Su, W. LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000332162906292
Safety and Effectiveness of Atrial Fibrillation Ablation Using the Arctic Front Advance Cryoballoon With Reduced Dosing Al-Zubaidi, M., Whittington, W., Tseng, A., Wang, P., Su, W. LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000332162906297
Prognostic Significance of Left Ventricular Lead Pacing Polarity in CRT-D Patients - A MADIT-CRT Substudy Jame, S., Kutyifa, V., McNitt, S., Al-Ahmad, A., Aktas, M., Zareba, W., Moss, A., Wang, P. J. LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000332162901225
The Influence of Percent Biventricular Pacing on CRT Efficacy Compared to ICD Therapy on Outcomes and Reverse Remodeling Ruwald, A. H., Moss, A. I., Ruwald, M. H., Tanabe, K., Kutyifa, V., Brenyo, A., Jons, C., McNitt, S., Daubert, J. P., Al-Ahmad, A., Wang, P. J., Zareba, W. LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000332162901410
PHLEBITIS IN AMIODARONE ADMINISTRATION: INCIDENCE, CONTRIBUTING FACTORS, AND CLINICAL IMPLICATIONS AMERICAN JOURNAL OF CRITICAL CARE Norton, L., Ottoboni, L. K., Varady, A., Yang-Lu, C., Becker, N., Cotter, T., Pummer, E., Haynes, A., Forsey, L., Matsuda, K., Wang, P. 2013; 22 (6): 498-505
Abstract

Intravenous amiodarone is an important treatment for arrhythmias, but peripheral infusion is associated with direct irritation of vessel walls and phlebitis rates of 8% to 55%. Objectives To determine the incidence and factors contributing to the development of amiodarone-induced phlebitis in the coronary care unit in an academic medical center and to refine the current practice protocol.Medical records from all adult patients during an 18-month period who received intravenous amiodarone while in the critical care unit were reviewed retrospectively. Route of administration, location, concentration, and duration of amiodarone therapy and factors associated with occurrence of phlebitis were examined. Descriptive statistics and regression methods were used to identify incidence and phlebitis factors.In the final sample of 105 patients, incidence of phlebitis was 40%, with a 50% recurrence rate. All cases of phlebitis occurred in patients given a total dose of 3 g via a peripheral catheter, and one-quarter of these cases (n = 10) developed at dosages less than 1 g. Pain, redness, and warmth were the most common indications of phlebitis. Total dosage given via a peripheral catheter, duration of infusion, and number of catheters were significantly associated with phlebitis.Amiodarone-induced phlebitis occurred in 40% of this sample at higher drug dosages. A new practice protocol resulted from this study. An outcome study is in progress.

View details for DOI 10.4037/ajcc2013460

View details for Web of Science ID 000328167700012

View details for PubMedID 24186821
Outcomes from a Postgraduate Biomedical Technology Innovation Training Program: The First 12 Years of Stanford Biodesign ANNALS OF BIOMEDICAL ENGINEERING Brinton, T. J., Kurihara, C. Q., Camarillo, D. B., Pietzsch, J. B., Gorodsky, J., Zenios, S. A., Doshi, R., Shen, C., Kumar, U. N., Mairal, A., Watkins, J., Popp, R. L., Wang, P. J., Makower, J., Krummel, T. M., Yock, P. G. 2013; 41 (9): 1803-1810
Abstract

The Stanford Biodesign Program began in 2001 with a mission of helping to train leaders in biomedical technology innovation. A key feature of the program is a full-time postgraduate fellowship where multidisciplinary teams undergo a process of sourcing clinical needs, inventing solutions and planning for implementation of a business strategy. The program places a priority on needs identification, a formal process of selecting, researching and characterizing needs before beginning the process of inventing. Fellows and students from the program have gone on to careers that emphasize technology innovation across industry and academia. Biodesign trainees have started 26 companies within the program that have raised over $200�million and led to the creation of over 500 new jobs. More importantly, although most of these technologies are still at a very early stage, several projects have received regulatory approval and so far more than 150,000 patients have been treated by technologies invented by our trainees. This paper reviews the initial outcomes of the program and discusses lessons learned and future directions in terms of training priorities.

View details for DOI 10.1007/s10439-013-0761-2

View details for Web of Science ID 000323736800002

View details for PubMedID 23404074
Risk factors for atrial fibrillation and their population burden in postmenopausal women: the Women's Health Initiative Observational Study. Heart Perez, M. V., Wang, P. J., Larson, J. C., Soliman, E. Z., Limacher, M., Rodriguez, B., Klein, L., Manson, J. E., Martin, L. W., Prineas, R., Connelly, S., Hlatky, M., Wassertheil-Smoller, S., Stefanick, M. L. 2013; 99 (16): 1173-1178
Abstract

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia in women. Large studies evaluating key AF risk factors in older women are lacking. We aimed to identify risk factors for AF in postmenopausal women and measure population burden of modifiable risk factors. DESIGN: Prospective observational study. SETTING: The Women's Health Initiative (WHI) Observational Study. PATIENTS: 93 676 postmenopausal women were followed for an average of 9.8 years for cardiovascular outcomes. After exclusion of women with prevalent AF or incomplete data, 8252 of the remaining 81 892 women developed incident AF. MAIN OUTCOME MEASURES: Incident AF was identified by WHI-ascertained hospitalisation records and diagnosis codes from Medicare claims. Multivariate Cox hazard regression analysis identified independent risk factors for incident AF. RESULTS: Age, hypertension, obesity, diabetes, myocardial infarction and heart failure were independently associated with incident AF. Hypertension and overweight status accounted for 28.3% and 12.1%, respectively, of the population attributable risk. Hispanic and African-American participants had lower rates of incident AF (HR 0.58, 95% CI 0.47 to 0.70 and HR 0.59, 95% CI 0.53 to 0.65, respectively) than Caucasians. CONCLUSIONS: Caucasian ethnicity, traditional cardiovascular risk factors and peripheral arterial disease were independently associated with higher rates of incident AF in postmenopausal women. Hypertension and overweight status accounted for a large proportion of population attributable risk. Measuring burden of modifiable AF risk factors in older women may help target interventions.

View details for DOI 10.1136/heartjnl-2013-303798

View details for PubMedID 23756655
ATP during charging: A failure of therapy? Heart rhythm Santangeli, P., Tsiperfal, A., Wang, P. J., Al-Ahmad, A. 2013; 10 (7): 1091-1093
View details for DOI 10.1016/j.hrthm.2013.03.010

View details for PubMedID 23499622
Clinical significance of ventricular tachyarrhythmias in patients treated with CRT-D HEART RHYTHM Kutyifa, V., Klein, H. U., Wang, P. J., McNitt, S., Polonsky, B., Zima, E., Merkely, B., Moss, A. J., Zareba, W. 2013; 10 (7): 943-950
Abstract

Data on the outcome of cardiac resynchronization therapy with defibrillator (CRT-D) in patients developing ventricular arrhythmias are limited.To evaluate the prognostic value of ventricular tachycardia (VT) or ventricular fibrillation (VF) episodes by heart rate in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial.Slow VT was defined as VTs with heart rate < 200 beats/min. Fast VT with a heart rate ?200 beats/min and VF (>250 beats/min) were considered as a combined category. Primary end point was heart failure (HF) or death. Secondary end point included all-cause mortality.There were 228 (12.7%) patients with slow VT and 198 (11.1%) with fast VT/VF. In time-dependent analysis, slow VT was associated with an increased risk of HF/death in CRT-D patients with left branch bundle block (LBBB; hazard ratio [HR] 3.19; 95% confidence interval [CI] 1.83-5.55; P < .001), but not in patients with implantable cardioverter-defibrillator (ICD) (HR 1.03; 95% CI 0.52-2.19; P = .867; interaction P value = .017). CRT-D patients with LBBB and fast VT/VF doubled their risk of HF/death compared to ICD patients (interaction P value = .06). Slow VT events were also predictive of death in CRT-D patients with LBBB (HR 3.48; 95% CI 1.66-7.28; P < .001), but not in ICD patients (interaction P value = .06). Slow VTs were highly predictive of subsequent fast VT/VF (HR 4.33; 95% CI 3.01-6.24; P < .001).Slow VT episodes are predictive of subsequent fast VT/VF. Slow VT and fast VT/VF episodes in CRT-D patients are associated with an increased risk of subsequent HF/death. CRT-D-treated LBBB patients with slow VTs have a significantly higher risk of mortality.

View details for DOI 10.1016/j.hrthm.2013.04.006

View details for Web of Science ID 000321497500001

View details for PubMedID 23639624
Frequency of Inappropriate Therapy in Patients Implanted with Dual- Versus Single-Chamber ICD Devices in the ICD Arm of MADIT-CRT JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Ruwald, A. H., Sood, N., Ruwald, M. H., Jons, C., Clyne, C. A., McNitt, S., Wang, P., Zareba, W., Moss, A. J. 2013; 24 (6): 672-679
Abstract

The majority of implantable cardioverter defibrillators (ICDs) are dual-chamber devices, but studies on the frequency of inappropriate therapy in dual- versus single-chamber devices have shown conflicting results. The aim of this study is to determine whether implantation of dual-chamber ICD devices decrease the incidence of inappropriate therapy without an unacceptable increase in complications.In the ICD arm of the MADIT-CRT study (N = 704), comparisons of single- versus dual-chamber ICD devices were investigated on the endpoints of inappropriate therapy (antitachycardia pacing [ATP] and shocks) and device- and procedure-related complications by use of multivariate Cox proportional hazard regression analysis (hazard ratio dual:single chamber) adjusting for relevant covariates.The frequency of inappropriate therapies in single- and dual-chamber recipients was 41/294 (14%) and 50/410 (12%), respectively. There was no significant difference in overall inappropriate therapy (hazard ratio [HR] = 0.95 [CI: 0.63-1.45], P = 0.95) or inappropriate ATP (HR = 0.98 [CI: 0.61-1.58], P = 0.94), between single- and dual-chamber devices, using single-chamber as a reference (Dual:Single). However, there was a trend toward a decrease in inappropriate shocks (HR = 0.60 [CI: 0.34-1.08], P = 0.09) in the dual-chamber group. The same was evident when only analyzing inappropriate therapy for atrial tachyarrhythmias (HR = 0.88 [CI: 0.56-1.38], P = 0.58). There was no significant difference between the groups in device- or procedure-related complications (HR = 1.54 [CI: 0.82-2.90], P = 0.18).No significant difference was found in inappropriate therapy or complications in patients treated with single- versus dual-chamber ICD devices.

View details for DOI 10.1111/jce.12099

View details for Web of Science ID 000319898500011

View details for PubMedID 23445493
Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation Liang, P., Lan, F., Lee, A. S., Gong, T., Sanchez-Freire, V., Wang, Y., Diecke, S., Sallam, K., Knowles, J. W., Wang, P. J., Nguyen, P. K., Bers, D. M., Robbins, R. C., Wu, J. C. 2013; 127 (16): 1677-1691
Abstract

Cardiotoxicity is a leading cause for drug attrition during pharmaceutical development and has resulted in numerous preventable patient deaths. Incidents of adverse cardiac drug reactions are more common in patients with preexisting heart disease than the general population. Here we generated a library of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients with various hereditary cardiac disorders to model differences in cardiac drug toxicity susceptibility for patients of different genetic backgrounds.Action potential duration and drug-induced arrhythmia were measured at the single cell level in hiPSC-CMs derived from healthy subjects and patients with hereditary long QT syndrome, familial hypertrophic cardiomyopathy, and familial dilated cardiomyopathy. Disease phenotypes were verified in long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy hiPSC-CMs by immunostaining and single cell patch clamp. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and the human ether-a-go-go-related gene expressing human embryonic kidney cells were used as controls. Single cell PCR confirmed expression of all cardiac ion channels in patient-specific hiPSC-CMs as well as hESC-CMs, but not in human embryonic kidney cells. Disease-specific hiPSC-CMs demonstrated increased susceptibility to known cardiotoxic drugs as measured by action potential duration and quantification of drug-induced arrhythmias such as early afterdepolarizations and delayed afterdepolarizations.We have recapitulated drug-induced cardiotoxicity profiles for healthy subjects, long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy patients at the single cell level for the first time. Our data indicate that healthy and diseased individuals exhibit different susceptibilities to cardiotoxic drugs and that use of disease-specific hiPSC-CMs may predict adverse drug responses more accurately than the standard human ether-a-go-go-related gene test or healthy control hiPSC-CM/hESC-CM screening assays.

View details for DOI 10.1161/CIRCULATIONAHA.113.001883

View details for PubMedID 23519760

View details for PubMedCentralID PMC3870148
Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation Liang, P., Lan, F., Lee, A. S., Gong, T., Sanchez-Freire, V., Wang, Y., Diecke, S., Sallam, K., Knowles, J. W., Wang, P. J., Nguyen, P. K., Bers, D. M., Robbins, R. C., Wu, J. C. 2013; 127 (16): 1677-1691
View details for DOI 10.1161/CIRCULATIONAHA.113.001883

View details for PubMedID 23519760
Dyssynchrony and the Risk of Ventricular Arrhythmias JACC-CARDIOVASCULAR IMAGING Kutyifa, V., Pouleur, A., Knappe, D., Al-Ahmad, A., Gibinski, M., Wang, P. J., McNitt, S., Merkely, B., Goldenberg, I., Solomon, S. D., Moss, A. J., Zareba, W. 2013; 6 (4): 432-444
Abstract

The aim of our study was to evaluate the relationship between left ventricular (LV) dyssynchrony and the risk of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) trial.Intraventricular mechanical dyssynchrony might be an important factor in ventricular arrhythmogenesis by enhancing electrical heterogeneity in heart failure patients. The effects of dyssynchrony have not yet been evaluated in a large cohort of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy with defibrillator (CRT-D) patients.LV dyssynchrony was measured at baseline and at 12-months by speckle-tracking echocardiography, defined as the standard deviation of time to peak systolic strain in 12 LV myocardial segments. The endpoint was the first VT/VF/death or VT/VF. LV dyssynchrony was evaluated in 764 left bundle branch block (LBBB) patients and in 312 non-LBBB patients.Baseline LV dyssynchrony was not predictive of VT/VF/death or VT/VF in LBBB or non-LBBB patients in either treatment arm. In CRT-D patients with LBBB, improvement in LV dyssynchrony over a year was associated with significantly lower incidence of VT/VF/death (p < 0.001) and VT/VF (p < 0.001) compared to ICD patients and to CRT-D patients with unchanged or worsening dyssynchrony. Among LBBB patients, 15% decrease in LV dyssynchrony was associated with lower risk of VT/VF/death (hazard ratio: 0.49, 95% confidence interval: 0.24 to 0.99, p = 0.049) and VT/VF (hazard ratio: 0.30, 95% confidence interval: 0.12 to 0.77, p = 0.009) as compared to ICD patients. Patients without LBBB receiving CRT-D did not show reduction in VT/VF/death or in VT/VF in relation to improving dyssynchrony when evaluating cumulative event rates or risk of events.Baseline LV dyssynchrony did not predict VT/VF/death or VT/VF in mild heart failure patients with or without LBBB. CRT-induced improvement of LV dyssynchrony was associated with significant reduction of ventricular arrhythmias in patients with LBBB.

View details for DOI 10.1016/j.jcmg.2012.12.008

View details for Web of Science ID 000317842300003

View details for PubMedID 23579010
PAROXYSMAL ATRIAL FIBRILLATION IS ASSOCIATED WITH EXERCISE INTOLERANCE AMONG INDIVIDUALS WITH HYPERTROPHIC CARDIOMYOPATHY 62nd Annual Scientific Session of the American-College-of-Cardiology Azarbal, F., Singh, M., Finocchiaro, G., Le, V., Schnittger, I., Wang, P., Myers, J., Perez, M., Ashley, E. ELSEVIER SCIENCE INC. 2013: E1617?E1617
View details for Web of Science ID 000316555201722
DECLINE IN DEVICE-DERIVED ACTIVITY LEVEL IS A SHORT-TERM PROGNOSTIC PREDICTOR OF DEATH 62nd Annual Scientific Session of the American-College-of-Cardiology Jame, S., Polonsky, B., McNitt, S., Al-Ahmad, A., Moss, A., Zareba, W., Wang, P. ELSEVIER SCIENCE INC. 2013: E658?E658
View details for Web of Science ID 000316555200658
Effects of cardiac resynchronization therapy on left ventricular mass and wall thickness in mild heart failure patients in MADIT-CRT HEART RHYTHM Kutyifa, V., Solomon, S. D., Bourgoun, M., Shah, A. M., Pouleur, A., Knappe, D., McNitt, S., Wang, P. J., Merkely, B., Pfeffer, M., Moss, A. J., Zareba, W. 2013; 10 (3): 354-360
Abstract

The effect of cardiac resynchronization therapy (CRT) on left ventricular wall thickness and left ventricular mass (LVM) is unknown.To evaluate the effects of CRT on septal and posterior wall thickness (SWT and PWT) and LVM in patients with left bundle branch block (LBBB) and non-LBBB vs implantable cardioverter-defibrillator patients and to assess the relationship between CRT-induced changes and cardiac events.We investigated 843 patients with LBBB and 366 patients with non-LBBB enrolled in the Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy (MADIT-CRT) trial to analyze changes in SWT, PWT, and LVM at 12 months and subsequent outcome. The primary end point was heart failure or death; secondary end points included ventricular tachycardia, ventricular fibrillation, or death.In LBBB patients, reduction in SWT, PWT, and LVM was more pronounced in CRT defibrillator (CRT-D) than in implantable cardioverter-defibrillator (SWT:-6.7% � 4.4% vs-1.0% � 1.9%; PWT:-6.4% � 4.3% vs-0.8% � 1.9%; LVM:-23.6% � 9.9% vs-5.1% � 5.1%; P<.001 for all). In CRT-D patients with non-LBBB, LVM reduction was less pronounced; however, changes in SWT and PWT were comparable. Changes in LVM correlated with changes in left ventricular end-diastolic volume. In CRT-D patients with LBBB, reduction in SWT and LVM was associated with reduction in heart failure/death (SWT: hazard ratio 0.94; 95% confidence interval 0.89-0.99 per percent change; P = .03) and ventricular tachycardia/ventricular fibrillation/death (SWT: hazard ratio 0.95; 95% confidence interval 0.91-1.00; P = .04). CRT-D patients with non-LBBB did not show favorable reduction in clinical or arrhythmic end points related to changes in SWT, PWT, or LVM.CRT-D was associated with significant reduction in SWT, PWT, and LVM in patients with LBBB along with left ventricular volume changes and associated favorable clinical and arrhythmia outcomes.

