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Impact of Cardiac Resynchronization Therapy on Heart Transplant-Free Survival in Pediatric and Congenital Heart Disease Patients. Circulation. Arrhythmia and electrophysiology Chubb, H., Rosenthal, D. N., Almond, C. S., Ceresnak, S. R., Motonaga, K. S., Arunamata, A. A., Long, J., Trela, A. V., Hanisch, D., McElhinney, D. B., Dubin, A. M. 2020
Abstract

Background - Cardiac resynchronization therapy (CRT) studies in pediatric and/or congenital heart disease (CHD) patients have shown an improvement in ejection fraction and heart failure symptoms. However, a survival benefit of CRT in this population has not been established. This study aimed to evaluate the impact of CRT upon heart transplant-free survival in pediatric and CHD patients, using a propensity score-matched analysis. Methods - This single-center study compared CRT patients (implant date 2004-2017) and controls, matched by 1:1 propensity-score matching (PSM) using 21 comprehensive baseline indices for risk stratification. CRT patients were <21 years or had CHD; had systemic ventricular ejection fraction <;45%; symptomatic heart failure; and had significant electrical dyssynchrony, all prior to CRT implant. Controls were screened from non-selective imaging and ECG databases. Controls were retrospectively enrolled when they achieved the same inclusion criteria at an outpatient clinical encounter, within the same time period. Results - Of 133 patients who received CRT during the study period, 84 met all study inclusion criteria. 133 controls met all criteria at an outpatient encounter. Following PSM, 63 matched CRT-control pairs were identified with no significant difference between groups across all baseline indices. Heart transplant or death occurred in 12 (19%) PSM-CRT subjects and 37 (59%) PSM-controls with a median follow-up of 2.7 years (quartiles 0.8-6.1 years). CRT was associated with markedly reduced risk of heart transplant or death (hazard ratio 0.24 [95% CI 0.12-0.46], p<0.001). There was no CRT procedural mortality and one system infection at 54 months post-implant. Conclusions - In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplant-free survival.

View details for DOI 10.1161/CIRCEP.119.007925

View details for PubMedID 32202126
Weakly supervised classification of rare aortic valve malformations using unlabeled cardiac MRI sequences Nature Communications Fries, J. A., Varma, P., Chen, V. S., Xiao, K., Tejeda, H., Saha, P., Dunnmon, J., Chubb, H., Maskatia, S., Fiterau, M., Delp, S., Ashley, E., R�, C., Priest, J. R. 2019; 10
View details for DOI 10.1038/s41467-019-11012-3
The reproducibility of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Chubb, H., Karim, R., Roujol, S., Nu�ez-Garcia, M., Williams, S. E., Whitaker, J., Harrison, J., Butakoff, C., Camara, O., Chiribiri, A., Schaeffter, T., Wright, M., O'Neill, M., Razavi, R. 2018; 20 (1): 21
Abstract

Cardiovascular magnetic resonance (CMR) imaging has been used to visualise post-ablation atrial scar (PAAS), generally employing a three-dimensional (3D) late gadolinium enhancement (LGE) technique. However the reproducibility of PAAS imaging has not been determined. This cross-over study is the first to investigate the reproducibility of the technique, crucial for both future research design and clinical implementation.Forty subjects undergoing first time ablation for atrial fibrillation (AF) had detailed CMR assessment of PAAS. Following baseline pre-ablation scan, two scans (separated by 48�h) were performed at three months post-ablation. Each scan session included 3D LGE acquisition at 10, 20 and 30�min post administration of gadolinium-based contrast agent (GBCA). Subjects were allocated at second scan post-ablation to identical imaging parameters ('Repro', n?=?10), 3�T scanner ('3�T', n?=?10), half-slice thickness ('Half-slice', n?=?10) or half GBCA dose ('Half-gad', n?=?10). PAAS was compared to baseline scar and then reproducibility was assessed for two measures of thresholded scar (% left atrial (LA) occupied by PAAS (%LA PAAS) and Pulmonary Vein Encirclement (PVE)), and then four measures of non-thresholded scar (point-by-point assessment of PAAS, four normalisation methods). Thresholded measures of PAAS were evaluated against procedural outcome (AF recurrence).A total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. At 20 and 30�min, inter-scan reproducibility was good to excellent (coefficient of variation at 20�min and 30�min: %LA PAAS 0.41 and 0.20; PVE 0.13 and 0.04 respectively for 'Repro' group). Changes in imaging parameters, especially reduced GBCA dose, reduced inter-scan reproducibility, but for most measures remained good to excellent (ICC for %LA PAAS 0.454-0.825, PVE 0.618-0.809 at 30�min). For non-thresholded scar, highest reproducibility was observed using blood pool z-score normalisation technique: inter-scan ICC 0.759 (absolute agreement, 'Repro' group). There was no significant relationship between indices of PAAS and AF recurrence.PAAS imaging is a reproducible finding. Imaging should be performed at least 20�min post-GBCA injection, and a blood pool z-score should be considered for normalisation of signal intensities. The clinical implications of these findings remain to be established in the absence of a simple correlation with arrhythmia outcome.United Kingdom National Research Ethics Service 08/H0802/68 - 30th September 2008.

View details for PubMedID 29554919

View details for PubMedCentralID PMC5858144
Development, Pre-Clinical Validation and Clinical Translation of a Cardiac Magnetic Resonance-Electrophysiology System with Active Catheter Tracking for Ablation of Cardiac Arrhythmia Journal of the American College of Cardiology: Clinical Electrophysiology Chubb, H., Harrison, J. L., Weiss, S., Krueger, S., Koken, P., Bloch, L., Kim, W., Stenzel, G., Weisz, J. L., Gill, J., Schaeffter, T., O'Neill, M. D., Razavi, R. 2017; 3 (2): 89-103
View details for DOI 10.1016/j.jacep.2016.07.005
Tachyarrhythmias and catheter ablation in adult congenital heart disease. Expert review of cardiovascular therapy Chubb, H., Williams, S. E., Wright, M., Rosenthal, E., O'Neill, M. 2014; 12 (6): 751-770
Abstract

Advances in surgical technique have had an immense impact on longevity and quality of life in patients with congenital heart disease. However, an inevitable consequence of these surgical successes is the creation of a unique patient population whose anatomy, surgical history and haemodynamics result in the development of a challenging and complex arrhythmia substrate. Furthermore, this patient group remains susceptible to the arrhythmias seen in the general adult population. It is through a thorough appreciation of the cardiac structural defect, the surgical corrective approach, and haemodynamic impact that the most effective arrhythmia care can be delivered. Catheter ablation techniques offer a highly effective management option but require a meticulous attention to the real-time integration of anatomical and electrophysiological information to identify and eliminate the culprit arrhythmia substrate. This review describes the current approach to the interventional management of patients with tachyarrhythmias in the context of congenital heart disease.

View details for DOI 10.1586/14779072.2014.914434

View details for PubMedID 24783943
The use of Z-scores in paediatric cardiology. Annals of pediatric cardiology Chubb, H., Simpson, J. M. 2012; 5 (2): 179-184
Abstract

Z-scores are a means of expressing the deviation of a given measurement from the size or age specific population mean. By taking account of growth or age, Z-scores are an excellent means of charting serial measurements in paediatric cardiological practice. They can be applied to echocardiographic measurements, blood pressure and patient growth, and thus may assist in clinical decision-making.