View details for DOI 10.1016/j.hrthm.2012.11.007

View details for Web of Science ID 000315773000009

View details for PubMedID 23174486
Differences and trends in stroke prevention anticoagulation in primary care vs cardiology specialty management of new atrial fibrillation: The Retrospective Evaluation and Assessment of Therapies in AF (TREAT-AF) study. American heart journal Turakhia, M. P., Hoang, D. D., Xu, X., Frayne, S., Schmitt, S., Yang, F., Phibbs, C. S., Than, C. T., Wang, P. J., Heidenreich, P. A. 2013; 165 (1): 93-101 e1
Abstract

Atrial fibrillation and flutter (AF, collectively) cause stroke. We evaluated whether treating specialty influences warfarin prescription in patients with newly diagnosed AF.In the TREAT-AF study, we used Veterans Health Administration health record and claims data to identify patients with newly diagnosed AF between October 2004 and November 2008 and at least 1 internal medicine/primary care or cardiology outpatient encounter within 90 days after diagnosis. The primary outcome was prescription of warfarin.In 141,642 patients meeting the inclusion criteria, the mean age was 72.3 � 10.2 years, 1.48% were women, and 25.8% had cardiology outpatient care. Cardiology-treated patients had more comorbidities and higher mean CHADS2 scores (1.8 vs 1.6, P < .0001). Warfarin use was higher in cardiology-treated vs primary care only-treated patients (68.6% vs 48.9%, P < .0001). After covariate and site-level adjustment, cardiology care was significantly associated with warfarin use (odds ratio [OR] 2.05, 95% CI 1.99-2.11). These findings were consistent across a series of adjusted models (OR 2.05-2.20), propensity matching (OR 1.98), and subgroup analyses (OR 1.58-2.11). Warfarin use in primary-care-only patients declined from 2004 to 2008 (51.6%-44.0%, P < .0001), whereas the adjusted odds of warfarin receipt with cardiology care (vs primary care) increased from 2004 to 2008 (1.88-2.24, P < .0001).In patients with newly diagnosed AF, we found large differences in anticoagulation use by treating specialty. A divergent 5-year trend of risk-adjusted warfarin use was observed. Treating specialty influences stroke prevention care and may impact clinical outcomes.

View details for DOI 10.1016/j.ahj.2012.10.010

View details for PubMedID 23237139
Differences and trends in stroke prevention anticoagulation in primary care vs cardiology specialty management of new atrial fibrillation: The Retrospective Evaluation and Assessment of Therapies in AF (TREAT-AF) study AMERICAN HEART JOURNAL Turakhia, M. P., Hoang, D. D., Xu, X., Frayne, S., Schmitt, S., Yang, F., Phibbs, C. S., Than, C. T., Wang, P. J., Heidenreich, P. A. 2013; 165 (1): 93-?
Abstract

Atrial fibrillation and flutter (AF, collectively) cause stroke. We evaluated whether treating specialty influences warfarin prescription in patients with newly diagnosed AF.In the TREAT-AF study, we used Veterans Health Administration health record and claims data to identify patients with newly diagnosed AF between October 2004 and November 2008 and at least 1 internal medicine/primary care or cardiology outpatient encounter within 90 days after diagnosis. The primary outcome was prescription of warfarin.In 141,642 patients meeting the inclusion criteria, the mean age was 72.3 � 10.2 years, 1.48% were women, and 25.8% had cardiology outpatient care. Cardiology-treated patients had more comorbidities and higher mean CHADS2 scores (1.8 vs 1.6, P < .0001). Warfarin use was higher in cardiology-treated vs primary care only-treated patients (68.6% vs 48.9%, P < .0001). After covariate and site-level adjustment, cardiology care was significantly associated with warfarin use (odds ratio [OR] 2.05, 95% CI 1.99-2.11). These findings were consistent across a series of adjusted models (OR 2.05-2.20), propensity matching (OR 1.98), and subgroup analyses (OR 1.58-2.11). Warfarin use in primary-care-only patients declined from 2004 to 2008 (51.6%-44.0%, P < .0001), whereas the adjusted odds of warfarin receipt with cardiology care (vs primary care) increased from 2004 to 2008 (1.88-2.24, P < .0001).In patients with newly diagnosed AF, we found large differences in anticoagulation use by treating specialty. A divergent 5-year trend of risk-adjusted warfarin use was observed. Treating specialty influences stroke prevention care and may impact clinical outcomes.

View details for DOI 10.1016/j.ahj.2012.10.010

View details for Web of Science ID 000312272900017

View details for PubMedID 23237139
Left ventricular lead location and the risk of ventricular arrhythmias in the MADIT-CRT trial EUROPEAN HEART JOURNAL Kutyifa, V., Zareba, W., McNitt, S., Singh, J., Hall, W. J., Polonsky, S., Goldenberg, I., Huang, D. T., Merkely, B., Wang, P. J., Moss, A. J., Klein, H. 2013; 34 (3): 184-190
Abstract

We aimed to evaluate the influence of left ventricular (LV) lead position on the risk of ventricular tachyarrhythmias in cardiac resynchronization therapy (CRT) patients.Left ventricular (LV) lead position was evaluated by biplane coronary venograms and anterior/posterior, lateral chest X-rays in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy (MADIT-CRT). The LV lead location could be defined in 797 of 1089 patients (73%). The LV lead was placed at the LV apex in 110 (14%) patients, in the anterior position in 146 (18%), in the lateral position in 448 (56%), and in the posterior position in 93 (12%) patients. After adjustment for clinical covariates, lateral or posterior lead location was associated with significantly lower risk of ventricular tachycardia (VT)/ventricular fibrillation (VF) [hazard ratio (HR) = 0.57, 95% confidence interval (CI): 0.38-0.85; P = 0.006] when compared with an anterior lead location. Patients with anterior lead position had similar risk of VT/VF as patients with implantable cardioverter defibrillator (ICD)-only (HR = 1.04, 95% CI: 0.72-1.81; P = 0.837). There was no difference in the risk of mortality between posterior or lateral and anterior LV lead locations.Cardiac resynchronization therapy with posterior or lateral LV lead position is associated with decreased risk of arrhythmic events in comparison with anterior lead location and ICD-only patients. There is no evidence for increased risk of VT/VF episodes associated with CRT.

View details for DOI 10.1093/eurheartj/ehs334

View details for Web of Science ID 000313831000009

View details for PubMedID 23053173
Effects of Postmenopausal Hormone Therapy on Incident Atrial Fibrillation The Women's Health Initiative Randomized Controlled Trials CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Perez, M. V., Wang, P. J., Larson, J. C., Virnig, B. A., Cochrane, B., Curb, J. D., Klein, L., Manson, J. E., Martin, L. W., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. L. 2012; 5 (6): 1108-1116
Abstract

Atrial fibrillation (AF) is less prevalent in women versus men, but associated with higher risks of stroke and death in women. The role hormone therapy plays in AF is not well understood.The Women's Health Initiative randomized postmenopausal women to placebo or conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a uterus (N=16 608) or to conjugated equine estrogens only if they had prior hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes from Medicare claims or hospitalization records. Hazard ratios for incident AF were estimated using Cox proportional hazards regression. After excluding participants with baseline AF, there were 611 incident AF cases over a mean of 5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a mean of 7.1 years among 10 251 conjugated equine estrogens alone participants. Incident AF was more frequent in the active groups of both trials, reaching statistical significance in the trial of conjugated equine estrogens alone in women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00-1.36; P=0.045) and in the pooled analysis (hazard ratio, 1.12; CI, 1.00-1.24; P=0.05), but not in the estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91-1.25; P=0.44). These results were only minimally affected by adjustment for incident stroke, coronary heart disease, and heart failure.Incident AF was modestly elevated in hysterectomized women randomized to postmenopausal E-alone, and in the pooled group randomized to E-alone or estrogen plus progestin. The trend in women with intact uterus receiving estrogen plus progestin, considered separately, was not statistically significant.ClinicalTrials.gov; Identifier: NCT00000611.

View details for DOI 10.1161/CIRCEP.112.972224

View details for Web of Science ID 000313586900018

View details for PubMedID 23169946
AF Ablation: Do You Need a Mapping System for Ablation? Cardiac electrophysiology clinics Tanimoto, K., Wang, P. J., Al-Ahmad, A. 2012; 4 (3): 375?81
Abstract

Radiofrequency ablation has become a mainstay in the therapy for atrial fibrillation (AF). Although there are many different techniques for achieving adequate results, the cornerstone of AF remains pulmonary vein isolation. Three-dimensional (3D) electroanatomical mapping systems play an important role in the reduction of fluoroscopy and the identification of electrical and anatomic landmarks and are used commonly in AF ablation procedures. In this article, the authors discuss the advantages and limitations of 3D mapping systems and try to answer the question: Are they needed for successful AF ablation?

View details for PubMedID 26939957
Reduction in Life-Threatening Ventricular Tachyarrhythmias in Statin-Treated Patients With Nonischemic Cardiomyopathy Enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Buber, J., Goldenberg, I., Moss, A. J., Wang, P. J., McNitt, S., Hall, W. J., Eldar, M., Barsheshet, A., Shechter, M. 2012; 60 (8): 749-755
Abstract

This study hypothesized that time-dependent statin therapy will reduce the risk of life-threatening ventricular tachyarrhythmias among patients with nonischemic cardiomyopathy (NICM) enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).Prior studies suggested that statin therapy exerts antiarrhythmic properties among patients with coronary artery disease. However, data regarding the effect of statins on arrhythmic risk among patients with NICM are limited.Multivariate Cox proportional hazards regression modeling was used to assess the effect of statin therapy, evaluated as a time-dependent covariate, on the risk of appropriate defibrillator therapy for fast ventricular tachycardia (VT) (defined as a rate faster than 180 beats/min)/ventricular fibrillation (VF) or death (primary endpoint) and appropriate defibrillator shocks (secondary endpoint) among 821 patients with NICM enrolled in the MADIT-CRT trial.Statin users (n = 499) were older and had a higher prevalence of diabetes and hypertension yet were less frequently smokers. Multivariate analysis showed that time-dependent statin therapy was independently associated with a significant 77% reduction in the risk of fast VT/VF or death (p < 0.001) and with a significant 46% reduction in the risk of appropriate implantable cardioverter defibrillator shocks (p = 0.01). Consistent with these findings, the cumulative probability of fast VT/VF or death at 4 years of follow-up was significantly lower among patients who were treated with statins (11%) as compared with study patients who were not treated with statins (19%; p = 0.006 for the overall difference during follow-up).Statin use was associated with a significant reduction in the risk of life-threatening ventricular tachyarrhythmias among patients with NICM.

View details for DOI 10.1016/j.jacc.2012.03.041

View details for Web of Science ID 000307463800008

View details for PubMedID 22703927
Abrupt bradycardia and grouped beating during treadmill testing: A mimic of upper rate behavior HEART RHYTHM Woods, C. E., Friday, K., Wang, P., Turakhia, M. P. 2012; 9 (7): 1165-1167
View details for DOI 10.1016/j.hrthm.2011.12.020

View details for PubMedID 22209946
Incidence and clinical predictors of low defibrillation safety margin at time of implantable defibrillator implantation JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Cheng, Z., Turakhia, M., Lo, R., Gupta, A., Zei, P. C., Hsia, H. H., Al-Ahmad, A., Wang, P. J. 2012; 34 (1): 93-100
Abstract

Determination of the defibrillation safety margin (DSM) is the most common method of testing device effectiveness at the time of implantation of implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRTD). Low DSM remains a problem in clinical practice.The purpose of this study is to ascertain the incidence and clinical predictors of low DSM and the treatment strategies for low DSM in ICD or CRTD recipients.Selected ICD or CRTD recipients from January 2006 to May 2008 who underwent DSM test at the time of implantation were included. Low DSM patients were defined as patients who had a DSM within 10 J of the maximum delivered energy of the device. These patients were compared to patients who had DSM?>?10 J.This study included 243 patients. Of these, 13 (5.3%) patients had low DSM, and 230 patients had adequate DSM. Patients with low DSM had a high prevalence of amiodarone use (69% vs 13%, p?
View details for DOI 10.1007/s10840-011-9648-z

View details for Web of Science ID 000303541200013

View details for PubMedID 22391960
EFFECTS OF POSTMENOPAUSAL HORMONE THERAPY ON INCIDENT ATRIAL FIBRILLATION: THE WOMEN'S HEALTH INITIATIVE RANDOMIZED CONTROLLED TRIALS 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)/Conference on ACC-i2 with TCT Perez, M. V., Wang, P., Larson, J., Virnig, B. A., Cochrane, B., Curb, D., Klein, L., Manson, J., Martin, L., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. ELSEVIER SCIENCE INC. 2012: E661?E661
View details for Web of Science ID 000302326700663
Ability of microvolt T-wave alternans to modify risk assessment of ventricular tachyarrhythmic events: A meta-analysis AMERICAN HEART JOURNAL Gupta, A., Hoang, D. D., Karliner, L., Tice, J. A., Heidenreich, P., Wang, P. J., Turakhia, M. P. 2012; 163 (3): 354-364
Abstract

Prior studies have indicated that the magnitude of risk association of microvolt T-wave alternans (MTWA) testing appears to vary with the population studied. We performed a meta-analysis to determine the ability of MTWA to modify risk assessment of ventricular tachyarrhythmic events (VTEs) and sudden cardiac death (SCD) across a series of patient risk profiles using likelihood ratio (LR) testing, a measure of test performance independent of disease prevalence.We identified original research articles published from January 1990 to January 2011 that investigate spectrally derived MTWA. Ventricular tachyarrhythmic event was defined as the total and arrhythmic mortality and nonfatal sustained or implantable cardioverter-defibrillator-treated ventricular tachyarrhythmias. Summary estimates were created for positive and nonnegative MTWA results using a random-effects model and were expressed as positive (LR+) and negative (LR-) LRs.Of 1,534 articles, 20 prospective cohort studies met our inclusion criteria, consisting of 5,945 subjects predominantly with prior myocardial infarction or left ventricular dysfunction. Although there was a modest association between positive MTWA and VTE (relative risk 2.45, 1.58-3.79) and nonnegative MTWA and VTE (3.68, 2.23-6.07), test performance was poor (positive MTWA: LR+ 1.78, LR- 0.43; nonnegative MTWA: LR+ 1.38, LR- 0.56). Subgroup analyses of subjects classified as prior VTE, post-myocardial infarction, SCD-HeFT type, and MADIT-II type had a similar poor test performance. A negative MTWA result would decrease the annualized risk of VTE from 8.85% to 6.37% in MADIT-II-type patients and from 5.91% to 2.60% in SCD-HeFT-type patients.Despite a modest association, results of spectrally derived MTWA testing do not sufficiently modify the risk of VTE to change clinical decisions.

View details for DOI 10.1016/j.ahj.2011.11.021

View details for PubMedID 22424005
Catheter ablation of atrial fibrillation: state-of-the-art techniques and future perspectives JOURNAL OF CARDIOVASCULAR MEDICINE Santangeli, P., Di Biase, L., Burkhardt, D. J., Horton, R., Sanchez, J., Bai, R., Pump, A., Perez, M., Wang, P. J., Natale, A., Al-Ahmad, A. 2012; 13 (2): 108-124
Abstract

The impact of atrial fibrillation on the healthcare systems of Western countries is overwhelming, due to its independent association with death, systemic thromboembolism, impaired quality of life and hospitalizations. Catheter ablation is the only treatment thus far demonstrated capable of achieving cure in a substantial proportion of patients. Pulmonary vein antrum isolation (PVAI) is the cornerstone of current atrial fibrillation ablation techniques, with the greatest efficacy as a stand-alone procedure in patients with paroxysmal atrial fibrillation. Use of general anesthesia, open-irrigated ablation catheters and maintenance of periprocedural therapeutic warfarin has been demonstrated to increase the safety and effectiveness of PVAI. In patients with paroxysmal atrial fibrillation, the systematic addition of superior vena cava isolation increases the long-term freedom from atrial fibrillation recurrence. A more extensive ablation approach extending to the entire left atrial posterior wall and to complex fractionated electrograms (CFAEs) is warranted in nonparoxysmal atrial fibrillation patients, in whom nonpulmonary vein trigger sites are frequently identified. Up to one-third of these patients experiencing atrial fibrillation recurrence after ablation have evidence of triggers from the left atrial appendage. Isolation of this structure is the best treatment strategy to improve the long-term success rate. In recent years, in addition to the development of ablation techniques to increase the success rate, outcomes of atrial fibrillation treatment trials have been reconsidered. In particular, reduction of hospitalization, stroke and mortality, as well as economic factors, have all been considered relevant to evaluate the effectiveness of atrial fibrillation treatment. Large ongoing trials are specifically evaluating the impact of atrial fibrillation ablation on these outcomes. This article will summarize the state-of-the art techniques for atrial fibrillation ablation, and will discuss the contribution of ongoing studies to the future of atrial fibrillation ablation.

View details for DOI 10.2459/JCM.0b013e32834f2371

View details for Web of Science ID 000299652200004

View details for PubMedID 22193837
Procedural Complications, Rehospitalizations, and Repeat Procedures After Catheter Ablation for Atrial Fibrillation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Shah, R. U., Freeman, J. V., Shilane, D., Wang, P. J., Go, A. S., Hlatky, M. A. 2012; 59 (2): 143-149
Abstract

The purpose of this study was to estimate rates and identify predictors of inpatient complications and 30-day readmissions, as well as repeat hospitalization rates for arrhythmia recurrence following atrial fibrillation (AF) ablation.AF is the most common clinically significant arrhythmia and is associated with increased morbidity and mortality. Radiofrequency or cryotherapy ablation of AF is a relatively new treatment option, and data on post-procedural outcomes in large general populations are limited.Using data from the California State Inpatient Database, we identified all adult patients who underwent their first AF ablation from 2005 to 2008. We used multivariable logistic regression to identify predictors of complications and/or 30-day readmissions and Kaplan-Meier analyses to estimate rates of all-cause and arrhythmia readmissions.Among 4,156 patients who underwent an initial AF ablation, 5% had periprocedural complications, most commonly vascular, and 9% were readmitted within 30 days. Older age, female, prior AF hospitalizations, and less hospital experience with AF ablation were associated with higher adjusted risk of complications and/or 30-day readmissions. The rate of all-cause hospitalization was 38.5% by 1 year. The rate of readmission for recurrent AF, atrial flutter, and/or repeat ablation was 21.7% by 1 year and 29.6% by 2 years.Periprocedural complications occurred in 1 of 20 patients undergoing AF ablation, and all-cause and arrhythmia-related rehospitalizations were common. Older age, female sex, prior AF hospitalizations, and recent hospital procedure experience were associated with a higher risk of complications and/or 30-day readmission after AF ablation.