View details for DOI 10.4103/0974-2069.99622

View details for PubMedID 23129909

View details for PubMedCentralID PMC3487208
Long-Term Outcome Following Catheter Valvotomy for Pulmonary Atresia With Intact Ventricular Septum JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Chubb, H., Pesonen, E., Sivasubramanian, S., Tibby, S. M., Simpson, J. M., Rosenthal, E., Qureshi, S. A. 2012; 59 (16): 1468-1476
Abstract

This study investigated the outcome for all patients undergoing catheter valve perforation for pulmonary atresia with intact ventricular septum (PAIVS) 21 years after the first procedure at their center.Catheter perforation for PAIVS is now an established procedure. However, the management of the borderline right ventricle (RV) is controversial, and there may be a place for novel techniques such as stenting of the arterial duct.There were 37 successful valve perforations (total 39 patients). Median length of follow-up was 9.2 years (range 2.2 to 21.0 years). Seventeen patients had stenting of the arterial duct. The mean (SD) initial z-score for the tricuspid valve was -5.1 (�3.4), and a further 142 sets of measurements were taken to assess the growth of the RV of survivors.There were 8 deaths (21%), and no deaths after the first 35 days. There were no late arrhythmias or ischemic events. Twenty-five patients (83% of survivors) have a biventricular circulation. For patients who had stenting of the arterial duct, significant reductions in early reintervention (0 vs. 7 patients, p = 0.009) and hospital stay (17.4 � 18.1 days vs. 33.8 � 28.6 days, p = 0.012) occurred, with no increase in mortality or morbidity. There was no catch-up growth of the RV in patients who had a biventricular outcome (z-score increase +0.08/year, p = 0.26).Long-term survival is good, and even small RVs may be amenable to this procedure. Multiple interventions may be required to achieve biventricular circulation, but stenting of the arterial duct may reduce hospital stay and repeat procedures.

View details for DOI 10.1016/j.jacc.2012.01.022

View details for Web of Science ID 000302785500009

View details for PubMedID 22497827
Clinical outcomes and programming strategies of implantable cardioverter-defibrillator devices in paediatric hypertrophic cardiomyopathy: a UK National Cohort Study. 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 Norrish, G., Chubb, H., Field, E., McLeod, K., Ilina, M., Spentzou, G., Till, J., Daubeney, P. E., Stuart, A. G., Matthews, J., Hares, D., Brown, E., Linter, K., Bhole, V., Pillai, K., Bowes, M., Jones, C. B., Uzun, O., Wong, A., Yue, A., Sadagopan, S., Bharucha, T., Yap, N., Rosenthal, E., Mathur, S., Adwani, S., Reinhardt, Z., Mangat, J., Kaski, J. P. 2020
Abstract

AIMS: Sudden cardiac death (SCD) is the most common mode of death in paediatric hypertrophic cardiomyopathy (HCM). This study describes the implant and programming strategies with clinical outcomes following implantable cardioverter-defibrillator (ICD) insertion in a well-characterized national paediatric HCM cohort.METHODS AND RESULTS: Data from 90 patients undergoing ICD insertion at a median age 13 (�3.5) for primary (n=67, 74%) or secondary prevention (n=23, 26%) were collected from a retrospective, longitudinal multi-centre cohort of children (<16years) with HCM from the UK. Seventy-six (84%) had an endovascular system [14 (18%) dual coil], 3 (3%) epicardial, and 11 (12%) subcutaneous system. Defibrillation threshold (DFT) testing was performed at implant in 68 (76%). Inadequate DFT in four led to implant adjustment in three patients. Over a median follow-up of 54months (interquartile range 28-111), 25 (28%) patients had 53 appropriate therapies [ICD shock n=45, anti-tachycardia pacing (ATP) n=8], incidence rate 4.7 per 100 patient years (95% CI 2.9-7.6). Eight inappropriate therapies occurred in 7 (8%) patients (ICD shock n=4, ATP n=4), incidence rate 1.1/100 patient years (95% CI 0.4-2.5). Three patients (3%) died following arrhythmic events, despite a functioning device. Other device complications were seen in 28 patients (31%), including lead-related complications (n=15) and infection (n=10). No clinical, device, or programming characteristics predicted time to inappropriate therapy or lead complication.CONCLUSION: In a large national cohort of paediatric HCM patients with an ICD, device and programming strategies varied widely. No particular strategy was associated with inappropriate therapies, missed/delayed therapies, or lead complications.

View details for DOI 10.1093/europace/euaa307

View details for PubMedID 33221861
Identifying locations of re-entrant drivers from patient-specific distribution of fibrosis in the left atrium. PLoS computational biology Roy, A., Varela, M., Chubb, H., MacLeod, R., Hancox, J. C., Schaeffter, T., Aslanidi, O. 2020; 16 (9): e1008086
Abstract

Clinical evidence suggests a link between fibrosis in the left atrium (LA) and atrial fibrillation (AF), the most common sustained arrhythmia. Image-derived fibrosis is increasingly used for patient stratification and therapy guidance. However, locations of re-entrant drivers (RDs) sustaining AF are unknown and therapy success rates remain suboptimal. This study used image-derived LA models to explore the dynamics of RD stabilization in fibrotic regions and generate maps of RD locations. LA models with patient-specific geometry and fibrosis distribution were derived from late gadolinium enhanced magnetic resonance imaging of 6 AF patients. In each model, RDs were initiated at multiple locations, and their trajectories were tracked and overlaid on the LA fibrosis distributions to identify the most likely regions where the RDs stabilized. The simulations showed that the RD dynamics were strongly influenced by the amount and spatial distribution of fibrosis. In patients with fibrosis burden greater than 25%, RDs anchored to specific locations near large fibrotic patches. In patients with fibrosis burden below 25%, RDs either moved near small fibrotic patches or anchored to anatomical features. The patient-specific maps of RD locations showed that areas that harboured the RDs were much smaller than the entire fibrotic areas, indicating potential targets for ablation therapy. Ablating the predicted locations and connecting them to the existing pulmonary vein ablation lesions was the most effective in-silico ablation strategy.

View details for DOI 10.1371/journal.pcbi.1008086

View details for PubMedID 32966275
Pectoral Nerve Blocks Decrease Postoperative Pain and Opioid Use After Pacemaker or Implantable Cardioverter-Defibrillator Placement in Children. Heart rhythm Yang, J. K., Char, D. S., Motonaga, K. S., Navaratnam, M., Dubin, A. M., Trela, A., Hanisch, D. G., McFadyen, G., Chubb, H., Goodyer, W., Ceresnak, S. R. 2020
Abstract

BACKGROUND: Pectoral nerve blocks (PECS) can reduce intra-procedural anesthetic requirements and postoperative pain. Little is known on the utility of PECS in reducing pain and narcotic use after pacemaker (PM) or implantable cardioverter defibrillator (ICD) placement in children.OBJECTIVE: To determine whether PECS can decrease postoperative pain and opioid use after PM or ICD placement in children.METHODS: A single center, retrospective review of pediatric patients undergoing transvenous PM or ICD placement between 2015-2020 was performed. Patients with recent cardiothoracic surgery or neurologic/developmental deficits were excluded. Demographics, procedural variables, postoperative pain, and postoperative opioid usage were compared between patients who underwent PECS and those who underwent conventional local anesthetic (CONTROL).RESULTS: A total of 74 patients underwent PM or ICD placement with 20 patients (27%) undergoing PECS. There were no differences between PECS and CONTROL with regard to age, weight, gender, type of device placed, presence of congenital heart disease, type of anesthesia, procedural time or complication rates. Patients who underwent PECS had lower pain scores at 1, 2, 6, 18, and 24-hours compared to CONTROL. PECS patients had a lower mean cumulative pain score [PECS 1.5 (95%-CI 0.8-2.2) vs CONTROL 3.1 (95%-CI 2.7-3.5); P<0.001] and lower total opioid use [PECS 6.0 MME/m2 (95%-CI 3.4-8.6) vs CONTROL 15.0 MME/m2 (95%-CI 11.8-18.2); P=0.001] over the 24-hours post-implant.CONCLUSIONS: Pectoralis nerve blocks reduce postoperative pain scores and lower total opioid usage after ICD or PM placement. PECS should be considered at the time of transvenous device placement in children.

View details for DOI 10.1016/j.hrthm.2020.03.009

View details for PubMedID 32201270
Fully Automatic Atrial Fibrosis Assessment Using a Multilabel Convolutional Neural Network. Circulation. Cardiovascular imaging Razeghi, O., Sim, I., Roney, C. H., Karim, R., Chubb, H., Whitaker, J., O'Neill, L., Mukherjee, R., Wright, M., O'Neill, M., Williams, S. E., Niederer, S. 2020; 13 (12): e011512
Abstract

Pathological atrial fibrosis is a major contributor to sustained atrial fibrillation. Currently, late gadolinium enhancement (LGE) scans provide the only noninvasive estimate of atrial fibrosis. However, widespread adoption of atrial LGE has been hindered partly by nonstandardized image processing techniques, which can be operator and algorithm dependent. Minimal validation and limited access to transparent software platforms have also exacerbated the problem. This study aims to estimate atrial fibrosis from cardiac magnetic resonance scans using a reproducible operator-independent fully automatic open-source end-to-end pipeline.A multilabel convolutional neural network was designed to accurately delineate atrial structures including the blood pool, pulmonary veins, and mitral valve. The output from the network removed the operator dependent steps in a reproducible pipeline and allowed for automated estimation of atrial fibrosis from LGE-cardiac magnetic resonance scans. The pipeline results were compared against manual fibrosis burdens, calculated using published thresholds: image intensity ratio 0.97, image intensity ratio 1.61, and mean blood pool signal +3.3 SD.We validated our methods on a large 3-dimensional LGE-cardiac magnetic resonance data set from 207 labeled scans. Automatic atrial segmentation achieved a 91% Dice score, compared with the mutual agreement of 85% in Dice seen in the interobserver analysis of operators. Intraclass correlation coefficients of the automatic pipeline with manually generated results were excellent and better than or equal to interobserver correlations for all 3 thresholds: 0.94 versus 0.88, 0.99 versus 0.99, 0.99 versus 0.96 for image intensity ratio 0.97, image intensity ratio 1.61, and +3.3 SD thresholds, respectively. Automatic analysis required 3 minutes per case on a standard workstation. The network and the analysis software are publicly available.Our pipeline provides a fully automatic estimation of fibrosis burden from LGE-cardiac magnetic resonance scans that is comparable to manual analysis. This removes one key source of variability in the measurement of atrial fibrosis.

View details for DOI 10.1161/CIRCIMAGING.120.011512

View details for PubMedID 33317334
Kinetics of SARS-CoV-2 positivity of infected and recovered patients from a single center. Scientific reports Huang, J., Zheng, L., Li, Z., Hao, S., Ye, F., Chen, J., Gans, H. A., Yao, X., Liao, J., Wang, S., Zeng, M., Qiu, L., Li, C., Whitin, J. C., Tian, L., Chubb, H., Hwa, K. Y., Ceresnak, S. R., Zhang, W., Lu, Y., Maldonado, Y. A., McElhinney, D. B., Sylvester, K. G., Cohen, H. J., Liu, L., Ling, X. B. 2020; 10 (1): 18629
Abstract

Recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive detection in infected but recovered individuals has been reported. Patients who have recovered from coronavirus disease 2019 (COVID-19) could profoundly impact the health care system. We sought to define the kinetics and relevance of PCR-positive recurrence during recovery from acute COVID-19 to better understand risks for prolonged infectivity and reinfection. A series of 414 patients with confirmed SARS-Cov-2 infection, at The Second Affiliated Hospital of Southern University of Science and Technology in Shenzhen, China from January 11 to April 23, 2020. Statistical analyses were performed of the clinical, laboratory, radiologic image, medical treatment, and clinical course of admission/quarantine/readmission data, and a recurrence predictive algorithm was developed. 16.7% recovered patients with PCR positive recurring one to three times, despite being in strict quarantine. Younger patients with mild pulmonary respiratory syndrome had higher risk of PCR positivity recurrence. The recurrence prediction model had an area under the ROC curve of 0.786. This case series provides characteristics of patients with recurrent SARS-CoV-2 positivity. Use of a prediction algorithm may identify patients at high risk of recurrent SARS-CoV-2 positivity and help to establish protocols for health policy.

View details for DOI 10.1038/s41598-020-75629-x

View details for PubMedID 33122706
A proposed approach to the asymptomatic pediatric patient with Wolff-Parkinson-White pattern. HeartRhythm case reports Chubb, H., Ceresnak, S. R. 2020; 6 (1): 2?7
View details for DOI 10.1016/j.hrcr.2019.09.003

View details for PubMedID 31956492
High-throughput quantitation of serological ceramides/dihydroceramides by LC/MS/MS: Pregnancy baseline biomarkers and potential metabolic messengers. Journal of pharmaceutical and biomedical analysis Huang, Q., Hao, S., Yao, X., You, J., Li, X., Lai, D., Han, C., Schilling, J., Hwa, K. Y., Thyparambil, S., Whitin, J., Cohen, H. J., Chubb, H., Ceresnak, S. R., McElhinney, D. B., Wong, R. J., Shaw, G. M., Stevenson, D. K., Sylvester, K. G., Ling, X. B. 2020; 192: 113639
Abstract

Ceramides and dihydroceramides are sphingolipids that present in abundance at the cellular membrane of eukaryotes. Although their metabolic dysregulation has been implicated in many diseases, our knowledge about circulating ceramide changes during the pregnancy remains limited. In this study, we present the development and validation of a high-throughput liquid chromatography-tandem mass spectrometric method for simultaneous quantification of 16 ceramides and 10 dihydroceramides in human serum within 5 min. by using stable isotope-labeled ceramides as internal standards. This method employs a protein precipitation method for high throughput sample preparation, reverse phase isocratic elusion for chromatographic separation, and Multiple Reaction Monitoring for mass spectrometric detection. To qualify for clinical applications, our assay has been validated against the FDA guidelines for Lower Limit of Quantitation (1 nM), linearity (R2>0.99), precision (imprecision<15 %), accuracy (inaccuracy<15 %), extraction recovery (>90 %), stability (>85 %), and carryover (<0.01 %). With enhanced sensitivity and specificity from this method, we have, for the first time, determined the serological levels of ceramides and dihydroceramides to reveal unique temporal gestational patterns. Our approach could have value in providing insights into disorders of pregnancy.

View details for DOI 10.1016/j.jpba.2020.113639

View details for PubMedID 33017796
Cardiac resynchronization and implantable defibrillators in adults with congenital heart disease. Heart failure reviews Chubb, H., Motonaga, K. S. 2019
Abstract

Cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICDs) are well-established therapies for adult patients with heart failure that have been shown to improve morbidity and mortality. However, the benefits and indications for use in adults with congenital heart disease (ACHD) are less defined with no significant large prospective studies in this population. There are, however, multiple retrospective studies that demonstrate the efficacy of these devices in the ACHD population. These indicate a role for both CRT and ICDs in select patients with ACHD. The clinician and patient must balance the risks and benefits, summarized in complex evidence that reflects the heterogeneity of the ACHD patient group, and apply them in a patient-specific manner to optimize the utility of CRT and ICDs.

View details for DOI 10.1007/s10741-019-09886-y

View details for PubMedID 31754907
Improved co-registration of ex-vivo and in-vivo cardiovascular magnetic resonance images using heart-specific flexible 3D printed acrylic scaffold combined with non-rigid registration. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Whitaker, J., Neji, R., Byrne, N., Puyol-Anton, E., Mukherjee, R. K., Williams, S. E., Chubb, H., O'Neill, L., Razeghi, O., Connolly, A., Rhode, K., Niederer, S., King, A., Tschabrunn, C., Anter, E., Nezafat, R., Bishop, M. J., O'Neill, M., Razavi, R., Roujol, S. 2019; 21 (1): 62
Abstract