View details for DOI 10.1016/j.jacc.2011.08.068

View details for Web of Science ID 000298796600009

View details for PubMedID 22222078
Similar Patterns and Proportions of Ventricular Tachycardia Initiation With Pacing in Patients With CRT-D versus ICD Chia, K. K., Myall, N., Al-Ahmad, A., Zareba, W., Moss, A. J., Wang, P. J. LIPPINCOTT WILLIAMS & WILKINS. 2011
View details for Web of Science ID 000299738705378
Cardiac Resynchronization Therapy Reduces Left Atrial Volume and the Risk of Atrial Tachyarrhythmias in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Brenyo, A., Link, M. S., Barsheshet, A., Moss, A. J., Zareba, W., Wang, P. J., McNitt, S., Huang, D., Foster, E., Estes, M., Solomon, S. D., Goldenberg, I. 2011; 58 (16): 1682-1689
Abstract

We hypothesized that reductions in left atrial volume (LAV) with a cardiac resynchronization therapy-defibrillator (CRT-D) would translate into a subsequent reduction in the risk of atrial tachyarrhythmias (AT).There is limited information regarding the effect of CRT-D on the risk of AT.Percent reduction in LAV at 1 year following CRT-D implantation (pre-specified as low [lowest quartile: <20% reduction in LAV] and high [?20% reduction in LAV] response to CRT-D) were related to the risk of subsequent AT (comprising atrial fibrillation, atrial flutter, atrial tachycardia, and supraventricular tachyarrhythmias) among patients enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).The cumulative probability of AT 2.5 years after assessment of echocardiographic response was lowest among high LAV responders to CRT-D (3%) and significantly higher among both low LAV responders to CRT-D (9%) and implantable cardioverter-defibrillator-only patients (7%; p = 0.03 for the difference among the 3 groups). Consistently, multivariate analysis showed that high LAV responders to CRT-D experienced a significant 53% (p = 0.01) reduction in the risk of subsequent AT as compared with implantable cardioverter-defibrillator-only patients, whereas low LAV responders did not derive a significant risk reduction with CRT-D therapy (hazard ratio [HR]: 1.05 [95% confidence interval (CI): 0.54 to 2.00]; p = 0.89). Patients who developed in-trial AT experienced significant increases in the risk for both the combined endpoint of heart failure or death (HR: 2.28 [95% CI: 1.45 to 3.59]; p < 0.001) and the separate occurrence of all-cause mortality (HR: 1.89 [95% CI: 1.08 to 3.62]; p = 0.01).In the MADIT-CRT study, favorable reverse remodeling of the left atrium with CRT-D therapy was associated with a significant reduction in risk of subsequent AT. (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).

View details for DOI 10.1016/j.jacc.2011.07.020

View details for Web of Science ID 000295882800008

View details for PubMedID 21982313
3D INTRACARDIAC ECHOCARDIOGRAPHY IN LEFT ATRIAL ABLATION Venice Arrhythmias Conference Al Ahmad, A., Chia, K., Evans, J., Schoenhard, J., Harwood, M., Perez, M., Zei, P., Hsia, H., Wang, P. WILEY-BLACKWELL. 2011: S43?S43
View details for Web of Science ID 000296255000115
Intraprocedure Visualization of the Esophagus Using Interventional C-arm CT as Guidance for Left Atrial Radiofrequency Ablation ACADEMIC RADIOLOGY Tognolini, A., Al-Ahmad, A., Wang, P. J., Hsia, H. H., Herfkens, R. J., Girard, E., Moore, T., Fahrig, R. 2011; 18 (7): 850-857
Abstract

During radiofrequency catheter ablation for atrial fibrillation, the esophagus is at risk for thermal injury. In this study, C-arm computed tomography (CT) was compared to clinical CT, without the administration of oral contrast, to visualize the esophagus and its relationship to the left atrium and the ostia of the pulmonary veins (PVs) during the radiofrequency ablation procedure.Sixteen subjects underwent both cardiac clinical CT and C-arm CT. Computed tomographic scans were performed on a multidetector scanner using a standard electrocardiographically gated protocol. C-arm computed tomographic scans were obtained using either a multisweep protocol with retrospective electrocardiographic gating or a non-gated single-sweep protocol. C-arm and clinical computed tomographic scans were analyzed in a random order and then compared for the following criteria: (1) visualization of the esophagus (yes or no), (2) relationship of esophageal position to the four PVs, and (3) direct contact or absence of a fat pad between the esophagus and the PV antrum.The esophagus was identified in all C-arm and clinical computed tomographic scans. In four cases, orthogonal planes were needed on C-arm CT (inferior PV level). In six patients, the esophageal location on C-arm CT was different from that on CT. Direct contact was reported in 19 of 64 of the segments (30%) examined on CT and in 26 of 64 (41%) on C-arm CT. In five of 64 segments (8%), C-arm CT overestimated a direct contact of the esophagus to the left atrium.C-arm computed tomographic image quality without the administration of oral contrast agents was shown to be sufficient for visualization of the esophagus location during a radiofrequency catheter ablation procedure for atrial fibrillation.

View details for DOI 10.1016/j.acra.2011.01.023

View details for Web of Science ID 000292066200010

View details for PubMedID 21440465

View details for PubMedCentralID PMC3115455
Guidance for the Heart Rhythm Society Pertaining to Interactions with Industry Endorsed by the Heart Rhythm Society on April 26, 2011 HEART RHYTHM Lindsay, B. D., Asirvatham, S. J., Curtis, A. B., Gura, M. T., Hayes, D. L., Jalife, J., Klein, G. J., Knight, B. P., Lampert, R., Natale, A., Packer, D. L., Page, R. L., Scheinman, M. M., Shanker, A. J., Wang, P. J., Weiss, J. P., Wilkoff, B. L., Busky, C. D. 2011; 8 (7): E19-E23
View details for DOI 10.1016/j.hrthm.2011.05.011

View details for Web of Science ID 000292243400002

View details for PubMedID 21722853
Reverse Remodeling and the Risk of Ventricular Tachyarrhythmias in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Barsheshet, A., Wang, P. J., Moss, A. J., Solomon, S. D., Al-Ahmad, A., McNitt, S., Foster, E., Huang, D. T., Klein, H. U., Zareba, W., Eldar, M., Goldenberg, I. 2011; 57 (24): 2416-2423
Abstract

We aimed to evaluate the relationship between echocardiographic response to cardiac resynchronization therapy (CRT) and the risk of subsequent ventricular tachyarrhythmias (VTAs).Current data regarding the effect of CRT on the risk of VTA are limited and conflicting.The risk of a first appropriate implantable cardioverter-defibrillator (ICD) therapy for VTA (including ventricular tachycardia, ventricular fibrillation, and ventricular flutter) was compared between high- and low-echocardiographic responders to CRT defibrillator (CRT-D) therapy (defined as ? 25% and <25% reductions, respectively, in left ventricular end-systolic volume [LVESV] at 1 year compared with baseline) and ICD-only patients enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy).The cumulative probability of a first VTA at 2 years after assessment of echocardiographic response was highest among low responders to CRT-D (28%), intermediate among ICD-only patients (21%), and lowest among high responders to CRT-D (12%), with p < 0.001 for the overall difference during follow-up. Multivariate analysis showed that high responders to CRT-D experienced a significant 55% reduction in the risk of VTA compared with ICD-only patients (p < 0.001), whereas the risk of VTA was not significantly different between low responders and ICD-only patients (hazard ratio [HR]: 1.26; p = 0.21). Consistently, assessment of response to CRT-D as a continuous measure showed that incremental 10% reductions in left ventricular end-systolic volume were associated with corresponding reductions in the risk of subsequent VTA (HR: 0.80; p < 0.001), VTA/death (HR: 0.79; p < 0.001), ventricular tachycardia (HR: 0.80; p < 0.001), and ventricular fibrillation/ventricular flutter (HR: 0.75; p = 0.044).In patients with left ventricular dysfunction enrolled in the MADIT-CRT trial, reverse remodeling was associated with a significant reduction in the risk of subsequent life-threatening VTAs. (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).

View details for DOI 10.1016/j.jacc.2010.12.041

View details for Web of Science ID 000291424100007

View details for PubMedID 21658562
Subcutaneous Implantable Cardioverter-Defibrillator Technology HEART FAILURE CLINICS Gupta, A., Al-Ahmad, A., Wang, P. J. 2011; 7 (2): 287-?
Abstract

The advent of subcutaneous implantable cardioverter-defibrillator (ICD) systems represents a paradigm shift for the detection and therapy of ventricular tachyarrhythmias. Despite advances in transvenous lead technology, problems remain that notably include requirement for technical expertise; periprocedural complications during implantation and explantation; and long-term lead failure. Although subcutaneous ICD systems may mitigate some of these risks, they provide new shortcomings, such as inability to provide pacing therapy for bradyarrhythmias, ventricular tachyarrhythmias, and cardiac resynchronization. Ongoing clinical evaluation and development are required before the role of subcutaneous ICDs as an adjunctive or primary therapy can be defined. This article examines studies investigating the subcutaneous ICD and discusses its possible advantages and disadvantages as compared with current transvenous ICD systems.

View details for DOI 10.1016/j.hfc.2011.01.005

View details for Web of Science ID 000307488700016

View details for PubMedID 21439506
Effectiveness of Cardiac Resynchronization Therapy by QRS Morphology in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) CIRCULATION Zareba, W., Klein, H., Cygankiewicz, I., Hall, W. J., McNitt, S., Brown, M., Cannom, D., Daubert, J. P., Eldar, M., Gold, M. R., Goldberger, J. J., Goldenberg, I., Lichstein, E., Pitschner, H., Rashtian, M., Solomon, S., Viskin, S., Wang, P., Moss, A. J. 2011; 123 (10): 1061-1072
Abstract

This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) trial.Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients who only received an implantable cardioverter defibrillator (ICD) were significantly (P < 0.001) lower in LBBB patients (0.47; P < 0.001) than in non-LBBB patients (1.24; P = 0.257). The risk of ventricular tachycardia, ventricular fibrillation, or death was decreased significantly in CRT-D patients with LBBB but not in non-LBBB patients. Echocardiographic parameters showed significantly (P < 0.001) greater reduction in left ventricular volumes and increase in ejection fraction with CRT-D in LBBB than in non-LBBB patients.Heart failure patients with New York Heart Association class I or II and ejection fraction ? 30% and LBBB derive substantial clinical benefit from CRT-D: a reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias. No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances).URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

View details for DOI 10.1161/CIRCULATIONAHA.110.960898

View details for Web of Science ID 000288369900011

View details for PubMedID 21357819
Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation ANNALS OF INTERNAL MEDICINE Freeman, J. V., Zhu, R. P., Owens, D. K., Garber, A. M., Hutton, D. W., Go, A. S., Wang, P. J., Turakhia, M. P. 2011; 154 (1): 1-U129
Abstract

Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin.To estimate the quality-adjusted survival, costs, and cost-effectiveness of dabigatran compared with adjusted-dose warfarin for preventing ischemic stroke in patients 65 years or older with nonvalvular AF.Markov decision model.The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial and other published studies of anticoagulation. The cost of dabigatran was estimated on the basis of pricing in the United Kingdom.Patients aged 65 years or older with nonvalvular AF and risk factors for stroke (CHADS? score ?1 or equivalent) and no contraindications to anticoagulation.Lifetime.Societal.Warfarin anticoagulation (target international normalized ratio, 2.0 to 3.0); dabigatran, 110 mg twice daily (low dose); and dabigatran, 150 mg twice daily (high dose).Quality-adjusted life-years (QALYs), costs (in 2008 U.S. dollars), and incremental cost-effectiveness ratios.The quality-adjusted life expectancy was 10.28 QALYs with warfarin, 10.70 QALYs with low-dose dabigatran, and 10.84 QALYs with high-dose dabigatran. Total costs were $143 193 for warfarin, $164 576 for low-dose dabigatran, and $168 398 for high-dose dabigatran. The incremental cost-effectiveness ratios compared with warfarin were $51 229 per QALY for low-dose dabigatran and $45 372 per QALY for high-dose dabigatran.The model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs. The incremental cost-effectiveness ratio increased to $50 000 per QALY at a cost of $13.70 per day for high-dose dabigatran but remained less than $85 000 per QALY over the full range of model inputs evaluated. The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage.Event rates were largely derived from a single randomized clinical trial and extrapolated to a 35-year time frame from clinical trials with approximately 2-year follow-up.In patients aged 65 years or older with nonvalvular AF at increased risk for stroke (CHADS? score ?1 or equivalent), dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States.American Heart Association and Veterans Affairs Health Services Research & Development Service.

View details for PubMedID 21041570
Cost-Effectiveness of Genetic Testing in Family Members of Patients With Long-QT Syndrome CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Perez, M. V., Kumarasamy, N. A., Owens, D. K., Wang, P. J., Hlatky, M. A. 2011; 4 (1): 76-84
Abstract

Family members of patients with established long-QT syndrome (LQTS) often lack definitive clinical findings, yet may have inherited an LQTS mutation and be at risk of sudden death. Genetic testing can identify mutations in 75% of patients with LQTS, but genetic testing of family members remains controversial.We used a Markov model to assess the cost-effectiveness of 3 strategies for treating an asymptomatic 10-year-old, first-degree relative of a patient with clinically evident LQTS. In the genetic testing strategy, relatives undergo genetic testing only for the mutation identified in the index patient, and relatives who test positive for the mutation are treated with ?-blockers. This strategy was compared with (1) empirical treatment of relatives with ?-blockers and (2) watchful waiting, with treatment only after development of symptoms. The genetic testing strategy resulted in better survival and quality-adjusted life years at higher cost, with a cost-effectiveness ratio of $67 400 per quality-adjusted life year gained compared with watchful waiting. The cost-effectiveness of the genetic testing strategy improved to less than $50 000 per quality-adjusted life year gained when applied selectively either to (1) relatives with higher clinical suspicion of LQTS (pretest probability 65% to 81%), or to (2) families with a higher than average risk of sudden death, or to (3) larger families (2 or more first-degree relatives tested).Genetic testing of young first-degree relatives of patients with definite LQTS is moderately expensive, but can reach acceptable thresholds of cost-effectiveness when applied to selected patients.

View details for DOI 10.1161/CIRCOUTCOMES.110.957365

View details for PubMedID 21139095
Dyssynchrony Assessment with Tissue Doppler Imaging and Regional Volumetric Analysis by 3D Echocardiography Do Not Predict Long-Term Response to Cardiac Resynchronization Therapy CARDIOLOGY RESEARCH AND PRACTICE Kuppahally, S. S., Fowler, M. B., Vagelos, R., Wang, P., Al-Ahmad, A., Hsia, H., Liang, D. 2011
View details for DOI 10.4061/2011/568918

View details for Web of Science ID 000214709000072
A Novel Method for Patient-Specific QTc-Modeling QT-RR Hysteresis ANNALS OF NONINVASIVE ELECTROCARDIOLOGY Hadley, D. M., Froelicher, V. F., Wang, P. J. 2011; 16 (1): 3-12
Abstract

Cardiac repolarization adaptation to cycle length change is patient dependent and results in complex QT-RR hysteresis. We hypothesize that accurate patient-specific QT-RR curves and rate corrected QT values (QTc) can be derived through patient-specific modeling of hysteresis.Model development was supported by QT-RR observations from 1959 treadmill tests, allowing extensive exploration of the influences of autonomic function on QT adaptation to rate changes. The methodology quantifies and then removes patient-specific repolarization adaptation rates. The estimated average 95% QT confidence limit was approximately 1 msec for the studied population. The model was validated by comparing QT-RR curves derived from a submaximal exercise protocol with rapid exercise and recovery phases, characterized by high hysteresis, with QT-RR values derived from an incremental stepped protocol that held heart rate constant for 5 minutes at each stage of exercise and recovery.The underlying physiologic changes affecting QT dynamics during the transitions from rest to exercise to recovery are quite complex. Nevertheless, a simple patient-specific model, comprising only three parameters and based solely on the preceding history of RR intervals and trend, is sufficient to accurately model QT hysteresis over an entire exercise test for a diverse population. A brief recording of a resting ECG, combined with a short period of submaximal exercise and recovery, provides sufficient information to derive an accurate patient-specific QT-RR curve, eliminating QTc bias inherent in population-based correction formulas.

View details for DOI 10.1111/j.1542-474X.2010.00401.x

View details for Web of Science ID 000286428400002

View details for PubMedID 21251128
Inappropriate Pacing in a Patient with Managed Ventricular Pacing: What Is the Cause? HEART RHYTHM Perez, M. V., Al-Ahmad, A. A., Wang, P. J., Turakhia, M. P. 2010; 7 (12)
View details for Web of Science ID 000284875500003
Cardiac Resynchronization Therapy Decreases the Risk of Ventricular Tachyarrhythmias in the MADIT-CRT Trial Wang, P. J., Al-Ahmad, A., Evans, J., Turakhia, M., McNitt, S., Moss, A., Zareba, W. LIPPINCOTT WILLIAMS & WILKINS. 2010
View details for Web of Science ID 000208231602200
Optical Control of Cardiomyocyte Depolarization and Inhibition Utilizing Channelrhodopsin-2 (ChR2) and a Third Generation Halorhodopsin (eNpHR3.0) Park, S., Vijaykumar, R., Yock, P. G., Wang, P. J., Deisseroth, K. LIPPINCOTT WILLIAMS & WILKINS. 2010
View details for Web of Science ID 000208231601701
Time dependence of life-threatening ventricular tachyarrhythmias after coronary revascularization in MADIT-CRT HEART RHYTHM Barsheshet, A., Goldenberg, I., Narins, C. R., Moss, A. J., McNitt, S., Wang, P. J., Huang, D. T., Hall, W. J., Zareba, W., Eldar, M., Guetta, V. 2010; 7 (10): 1421-1427
Abstract

Coronary revascularization (CR) may confer electrical stability in patients with ischemic cardiomyopathy. However, data regarding the effect of CR on the development of ventricular tachyarrhythmias in this population are limited.The purpose of this study was to evaluate the association between CR and arrhythmic risk in postmyocardial infarction (post-MI) patients with left ventricular dysfunction.The risk for life-threatening ventricular tachyarrhythmias (defined as a first appropriate defibrillator therapy for ventricular tachycardia [VT]/ventricular fibrillation [VF] or death) was compared between post-MI patients with and those without prior CR (n = 612 and 147, respectively) enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT).The 3-year cumulative rate of VT/VF or death was significantly higher among patients without prior CR (42%) than in patients who underwent prior CR (32%, P = .02). Multivariate analysis demonstrated that patients without prior CR had 48% increased risk (P = .01) for VT/VF or death. Risk reduction associated with CR was related to elapsed time from CR, assessed both as a categorical variable (tertiles for time from CR: ?7 years, hazard ratio [HR] = 1.93, P = .001; 1.5-7 years, HR = 1.70, P = .01 vs <1.5 years) and as a continuous measure (4%, P = .002, increased risk for VT/VF or death per 1-year increment of elapsed time from CR). The effect of CR on arrhythmic risk was similar in patients treated with a defibrillator alone or when combined with cardiac resynchronization therapy.Post-MI patients with left ventricular dysfunction who undergo CR experience a time-dependent reduction in the risk for subsequent life-threatening ventricular tachyarrhythmias.

View details for DOI 10.1016/j.hrthm.2010.07.005

View details for Web of Science ID 000282187300014

View details for PubMedID 20620231
Inappropriate pacing in a patient with managed ventricular pacing: What is the cause? HEART RHYTHM Perez, M. V., Al-Ahmad, A. A., Wang, P. J., Turakhia, M. P. 2010; 7 (9): 1336-1337
Abstract

A case of inappropriate atrial pacing in a patient with a pacemaker programmed with Managed Ventricular Pacing (MVP) mode, a proprietary algorithm in Medtronic devices, is presented. The patient was an 84-year-old woman who presented in sinus rhythm with complete atrioventricular block. A dual-chamber pacemaker was implanted and programmed to an MVP pacing mode. After the implant, the patient developed a relatively slow atrial tachyarrhythmia with 2:1 atrioventricular block and inappropriate atrial pacing, followed by a delay in tracking of the atrial tachyarrhythmia. The mechanisms for these behaviors are described.