BACKGROUND: Ex-vivo cardiovascular magnetic resonance (CMR) imaging has played an important role in the validation of in-vivo CMR characterization of pathological processes. However, comparison between in-vivo and ex-vivo imaging remains challenging due to shape changes occurring between the two states, which may be non-uniform across the diseased heart. A novel two-step process to facilitate registration between ex-vivo and in-vivo CMR was developed and evaluated in a porcine model of chronic myocardial infarction (MI).METHODS: Sevenweeks after ischemia-reperfusion MI, 12 swine underwent in-vivo CMR imaging with late gadolinium enhancement followed by ex-vivo CMR 1 week later. Five animals comprised the control group, in which ex-vivo imaging was undertaken without any support in the LV cavity, 7 animals comprised the experimental group, in which a two-step registration optimization process was undertaken. The first step involved a heart specific flexible 3D printed scaffold generated from in-vivo CMR, which was used to maintain left ventricular (LV) shape during ex-vivo imaging. In the second step, a non-rigid co-registration algorithm was applied to align in-vivo and ex-vivo data. Tissue dimension changes between in-vivo and ex-vivo imaging were compared between the experimental and control group. In the experimental group, tissue compartment volumes and thickness were compared between in-vivo and ex-vivo data before and after non-rigid registration. The effectiveness of the alignment was assessed quantitatively using the DICE similarity coefficient.RESULTS: LV cavity volume changed more in the control group (ratio of cavity volume between ex-vivo and in-vivo imaging in control and experimental group 0.14 vs 0.56, p<0.0001) and there was a significantly greater change in the short axis dimensions in the control group (ratio of short axis dimensions in control and experimental group 0.38 vs 0.79, p<0.001). In the experimental group, prior to non-rigid co-registration the LV cavity contracted isotropically in the ex-vivo condition by less than 20% in each dimension. There was a significant proportional change in tissue thickness in the healthy myocardium (change=29�21%), but not in dense scar (change=-2�2%, p=0.034). Following the non-rigid co-registration step of the process, the DICE similarity coefficients for the myocardium, LV cavity and scar were 0.93 (�0.02), 0.89 (�0.01) and 0.77 (�0.07) respectively and the myocardial tissue and LV cavity volumes had a ratio of 1.03 and 1.00 respectively.CONCLUSIONS: The pattern of the morphological changes seen between the in-vivo and the ex-vivo LV differs between scar and healthy myocardium. A 3D printed flexible scaffold based on the in-vivo shape of the LV cavity is an effective strategy to minimize morphological changes in the ex-vivo LV. The subsequent non-rigid registration step further improved the co-registration and local comparison between in-vivo and ex-vivo data.

View details for DOI 10.1186/s12968-019-0574-z

View details for PubMedID 31597563
A comprehensive multi-index cardiac magnetic resonance-guided assessment of atrial fibrillation substrate prior to ablation: prediction of long-term outcomes. Journal of cardiovascular electrophysiology Chubb, H., Karim, R., Mukherjee, R., Williams, S. E., Whitaker, J., Harrison, J., Niederer, S. E., Staab, W., Gill, J., Schaeffter, T., Wright, M., O'Neill, M., Razavi, R. 2019
Abstract

INTRODUCTION: Multiple CMR-derived indices of atrial fibrillation (AF) substrate have been shown in isolation to predict long-term outcome following catheter ablation. Left atrial (LA) fibrosis, LA volume, LA ejection fraction (EF), LVEF, LA shape (sphericity) and pulmonary vein anatomy have all been shown to correlate with late AF recurrence. This study aimed to validate and assess the relative contribution of multiple indices in a long-term single-center study.METHODS AND RESULTS: 89 patients (53% PAF, 73% male) underwent comprehensive CMR study prior to first-time AF ablation (median follow-up 726days (IQR 418-1010days)). 3D LGE acquisition (1.5T, 1.3x1.3x2mm) was quantified for fibrosis, LA volume and sphericity assessed on manual segmentation at atrial diastole, LA and LV ejection fraction (EF) quantified on multi-slice cine imaging. AF recurred in 43 patients (48%) overall (31 at one year). In the recurrence group, LA fibrosis was higher (42% vs 29%, HR 1.032, p=0.002), LAEF lower (25% vs 34%, HR 0.063, p=0.016) and LVEF lower (57% vs 63%, HR 0.011, p=0.008). LA volume (63 vs 61 ml/m2) and sphericity (0.819 vs 0.822) were similar. Multivariate Cox regression analysis was adjusted for age and sex (model 1), additionally AF type (model 2) and combined (model 3). In models 1 and 2, LA fibrosis, LAEF and LVEF were independently associated with outcome, but only LA fibrosis was independent in model 3 (HR 1.021, p=0.022).CONCLUSIONS: LAEF, LVEF and LA fibrosis differed significantly in the AF recurrence cohort. However, on combined multivariate analysis only LA fibrosis remained independently associated with outcome. This article is protected by copyright. All rights reserved.

View details for DOI 10.1111/jce.14111

View details for PubMedID 31397511
Management of Asymptomatic Wolff-Parkinson-White Pattern by Pediatric Electrophysiologists. The Journal of pediatrics Chubb, H., Campbell, R. M., Motonaga, K. S., Ceresnak, S. R., Dubin, A. M. 2019
Abstract

OBJECTIVE: To determine the present-day approach of pediatric cardiac electrophysiologists to asymptomatic Wolff-Parkinson-White (WPW) pattern and to contrast to both published consensus statements and a similar survey.STUDY DESIGN: A questionnaire was sent to 266 Pediatric and Congenital Electrophysiology Society physician members in 25 countries; 21 questions from the 2003 survey were repeated, with new questions added regarding risk stratification and decision making.RESULTS: We received 113 responses from 13 countries, with responders having extensive electrophysiology experience (median 15years [IQR 8.5-25years]). Only 12 (11%) believed that intermittent pre-excitation and 37 (33%) that sudden loss of pre-excitation on exercise test were sufficient evidence of accessory pathway safety to avoid an invasive electrophysiology study. Optimal weight for electrophysiology study was 20kg (IQR 18-22.5kg), and 61% and 58% would then ablate all right-sided or left-sided accessory pathways, respectively, regardless of electrophysiological properties, whereas only 23% would ablate all septal accessory pathways (P<.001). Compared with 2003, respondents were more likely to consider inducible arrhythmia (77% vs 26%, P<.001) as sufficient indication alone for ablation.CONCLUSIONS: In the context of recent literature regarding the reliability of risk-stratification tools, most operators are now performing electrophysiology study for asymptomatic Wolff-Parkinson-White regardless of noninvasive findings. Many will then proceed to default ablation of all accessory pathways distant from critical conduction structures.

View details for DOI 10.1016/j.jpeds.2019.05.058

View details for PubMedID 31235382
Evaluation of a real-time magnetic resonance imaging-guided electrophysiology system for structural and electrophysiological ventricular tachycardia substrate assessment. 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 Mukherjee, R. K., Costa, C. M., Neji, R., Harrison, J. L., Sim, I., Williams, S. E., Whitaker, J., Chubb, H., O'Neill, L., Schneider, R., Lloyd, T., Pohl, T., Roujol, S., Niederer, S. A., Razavi, R., O'Neill, M. D. 2019
Abstract

AIMS: Potential advantages of real-time magnetic resonance imaging (MRI)-guided electrophysiology (MR-EP) include contemporaneous three-dimensional substrate assessment at the time of intervention, improved procedural guidance, and ablation lesion assessment. We evaluated a novel real-time MR-EP system to perform endocardial voltage mapping and assessment of delayed conduction in a porcine ischaemia-reperfusion model.METHODS AND RESULTS: Sites of low voltage and slow conduction identified using the system were registered and compared to regions of late gadolinium enhancement (LGE) on MRI. The Sorensen-Dice similarity coefficient (DSC) between LGE scar maps and voltage maps was computed on a nodal basis. A total of 445 electrograms were recorded in sinus rhythm (range: 30-186) using the MR-EP system including 138 electrograms from LGE regions. Pacing captured at 103 sites; 47 (45.6%) sites had a stimulus-to-QRS (S-QRS) delay of ?40ms. Using conventional (0.5-1.5mV) bipolar voltage thresholds, the sensitivity and specificity of voltage mapping using the MR-EP system to identify MR-derived LGE was 57% and 96%, respectively. Voltage mapping had a better predictive ability in detecting LGE compared to S-QRS measurements using this system (area under curve: 0.907 vs. 0.840). Using an electrical threshold of 1.5mV to define abnormal myocardium, the total DSC, scar DSC, and normal myocardium DSC between voltage maps and LGE scar maps was 79.0 � 6.0%, 35.0 � 10.1%, and 90.4 � 8.6%, respectively.CONCLUSION: Low-voltage zones and regions of delayed conduction determined using a real-time MR-EP system are moderately associated with LGE areas identified on MRI.