View details for DOI 10.1016/j.hrthm.2010.04.028

View details for PubMedID 20435165
Factors Influencing Pacemaker Generator Longevity: Results from the Complete Automatic Pacing Threshold Utilization Recorded in the CAPTURE Trial PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Rosenthal, L. S., Mester, S., Rakovec, P., Penaranda, J., Sherman, J. R., Sheldon, T. J., Zeng, C., Wang, P., CAPTURE Trial Investigators 2010; 33 (8): 1020?30
Abstract

The CAPTURE study evaluated the accuracy of automated atrial and right ventricular (RV) threshold algorithms.Modern pacemakers include many added features designed to improve the ease of patient follow-up, as well as algorithms to reduce pacing outputs and/or reduce the atrial or ventricular pacing percentages, thus improving longevity.Automated atrial and RV threshold measurements were assessed versus manual measurements at 6 months. The projected longevity was assessed and compared between subjects with the threshold-tracking feature On versus Off. In addition, the projected longevity effect of device features to reduce atrial pacing and reduce ventricular pacing, and device characteristics such as battery size and high impedance leads (> or =1,000 ohms), was investigated.Atrial and RV manual versus automatic measurements were equivalent in 683 of 691 subjects (98.8%) and 736 of 746 subjects (98.7%), respectively. Thresholds were stable with 99.6% of atrial and 99.2% of RV consecutive measurements within +/-0.25V. Algorithms for threshold tracking, reducing ventricular pacing, and reducing atrial pacing were associated with 0.8, 0.9, and 0.2 years projected longevity improvements. High impedance leads were associated with a 0.8-year projected longevity improvement. Approximately 2 years of longevity improvement was projected for a 1-cc increase in device size.The atrial and RV algorithms were accurate and reliable in all leads tested. Threshold tracking, reduced ventricular pacing, and high impedance leads result in increased device longevity. Battery capacity was the strongest determinant of increased projected longevity.

View details for DOI 10.1111/j.1540-8159.2010.02809.x

View details for Web of Science ID 000280637700020

View details for PubMedID 20545869
Left Atrial Appendage An Underrecognized Trigger Site of Atrial Fibrillation CIRCULATION Di Biase, L., Burkhardt, J. D., Mohanty, P., Sanchez, J., Mohanty, S., Horton, R., Gallinghouse, G. J., Bailey, S. M., Zagrodzky, J. D., Santangeli, P., Hao, S., Hongo, R., Beheiry, S., Themistoclakis, S., Bonso, A., Rossillo, A., Corrado, A., Raviele, A., Al-Ahmad, A., Wang, P., Cummings, J. E., Schweikert, R. A., Pelargonio, G., Dello Russo, A., Casella, M., Santarelli, P., Lewis, W. R., Natale, A. 2010; 122 (2): 109-U26
Abstract

Together with pulmonary veins, many extrapulmonary vein areas may be the source of initiation and maintenance of atrial fibrillation. The left atrial appendage (LAA) is an underestimated site of initiation of atrial fibrillation. Here, we report the prevalence of triggers from the LAA and the best strategy for successful ablation.Nine hundred eighty-seven consecutive patients (29% paroxysmal, 71% nonparoxysmal) undergoing redo catheter ablation for atrial fibrillation were enrolled. Two hundred sixty-six patients (27%) showed firing from the LAA and became the study population. In 86 of 987 patients (8.7%; 5 paroxysmal, 81 nonparoxysmal), the LAA was found to be the only source of arrhythmia with no pulmonary veins or other extrapulmonary vein site reconnection. Ablation was performed either with focal lesion (n=56; group 2) or to achieve LAA isolation by placement of the circular catheter at the ostium of the LAA guided by intracardiac echocardiography (167 patients; group 3). In the remaining patients, LAA firing was not ablated (n=43; group 1). At the 12+/-3-month follow-up, 32 patients (74%) in group 1 had recurrence compared with 38 (68%) in group 2 and 25 (15%) in group 3 (P<0.001).The LAA appears to be responsible for arrhythmias in 27% of patients presenting for repeat procedures. Isolation of the LAA could achieve freedom from atrial fibrillation in patients presenting for a repeat procedure when arrhythmias initiating from this structure are demonstrated.

View details for DOI 10.1161/CIRCULATIONAHA.109.928903

View details for Web of Science ID 000279801700003

View details for PubMedID 20606120
Periprocedural Stroke and Management of Major Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation CIRCULATION Di Biase, L., Burkhardt, J. D., Mohanty, P., Sanchez, J., Horton, R., Gallinghouse, G. J., Lakkireddy, D., Verma, A., Khaykin, Y., Hongo, R., Hao, S., Beheiry, S., Pelargonio, G., Dello Russo, A., Casella, M., Santarelli, P., Santangeli, P., Wang, P., Al-Ahmad, A., Patel, D., Themistoclakis, S., Bonso, A., Rossillo, A., Corrado, A., Raviele, A., Cummings, J. E., Schweikert, R. A., Lewis, W. R., Natale, A. 2010; 121 (23): 2550-2556
Abstract

Catheter ablation of atrial fibrillation is associated with the potential risk of periprocedural stroke, which can range between 1% and 5%. We developed a prospective database to evaluate the prevalence of stroke over time and to assess whether the periprocedural anticoagulation strategy and use of open irrigation ablation catheter have resulted in a reduction of this complication.We collected data from 9 centers performing the same ablation procedure with the same anticoagulation protocol. We divided the patients into 3 groups: ablation with an 8-mm catheter off warfarin (group 1), ablation with an open irrigated catheter off warfarin (group 2), and ablation with an open irrigated catheter on warfarin (group 3). Outcome data on stroke/transient ischemic attack and bleeding complications during and early after the procedures were collected. Of 6454 consecutive patients in the study, 2488 were in group 1, 1348 were in group 2, and 2618 were in group 3. Periprocedural stroke/transient ischemic attack occurred in 27 patients (1.1%) in group 1 and 12 patients (0.9%) in group 2. Despite a higher prevalence of nonparoxysmal atrial fibrillation and more patients with CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score >2, no stroke/transient ischemic attack was reported in group 3. Complications among groups 1, 2, and 3, including major bleeding (10 [0.4%], 11 [0.8%], and 10 [0.4%], respectively; P>0.05) and pericardial effusion (11 [0.4%], 11 [0.8%], and 12 [0.5%]; P>0.05), were equally distributed.The combination of an open irrigation ablation catheter and periprocedural therapeutic anticoagulation with warfarin may reduce the risk of periprocedural stroke without increasing the risk of pericardial effusion or other bleeding complications.

View details for DOI 10.1161/CIRCULATIONAHA.109.921320

View details for Web of Science ID 000278754900002

View details for PubMedID 20516376
Measurement Precision in the Optimization of Cardiac Resynchronization Therapy CIRCULATION-HEART FAILURE Turcott, R. G., Witteles, R. M., Wang, P. J., Vagelos, R. H., Fowler, M. B., Ashley, E. A. 2010; 3 (3): 395-404
Abstract

Cardiac resynchronization therapy improves morbidity and mortality in appropriately selected patients. Whether atrioventricular (AV) and interventricular (VV) pacing interval optimization confers further clinical improvement remains unclear. A variety of techniques are used to estimate optimum AV/VV intervals; however, the precision of their estimates and the ramifications of an imprecise estimate have not been characterized previously.An objective methodology for quantifying the precision of estimated optimum AV/VV intervals was developed, allowing physiologic effects to be distinguished from measurement variability. Optimization using multiple conventional techniques was conducted in individual sessions with 20 patients. Measures of stroke volume and dyssynchrony were obtained using impedance cardiography and echocardiographic methods, specifically, aortic velocity-time integral, mitral velocity-time integral, A-wave truncation, and septal-posterior wall motion delay. Echocardiographic methods yielded statistically insignificant data in the majority of patients (62%-82%). In contrast, impedance cardiography yielded statistically significant results in 84% and 75% of patients for AV and VV interval optimization, respectively. Individual cases demonstrated that accepting a plausible but statistically insignificant estimated optimum AV or VV interval can result in worse cardiac function than default values.Consideration of statistical significance is critical for validating clinical optimization data in individual patients and for comparing competing optimization techniques. Accepting an estimated optimum without knowledge of its precision can result in worse cardiac function than default settings and a misinterpretation of observed changes over time. In this study, only impedance cardiography yielded statistically significant AV and VV interval optimization data in the majority of patients.

View details for DOI 10.1161/CIRCHEARTFAILURE.109.900076

View details for PubMedID 20176716
Finite element modeling of subcutaneous implantable defibrillator electrodes in an adult torso HEART RHYTHM Jolley, M., Stinstra, J., Tate, J., Pieper, S., MacLeod, R., Chu, L., Wang, P., Triedman, J. K. 2010; 7 (5): 692-698
Abstract

Total subcutaneous implantable subcutaneous defibrillators are in development, but optimal electrode configurations are not known.We used image-based finite element models (FEM) to predict the myocardial electric field generated during defibrillation shocks (pseudo-DFT) in a wide variety of reported and innovative subcutaneous electrode positions to determine factors affecting optimal lead positions for subcutaneous implantable cardioverter-defibrillators (S-ICD).An image-based FEM of an adult man was used to predict pseudo-DFTs across a wide range of technically feasible S-ICD electrode placements. Generator location, lead location, length, geometry and orientation, and spatial relation of electrodes to ventricular mass were systematically varied. Best electrode configurations were determined, and spatial factors contributing to low pseudo-DFTs were identified using regression and general linear models.A total of 122 single-electrode/array configurations and 28 dual-electrode configurations were simulated. Pseudo-DFTs for single-electrode orientations ranged from 0.60 to 16.0 (mean 2.65 +/- 2.48) times that predicted for the base case, an anterior-posterior configuration recently tested clinically. A total of 32 of 150 tested configurations (21%) had pseudo-DFT ratios
View details for DOI 10.1016/j.hrthm.2010.01.030

View details for PubMedID 20230927
The impact of statins and renin-angiotensin-aldosterone system blockers on pulmonary vein antrum isolation outcomes in post-menopausal females EUROPACE Patel, D., Mohanty, P., Di Biase, L., Wang, Y., Shaheen, M. H., Sanchez, J. E., Horton, R. P., Gallinghouse, G. J., Zagrodzky, J. D., Bailey, S. M., Burkhardt, J. D., Lewis, W. R., Diaz, A., Beheiry, S., Hongo, R., Al-Ahmad, A., Wang, P., Schweikert, R., Natale, A. 2010; 12 (3): 322-330
Abstract

To assess whether treatment with statins or renin-angiotensin-aldosterone system (RAAS) inhibitors as potential procedural 'augmenting agents' improved atrial fibrillation (AF) catheter ablation recurrence rates in post-menopausal females (PMFS).Five hundred and eighteen consecutive female patients had undergone AF catheter ablation from January 2005 to May 2008. Post-menopausal females were selected and procedure outcomes were compared between cohorts of PMFS treated with statins or RAAS inhibitors to untreated PMFS. Out of 408 PMFS, 36 (8.8%) were treated with a combination of RAAS inhibitors and statins, thus were excluded leaving a total of 372 (91.2%) patients in the study. Out of 372 patients, 111 (29.8%) were on statins (Group 1), 59 (15.9%) on RAAS inhibitors (Group 2), and 202 (54.3%) without RAAS inhibitors or statins [(Group 3) control population]. Over a mean follow-up time of 24 +/- 8.3 (median 25) months, 78 (70.6%) in Group 1, 38 (65.4%) in Group 2, and 139 (68.8%) in Group 3 had procedural success. Statin or RAAS inhibitor use did not predict lower recurrence rates [hazard ratio (HR): 1.26, P = 0.282 and HR: 1.14, P = 0.728, respectively]. When compared with controls, no difference in the cumulative incidence of recurrence was found with statin or RAAS inhibitors use (P = 0.385 and P = 0.761, respectively).Treatment with statins or RAAS inhibitors did not improve catheter ablation success rates among PMFS. Thereby, from a clinical standpoint, PMFS should not be started on these treatments as a procedural 'augmenting agent' at this time.

View details for DOI 10.1093/europace/eup387

View details for Web of Science ID 000276050200010

View details for PubMedID 20064822
Outcomes and complications of catheter ablation for atrial fibrillation in females HEART RHYTHM Patel, D., Mohanty, P., Di Biase, L., Sanchez, J. E., Shaheen, M. H., Burkhardt, J. D., Bassouni, M., Cummings, J., Wang, Y., Lewis, W. R., Diaz, A., Horton, R. P., Beheiry, S., Hongo, R., Gallinghouse, G. J., Zagrodzky, J. D., Bailey, S. M., Al-Ahmad, A., Wang, P., Schweikert, R. A., Natale, A. 2010; 7 (2): 167-172
Abstract

Most atrial fibrillation (AF) ablation studies have consisted predominantly of males; accordingly, there is a paucity of information on the safety and efficacy of catheter ablation in a large cohort of female AF patients.The purpose of this study was to evaluate catheter ablation for AF in female patients.From January 2005 to May 2008, 3265 females underwent pulmonary vein antrum isolation. Success rates, patient profiles, and complications were collected.Approximately 16% of our population was female (P <.001). Females were older (59 +/- 13 vs. 56 +/- 19 years; P <.01) and had a lower prevalence of paroxysmal atrial fibrillation (PAF; 46% vs. 55%; P <.001). Females failed more antiarrhythmics (4 +/- 1 vs. 2 +/- 3; P = .04) and were referred later for catheter ablation (6.51 +/- 7 vs. 4.85 +/- 6.5 years; P = .02) than males. More females failed ablation (31.5% vs. 22.5%; P = .001) and had nonantral sites of firing than males (P <.001). Female patients had 11 (2.1%) hematomas versus 27 (0.9%) in males.Five times as many males underwent catheter ablation than females. Females failed more ablations possibly because of a higher prevalence of nonantral firing, non-PAF, and longer history of AF. Females had more bleeding complications than males.

View details for DOI 10.1016/j.hrthm.2009.10.025

View details for Web of Science ID 000276189400005

View details for PubMedID 20022814
Dyssynchrony Assessment with Tissue Doppler Imaging and Regional Volumetric Analysis by 3D Echocardiography Do Not Predict Long-Term Response to Cardiac Resynchronization Therapy. Cardiology research and practice Kuppahally, S. S., Fowler, M. B., Vagelos, R., Wang, P., Al-Ahmad, A., Hsia, H., Liang, D. 2010; 2011: 568918-?
Abstract

Background. Currently there are no reliable predictors of response to cardiac resynchronization therapy (CRT) before implantation. We compared pre-CRT left ventricular (LV) dyssynchrony by tissue Doppler imaging (TDI) and regional volumetric analysis by 3-dimensional transthoracic echocardiography (3DTTE) in predicting response to CRT. Methods. Thirty-eight patients (79% nonischemic cardiomyopathy) with symptomatic heart failure who underwent CRT were enrolled. Clinical and echocardiographic responses were defined as improvement in one NYHA class and reduction in LV end-systolic volume by ?15% respectively. Functional status was assessed by Minnesota Living with Heart Failure questionnaire and 6-minute walk distance. Results. In 33 patients, after CRT for 7.86 � 2.27 months, there were 24 (73%) clinical and 19 (58%) echocardiographic responders. Functional parameters, LV dimensions, volumes and synchrony by TDI and 3DTTE improved significantly in responders. There was no difference in the number of responders and nonresponders when cut-off values for dyssynchrony by different measurements validated in other trials were applied. Area under receiver-operating-characteristic curve ranged from 0.4 to 0.6. Conclusion. CRT improves clinical and echocardiographic parameters in patients with systolic heart failure. The dyssynchrony measurements by TDI and 3DTTE are not comparable and are unable to predict response to CRT.

View details for DOI 10.4061/2011/568918

View details for PubMedID 21234100

View details for PubMedCentralID PMC3014673
Subcutaneous Implantable Cardioverter-Defibrillator Technology. Cardiac electrophysiology clinics Gupta, A., Al-Ahmad, A., Wang, P. J. 2009; 1 (1): 147?54
Abstract

The advent of subcutaneous implantable cardioverter-defibrillator (ICD) systems represents a paradigm shift for the detection and therapy of ventricular tachyarrhythmias. Despite advances in transvenous lead technology, problems remain that notably include requirement for technical expertise; periprocedural complications during implantation and explantation; and long-term lead failure. Although subcutaneous ICD systems may mitigate some of these risks, they provide new shortcomings, such as inability to provide pacing therapy for bradyarrhythmias, ventricular tachyarrhythmias, and cardiac resynchronization. Ongoing clinical evaluation and development are required before the role of subcutaneous ICDs as an adjunctive or primary therapy can be defined. This article examines studies investigating the subcutaneous ICD and discusses its possible advantages and disadvantages as compared with current transvenous ICD systems.

View details for PubMedID 28770781
Independent Clinical Correlates of Atrial Fibrillation in Postmenopausal Women: The Women's Health Initiative Observational Study 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Perez, M., Wang, P. J., Klein, L., Connelly, S., Larson, J., Limacher, M., Manson, J., Martin, L. W., Prineas, R., Rodriguez, B. L., Smoller, S., Soliman, E., Stefanick, M. L. LIPPINCOTT WILLIAMS & WILKINS. 2009: S520?S520
View details for Web of Science ID 000271831501093
Periprocedural Stroke in Patients Undergoing Catheter Ablation of Atrial Fibrillation: The Impact of Periprocedural Thereapeutic INR Di Biase, L., Burkhardt, J., Horton, R., Sanchez, J., Gallinghouse, G., Bailey, S., Mohanty, P., Patel, D., Cummings, J. E., Schweikert, R. A., Lakkireddy, D., Verma, A., Hao, S., Hongo, R., Beheiry, S., Al-Ahmad, A., Wang, P., Dello Russo, A., Pelargonio, G., Casella, M., Lewis, W. R., Bonso, A., Themistoclakis, S., Raviele, A., Natale, A. LIPPINCOTT WILLIAMS & WILKINS. 2009: S658
View details for Web of Science ID 000271831501661
Finite Element Modeling of Subcutaneous ICD Predicts Alternative Optimized Lead Configurations Jolley, M. A., Stinstra, J., Pieper, S., Tate, J., Macleod, R., Wang, P., Triedman, J. K. LIPPINCOTT WILLIAMS & WILKINS. 2009: S713?S714
View details for Web of Science ID 000271831502061
Left Atrial Appendage: An Undercognized Trigger Site of Atrial Fibrillation 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Di Biase, L., Burkhardt, J. D., Horton, R., Sanchez, J., Bailey, S., Mohanty, P., Patel, D., Hao, S., Hongo, R., Behelry, S., Al-Ahamad, A., Wang, P., Casella, M., Santarelli, P., Pelargonio, G., Dello Russo, A., Natale, A. LIPPINCOTT WILLIAMS & WILKINS. 2009: S690?S691
View details for Web of Science ID 000271831501793
Management of Pericardial Effusion During and After Ablation for Atrial Fibrillation in Patients Undergoing the Procedure With Therapeutic INR 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Di Biase, L., Burkhardt, J. D., Horton, R., Sanchez, J., Gallinghouse, G. J., Bailey, S., Mohanty, P., Patel, D., Schweikert, R. A., Cummings, J. E., Lakkireddy, D., Verma, A., Hao, S., Hongo, R., Beheiry, S., Al-Ahamad, A., Wang, P., Dello Russo, A., Pelargonio, G., Casella, M., Lewis, W. R., Bonso, A., Themistoclakis, S., Raviele, A., Natale, A. LIPPINCOTT WILLIAMS & WILKINS. 2009: S658?S658
View details for Web of Science ID 000271831501662
Effects of Postmenopausal Hormone Therapy on Atrial Fibrillation: The Women's Health Initiative Randomized Controlled Trials 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Perez, M., Wang, P. J., Cochrane, B., Curb, J. D., Klein, L., Larson, J., Manson, J., Martin, L. W., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. LIPPINCOTT WILLIAMS & WILKINS. 2009: S519?S519
View details for Web of Science ID 000271831501090
Atrial Mechanical Function Using Left Atrial Pressure Waveform Analysis in Persistent and Paroxysmal Atrial Fibrillation Patients 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Cheng, Z., Lo, R., Gupta, A., Perez, M., Zei, P., Hsia, H. H., Turakhia, M., Al-Ahmad, A., Wang, P. J. LIPPINCOTT WILLIAMS & WILKINS. 2009: S628?S628
View details for Web of Science ID 000271831501532
Electrocardiographic predictors of atrial fibrillation AMERICAN HEART JOURNAL Perez, M. V., Dewey, F. E., Marcus, R., Ashley, E. A., Al-Ahmad, A. A., Wang, P. J., Froelicher, V. F. 2009; 158 (4): 622-628
Abstract

Atrial fibrillation (AF) is the most prevalent arrhythmia in the United States and accounts for more than 750,000 strokes per year. Noninvasive predictors of AF may help identify patients at risk of developing AF. Our objective was to identify the electrocardiographic characteristics associated with onset of AF.This was a retrospective cohort analysis of 42,751 patients with electrocardiograms (ECGs) ordered by physician's discretion and analyzed using a computerized system. The population was followed for detection of AF on subsequent ECGs. Cox proportional hazard regression analysis was performed to test the association between these ECG characteristics and development of AF.For a mean follow-up of 5.3 years, 1,050 (2.4%) patients were found to have AF on subsequent ECG recordings. Several ECG characteristics, such as P-wave dispersion (the difference between the widest and narrowest P waves), premature atrial contractions, and an abnormal P axis, were predictive of AF with hazard ratio of approximately 2 after correcting for age and sex. P-wave index, the SD of P-wave duration across all leads, was one of the strongest predictors of AF with a concordance index of 0.62 and a hazard ratio of 2.7 (95% CI 2.1-3.3) for a P-wave index >35. These were among the several independently predictive markers identified on multivariate analysis.Several ECG markers are independently predictive of future onset of AF. The P index, a measurement of disorganized atrial depolarization, is one of the strongest predictors of AF. The ECG contains valuable prognostic information that can identify patients at risk of AF.

View details for DOI 10.1016/j.ahj.2009.08.002

View details for PubMedID 19781423
Visualizing ablation gaps in vitro using a deflectable fiber optic endocardial visualization catheter JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Irani, A. R., Lin, B., Eversull, C., Hsia, H. H., Zei, P. C., Wang, P. J., Al-Ahmad, A. 2009; 25 (2): 107-110
Abstract

The efficacy of pulmonary vein isolation for the treatment of atrial fibrillation may be limited by the ability to make continuous and transmural lesions utilizing an ablation catheter. Gaps often persist between ablation lesions leading to failed electrical isolation and thus failed ablation. Recently, a deflectable fiberoptic endocardial visualization catheter has been introduced for use in imaging the coronary sinus using light in the visible spectrum. We utilize this catheter to visualize the endocardial surface and examine radiofrequency ablation lesions in porcine endocardium to determine the presence of gaps between radiofrequency lesions.Videos were taken of the lesions and shown to two readers who were asked to identify the gaps ranging from less than 0.1 mm-9.8 mm.Ninety-four lesion gaps were reviewed. The readers demonstrated a combined accuracy of 98.4% at identifying gaps.Gaps between ablation lesions can be accurately identified down to less than 1 mm distances in vitro using a direct visualization catheter. Further studies are warranted to confirm these finding in vivo.

View details for DOI 10.1007/s10840-008-9338-7

View details for Web of Science ID 000267683500004

View details for PubMedID 19148727
"Low ejection fraction prophylaxis" with implantable defibrillators in the elderly: Call for a randomized trial? HEART RHYTHM Turakhia, M. P., Wang, P. J. 2009; 6 (8): 1144-1145
View details for DOI 10.1016/j.hrthm.2009.04.031

View details for Web of Science ID 000268867700006

View details for PubMedID 19632625
Worsening of Left Ventricular End-Systolic Volume and Mitral Regurgitation without Increase in Left Ventricular Dyssynchrony on Acute Interruption of Cardiac Resynchronization Therapy ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Kuppahally, S. S., Fowler, M. B., Vagelos, R., Wang, P., Al-Ahmad, A., Paloma, A., Liang, D. 2009; 26 (7): 759-765
Abstract

Responders to cardiac resynchronization therapy (CRT) have greater left ventricular (LV) dyssynchrony than nonresponders prior to CRT.We conducted this study to see whether the long term responders have more worsening of LV dyssynchrony and LV function on acute interruption of CRT.We identified 22 responders and 13 nonresponders who received CRT as per standard criteria for 23.73 +/- 7.9 months (median 24.5 months). We assessed the acute change in LV function, mitral regurgitation (MR) and compared LV dyssynchrony in CRT on and off modes.On turning off CRT, there was no significant worsening of LV dyssynchrony in both responders and nonresponders. The dyssynchrony measurements by SPWMD, TDI and 3D echocardiography did not correlate significantly. LVESV increased (p = 0.02) and MR (p = 0.01) worsened in CRT-off mode in responders only without significant change in LVEF or LV dimensions. Discussion andIn long-term responders to CRT, there is alteration in the function of remodeled LV with acute interruption of CRT, without significant worsening of LV dyssynchrony. The role of different echocardiographic parameters in the assessment of LV dyssynchrony remains controversial. Even after long-term CRT reversely remodels the LV, the therapy needs to be continued uninterrupted for sustained benefits.

View details for DOI 10.1111/j.1540-8175.2008.00887.x

View details for Web of Science ID 000268457100002

View details for PubMedID 19558521
Prevention of phrenic nerve injury during epicardial ablation: Comparison of methods for separating the phrenic nerve from the epicardial surface HEART RHYTHM Di Biase, L., Burkhardt, J. D., Pelargonio, G., Dello Russo, A., Casella, M., Santarelli, P., Horton, R., Sanchez, J., Gallinghouse, J. G., Al-Ahmad, A., Wang, P., Cummings, J. E., Schweikert, R. A., Natale, A. 2009; 6 (7): 957-961
Abstract

The proximity of the phrenic nerve (PN) to cardiac tissue relevant to arrhythmias may increase the risk of PN injury. Strategies for preventing PN injury in the pericardial space are limited.The purpose of this study was to compare methods for separating the PN from the epicardial surface in order to prevent PN injury.Eight patients referred for epicardial ablation of arrhythmias were enrolled in the study. All patients required ablation near the PN. Endocardial and epicardial access was obtained in all patients. A three-dimensional mapping system was used to guide mapping and ablation. All patients underwent epicardial catheter ablation. Pacing via the ablation catheter identified the location of the PN. In order to prevent PN injury, four new strategies were tested in each patient. We sought to increase the distance between the epicardium and the PN by (1) placing a large-diameter balloon between the nerve and the myocardium, (2) introducing saline in steps of 20 ml until PN capture was lost or blood pressure dropped below 60 mmHg, (3) introducing air until PN capture was lost or blood pressure dropped below 60 mmHg, or (4) introducing a combination of saline and air until PN capture was lost or blood pressure dropped below 60 mmHg.At each step, epicardial pacing was performed to assess for PN stimulation. The combination of air and saline resulted in the greatest decrease of PN stimulation. Saline only failed in all cases. Air only and balloon placement were infrequently successful.Controlled and progressive inflation of air and saline together with careful monitoring of hemodynamic parameters appears to be the best strategy for preventing PN injury during epicardial ablation. Placement of a large balloon in the appropriate location can be difficult.

View details for DOI 10.1016/j.hrthm.2009.03.022

View details for Web of Science ID 000267791900005

View details for PubMedID 19560084
Direct Visualization of Cardiac Radiofrequency Ablation Lesions JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH Eversull, C. S., Lin, B., Irani, A. R., Quigley, M. L., Mourlas, N. J., Hsia, H. H., Zei, P. C., Al-Ahmad, A., Wang, P. J. 2009; 2 (2): 198-201
Abstract

Effective ablation of atrial fibrillation and other cardiac arrhythmias requires precise catheter navigation and controlled delivery of energy to cardiac tissue. In this study, we summarize our initial experience using a fiber optic direct visualization catheter to evaluate and guide placement of endocardial radiofrequency (RF) ablation lesions. RF lesions were created in cadaveric porcine hearts and examined in a blood-filled field using a direct visualization catheter. Direct visualization of RF lesions was repeated in vivo using an ovine model. Lesions and interlesion gaps were clearly identifiable using the direct visualization catheter. It was possible to place lesions in proximity to anatomical landmarks and in relation to one another. Catheter-generated images correlated well with lesion appearance on gross examination. Direct catheter-based visualization is a feasible technique for guiding RF lesion placement, estimating lesion size, and identifying interlesion gaps. Future work is needed to correlate surface appearance with transmurality and electrical isolation.

View details for DOI 10.1007/s12265-009-9094-9

View details for Web of Science ID 000284690100010

View details for PubMedID 20559988
The Efficacy of Implantable Cardioverter-Defibrillators in Heart Transplant Recipients Results From a Multicenter Registry CIRCULATION-HEART FAILURE Tsai, V. W., Cooper, J., Garan, H., Natale, A., Ptaszek, L. M., Ellinor, P. T., Hickey, K., Downey, R., Zei, P., Hsia, H., Wang, P., Hunt, S., Haddad, F., Al-Ahmad, A. 2009; 2 (3): 197-201
Abstract

Sudden cardiac death among orthotopic heart transplant recipients is an important mechanism of death after cardiac transplantation. The role for implantable cardioverter-defibrillators (ICDs) in this population is not well established. This study sought to determine whether ICDs are effective in preventing sudden cardiac death in high-risk heart transplant recipients.We retrospectively analyzed the records of all orthotopic heart transplant patients who had ICD implantation between January 1995 and December 2005 at 5 heart transplant centers. Thirty-six patients were considered high risk for sudden cardiac death. The mean age at orthotopic heart transplant was 44+/-14 years, the majority being male (n=29). The mean age at ICD implantation was 52+/-14 years, whereas the average time from orthotopic heart transplant to ICD implant was 8 years +/-6 years. The main indications for ICD implantation were severe allograft vasculopathy (n=12), unexplained syncope (n=9), history of cardiac arrest (n=8), and severe left ventricular dysfunction (n=7). Twenty-two shocks were delivered to 10 patients (28%), of whom 8 (80%) received 12 appropriate shocks for either rapid ventricular tachycardia or ventricular fibrillation. The shocks were effective in terminating the ventricular arrhythmias in all cases. Three (8%) patients received 10 inappropriate shocks. Underlying allograft vasculopathy was present in 100% (8 of 8) of patients who received appropriate ICD therapy.Use of ICDs after heart transplantation may be appropriate in selected high-risk patients. Further studies are needed to establish an appropriate prevention strategy in this population.

View details for DOI 10.1161/CIRCHEARTFAILURE.108.814525

View details for Web of Science ID 000269161600007

View details for PubMedID 19808340
Atrial Fibrillation Ablation Strategies for Paroxysmal Patients Randomized Comparison Between Different Techniques CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Di Biase, L., Elayi, C. S., Fahmy, T. S., Martin, D. O., Ching, C. K., Barrett, C., Bai, R., Patel, D., Khaykin, Y., Hongo, R., Hao, S., Beheiry, S., Pelargonio, G., Dello Russo, A., Casella, M., Santarelli, P., Potenza, D., Fanelli, R., Massaro, R., Wang, P., Al-Ahmad, A., Arruda, M., Themistoclakis, S., Bonso, A., Rossillo, A., Raviele, A., Schweikert, R. A., Burkhardt, D. J., Natale, A. 2009; 2 (2): 113-119
Abstract

Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) long-term freedom from AF/atrial tachyarrhythmia is unclear. We sought to compare the effect of 3 different ablation approaches on the long-term success in patients with paroxysmal AF.One hundred three consecutive patients with paroxysmal AF scheduled for ablation and presenting in the electrophysiology laboratory in AF were selected for this study. Patients were randomized to pulmonary vein antrum isolation (PVAI; n=35) versus biatrial ablation of the complex fractionated atrial electrograms (CFAEs; n=34) versus PVAI followed by CFAEs (n=34). Patients were given event recorders and followed up at 3, 6, 9, 12, and 15 months postablation. There was no statistical significant difference between the groups in term of sex, age, AF duration, left atrial size, and ejection fraction. At 1 year follow-up, freedom from AF/atrial tachyarrhythmia was documented in 89% of patients in the PVAI group, 91% in the PVAI plus CFAEs group, and 23% in the CFAEs group (P<0.001) after a single procedure and with antiarrhythmic drugs.No difference in terms of success rate was seen between PVAI alone and PVAI associated with defragmentation. CFAEs ablation alone had the smallest impact on AF recurrences at 1-year follow-up. These results suggest that antral isolation is sufficient to treat most patients with paroxysmal AF.

View details for DOI 10.1161/CIRCEP.108.798447

View details for Web of Science ID 000266127400005

View details for PubMedID 19808455
Relationship Between Catheter Forces, Lesion Characteristics, "Popping," and Char Formation: Experience with Robotic Navigation System JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Di Biase, L., Natale, A., Barrett, C., Tan, C., Elayi, C. S., Ching, C. K., Wang, P., Al-Ahmad, A., Arruda, M., Burkhardt, J. D., Wisnoskey, B. J., Chowdhury, P., De Marco, S., Armaganijan, L., Litwak, K. N., Schweikert, R. A., Cummings, J. E. 2009; 20 (4): 436-440
Abstract

Popping, char and perforation are complications that can occur following catheter ablation. We measured the amount of grams (g) applied to the endocardium during ablation using a sensor incorporated in the long sheath of a robotic system. We evaluated the relationship between lesion formation, pressure, and the development of complications.Using a robotic navigation system, lesions were placed in the left atrium (LA) at six settings, using a constant duration (40 seconds) and flow rate of either 17 cc/min or 30 cc/min with an open irrigated catheter (OIC). Evidence of complications was noted and lesion location recorded for later analysis at necropsy.Lesions using 30 Watts (W) were more likely to be transmural at higher (>40 g) than lower (<30 g) pressures (75% vs 25%, P < 0.001). Significantly higher number of lesions using >40 g of pressure demonstrated "popping" and crater formation as compared with lesions with 20-30 g of pressure (41% vs 15%, P = 0.008). A majority of lesions placed using higher power (45 W) with higher pressures (>40 g) were associated with char and crater formation (66.7%). No lesions using 10 g of pressure were transmural, regardless of the power. Lesions placed with a power setting less than 35 W were more likely to result in "relative" sparing of the endocardial surface than lesions at a power setting higher than 35 W (62% vs 33.3%, P = 0.02) regardless of the pressure.When using an OIC, lower power settings (
View details for DOI 10.1111/j.1540-8167.2008.01355.x

View details for Web of Science ID 000264549800013

View details for PubMedID 19017335
Statin Use and Ventricular Arrhythmias During Clinical Treadmill Testing JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Dewey, F. E., Perez, M., Hadley, D., Freeman, J. V., Wang, P., Ashley, E. A., Myers, J., Froelicher, V. F. 2009; 20 (2): 193-199
Abstract

Premature ventricular complexes (PVCs) during exercise are associated with adverse prognosis, particularly in patients with intermediate treadmill test findings. Statin use reduces the incidence of resting ventricular arrhythmias in patients with coronary artery disease; however, the relationship between statin use and exercise-induced ventricular arrhythmias has not been investigated.We evaluated the association between statin use and PVCs in 1,847 heart-failure-free patients (mean age 58, 95% male) undergoing clinical exercise treadmill testing between 1997 and 2004 in the VA Palo Alto Health Care System. PVCs were quantified in beats per minute and frequent PVCs were defined as PVC rates greater than the median value (0.43 and 0.60 PVCs per minute for exercise and recovery, respectively). Propensity-adjusted logistic regression was used to evaluate the odds of developing PVCs during exercise and recovery periods associated with statin use. There were 431 subjects who developed frequent PVCs during exercise and 284 subjects had frequent recovery PVCs. After propensity score adjustment, subjects treated with statins (n = 145) had 42% lower odds of developing frequent PVCs during exercise (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.37-0.93) and 44% lower odds of developing frequent PVCs during recovery (OR 0.56, 95% CI 0.30-0.94). These effects were not modified by age, prior coronary disease, hypercholesterolemia, exercise-induced angina, or exercise capacity.Statin use was associated with reduced odds of frequent PVCs during and after clinical exercise testing in a manner independent of associations with coronary disease or ischemia in our study population.

View details for DOI 10.1111/j.1540-8167.2008.01284.x

View details for PubMedID 18775041
A New Approach for ICD Rhythm Classification based on Support Vector Machines Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society Kamousi, B., Tewfik, A., Lin, B., Al-Ahmad, A., Hsia, H., Zei, P., Wang, P. IEEE. 2009: 2478?2481
Abstract

Inappropriate shocks due to misclassification of supraventricular and ventricular arrhythmias remain a major problem in the care of patients with Implantable Cardioverter Defibrillators (ICDs). The purpose of this study was to investigate the ability of a new covariance-based support vector machine classifier, to distinguish ventricular tachycardia from other rhythms such as supraventricular tachycardia. The proposed algorithm is applicable on both single and dual chamber ICDs and has a low computational demand. The results demonstrate that suggested algorithm has considerable promise and merits further investigation.

View details for Web of Science ID 000280543601357

View details for PubMedID 19964965
Pulmonary-vein isolation for atrial fibrillation in patients with heart failure NEW ENGLAND JOURNAL OF MEDICINE Khan, M. N., Jais, P., Cummings, J., Di Biase, L., Sanders, P., Martin, D. O., Kautzner, J., Hao, S., Themistoclakis, S., Fanelli, R., Potenza, D., Massaro, R., Wazni, O., Schweikert, R., Saliba, W., Wang, P., Al-Ahmad, A., Beheiry, S., Santarelli, P., Starling, R. C., Dello Russo, A., Pelargonio, G., Brachmann, J., Schibgilla, V., Bonso, A., Casella, M., Raviele, A., Haissaguerre, M., Natale, A. 2008; 359 (17): 1778-1785
Abstract

Pulmonary-vein isolation is increasingly being used to treat atrial fibrillation in patients with heart failure.In this prospective, multicenter clinical trial, we randomly assigned patients with symptomatic, drug-resistant atrial fibrillation, an ejection fraction of 40% or less, and New York Heart Association class II or III heart failure to undergo either pulmonary-vein isolation or atrioventricular-node ablation with biventricular pacing. All patients completed the Minnesota Living with Heart Failure questionnaire (scores range from 0 to 105, with a higher score indicating a worse quality of life) and underwent echocardiography and a 6-minute walk test (the composite primary end point). Over a 6-month period, patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation.In all, 41 patients underwent pulmonary-vein isolation, and 40 underwent atrioventricular-node ablation with biventricular pacing; none were lost to follow-up at 6 months. The composite primary end point favored the group that underwent pulmonary-vein isolation, with an improved questionnaire score at 6 months (60, vs. 82 in the group that underwent atrioventricular-node ablation with biventricular pacing; P<0.001), a longer 6-minute-walk distance (340 m vs. 297 m, P<0.001), and a higher ejection fraction (35% vs. 28%, P<0.001). In the group that underwent pulmonary-vein isolation, 88% of patients receiving antiarrhythmic drugs and 71% of those not receiving such drugs were free of atrial fibrillation at 6 months. In the group that underwent pulmonary-vein isolation, pulmonary-vein stenosis developed in two patients, pericardial effusion in one, and pulmonary edema in another; in the group that underwent atrioventricular-node ablation with biventricular pacing, lead dislodgment was found in one patient and pneumothorax in another.Pulmonary-vein isolation was superior to atrioventricular-node ablation with biventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation. (ClinicalTrials.gov number, NCT00599976.)