View details for DOI 10.1093/europace/euz165

View details for PubMedID 31219547
Virtual Catheter Ablation Of Target Areas Identified from Image-Based Models of Atrial Fibrillation Functional Imaging and Modeling of the Heart. Lecture Notes in Computer Science Roy, A., Varela, M., Chubb, H., MacLeod, R. S., Hancox, J., Schaeffter, T., O'Neill, M., Aslanidi, O. 2019; 11504: 11-19
View details for DOI 10.1007/978-3-030-21949-9_2
A proposed method for the calculation of age-dependent QRS duration z-scores. Journal of electrocardiology Chubb, H., Ceresnak, S. R., Motonaga, K. S., Dubin, A. M. 2019; 58: 132?34
Abstract

There are currently no published algorithms for calculation of age-dependent QRS duration z-scores. The absence of a standardized measure has limited researchers' abilities to compare ECG measurements of electrical synchrony between subjects of different ages or longitudinally over time.Four existing studies of normal ECG measurements (total 19,062 subjects) were used to estimate age and sex-dependent means and standard deviations.Weighted means and standard deviations were best estimated by cubic functions to create z-score algorithms.Nomograms and algorithms for QRS duration z-scores may be estimated to compare ECG findings in both children and adults.

View details for DOI 10.1016/j.jelectrocard.2019.12.004

View details for PubMedID 31846856
Advances in Real-Time MRI-Guided Physiology Current Cardiovascular Imaging Reports Mukherjee, R., Chubb, H., Roujol, S., Razavi, R., O'Neill, M. 2019; 12 (6): 6
Abstract

Theoretical benefits of real-time MRI guidance over conventional electrophysiology include contemporaneous 3D substrate assessment and accurate intra-procedural guidance and evaluation of ablation lesions. We review the unique challenges inherent to MRI-guided electrophysiology and how to translate the potential benefits in the treatment of cardiac arrhythmias.Over the last 5 years, there has been substantial progress, initially in animal models and more recently in clinical studies, to establish methods and develop workflows within the MR environment that resemble those of conventional electrophysiology laboratories. Real-time MRI-guided systems have been used to perform electroanatomic mapping and ablation in patients with atrial flutter, and there is interest in developing the technology to tackle more complex arrhythmias including atrial fibrillation and ventricular tachycardia.Mainstream adoption of real-time MRI-guided electrophysiology will require demonstration of clinical benefit and will be aided by increased availability of devices suitable for use in the MRI environment.

View details for DOI 10.1007/s12410-019-9481-9

View details for PubMedCentralID PMC6733706
The value of ablation parameter indices for predicting mature atrial scar formation in humans: An in vivo assessment using cardiac magnetic resonance imaging JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Chubb, H., Lal, K., Kiedrowicz, R., Karim, R., Williams, S. E., Harrison, J., Whitaker, J., Wright, M., Razavi, R., O'Neill, M. 2019; 30 (1): 67?77
View details for DOI 10.1111/jce.13754

View details for Web of Science ID 000455052400010
Mind the gap: Quantification of incomplete ablation patterns after pulmonary vein isolation using minimum path search MEDICAL IMAGE ANALYSIS Nunez-Garcia, M., Camara, O., O'Neill, M. D., Razavi, R., Chubb, H., Butakoff, C. 2019; 51: 1?12
View details for DOI 10.1016/j.media.2018.10.001

View details for Web of Science ID 000454368400001
Reproducibility of Atrial Fibrosis Assessment Using CMR Imaging and an Open Source Platform. JACC. Cardiovascular imaging Sim, I., Razeghi, O., Karim, R., Chubb, H., Whitaker, J., O'Neill, L., Mukherjee, R. K., Roney, C. H., Razavi, R., Wright, M., O'Neill, M., Niederer, S., Williams, S. E. 2019
View details for DOI 10.1016/j.jcmg.2019.03.027

View details for PubMedID 31202748
Modeling Left Atrial Flow, Energy, Blood Heating Distribution in Response to Catheter Ablation Therapy FRONTIERS IN PHYSIOLOGY Dillon-Murphy, D., Marlevi, D., Ruijsink, B., Qureshi, A., Chubb, H., Kerfoot, E., O'Neill, M., Nordsleffen, D., Aslanidi, O., de Vecchi, A. 2018; 9
View details for DOI 10.3389/fphys.2018.01757

View details for Web of Science ID 000453417500001
Mind the gap: Quantification of incomplete ablation patterns after pulmonary vein isolation using minimum path search. Medical image analysis Nunez-Garcia, M., Camara, O., O'Neill, M. D., Razavi, R., Chubb, H., Butakoff, C. 2018; 51: 1?12
Abstract

Pulmonary vein isolation (PVI) is a common procedure for the treatment of atrial fibrillation (AF) since the initial trigger for AF frequently originates in the pulmonary veins. A successful isolation produces a continuous lesion (scar) completely encircling the veins that stops activation waves from propagating to the atrial body. Unfortunately, the encircling lesion is often incomplete, becoming a combination of scar and gaps of healthy tissue. These gaps are potential causes of AF recurrence, which requires a redo of the isolation procedure. Late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) is a non-invasive method that may also be used to detect gaps, but it is currently a time-consuming process, prone to high inter-observer variability. In this paper, we present a method to semi-automatically identify and quantify ablation gaps. Gap quantification is performed through minimum path search in a graph where every node is a scar patch and the edges are the geodesic distances between patches. We propose the Relative Gap Measure (RGM) to estimate the percentage of gap around a vein, which is defined as the ratio of the overall gap length and the total length of the path that encircles the vein. Additionally, an advanced version of the RGM has been developed to integrate gap quantification estimates from different scar segmentation techniques into a single figure-of-merit. Population-based statistical and regional analysis of gap distribution was performed using a standardised parcellation of the left atrium. We have evaluated our method on synthetic and clinical data from 50 AF patients who underwent PVI with radiofrequency ablation. The population-based analysis concluded that the left superior PV is more prone to lesion gaps while the left inferior PV tends to have less gaps (p?
View details for PubMedID 30347332
The Value of Ablation Parameter Indices for Predicting Mature Atrial Scar Formation in Humans: An In Vivo Assessment using Cardiac Magnetic Resonance Imaging. Journal of cardiovascular electrophysiology Chubb, H., Lal, K., Kiedrowicz, R., Karim, R., Williams, S. E., Harrison, J., Whitaker, J., Wright, M., Razavi, R., O'Neill, M. 2018
Abstract

INTRODUCTION: The VisiTag module (CARTO3) provides an objective assessment of radiofrequency (RF) ablation parameters. This study aimed to determine the predictive value and optimal VisiTag threshold settings for prediction of gaps in mature atrial scar, as assessed non-invasively using cardiac magnetic resonance (CMR) imaging.METHODS: 24 subjects (11 paroxysmal AF) underwent first-time RF ablation with operators blinded to VisiTag data. 3D LGE CMR scans were performed at 3 months (1.3x1.3x4mm3 ). A survey of UK operators defined standard VisiTag settings ('Force' 8g, 'Time' 10seconds, 'Percentage Time' 50%, 'Range' 3mm, 'Impedance' and 'Temperature' 'off'). Each ablation procedure was exported 27 times, varying single VisiTag parameters from default values. The presence of gaps in VisiTag markers (18 sectors) was assessed for each export and compared to gaps in CMR enhancement.RESULTS: At default settings, VisiTag gaps were specific (97.5%) but less sensitive (50.4%) for CMR gaps. Sensitivity improved at higher thresholds (89.2% at 20g, 85.6% at 30sec, 88.5% Impedance 10Omega, 92.8% Temperature 42�C), but with lower positive predictive value (42.3%, 42.7%, 41.1% and 37.7%, respectively, versus 90.9% at baseline). 'Force' thresholds demonstrated stable PPV from 2-8g (p=0.24), but a rapid fall at forces >10g. Binomial logistic regression model explained 41.7% of gaps (chi2(4)=148, p<0.0001), correctly classifying 82% of cases (specificity 94.9%, sensitivity 56.8%).CONCLUSION: Gaps in VisiTags predict gaps in CMR LGE enhancement with high specificity at default settings. Sensitivity may be improved using more stringent thresholds, but at the potential cost of unnecessary ablation, particularly when a force >10g is stipulated. This article is protected by copyright. All rights reserved.