View details for Web of Science ID 000260245800005

View details for PubMedID 18946063
Optimal Programming of ICDs for Prevention of Appropriate and Inappropriate Shocks. Current treatment options in cardiovascular medicine Lo, R., Al-Ahmad, A., Hsia, H., Zei, P. C., Wang, P. J. 2008; 10 (5): 408-416
Abstract

Expansion of indications for implantable cardioverter-defibrillators (ICDs) has led to a significant increase in the number of patients receiving ICDs and the number of lives saved because of ICD therapy. However, appropriate or inappropriate shocks are frequent and may result in a significant decrease in quality of life in patients with ICDs. Atrial fibrillation with rapid ventricular response, sinus tachycardia, atrial tachycardia or atrial flutter with rapid conduction, and other supraventricular tachycardias are the most common arrhythmias causing inappropriate therapy. Other causes include oversensing of diaphragmatic potentials or myopotentials, T-wave oversensing, double or triple counting of intracardiac signals, lead fractures or header connection problems, lead chatter or noise, and electromagnetic interference. Strategies to reduce inappropriate therapy using device programming rely on the ability to distinguish supraventricular and atrial arrhythmias from ventricular tachycardia. Avoiding therapy for nonsustained ventricular arrhythmias and increasing the role of antitachycardia pacing to terminate ventricular tachycardia are key approaches to reducing shocks for ventricular arrhythmias. Optimal programming holds great promise for decreasing the overall incidence of shock therapy and increasing ICD acceptance.

View details for PubMedID 18814830
Impedance cardiography is superior to echocardiographic methods for pacing interval optimization Turcott, R. G., Witteles, R. M., Wang, P. J., Vagelos, R. H., Fowler, M. B., Ashley, E. A. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2008: S65
View details for Web of Science ID 000258565100208
Pacemaker alternans terminated by telemetry wand: What is the mechanism? HEART RHYTHM Chun, H. J., Cook, K., Wang, P. J., Al-Ahmad, A. 2008; 5 (7): 1080-1082
View details for DOI 10.1016/j.hrthm.2008.03.007

View details for Web of Science ID 000257502900024

View details for PubMedID 18598969
Genetics of Arrhythmia: Disease Pathways Beyond Ion Channels JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH Perez, M. V., Wheeler, M., Ho, M., Pavlovic, A., Wang, P., Ashley, E. A. 2008; 1 (2): 155-165
Abstract

Diseases of the electrical conduction system that lead to irregularities in cardiac rhythm can have morbid and often lethal clinical outcomes. Linkage analysis has been the principal tool used to discover the genetic mutations responsible for Mendelian arrhythmic disease. Although the majority of arrhythmias can be accounted for by mutations in genes encoding ion channels, linkage analysis has also uncovered the role of other gene families such as those encoding members of the desmosome. With a list of candidates in mind, mutational analysis has helped confirm the suspicion that proteins found in caveolae or gap junctions also play a role in arrhythmogenesis. Atrial fibrillation and sudden cardiac death are relatively common arrhythmias that may be caused by multiple factors including common genetic variants. Genome-wide association studies are already revealing the important and poorly understood role of intergenic regions in atrial fibrillation. Despite the great advancements that have been made in our understanding of the genetics of these diseases, we are still far from able to routinely use genomic data to make clinical management decisions. There remain several hurdles in the study of genetics of arrhythmia, including the costs of genotyping, the need to find large affected families for linkage analysis, or to recruit large numbers of patients for genome-wide studies. Novel techniques that incorporate epigenetic information, such as known gene-gene interactions, biologic pathways, and experimental gene expression, will need to be developed to better interpret the large amount of genetic data that can now be generated. The study of arrhythmia genetics will continue to elucidate the pathophysiology of disease, help identify novel therapies, and ultimately allow us to deliver the individualized medical therapy that has long been anticipated.

View details for DOI 10.1007/s12265-008-9030-4

View details for Web of Science ID 000207734800012

View details for PubMedID 20559910
Time-resolved three-dimensional imaging of the left atrium and pulmonary veins in the interventional suite - A comparison between muttisweep gated rotational three-dimensional reconstructed fluoroscopy and multislice computed tomography HEART RHYTHM Al-Ahmad, A., Wigstroem, L., Sandner-Porkristl, D., Wang, P. J., Zei, P. C., Boese, J., Lauritsch, G., Moore, T., Chan, F., Fahrig, R. 2008; 5 (4): 513-519
Abstract

Cardiac computed tomography (CT) is commonly used to visualize left atrial (LA) anatomy for ablation of atrial fibrillation. We have developed a new imaging technique that allows acquisition and visualization of three-dimensional (3D) cardiac images in the catheter lab.We sought to compare LA and pulmonary vein (PV) dimensions acquired using gated multisweep rotational fluoroscopy (C-arm CT) system and multislice computed tomography (MSCT) in an in vivo porcine model.A Siemens AXIOM Artis dTA C-arm system (Siemens AG, Medical Solutions) was modified to allow acquisition of four bidirectional sweeps during synchronized acquisition of the electrocardiogram signal to allow retrospective gating. C-arm CT image volumes were then reconstructed. Gated MSCT (SOMATOM Sensation 16 and 64, Siemens AG, Medical Solutions) and C-arm CT images were acquired in six animals. The two main PV diameters were measured in orthogonal axes. LA volumes were calculated. C-arm CT measurements were compared with the MSCT measurements.The average PV diameters using the C-arm CT were 2.24 x 1.35 cm, versus 2.27 x 1.38 cm for CT. The average difference was 0.034 cm (1.9%) between the C-arm CT and standard CT. The average LA volume using MSCT was 49.1 +/- 12.7 cm(3), as compared with 51.0 +/- 8.7 cm(3) obtained by the C-arm CT. The average difference between the C-arm CT and the MSCT was 1.9 cm(3) (3.7%). There were no significant differences in either the PV or LA measurements.Visualization of 3D cardiac anatomy during ablation procedures is possible and highly accurate. The 3D cardiac reconstructions acquired during ablation procedures will be valuable for procedural planning and guidance.

View details for DOI 10.1016/j.hrthm.2007.12.027

View details for Web of Science ID 000254596600003

View details for PubMedID 18362018
Independent AV/VV pacing optimization requires operation along mechanical AV delay isochrones Turcott, R. G., Witteles, R., Wang, P. J., Ashley, E. A. ELSEVIER SCIENCE INC. 2008: A21
View details for Web of Science ID 000253997100088
Visualizing ablation gaps in vitro using a deflectable fiber optic endocardial visualization catheter Irani, A. R., Lin, B., Eversull, C., Wang, P. J., Al-Ahmad, A. ELSEVIER SCIENCE INC. 2008: A8
View details for Web of Science ID 000253997100035
Dynamic Time Warping: A novel algorithm for rhythm discrimination in ICDs Kamousi, B., Lin, B., Lee, G., Ai-Ahmad, A., Hsia, H. H., Zei, P. C., Wang, P. J. ELSEVIER SCIENCE INC. 2008: A14
View details for Web of Science ID 000253997100059
A Covariance-Based Algorithm: A Novel Technique for Rhythm Discrimination in ICDs 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society Kamousi, B., Lin, B., Al-Ahmad, A., Hsia, H., Zei, P., Natale, A., Moss, A., Daubert, J., Zareba, W., Wang, P. IEEE. 2008: 5478?5481
Abstract

Inappropriate shocks due to misclassification of supraventricular and ventricular arrhythmias remain a major problem in the care of patients with Implantable Cardioverter defibrillators (ICDs). In this study we have investigated the ability of a new covariance-based algorithm, to distinguish Ventricular Tachycardia from other rhythms such as Supraventricular Tachycardia. The proposed algorithm has a low computational demand and with a small adjustment is applicable on both single-chamber and dual-chamber ICDs. The results are promising and suggest that the new covariance-based algorithm may be an effective method for ICD rhythm classification and may decrease inappropriate shocks.

View details for Web of Science ID 000262404503170

View details for PubMedID 19163957
Characterization of human coronary sinus valves by direct visualization during biventricular pacemaker implantation PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Anh, D. J., Eversull, C. S., Chen, H. A., Mofrad, P., Mourlas, N. J., Mead, R. H., Zel, P. C., Hsia, H. H., Wang, P. J., Al-Ahmad, A. 2008; 31 (1): 78-82
Abstract

The precise reasons for failure to cannulate the coronary sinus during biventricular device implantation are unknown. Visualization of the coronary sinus ostium during electrophysiology procedures may enhance understanding of how unusual anatomy can affect successful cannulation of the coronary sinus.The aim of this study was to describe the morphology of valves at the coronary sinus ostium (CSO) visualized directly with an illuminated fiberoptic endoscope during implantation of biventricular devices.The coronary sinus anatomy of one hundred consecutive patients undergoing implantation of biventricular devices was investigated using a fiberoptic endocardial visualization catheter (EVC).The CSO was clearly visualized in 98 patients using the EVC. A Thebesian valve was seen in 54% of these. Almost all Thebesian valves were positioned at the inferior (61%) or posterior (33%) aspect of the CSO. Only six patients had Thebesian valves that covered more than 70% of the CSO, but all were successfully implanted with a transvenous left ventricular pacing lead after cannulating the coronary sinus under direct visualization.Over half of patients undergoing biventricular device implantation have identifiable Thebesian valves. Even valves covering the majority of the ostial area may be traversed using direct visualization and modern catheterization techniques.

View details for Web of Science ID 000253373400015

View details for PubMedID 18181913
Driving and implantable cardioverter-defibrillator shocks for ventricular arrhythmias JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Albert, C. M., Rosenthal, L., Calkins, H., Steinberg, J. S., Ruskin, J. N., Wang, P., Muller, J. E., Mittleman, M. A. 2007; 50 (23): 2233-2240
Abstract

This study examined the risk of implantable cardioverter-defibrillator (ICD) shocks for ventricular tachycardia (VT) or ventricular fibrillation (VF) associated with driving.Concerns regarding VT/VF occurring during driving are the basis for driving restrictions in ICD patients; however, limited data are available to inform recommendations.This study used a prospective nested case-crossover design to compare the risk of ICD shock for VT/VF both during and up to 60 min after an episode of driving as compared with that during other activities among 1,188 ICD patients enrolled in the TOVA (Triggers of Ventricular Arrhythmia) study.Over a median follow-up of 562 days, there were 193 ICD shocks for VT/VF with data on exposure to driving before ICD shock. The absolute risk of ICD shock for VT/VF within 1 h of driving was estimated to be 1 episode per 25,116 person-hours spent driving. The ICD shocks for VT/VF were twice as likely to occur within 1 h of driving a car as compared with other times (relative risk [RR] 2.24, 95% confidence interval [CI] 1.57 to 3.18). This risk was specific for shocks for VT/VF and occurred primarily during the 30-min period after driving (RR 4.46, 95% CI 2.92 to 6.82) rather than during the driving episode itself (RR 1.05, 95% CI 0.48 to 2.30).Although the risk of ICD shock for VT/VF was transiently increased in the 30-min period after driving, the risk was not elevated during driving and the absolute risk was low. These data provide reassurance that driving by ICD patients should not translate into an important rate of personal or public injury.

View details for DOI 10.1016/j.jacc.2007.06.059

View details for Web of Science ID 000251330800007

View details for PubMedID 18061071
The CREB leucine zipper regulates CREB phosphorylation, cardiomyopathy, and lethality in a transgenic model of heart failure AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Huggins, G. S., Lepore, J. J., Greytak, S., Patten, R., McNamee, R., Aronovitz, M., Wang, P. J., Reed, G. L. 2007; 293 (3): H1877?H1882
Abstract

Signaling through cAMP plays an important role in heart failure. Phosphorylation of cAMP response element binding protein (CREB) at serine-133 regulates gene expression in the heart. We examined the functional significance of CREB-S133 phosphorylation by comparing transgenic models in which a phosphorylation resistant CREB-S133A mutant containing either an intact or a mutated leucine zipper domain (CREB-S133A-LZ) was expressed in the heart. In vitro, CREB-S133A retained the ability to interact with wild-type CREB, whereas CREB-S133A-LZ did not. In vivo, CREB-S133A and CREB-S133A-LZ were expressed at comparable levels in the heart; however, CREB-S133A markedly suppressed the phosphorylation of endogenous CREB, whereas CREB-S133A-LZ had no effect. The one-year survival of mice from two CREB-S133A-LZ transgenic lines was equivalent to nontransgenic littermate control mice (NTG), whereas transgenic CREB-S133A mice died with heart failure at a median 30 wk of age (P < 0.0001). CREB-S133A mice had an altered gene expression characteristic of the failing heart, whereas CREB-S133A-LZ mice did not. Left ventricular contractile function was substantially reduced in CREB-S133A mice versus NTG mice and only modestly reduced in CREB-S133A-LZ mice (P < 0.02). When considered in light of other studies, these findings indicate that overexpression of the CREB leucine zipper is required for both inhibition of endogenous CREB phosphorylation and cardiomyopathy in this murine model of heart failure.

View details for DOI 10.1152/ajpheart.00516.2007.

View details for Web of Science ID 000249237800070

View details for PubMedID 17616745

View details for PubMedCentralID PMC3911886
Cardiac device infections complicated by erosion JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Tsai, V., Chen, H., Hsia, H., Zei, P., Wang, P., Al-Ahmad, A. 2007; 19 (2): 133-137
Abstract

Implantation of pacemakers and implantable cardioverter-defibrillators (ICDs) can be complicated by infection and device erosion. It is unclear if the clinical features of patients who have device erosion differ from those without erosion.We retrospectively examined the records of all patients referred for explantation of a pacemaker or defibrillator from January 2000 to May 2005. We examined demographic variables including age, gender, and body mass index (BMI) as well as clinical variables related to erosion and procedural variables.Seventy-two patients with infected pacemakers or ICDs were identified. Of these cases, 30 (42%) developed infection complicated by erosion, of which 8/28 (29%) were related to ICDs, and 22/44 (50%) were related to pacemakers.Device erosion was significantly associated with the presence of a non-systemic infection as opposed to cases without erosion. This finding may have implications in the timing of device re-implantation.

View details for DOI 10.1007/s10840-007-9143-8

View details for Web of Science ID 000249009800008

View details for PubMedID 17668305
VF and fatal cardiac arrest following ICD therapy delivery: What is the cause? PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Mofrad, P. S., Ottoboni, L., Zei, P. C., Hsia, H. H., Wang, P. J., Amin-Al-Ahmad 2007; 30 (4): 551-553
View details for Web of Science ID 000245642600018

View details for PubMedID 17437582
Initiation patterns of ventricular tachycardia determined from analysis of intracardiac electrograms in the MADIT II database Kanagasundram, A. N., Daubert, J., Zareba, W., Hsia, H., Al Ahmad, A., Wang, P., Moss, A., Zei, P. ELSEVIER SCIENCE INC. 2007: 22A?23A
View details for Web of Science ID 000244651800090
The effect of gender on mortality or appropriate shock in patients with nonischemic cardiomyopathy who have implantable cardioverter-defibrillators PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Chen, H. A., Hsia, H. H., Vagelos, R., Fowler, M., Wang, P., Al-Ahmad, A. 2007; 30 (3): 390-394
Abstract

As heart disease is increasingly recognized in women and as important studies have elucidated the benefit of implantable cardioverter defibrillators (ICDs) in patients with nonischemic cardiomyopathy (NICM), little is known regarding the effect of gender difference on arrhythmic risk in this population. We sought to determine if there are gender differences in arrhythmic risk and potential defibrillator benefit in patients with NICM.The records of 767 consecutive patients who underwent ICD implant at the Stanford Medical Center from 1984 to 2002 were reviewed. Only patients with NICM were considered (n = 201, 26.2%). Of these, 140 patients had clinical follow-up information available. Baseline variables were examined, including age, baseline heart rate, ejection fraction, and medications. We evaluated the time to first shock as well as all-cause mortality in this patient population. Kaplan-Meier survival curves were plotted, a log-rank test was used to evaluate significance, and Cox-proportional hazards test was used for multivariate analysis.There were 88 (62.9%) men and 52 (37.1%) women. Between male and female patients, there were no significant differences in baseline mean age (54.8 +/- 1.9 years vs 53.1 +/- 2.3 years, respectively), ejection fraction (35.2 +/- 2.0% vs 33.3 +/- 2.3%, respectively), and mean left ventricular end-diastolic dimension (6.4 +/- 0.3 cm vs 5.9 +/- 0.2 cm, respectively). Mean follow-up time was 30.8 months. Thirty-two male patients (36.4 +/- 0.05%) received appropriate shocks compared with 20 female patients (38.5 +/- 0.07%). Mean time to the first appropriate shock was 11.9 +/- 3.9 months for male patients and 21.3 +/- 5.8 months for female patients (P = 0.2). Nineteen male patients (21.6 +/- 0.05%) died or received heart transplant during the follow-up period compared with 6 female patients (11.5 +/- 0.04%) (P = 0.11).Male and female patients with NICM who received ICDs had similar rate of appropriate shock and mortality. In this population gender does not appear to be an important risk factor for mortality or arrhythmic events.

View details for Web of Science ID 000244886500013

View details for PubMedID 17367359
Inappropriate shock: A failure of SVT discriminators in a dual chamber ICD? PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Al-Ahmad, A., Tsiperfal, A., Hsia, H. H., Wang, P. J. 2006; 29 (12): 1413-1415
Abstract

Inappropriate shock remains a major issue in patients with implantable cardioverter defibrillators. We examine an inappropriate shock delivered in a patient with atrial tachycardia that conducted 1:1. We reconstruct the device algorithms that led to therapy delivery and discuss programming changes that could be considered.