View details for PubMedID 30255652
Epicardial electroanatomical mapping, radiofrequency ablation, and lesion imaging in the porcine left ventricle under real-time magnetic resonance imaging guidance-an in vivo feasibility study EUROPACE Mukherjee, R. K., Roujot, S., Chubb, H., Harrison, J., Williams, S., Whitaker, J., O'Neill, L., Silberbauer, J., Neji, R., Schneider, R., Pohl, T., Lloyd, T., O'Neill, M., Razavi, R. 2018; 20: F254?F262
View details for DOI 10.1093/europace/eux341

View details for Web of Science ID 000450396600018
MR-guided Cardiac Interventions. Topics in magnetic resonance imaging : TMRI Pushparajah, K., Chubb, H., Razavi, R. 2018; 27 (3): 115?28
Abstract

Diagnostic and interventional cardiac catheterization is routinely used in the diagnosis and treatment of congenital heart disease. There are well-established concerns regarding the risk of radiation exposure to patients and staff, particularly in children given the cumulative effects of repeat exposure. Magnetic resonance imaging (MRI) offers the advantage of being able to provide better soft tissue visualization, tissue characterization, and quantification of ventricular volumes and vascular flow. Initial work using MRI catheterization employed fusion of x-ray and MRI techniques, with x-ray fluoroscopy to guide catheter placement and subsequent MRI assessment for anatomical and hemodynamic assessment. Image overlay of 3D previously acquired MRI datasets with live fluoroscopic imaging has also been used to guide catheter procedures.Hybrid x-ray and MRI-guided catheterization paved the way for clinical application and validation of this technique in the assessment of pulmonary vascular resistance and pharmacological stress studies. Purely MRI-guided catheterization also proved possible with passive catheter tracking. First-in-man MRI-guided cardiac catheter interventions were possible due to the development of MRI-compatible guidewires, but halted due to guidewire limitations.More recent developments in passive and active catheter tracking have led to improved visualization of catheters for MRI-guided catheterization. Improvements in hardware and software have also increased image quality and scanning times with better interactive tools for the operator in the MRI catheter suite to navigate through the anatomy as required in real time. This has expanded to MRI-guided electrophysiology studies and radiofrequency ablation in humans. Animal studies show promise for the utility of MRI-guided interventional catheterization. Ongoing investment and development of MRI-compatible guidewires will pave the way for MRI-guided diagnostic and interventional catheterization coming into the mainstream.

View details for PubMedID 29870464
The optimization of late gadolinium enhancement cardiac magnetic resonance imaging of post-ablation atrial scar: a cross-over study Journal of Cardiovascular Magnetic Resonance Chubb, H., Aziz, s., Karim, R., Sohns, C., Razeghi, O., Williams, S. E., Whitaker, J., Harrison, J., Chiribiri, A., Schaeffter, T., Wright, M., O'Neill, M., Razavi, R. 2018: 30
Abstract

Cardiovascular magnetic resonance (CMR) imaging may be used to visualize post-ablation atrial scar (PAAS), and three-dimensional late gadolinium enhancement (3D LGE) is the most widely employed technique for imaging of chronic scar. Detection of PAAS provides a unique non-invasive insight into the effects of the ablation and may help guide further ablation procedures. However, there is evidence that PAAS is often not detected by CMR, implying a significant sensitivity problem, and imaging parameters vary between leading centres. Therefore, there is a need to establish the optimal imaging parameters to detect PAAS.Forty subjects undergoing their first pulmonary vein isolation procedure for AF had detailed CMR assessment of atrial scar: one scan pre-ablation, and two scans post-ablation at 3 months (separated by 48�h). Each scan session included ECG- and respiratory-navigated 3D LGE acquisition at 10, 20 and 30�min post injection of a gadolinium-based contrast agent (GBCA). The first post-procedural scan was performed on a 1.5�T scanner with standard acquisition parameters, including double dose (0.2�mmol/kg) Gadovist and 4�mm slice thickness. Ten patients subsequently underwent identical scan as controls, and the other 30 underwent imaging with a reduced, single, dose GBCA (n?=?10), half slice thickness (n?=?10) or on a 3�T scanner (n?=?10). Apparent signal-to-noise (aSNR), contrast-to-noise (aCNR) and imaging quality (Likert Scale, 3 independent observers) were assessed. PAAS location and area (%PAAS scar) were assessed following manual segmentation. Atrial shells with standardised %PAAS at each timepoint were then compared to ablation lesion locations to assess quality of scar delineation.A total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. Likert scale of imaging quality had high interobserver and intraobserver intraclass correlation coefficients (0.89 and 0.96 respectively), and showed lower overall imaging quality on 3�T and at half-slice thickness. aCNR, and quality of scar delineation increased significantly with time. aCNR was higher with reduced, single, dose of GBCA (p?=?0.005).3D LGE CMR atrial scar imaging, as assessed qualitatively and quantitatively, improves with time from GBCA administration, with some indices continuing to improve from 20 to 30�min. Imaging should be performed at least 20�min post-GBCA injection, and a single dose of contrast should be considered.Trial registry- United Kingdom National Research Ethics Service 08/H0802/68 - 30th September 2008.

View details for DOI 10.1186/s12968-018-0449-8

View details for PubMedCentralID PMC5932811
Arrhythmias in Childhood and Patients with Congenital Heart Disease The ESC Textbook of Cardiovascular Medicine Chubb, H., Lowe, M. Oxford University Press. 2018; 3rd
Voltage and pace-capture mapping of linear ablation lesions overestimates chronic ablation gap size. 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 O'Neill, L., Harrison, J., Chubb, H., Whitaker, J., Mukherjee, R. K., Bloch, L. �., Andersen, N. P., Dam, H., Jensen, H. K., Niederer, S., Wright, M., O'Neill, M., Williams, S. E. 2018
Abstract

Conducting gaps in lesion sets are a major reason for failure of ablation procedures. Voltage mapping and pace-capture have been proposed for intra-procedural identification of gaps. We aimed to compare gap size measured acutely and chronically post-ablation to macroscopic gap size in a porcine model.Intercaval linear ablation was performed in eight G�ttingen minipigs with a deliberate gap of ?5?mm left in the ablation line. Gap size was measured by interpolating ablation contact force values between ablation tags and thresholding at a low force cut-off of 5?g. Bipolar voltage mapping and pace-capture mapping along the length of the line were performed immediately, and at 2?months, post-ablation. Animals were euthanized and gap sizes were measured macroscopically. Voltage thresholds to define scar were determined by receiver operating characteristic analysis as <0.56?mV (acutely) and <0.62?mV (chronically). Taking the macroscopic gap size as gold standard, error in gap measurements were determined for voltage, pace-capture, and ablation contact force maps. All modalities overestimated chronic gap size, by 1.4 � 2.0?mm (ablation contact force map), 5.1 � 3.4?mm (pace-capture), and 9.5 � 3.8?mm (voltage mapping). Error on ablation contact force map gap measurements were significantly less than for voltage mapping (P?=?0.003, Tukey's multiple comparisons test). Chronically, voltage mapping and pace-capture mapping overestimated macroscopic gap size by 11.9 � 3.7 and 9.8 � 3.5?mm, respectively.Bipolar voltage and pace-capture mapping overestimate the size of chronic gap formation in linear ablation lesions. The most accurate estimation of chronic gap size was achieved by analysis of catheter-myocardium contact force during ablation.

View details for PubMedID 29701778
Lesion Index-Guided Ablation Facilitates Continuous, Transmural, and Durable Lesions in a Porcine Recovery Model. Circulation. Arrhythmia and electrophysiology Whitaker, J., Fish, J., Harrison, J., Chubb, H., Williams, S. E., Fastl, T., Corrado, C., Van Zaen, J., Gibbs, J., O'Neill, L., Mukherjee, R., Rittey, D., Thorsten, J., Donskoy, E., Sohal, M., Rajani, R., Niederer, S., Wright, M., O'Neill, M. D. 2018; 11 (4): e005892
Abstract

The Lesion Index (LSI) is a proprietary algorithm from Abbott Medical combining contact force, radiofrequency application duration, and radiofrequency current. It can be displayed during ablation with the TactiCath contact force catheter. The LSI Index was designed to provide real-time lesion formation feedback and is hypothesized to estimate the lesion diameter.Before ablation, animals underwent cardiac computed tomography to assess atrial tissue thickness. Ablation lines (n=2-3 per animal) were created in the right atrium of 7 G�ttingen mini pigs with point lesions (25 W). Within each line of ablation, the catheter tip was moved a prescribed distance (D/mm) according to 1 of 3 strategies: D=LSI+0 mm; D=LSI+2 mm; or D=LSI+4 mm. Two weeks after ablation, serial sections of targeted atrial tissue were examined histologically to identify gaps in transmural ablation. LSI-guided lines had a lower incidence of histological gaps (4 gaps in 69 catheter moves, 5.8%) than LSI+2 mm lines (7 gaps in 33 catheter moves, 21.2%) and LSI+4 mm lines (15 gaps in 23 catheter moves, 65.2%, P<0.05 versus D=LSI). ?LSI was calculated retrospectively as the distance between 2 adjacent lesions above the mean LSI of the 2 lesions. ?LSI values of ?1.5 were associated with no gaps in transmural ablation.In this model of chronic atrial ablation, delivery of uninterrupted transmural linear lesions may be facilitated by using LSI to guide catheter movement. When ?LSI between adjacent lesions is ?1.5 mm, no gaps in atrial linear lesions should be expected.