View details for Web of Science ID 000243530800015

View details for PubMedID 17201851
Randomized controlled trial of pulmonary vein antrum isolation vs. AV node ablation with bi-ventricular pacing for treatment of atrial fibrillation in patients with congestive heart failure (PABA CHF) Khan, M. N., Jais, P., Cummings, J., Sanders, P., Kautzner, J., Hao, S., Themistoclakis, S., Fanelli, R., Potenza, D., Wazni, O., Schweikert, R., Saliba, W., Wang, P., Al-Ahmad, A., Beheiry, S., Santarelli, P., Starling, R., Dello Russo, A., Pelargonio, G., Brachmann, J., Schibgilla, V., Bonso, A., Raviele, A., Haissaguerre, M., Natale, A. LIPPINCOTT WILLIAMS & WILKINS. 2006: 2426
View details for Web of Science ID 000243477400029
Episodes of anger trigger ventricular arrhythmias in patients with implantable cardioverter defibrillators 79th Annual Scientific Session of the American-Heart-Association Albert, C. M., Lampert, R., Conti, J. B., Chung, M. K., Wang, P. J., Muller, J. E., Mittleman, M. A. LIPPINCOTT WILLIAMS & WILKINS. 2006: 831?31
View details for Web of Science ID 000241792805351
Clinical study to investigate the accuracy of the "post-pacing interval" method to detect the optimal site for catheter ablation in patients with WPW syndrome as a typical model of macro-reentry Azegami, K., Okishige, K., Wakimoto, H., Ohba, K., Zukeran, T., Uehara, H., Kurabayashi, M., Nakamura, K., Konishi, M., Hirao, K., Isobe, M., Wang, P. J. LIPPINCOTT WILLIAMS & WILKINS. 2006: 602
View details for Web of Science ID 000241792804050
Isolated giant cell myocarditis in the atrium: An incidental finding? PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Ahmad, I., Miller, D. C., Berry, G. J., Hsia, H. H., Wang, P. J., Al-Ahmad, A. 2006; 29 (10): 1179-1180
Abstract

Giant cell myocarditis (GCM) is an uncommon disorder that affects ventricular myocardium causing severe left ventricular dysfunction and ventricular arrhythmias. We report a case of GCM that only affected the atrium sparing the ventricle.

View details for PubMedID 17038151
Left ventricular dyssynchrony does not deteriorate acutely on cessation of cardiac resynchronization therapy in long term responders 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America Kuppahally, S., Fowler, M., Wang, P., Vagelos, R., Al-Ahmad, A., Paloma, A., Liang, D. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2006: S76?S76
View details for Web of Science ID 000240205000246
Early human experience with use of a deflectable fiberoptic endocardial visualization catheter to facilitate coronary sinus cannulation HEART RHYTHM Anh, D. J., Chen, H. A., Eversull, C. S., Mourlas, N. J., Mead, R. H., Liem, L. B., Hsia, H. H., Wang, P. J., Al-Ahmad, A. 2006; 3 (8): 875-878
Abstract

Despite improvements in cardiac resynchronization therapy (CRT) implantation techniques, a significant minority of CRT attempts are unsuccessful. Inability to cannulate the coronary sinus (CS) because of difficult anatomy is a major reason for unsuccessful CRT implantation. Direct visualization of intracardiac structures during the implant may facilitate access into the CS. The present study describes CRT implantation with the aid of an endocardial visualization catheter (EVC).Fifty-eight consecutive patients (mean age 72 +/- 12 years; ejection fraction 26.2% +/- 7.0%; New York Heart Association [NYHA] class 2.9) underwent CRT implantation using a steerable fiberoptic EVC (Acumen Medical, Inc., Sunnyvale, CA).The EVC was able to visualize the CS ostium in all cases. The CS was successfully cannulated in 57 (98.3%) of 58 patients. The time from vascular access to CS visualization was 6 +/- 5 minutes, and the total time to CS access was 8 +/- 6 minutes. Successful left ventricle (LV) lead implantation was accomplished in 55 (94.8%) of 58 patients. Three patients who had a previous history of failed LV lead implantation were successfully implanted using the EVC.Fiberoptic imaging of intracardiac structures during CRT implantation may be performed rapidly in a wide range of patients with an EVC. The ability to visualize right atrial anatomy may aid CS access and LV lead implantation.

View details for DOI 10.1016/j.hrthm.2006.04.029

View details for Web of Science ID 000239746400001

View details for PubMedID 16876731
Rate control - Is local better? CIRCULATION Wang, P. J. 2006; 113 (20): 2374?76
View details for DOI 10.1161/CIRCULATIONAHA.106.626036

View details for Web of Science ID 000237710700004

View details for PubMedID 16717161
Improvement in quality of life after radiofrequency ablation PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Hlatky, M. A., Wang, P. 2006; 29 (4): 341-342
View details for Web of Science ID 000237453300001

View details for PubMedID 16650259
Supraventricular tachycardia vs ventricular tachycardia: What is the rhythm HEART RHYTHM Al-Ahmad, A., Tsiperfal, A., Hsia, H. H., Wang, P. J. 2006; 3 (4): 490-491
View details for DOI 10.1016/j.hrthm.2005.11.031

View details for Web of Science ID 000236743400023

View details for PubMedID 16567303
Cryoablation of the pulmonary veins using a novel balloon catheter JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Garan, A., Al-Ahmad, A., Mihalik, T., Cartier, C., Capuano, L., Holtan, D., Song, C., Homoud, M. K., Link, M. S., Estes, N. A., Wang, P. J. 2006; 15 (2): 79-81
Abstract

Pulmonary vein (PV) isolation has emerged as a promising technique for the treatment of patients with drug-refractory atrial fibrillation, however, the achievement of transmural lesions has remained a challenge. We evaluated the ability of a novel balloon-based cryogenic catheter system in achieving transmural lesions for PV isolation.Six pulmonary vein ostia from three excised ovine hearts and lungs were used in this study. The balloon catheter was deployed and positioned at the ostia of the PVs and a full 8-minute ablation was then performed, while the heart was bathed in a circulating bath of normal saline at 37 degrees. Thermocouples positioned on the endocardial (balloon surface-tissue interface) and epicardial surfaces of the ostia were used to determine whether transmural freezing was achieved.The mean temperatures measured on the endocardial and epicardial tissue in six PV ablations were -38.8 +/- 6.9 degrees C and -10.0 +/- 7.5 degrees C, respectively. The average pulmonary vein thickness was 3.3 +/- 1.4 mm.A novel cryoablation balloon catheter is capable of achieving transmural freezing of the pulmonary vein. The catheter has promise for future clinical therapy of atrial fibrillation.

View details for DOI 10.1007/s10840-006-8519-5

View details for Web of Science ID 000238100500002

View details for PubMedID 16755335
Preserved heart rate variability identifies low-risk patients with nonischemic dilated cardiomyopathy: Results from the DEFINITE trial HEART RHYTHM Rashba, E. J., Estes, N. A., Wang, P., Schaechter, A., Howard, A., Zareba, W., Couderc, J. P., Perkiomaki, J., Levine, J., Kadish, A., Defibrillators Non-Ischemic Invest 2006; 3 (3): 281?86
Abstract

The recent expansion of indications for prophylactic implantable cardioverter-defibrillator (ICD) placement in subjects with nonischemic dilated cardiomyopathy has raised concerns about the cost-effectiveness of this therapy.The purpose of this study was to identify low-risk patients with nonischemic dilated cardiomyopathy who may not require prophylactic ICD placement.This was a prospective study of 274 participants in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a randomized controlled trial that evaluated the role of prophylactic ICD placement in patients with nonischemic dilated cardiomyopathy. The patients underwent 24-hour Holter recording for analysis of heart rate variability (HRV). The primary HRV variable was the standard deviation of normal R-R intervals (SDNN). Patients with atrial fibrillation and frequent ventricular ectopy (>25% of beats) were excluded from HRV analysis (23% of patients). SDNN was categorized in tertiles, and Kaplan-Meier analysis was performed to compare survival in the three tertiles and excluded patients.The study population was 73% male, with a mean age of 59 +/- 12 years and mean left ventricular ejection fraction of 21% +/- 6%. After 3-year follow-up, significant differences in mortality rates were observed: SDNN >113 ms: 0 (0%), SDNN 81-113 ms: 5 (7%), SDNN <81 ms: 7 (10%), excluded patients: 11 (17%) (P = .03). There were no deaths in the tertile with SDNN >113 ms regardless of treatment assignment (ICD vs control).Patients with nonischemic dilated cardiomyopathy and preserved HRV have an excellent prognosis and may not benefit from prophylactic ICD placement. Patients with severely depressed HRV and patients who are excluded from HRV analysis because of atrial fibrillation and frequent ventricular ectopy have the highest mortality.

View details for DOI 10.1016/j.hrthm.2005.11.028

View details for Web of Science ID 000235779600007

View details for PubMedID 16500299
Premature ventricular contractions causing pacemaker-mediated tachycardia: A failure of postventricular atrial refractory period after premature ventricular contraction extension? HEART RHYTHM Witteles, R., Engel, G., Wang, P. J., Al-Ahmad, A. 2005; 2 (12): 1389-1390
View details for DOI 10.1016/j.hrthm.2005.08.023

View details for PubMedID 16360099
Delivery of antitachycardia pacing after a full-energy shock during the same ventricular tachycardia episode: Appropriate device function? HEART RHYTHM Sirulnick, E., Tsiperfal, A., Wang, P. J., Al-Ahmad, A. 2005; 2 (11): 1266-1267
View details for Web of Science ID 000233102900018

View details for PubMedID 16253921
Randomized controlled trial of pulmonary vein antrum isolation vs. AV node ablation with bi-ventricular pacing for treatment of atrial fibrillation in patients with congestive heart failure (PABA CHF) Khan, M., Jais, P., Cummings, J. E., Sanders, P., Kautzner, J., Hao, S., Themistoclakis, S., Fanelli, R., Potenza, D., della Sofferenza, C. S., Belden, W., Wazni, O., Wang, P., Al-Ahmad, A., Beheiry, S., Pisano, E., Santarelli, P., della Sofferenza, C. S., Starling, R., Dello Russo, A., Pelargonio, G., Brachmann, J., Gunther, J., Coburg, K., Bonso, A., Raviele, A., Haissaguerre, M., Natale, A. LIPPINCOTT WILLIAMS & WILKINS. 2005: U454
View details for Web of Science ID 000232956402511
Addendum to the clinical competency statement: training pathways for implantation of cardioverter defibrillators and cardiac resynchronization devices (vol 1, pg 371, 2004) HEART RHYTHM Day, J. D., Curtis, A. B., Epstein, A. E., Goldschlager, N. F., Olshansky, B., Reynolds, D. W., Wang, P. J. 2005; 2 (10): 1161?63
View details for DOI 10.1016/j.hrthm.2005.08.025

View details for Web of Science ID 000232349400031

View details for PubMedID 16188603
Use of the implantable cardioverter-defibrillator in long-term survivors of orthotopic heart transplantation HEART RHYTHM Ptaszek, L. M., Wang, P. J., Hunt, S. A., Valantine, H., Perlroth, M., Al-Ahmad, A. 2005; 2 (9): 931-933
Abstract

Orthotopic heart transplantation is considered an effective treatment for patients with refractory heart failure. The long-term survival of orthotopic heart transplantation recipients has increased over the last several decades, but many long-term survivors of orthotopic heart transplantation develop graft atherosclerosis and associated left ventricular dysfunction. The risk of sudden cardiac death in long-term survivors of orthotopic heart transplantation with these complications is believed to be high. There are no data on the usefulness of implantable cardioverter-defibrillators (ICDs) in this population; therefore, we report our early experience with ICD placement in such patients.The purpose of this study was to examine the use of ICDs in adults who are long-term survivors of heart transplantation.We retrospectively reviewed all adult patients who underwent orthotopic heart transplantation at Stanford University Hospital (Stanford, CA, USA) from 1980 to 2004. All patients who received an ICD after transplant were included in this study. We reviewed demographic data, medical history, ejection fraction, presence of graft atherosclerosis, indication for ICD placement, and any device therapy delivered.Of the 925 patients who had orthotopic heart transplantation during this time period, 493 patients were alive at the beginning of the year 2000. Of these patients, 10 ( approximately 2%) had subsequent placement of an ICD. All 10 patients were male. The average age at orthotopic heart transplantation was 37.8 years. The average age at ICD placement was 50.5 years. The average time from orthotopic heart transplantation to ICD placement was 14.6 years. The average ejection fraction at the time of implant was 46.5%. Five of the 10 patients had a low ejection fraction (within this subgroup, the average ejection fraction was 31%, range 15%-45%) and graft atherosclerosis. ICDs were placed because of symptomatic episodes of ventricular tachycardia (3 patients), low ejection fraction and severe graft atherosclerosis without symptoms (3 patients), and after thorough evaluation for otherwise unexplained syncope (4 patients). The average follow-up after device implantation was 13 months. Complications related to ICD placement were an infected ICD system requiring explant in one patient and a lead fracture in another patient. Three patients had subsequent appropriate shocks for ventricular arrhythmias, and one patient underwent a second orthotopic heart transplantation. One patient died of malignancy.Use of the ICD in long-term survivors of orthotopic heart transplantation should be considered in appropriately selected patients. Further data are needed regarding ICD use in this population.

View details for DOI 10.1016/j.hrthm.2005.06.018

View details for Web of Science ID 000231986200008

View details for PubMedID 16171746
Depression as a predictor for appropriate shocks among patients with Implantable cardioverter-defibrillators - Results from the Triggers of Ventricular Arrhythmias (TOVA) study JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Whang, W., Albert, C. M., Sears, S. F., Lampert, R., Conti, J. B., Wang, P. J., Singh, J. P., Ruskin, J. N., Muller, J. E., Mittleman, M. A. 2005; 45 (7): 1090-1095
Abstract

We sought to examine the relationship between symptoms of depression and shock-treated ventricular arrhythmias among implantable cardioverter-defibrillator (ICD) patients.Depression predicts mortality in patients with coronary artery disease (CAD), but whether this is via an increased risk of fatal ventricular arrhythmias is unclear.We prospectively analyzed data on symptoms of depression and risk of ventricular arrhythmia (ventricular tachycardia/ventricular fibrillation [VT/VF]) resulting in ICD discharge in the Triggers of Ventricular Arrhythmias (TOVA) study. Symptoms were assessed by the Center for Epidemiologic Studies-Depression (CES-D) scale. Scores of 16 to 26 and > or =27 represented mild and moderate/severe depression, respectively. The Cox and Anderson-Gill proportional hazards models were used to test for associations among all patients and patients with CAD.Among 645 patients with baseline assessments, 90 (14%) were mildly depressed and 25 (3.9%) were moderately to severely depressed. Moderate/severe depression was associated with time to first shock for VT/VF (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.1 to 9.9) and all shocks for VT/VF including recurrent episodes (HR 3.2, 95% CI 1.2 to 8.6). Among the 476 CAD patients, the association with time to first shock (HR 6.4, 95% CI 1.9 to 21.1) and all shocks (HR 8.3, 95% CI 2.9 to 23.3) remained. The risk of shock for VT/VF was associated with depression severity in the total population (p for trend = 0.02) and among patients with CAD (p < 0.01), even after controlling for multiple confounders.More severe symptoms of depression predict shocks for VT/VF among ICD patients. The elevated risk of VT/VF among patients with CAD and depression suggests that arrhythmia may contribute significantly to total mortality in this subgroup.

View details for DOI 10.1016/j.jacc.2004.12.053

View details for Web of Science ID 000228055500020

View details for PubMedID 15808769
T-wave abnormalities are a better predictor of cardiovascular mortality than ST depression on the resting electrocardiogram ANNALS OF NONINVASIVE ELECTROCARDIOLOGY Beckerman, J., Yamazaki, T., Myers, J., Boyle, C., Chun, S., Wang, P., Froelicher, V. 2005; 10 (2): 146-151
Abstract

ST depression and T-wave amplitude abnormalities are known to be independent predictors of cardiovascular (CV) death, but a direct comparison between them has not been described.Analyses were performed on the first electrocardiogram (ECG) digitally recorded on 46,950 consecutive patients at the Palo Alto Veterans Affairs Medical Center since 1987. Females and patients with electrocardiograms exhibiting bundle branch block, left ventricular hypertrophy, electronic pacing, diagnostic Q waves, or Wolff-Parkinson-White syndrome were excluded, leaving 31,074 male patients for analysis (mean age 55 +/- 14). There were 1878 (6.0%) cardiovascular deaths (mean follow-up of 6 +/- 4 years). Electrocardiograms were classified using Minnesota code according to the degree of ST depression and T-wave abnormality, and the nine possible combinations of ST segment and T-wave abnormalities were recoded for analysis.The combination of major abnormalities in ST segments and T-waves carried the greatest hazard [3.2 (CI 2.7-3.8)]. Minor ST depression combined with more severe T-wave abnormalities carried a hazard of 3.1 (CI 2.5-3.7), whereas minor T-wave abnormalities combined with more severe ST depression carried a hazard of only 1.9 (CI 1.6-2.3).While both ST segment depression and abnormal T-wave amplitude are clinically important, T-wave abnormalities appear to be greater predictors of cardiovascular mortality.

View details for PubMedID 15842426
The clinical implications of cumulative right ventricular pacing in the Multicenter Automatic Defibrillator Trial II JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Steinberg, J. S., Fischer, A., Wang, P., Schuger, C., Daubert, J., McNitt, S., Andrews, M., Brown, M., Hall, W. J., Zareba, W., Moss, A. J., MADIT II Investigators 2005; 16 (4): 359?65
Abstract

This study was designed to assess whether right ventricular pacing in the implantable cardioverter defibrillator (ICD) arm of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II was associated with an unfavorable outcome.Data on the number of ventricular paced beats were available in 567 (76%) of 742 MADIT II patients with ICDs. The number of ventricular paced beats over the total number of beats showed a bimodal distribution with patients being predominantly paced or nonpaced. Therefore, patients were dichotomized at 0-50% and 51-100% of cumulative pacing with median pacing rate 0.2% and 95.6%, respectively. Endpoints included new or worsening heart failure, appropriate ICD therapy for VT/VF, and the combined endpoint of heart failure or death. Clinical features associated with frequent ventricular pacing included age >or=65 years, advanced NYHA heart failure class, LVEF < 0.25, first degree AV and bundle branch block, and amiodarone use. During follow-up, 119 patients (21%) had new or worsened heart failure, 130 (23%) had new or worsened heart failure or death, and 142 (25%) had appropriate therapy for VT/VF. In comparison to patients with infrequent pacing, those with frequent pacing had significantly higher risk of new or worsened heart failure (hazard ratio = 1.93; P = 0.002) and VT/VF requiring ICD therapy (HR = 1.50; P = 0.02).Patients in MADIT II who were predominantly paced had a higher rate of new or worsened heart failure and were more likely to receive therapy for VT/VF. These results suggest the deleterious consequences of RV pacing, particularly in the setting of severe LV dysfunction.

View details for DOI 10.1046/j.1540-8167.2005.50038.x

View details for Web of Science ID 000228047900001

View details for PubMedID 15828875
Early experience with a computerized robotically controlled catheter system JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Al-Ahmad, A., Grossman, J. D., Wang, P. J. 2005; 12 (3): 199-202
Abstract

Recently, the use of robotic assisted surgery has been utilized in cardiac surgical procedures. The use of robotics may offer benefits in precision, stability and control of instruments remotely. We report early experience with a novel remote robotic catheter control system (CCS).We used a computerized robotically controlled catheter system that enables the user to remotely manipulate the tip of a catheter precisely in three dimensions. We tested the robotic catheter control systems ability to navigate within the heart and to make precise, rapid and repeatable movements. We compared the CCS with the ability of a standard quadripolar steerable ablation catheter placed in a deflectable sheath to navigate and make precision movements. Twelve ex-vivo porcine hearts were utilized to permit accurate measurements of navigation and precision. Eight targets were selected for navigation and precision testing. Time was measured for the catheter to reach the predefined target from a specific starting point to test navigation. In addition, time was measured to contact a discrete 0.8 mm target in order to test precision.The use of the CCS reduced the time needed for both navigation (8.5 +/- 13.9 sec vs. 22.7 +/- 26.7 sec, p = 0.002) and significantly decreased the time for precision targeting (10.1 +/- 6.9 sec vs. 29.6 +/- 26.4 sec, p < 0.001) in the specific RA and LA sites in the ex-vivo hearts.The use of a computerized robotically assisted catheter control system is feasible and shows promise in rapid precision movement of the catheter. Further study is needed to elucidate the role of such a system in-vivo and in patient specific catheter ablation and mapping.