View details for DOI 10.1161/CIRCEP.117.005892

View details for PubMedID 29654131
Voltage and pace-capture mapping of linear ablation lesions overestimates chronic ablation gap size Europace O'Neill, L., Harrison, J., Chubb, H., Mukherjee, R. K., Bloch, L. �., Andersen, N. P., Dam, H., Jensen, H. K., Niederer, S., Wright, M., O'Neill, M., Williams, S. E. 2018: euy062
View details for DOI 10.1093/europace/euy062
Optimization of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Chubb, H., Aziz, S., Karim, R., Sohns, C., Razeghi, O., Williams, S. E., Whitaker, J., Harrison, J., Chiribiri, A., Schaeffter, T., Wright, M., O'Neill, M., Razavi, R. 2018; 20 (1): 30
Abstract

Cardiovascular magnetic resonance (CMR) imaging may be used to visualize post-ablation atrial scar (PAAS), and three-dimensional late gadolinium enhancement (3D LGE) is the most widely employed technique for imaging of chronic scar. Detection of PAAS provides a unique non-invasive insight into the effects of the ablation and may help guide further ablation procedures. However, there is evidence that PAAS is often not detected by CMR, implying a significant sensitivity problem, and imaging parameters vary between leading centres. Therefore, there is a need to establish the optimal imaging parameters to detect PAAS.Forty subjects undergoing their first pulmonary vein isolation procedure for AF had detailed CMR assessment of atrial scar: one scan pre-ablation, and two scans post-ablation at 3 months (separated by 48�h). Each scan session included ECG- and respiratory-navigated 3D LGE acquisition at 10, 20 and 30�min post injection of a gadolinium-based contrast agent (GBCA). The first post-procedural scan was performed on a 1.5�T scanner with standard acquisition parameters, including double dose (0.2�mmol/kg) Gadovist and 4�mm slice thickness. Ten patients subsequently underwent identical scan as controls, and the other 30 underwent imaging with a reduced, single, dose GBCA (n?=?10), half slice thickness (n?=?10) or on a 3�T scanner (n?=?10). Apparent signal-to-noise (aSNR), contrast-to-noise (aCNR) and imaging quality (Likert Scale, 3 independent observers) were assessed. PAAS location and area (%PAAS scar) were assessed following manual segmentation. Atrial shells with standardised %PAAS at each timepoint were then compared to ablation lesion locations to assess quality of scar delineation.A total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. Likert scale of imaging quality had high interobserver and intraobserver intraclass correlation coefficients (0.89 and 0.96 respectively), and showed lower overall imaging quality on 3�T and at half-slice thickness. aCNR, and quality of scar delineation increased significantly with time. aCNR was higher with reduced, single, dose of GBCA (p?=?0.005).3D LGE CMR atrial scar imaging, as assessed qualitatively and quantitatively, improves with time from GBCA administration, with some indices continuing to improve from 20 to 30�min. Imaging should be performed at least 20�min post-GBCA injection, and a single dose of contrast should be considered.Trial registry- United Kingdom National Research Ethics Service 08/H0802/68 - 30th September 2008.

View details for PubMedID 29720202

View details for PubMedCentralID PMC5932811
Modeling Left Atrial Flow, Energy, Blood Heating Distribution in Response to Catheter Ablation Therapy. Frontiers in physiology Dillon-Murphy, D., Marlevi, D., Ruijsink, B., Qureshi, A., Chubb, H., Kerfoot, E., O'Neill, M., Nordsletten, D., Aslanidi, O., de Vecchi, A. 2018; 9: 1757
Abstract

Introduction: Atrial fibrillation (AF) is a widespread cardiac arrhythmia that commonly affects the left atrium (LA), causing it to quiver instead of contracting effectively. This behavior is triggered by abnormal electrical impulses at a specific site in the atrial wall. Catheter ablation (CA) treatment consists of isolating this driver site by burning the surrounding tissue to restore sinus rhythm (SR). However, evidence suggests that CA can concur to the formation of blood clots by promoting coagulation near the heat source and in regions with low flow velocity and blood stagnation. Methods: A patient-specific modeling workflow was created and applied to simulate thermal-fluid dynamics in two patients pre- and post-CA. Each model was personalized based on pre- and post-CA imaging datasets. The wall motion and anatomy were derived from SSFP Cine MRI data, while the trans-valvular flow was based on Doppler ultrasound data. The temperature distribution in the blood was modeled using a modified Pennes bioheat equation implemented in a finite-element based Navier-Stokes solver. Blood particles were also classified based on their residence time in the LA using a particle-tracking algorithm. Results: SR simulations showed multiple short-lived vortices with an average blood velocity of 0.2-0.22 m/s. In contrast, AF patients presented a slower vortex and stagnant flow in the LA appendage, with the average blood velocity reduced to 0.08-0.14 m/s. Restoration of SR also increased the blood kinetic energy and the viscous dissipation due to the presence of multiple vortices. Particle tracking showed a dramatic decrease in the percentage of blood remaining in the LA for longer than one cycle after CA (65.9 vs. 43.3% in patient A and 62.2 vs. 54.8% in patient B). Maximum temperatures of 76� and 58�C were observed when CA was performed near the appendage and in a pulmonary vein, respectively. Conclusion: This computational study presents novel models to elucidate relations between catheter temperature, patient-specific atrial anatomy and blood velocity, and predict how they change from SR to AF. The models can quantify blood flow in critical regions, including residence times and temperature distribution for different catheter positions, providing a basis for quantifying stroke risks.

View details for PubMedID 30618785

View details for PubMedCentralID PMC6302108
Real-time MRI guidance of cardiac interventions. Journal of magnetic resonance imaging : JMRI Campbell-Washburn, A. E., Tavallaei, M. A., Pop, M., Grant, E. K., Chubb, H., Rhode, K., Wright, G. A. 2017
Abstract

Cardiac magnetic resonance imaging (MRI) is appealing to guide complex cardiac procedures because it is ionizing radiation-free and offers flexible soft-tissue contrast. Interventional cardiac MR promises to improve existing procedures and enable new ones for complex arrhythmias, as well as congenital and structural heart disease. Guiding invasive procedures demands faster image acquisition, reconstruction and analysis, as well as intuitive intraprocedural display of imaging data. Standard cardiac MR techniques such as 3D anatomical imaging, cardiac function and flow, parameter mapping, and late-gadolinium enhancement can be used to gather valuable clinical data at various procedural stages. Rapid intraprocedural image analysis can extract and highlight critical information about interventional targets and outcomes. In some cases, real-time interactive imaging is used to provide a continuous stream of images displayed to interventionalists for dynamic device navigation. Alternatively, devices are navigated relative to a roadmap of major cardiac structures generated through fast segmentation and registration. Interventional devices can be visualized and tracked throughout a procedure with specialized imaging methods. In a clinical setting, advanced imaging must be integrated with other clinical tools and patient data. In order to perform these complex procedures, interventional cardiac MR relies on customized equipment, such as interactive imaging environments, in-room image display, audio communication, hemodynamic monitoring and recording systems, and electroanatomical mapping and ablation systems. Operating in this sophisticated environment requires coordination and planning. This review provides an overview of the imaging technology used in MRI-guided cardiac interventions. Specifically, this review outlines clinical targets, standard image acquisition and analysis tools, and the integration of these tools into clinical workflow.1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:935-950.