View details for DOI 10.1007/s10840-005-0325-y

View details for Web of Science ID 000228972600004

View details for PubMedID 15875110
Atrial pacing above the sensor rate: What is the cause? HEART RHYTHM Al-Ahmad, A., Tsiperfal, A., Wang, P. J. 2005; 2 (2): 210-211
View details for DOI 10.1016/j.hrthm.2004.10.005

View details for Web of Science ID 000226953200022

View details for PubMedID 15851301
Spatial QRS-T angle predicts cardiac death in a clinical population HEART RHYTHM Yamazaki, T., Froelicher, V. F., Myers, J., Chun, S., Wang, P. 2005; 2 (1): 73-78
Abstract

The purpose of this study was to validate the prognostic value of computer-derived measurements of the spatial alignment of ventricular depolarization and repolarization from the standard 12-lead ECG in a general medical population.Analyses were performed on the first ECG digitally recorded from 46,573 consecutive patients since 1987. QRS and T vector were synthesized by deriving XYZ leads from the 12 leads using the inverse Dower weighting matrix. Subset analyses were considered in patients with and those without standard ECG diagnoses (i.e., atrial fibrillation, Q waves, left ventricular hypertrophy, prolonged QRS duration). The main outcome measure was cardiovascular mortality.During a mean follow-up of 6 years, 4,127 cardiovascular deaths occurred. After adjusting for age, heart rate, and gender in a Cox regression analysis, spatial QRS-T angle was the most significant predictor of cardiovascular mortality, outperforming all other ECG measurements and diagnostic statements. In the subset with ECGs free of any standard diagnoses, annual cardiovascular mortality was 0.8% for normal (0-50 degrees ), 2.3% for borderline (50-100 degrees ), and 5.1% for abnormal (100-180 degrees ) QRS-T angle groups. The borderline and abnormal angle groups had 1.5- and 1.9-fold higher risk, respectively, relative to the normal QRS-T angle group after adjustment for age, gender, and heart rate. Similar results were found when patients with standard ECG diagnosis were included or compared.Spatial QRS-T angle is a significant and independent predictor of cardiovascular mortality that provides greater prognostic discrimination than any of the commonly utilized ECG diagnostic classifications.

View details for DOI 10.1016/j.hrthm.2004.10.040

View details for PubMedID 15851268
Arrhythmia prevention and termination algorithms NEW ARRHYTHMIA TECHNOLOGIES Engel, G., Wang, P. J., Al-Ahmad, A., Wang, P. J. 2005: 178?86
View details for DOI 10.1002/9780470988725.ch19

View details for Web of Science ID 000298280100019
Advances in catheter control devices NEW ARRHYTHMIA TECHNOLOGIES Narayan, G., Wang, P. J., Al-Ahmad, A., Wang, P. J. 2005: 257?61
View details for DOI 10.1002/9780470988725.ch26

View details for Web of Science ID 000298280100026
New ICD indications NEW ARRHYTHMIA TECHNOLOGIES Sirulnick, E., Al-Ahmad, A., Wang, P. J., Wang, P. J. 2005: 219?29
View details for DOI 10.1002/9780470988725.ch23

View details for Web of Science ID 000298280100023
Rhythm classification by correlation-waveform morphology analysis of atrial and ventricular electrogram signals Cardiostim 2004 Meeting Saba, S., Qin, X., Ganz, L., Heggs, G., Clontz, R., Parkinson, D., Wang, P. J., Syed, Z. A. WILEY-BLACKWELL. 2005: S54?S56
Abstract

We tested the use of correlation-waveform analysis (CWA) of atrial and ventricular electrograms (EGMs) to distinguish ventricular tachycardia (VT) from supraventricular tachycardia (SVT). Patients undergoing electrophysiologic testing were enrolled. EGMs recorded during induced tachycardias were compared with EGMs recorded during sinus and paced rhythms, taken as templates, by assigning a CWA percent-match (CPM) score. Twenty-two patients were studied: 15 men and 7 women (mean age 48 years); 16 with SVT and 6 with VT. Using a sinus-rhythm template, the atrial CPM scores for SVT and VT were 66%+/- 20% and 93%+/- 5%, respectively (P = 0.0034). With a CPM-score cutoff of 85%, the sensitivity for correctly identifying VT was 100% and the specificity for rejection of SVT was 80%. The corresponding ventricular-CPM scores for SVT and VT were 81%+/- 12% and 72%+/- 24%, respectively (P = 0.13, cutoff = 65%, sensitivity = 50%, and specificity = 90%). Using a ventricular template with atrial pacing, the ventricular-CPM scores for SVT and VT were 87%+/- 9% and 76%+/- 14%, respectively (P = 0.028, cutoff = 70%, sensitivity = 50%, and specificity = 93%). Atrial CWA matching is superior to ventricular CWA matching in discriminating between SVT and VT. CWA matching in both chambers could potentially achieve better discrimination.

View details for Web of Science ID 000227338100015

View details for PubMedID 15683526
Implantable defibrillator sensing and discrimination algorithms NEW ARRHYTHMIA TECHNOLOGIES Richardson, K., Al-Ahmad, A., Wang, P. J., Wang, P. J. 2005: 163?77
View details for Web of Science ID 000298280100018
Loss of biventricular pacing: What is the cause? HEART RHYTHM Richardson, K., Cook, K., Wang, P. J., Al-Ahmad, A. 2005; 2 (1): 110-111
View details for DOI 10.1016/j.hrthm.2004.09.015

View details for Web of Science ID 000226446500023

View details for PubMedID 15851277
Atrial fibrillation, sleep apnea and obesity NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE Chung, M. K., Foldvary-Schaefer, N., Somers, V. K., Friedman, P. A., Wang, P. J. 2004; 1 (1): 56?59
Abstract

A 60-year-old male with obesity (body-mass index 43 kg/m(2)) presented with recurrent symptomatic atrial fibrillation (AF), which he had had since age 41 years. The AF was refractory to treatment with antiarrhythmic drugs. Pacemaker implantation for tachycardia-bradycardia syndrome was required as well as ablation for atrial flutter, and the patient underwent a total of four DC cardioversions. Sleep studies showed mild to moderate obstructive sleep apnea, but continuous positive airway pressure was not tolerated. Pacemaker interrogations demonstrated mode-switch episodes, indicating continuing AF. He was scheduled for catheter ablation targeting pulmonary vein antral isolation. He embarked on a weight-loss program, which successfully reduced AF burden.Echocardiography, stress testing, polysomnography, pacemaker interrogations and C-reactive protein.AF, atrial flutter, tachycardia-bradycardia syndrome, obstructive sleep apnea and morbid obesity.Antiarrhythmic drug therapy, DC cardioversion, anticoagulation, atrial flutter ablation, permanent pacemaker implantation, continuous positive airway pressure and weight loss.

View details for DOI 10.1038/ncpcardio0027

View details for Web of Science ID 000202931500015

View details for PubMedID 16265261
Electrocardiographic arrhythmia risk testing CURRENT PROBLEMS IN CARDIOLOGY Engel, G., Beckerman, J. G., Froelicher, V. F., Yamazaki, T., Chen, H. A., Richardson, K., McAuley, R. J., Ashley, E. A., Chun, S., Wang, P. J. 2004; 29 (7): 365-432
Abstract

Among the most compelling challenges facing cardiologists today is identification of which patients are at highest risk for sudden death. Automatic implantable cardioverter-defibrillators are now indicated in many of these patients, yet the role of noninvasive risk stratification in classifying patients at high risk is not well defined. The purpose of this review is to evaluate the various electrocardiographic (ECG) techniques that appear to have potential in assessment of risk for arrhythmia. The resting ECG (premature ventricular contractions, QRS duration, damage scores, QT dispersion, and ST segment and T wave abnormalities), T wave alternans, late potentials identified on signal-averaged ECGs, and heart rate variability are explored. Unequivocal evidence to support the widespread use of any single noninvasive technique is lacking; further research in this area is needed. It is likely that a combination of risk evaluation techniques will have the greatest predictive power in enabling identification of patients most likely to benefit from device therapy.

View details for DOI 10.1016/j.cpcardiol.2004.02.007

View details for PubMedID 15192691
Cardiovascular screening of athletes CLINICAL JOURNAL OF SPORT MEDICINE Beckerman, J., Wang, P., Hlatky, M. 2004; 14 (3): 127-133
Abstract

Cardiovascular screening of athletes is a challenging aspect of the preparticipation evaluation. While sudden cardiac death in young athletes is uncommon, preparticipation screening may identify some predisposing conditions that place individuals at increased risk. The most common pre-existing cardiac abnormalities in athletes causing sudden death in the United States are hypertrophic cardiomyopathy, congenital coronary anomalies, and Marfan syndrome. Preparticipation cardiovascular screening should pursue any history of cardiac symptoms or family history of premature cardiac disease, as well as abnormal cardiovascular physical findings. Positive findings should be investigated; an electrocardiogram, echocardiogram, or consultation with a specialist should be considered. Recommendations are then available to guide athletic participation according to the cardiovascular diagnosis.

View details for Web of Science ID 000230327200004

View details for PubMedID 15166900
Heart failure and the risk of shocks in patients with implantable cardioverter defibrillators - Results from the Triggers of Ventricular Arrhythmias (TOVA) study CIRCULATION Whang, W., Mittleman, M. A., Rich, D. Q., Wang, P. J., Ruskin, J. N., Tofler, G. H., Muller, J. E., Albert, C. M. 2004; 109 (11): 1386-1391
Abstract

Left ventricular ejection fraction (LVEF) predicts device discharges in patients with implantable cardioverter-defibrillators (ICDs). The relationship between severity of congestive heart failure (CHF) and ICD discharges is less clear.We prospectively analyzed the association between CHF and risk of appropriate ICD discharges in the Triggers Of Ventricular Arrhythmias (TOVA) study, a cohort study of ICD patients conducted at 31 centers in the United States. Reported shocks were confirmed for sustained ventricular tachycardia (VT) or fibrillation (VF) by analysis of stored electrograms. Proportional hazards models included CHF categorized by New York Heart Association class. Baseline CHF was present among 502 (44%) of 1140 patients; 170 (34%) had class I, 230 (46%) had class II, 97 (19%) had class III, and only 5 (1%) had class IV symptoms. During median follow-up of 212 days, 92 patients experienced 1 or more appropriate ICD discharges. Class III CHF was associated in a statistically significantly manner with ICD discharge for VT/VF (hazard ratio 2.40, 95% CI 1.16 to 4.98), even with adjustment for LVEF. The combination of LVEF <0.20 and class III symptoms resulted in a particularly high risk of shocks for VT/VF (hazard ratio 3.90, 95% CI 1.28 to 11.92).Class III CHF, an easily accessible clinical measure, is an independent risk factor, along with LVEF, for ventricular arrhythmias that require shock therapy among ICD patients. Whether patients with class III CHF benefit to a greater degree from ICDs and whether aggressive treatment of CHF in ICD patients may prevent ventricular arrhythmias remains to be determined.

View details for DOI 10.1161/01.CIR.0000120703.99433.1E

View details for Web of Science ID 000220364700011

View details for PubMedID 14993132
Frequent ICD shocks due to double sensing in patients with bi-ventricular implantable cardioverter defibrillators JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Al-Ahmad, A., Wang, P. J., Homoud, M. K., Estes, N. A., Link, M. S. 2003; 9 (3): 377-381
Abstract

Biventricular pacing has emerged as a modality for treatment of patients with heart failure. Combined biventricular pacers and implantable cardioverter defibrillators offer treatment of heart failure as well as protection from sudden cardiac death. However, inappropriate ICD shocks as a result of double sensing due to widely spaced ventricular bipoles may pose a significant problem in these patients. We examined the ICD records of twenty-three patients with biventricular ICDs, and evaluated all episodes of double sensing that resulted in aborted or delivered therapy. In follow-up of 3.7 +/- 2.6 months, thirty-three shocks in fifteen episodes occurred in five patients (21.7%) due to double sensing. Four patients (17.4%) had aborted shocks due to double sensing. All episodes resulting in shock occurred because of sinus tachycardia or supraventricular tachycardia above the upper programmed pacing rate of the device with resultant AV conduction and double sensing of the nonpaced ventricular depolarization. In conclusion, double sensing of the R-wave is a common and clinically important cause of inappropriate ICD detection and shock in patients with biventricular ICDs. Appropriate programming of the ICD can prevent episodes of inappropriate shocks.

View details for Web of Science ID 000186420900011

View details for PubMedID 14618060
Cardiac arrhythmias in the athlete: the evolving role of electrophysiology. Current sports medicine reports Link, M. S., Homoud, M. K., Wang, P. J., Estes, N. A. 2002; 1 (2): 75-85
Abstract

Arrhythmia management has undergone a revolution in the past decade. The diagnosis and treatment of arrhythmias in the athlete can be complicated by the need to compete and exercise. Some arrhythmias may be benign and asymptomatic, but others may be life threatening. Sinus bradyarrhythmias are common and even expected in athletes; these are rarely a cause for concern. Heart block is unusual and merits a thorough work-up. Atrial fibrillation may be more common in the athlete, and supraventricular tachycardias other than atrial fibrillation warrant consideration of radiofrequency ablation for cure. Ventricular arrhythmias in the athlete generally occur in the setting of structural heart disease that is genetically determined (hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, anomalous coronary arteries), or acquired (coronary artery disease, myocarditis, idiopathic dilated cardiomyopathies). In these conditions the arrhythmia is life threatening. Ventricular arrhythmias that occur in the athlete without structural heart disease are not thought to be life threatening. Athletes with structural heart disease and those with exertional syncope merit a complete evaluation.

View details for PubMedID 12831715
Advances in implantable cardioverter defibrillators CURRENT OPINION IN CARDIOLOGY Swygman, C., Wang, P. J., Link, M. S., Homoud, M. K., Estes, N. A. 2002; 17 (1): 24-28
Abstract

Implantable cardioverter defibrillators (ICDs) have become an important therapeutic modality for patients who have had a cardiac arrest or are at risk for life-threatening ventricular arrhythmias. Clinical trials have confirmed the role of the ICD for patients with sustained ventricular arrhythmias and have expanded the indications to include patients with coronary artery disease, left ventricular dysfunction, nonsustained ventricular tachycardia, and inducible ventricular tachycardia. Numerous technologic advances in ICDs have resulted in decreased size, greater ease of placement, and increased functionality. Important advancements have been made in the effectiveness of arrhythmia classification and electrogram storage. Dual-chamber ICDs have become increasingly sophisticated with rate-adaptive sensors. Biventricular pacing is being combined with ICD function in patients with heart failure, systolic dysfunction, and QRS widening. Future advances in devices will likely lead to improved arrhythmia classification, more advanced automated features, and additional features including more sophisticated sensors and biventricular pacing systems.

View details for Web of Science ID 000173100500004

View details for PubMedID 11790930
ECG findings in active patients - Differentiating the benign from the serious PHYSICIAN AND SPORTSMEDICINE Estes, N. A., Link, M. S., Homoud, M., Wang, P. J. 2001; 29 (3): 67-74
Abstract

ECGs and cardiac rhythms of normal athletes can vary widely. The heightened vagal tone from athletic conditioning can result in variant ECG findings that may mimic serious disorders. ECG patterns of long-QT syndrome, arrhythmogenic right ventricular dysplasia, Wolff-Parkinson-White syndrome, and hypertrophic cardiomyopathy signal the need for further evaluation, therapy, and possible participation restriction. Radiofrequency ablation may be appropriate when symptomatic supraventricular arrhythmias or Wolff-Parkinson-White syndrome is present. Further research is needed to effectively distinguish normal ECG changes in the athlete from changes that underlie cardiac disease. Improvements in identifying athletes at risk of serious or life-threatening arrhythmias are also needed.

View details for Web of Science ID 000167312200013

View details for PubMedID 20086567
Cardiac arrhythmias in the athlete. Cardiology in review Link, M. S., Homoud, M. K., Wang, P. J., Estes, N. A. 2001; 9 (1): 21-30
Abstract

Cardiac arrhythmias in the athlete are a frequent cause for concern. Some arrhythmias may be benign and asymptomatic, but others may be life threatening and a sign that serious cardiovascular disease is present. Physicians often are consulted with regard to arrhythmias, or symptoms consistent with arrhythmias, in athletes. Sinus bradyarrhythmias are common and even expected in athletes. These bradyarrhythmias are rarely a cause for concern. Heart block is unusual and merits a thorough workup. Atrial fibrillation may be more common in the athlete. Supraventricular tachycardias other than atrial fibrillation generally warrant consideration of radiofrequency ablation for cure of the tachyarrhythmia. Ventricular arrhythmias in the athlete generally occur in the setting of structural heart disease that is genetically determined (hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, anomalous coronary arteries) or acquired (coronary artery disease, myocarditis, idiopathic dilated cardiomyopathies). In these conditions, the arrhythmia generally is life threatening. Ventricular arrhythmias that occur in the athlete without structural heart disease are not thought to be life threatening. Athletes with structural heart disease and syncope and those with exertional syncope merit a complete evaluation.

View details for PubMedID 11174912
ANTITACHYCARDIA PACING AND LOW-ENERGY CARDIOVERSION FAR VENTRICULAR-TACHYCARDIA TERMINATION - A CLINICAL PERSPECTIVE Symposium on Electrical Device Therapy for Cardiac Arrhythmias: New Concepts, Problems, and Alternatives Estes, N. A., Haugh, C. J., Wang, P. J., Manolis, A. S. MOSBY-YEAR BOOK INC. 1994: 1038?46
Abstract

When incorporated into tiered therapy implantable cardioverter defibrillators (ICDs), antitachycardia pacing (ATP) techniques have proved useful for termination of sustained monomorphic ventricular tachycardias (VT) and have the advantages of rapid delivery, absence of patient discomfort, and minimal battery drain. The efficacy of low-energy cardioversion (LEC) is similar to that of pacing techniques for VT termination, but LEC has the disadvantages of patient discomfort, atrial proarrhythmia, and greater battery drain compared with ATP. Acceleration of VT occurs with similar frequency with each technique. Neither technique should be used without back-up defibrillation capability in an ICD. VT termination algorithms are currently empiric and require repetitive arrhythmia induction and trials of ATP or LEC. Future studies of the risk and benefits of each technique are likely to define optimal programming strategies in tiered therapy ICDs.

View details for Web of Science ID A1994NF85500011

View details for PubMedID 8160578

Paul J. Wang, MD

Professor of Medicine (Cardiovascular Medicine) at the Stanford University Medical Center and, by courtesy, of Bioengineering

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