View details for DOI 10.1002/jmri.25749

View details for PubMedID 28493526

View details for PubMedCentralID PMC5675556
Novel MRI Technique Enables Non-Invasive Measurement of Atrial Wall Thickness. IEEE transactions on medical imaging Varela, M., Morgan, R., Theron, A., Dillon-Murphy, D., Chubb, H., Whitaker, J., Henningsson, M., Aljabar, P., Schaeffter, T., Kolbitsch, C., Aslanidi, O. V. 2017
Abstract

Knowledge of atrial wall thickness (AWT) has the potential to provide important information for patient stratification and the planning of interventions in atrial arrhythmias. To date, information about AWT has only been acquired in post-mortem or poor-contrast computed tomography (CT) studies, providing limited coverage and highly variable estimates of AWT. We present a novel contrast agent-free MRI sequence for imaging AWT and use it to create personalized AWT maps and a biatrial atlas. A novel black-blood phase-sensitive inversion recovery protocol was used to image ten volunteers and, as proof of concept, two atrial fibrillation patients. Both atria were manually segmented to create subject-specific AWT maps using an average of nearest neighbors approach. These were then registered non-linearly to generate an AWT atlas. AWT was 2.4 � 0.7 and 2.7 � 0.7 mm in the left and right atria, respectively, in good agreement with post-mortem and CT data, where available. AWT was 2.6 � 0.7 mm in the left atrium of a patient without structural heart disease, similar to that of volunteers. In a patient with structural heart disease, the AWT was increased to 3.1 � 1.3 mm. We successfully designed an MRI protocol to non-invasively measure AWT and create the first whole-atria AWT atlas. The atlas can be used as a reference to study alterations in thickness caused by atrial pathology. The protocol can be used to acquire personalized AWT maps in a clinical setting and assist in the treatment of atrial arrhythmias.

View details for DOI 10.1109/TMI.2017.2671839

View details for PubMedID 28422654

View details for PubMedCentralID PMC5549842
Local activation time sampling density for atrial tachycardia contact mapping: how much is enough? Europace Williams, S. E., Harrison, J. L., Chubb, H., Whitaker, J., Kiedrowicz, R., Rinaldi, C. A., Cooklin, M., Wright, M., Niederer, S., O'Neill, M. D. 2017
Abstract

Local activation time (LAT) mapping forms the cornerstone of atrial tachycardia diagnosis. Although anatomic and positional accuracy of electroanatomic mapping (EAM) systems have been validated, the effect of electrode sampling density on LAT map reconstruction is not known. Here, we study the effect of chamber geometry and activation complexity on optimal LAT sampling density using a combined in silico and in vivo approach.In vivo 21 atrial tachycardia maps were studied in three groups: (1) focal activation, (2) macro-re-entry, and (3) localized re-entry. In silico activation was simulated on a 4�4cm atrial monolayer, sampled randomly at 0.25-10 points/cm2 and used to re-interpolate LAT maps. Activation patterns were studied in the geometrically simple porcine right atrium (RA) and complex human left atrium (LA). Activation complexity was introduced into the porcine RA by incomplete inter-caval linear ablation. In all cases, optimal sampling density was defined as the highest density resulting in minimal further error reduction in the re-interpolated maps. Optimal sampling densities for LA tachycardias were 0.67?�?0.17�points/cm2 (focal activation), 1.05?�?0.32�points/cm2 (macro-re-entry) and 1.23?�?0.26�points/cm2 (localized re-entry), P?=?0.0031. Increasing activation complexity was associated with increased optimal sampling density both in silico (focal activation 1.09?�?0.14�points/cm2; re-entry 1.44?�?0.49�points/cm2; spiral-wave 1.50?�?0.34�points/cm2, P?
View details for DOI 10.1093/europace/eux037

View details for PubMedID 28379525
Do we finally have the A to Z of Z scores? Circ Cardiovasc Imaging Simpson, J., Chubb, H. 2017: e007191
View details for DOI 10.1161/CIRCIMAGING.117.007191
Development, Preclinical Validation, and�Clinical Translation of a Cardiac Magnetic Resonance - Electrophysiology System With�Active Catheter Tracking for�Ablation of�Cardiac Arrhythmia. JACC. Clinical electrophysiology Chubb, H., Harrison, J. L., Weiss, S., Krueger, S., Koken, P., Bloch, L. �., Kim, W. Y., Stenzel, G. S., Wedan, S. R., Weisz, J. L., Gill, J., Schaeffter, T., O'Neill, M. D., Razavi, R. S. 2017; 3 (2): 89?103
Abstract

This study sought to develop an actively tracked cardiac magnetic resonance-guided electrophysiology (CMR-EP) system and perform first-in-human clinical ablation procedures.CMR-EP offers high-resolution anatomy, arrhythmia substrate, and ablation lesion visualization in the absence of ionizing radiation. Implementation of active tracking, where catheter position is continuously transmitted in a manner analogous to electroanatomic mapping (EAM), is crucial for CMR-EP to take the step from theoretical technology to practical clinical tool.The setup integrated a clinical 1.5-T scanner, an EP recording and ablation system, and a real-time image guidance platform with components undergoing ex�vivo validation. The full system was assessed using a preclinical study (5 pigs), including mapping and ablation with histological validation. For the clinical study, 10 human subjects with typical atrial flutter (age 62 � 15 years) underwent MR-guided cavotricuspid isthmus (CTI) ablation.The components of the CMR-EP system were safe (magnetically induced torque, radiofrequency heating) and effective in the CMR environment (location precision). Targeted radiofrequency ablation was performed in all animals and 9 (90%) humans. Seven patients had CTI ablation completed using CMR guidance alone; 2 patients required completion under fluoroscopy, with 2 late flutter recurrences. Acute and chronic CMR imaging demonstrated efficacious lesion formation, verified with histology in animals. Anatomic shape of the CTI was an independent predictor of procedural success.CMR-EP using active catheter tracking is safe and feasible. The CMR-EP setup provides an effective�workflow and has the potential to change the way in which ablation procedures may be performed.

View details for PubMedID 29759398
Do We Finally Have the A to Z of Z Scores? Circulation. Cardiovascular imaging Simpson, J. M., Chubb, H. 2017; 10 (11)
View details for PubMedID 29138233
Computational evaluation of radiofrequency catheter ablation settings for variable atrial tissue depth and blood flow conditions Computing in Cardiology Dillon-Murphy, D., Nordsletten, D., Soor, N., Chubb, H., O'Neill, M., de Vecchi, A., Aslandi, O. 2017; 44: 1-4
View details for DOI 10.22489/CinC.2017.212-082
Arrhythmia in Congenital Heart Disease - A Current Perspective European Journal of Arrhythmia and Electrophysiology O'Neill, L., Chubb, H., O'Neill, M. 2017
View details for DOI 10.17925/EIAE.2016.02.01.22
Standardized unfold mapping: a technique to permit left atrial regional data display and analysis. Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing Williams, S. E., Tobon-Gomez, C., Zuluaga, M. A., Chubb, H., Butakoff, C., Karim, R., Ahmed, E., Camara, O., Rhode, K. S. 2017; 50 (1): 125?31
Abstract

Left atrial arrhythmia substrate assessment can involve multiple imaging and electrical modalities, but visual analysis of data on 3D surfaces is time-consuming and suffers from limited reproducibility. Unfold maps (e.g., the left ventricular bull's eye plot) allow 2D visualization, facilitate multimodal data representation, and provide a common reference space for inter-subject comparison. The aim of this work is to develop a method for automatic representation of multimodal information on a left atrial standardized unfold map (LA-SUM).The LA-SUM technique was developed and validated using 18 electroanatomic mapping (EAM) LA geometries before being applied to ten cardiac magnetic resonance/EAM paired geometries. The LA-SUM was defined as an unfold template of an average LA mesh, and registration of clinical data to this mesh facilitated creation of new LA-SUMs by surface parameterization.The LA-SUM represents 24 LA regions on a flattened surface. Intra-observer variability of LA-SUMs for both EAM and CMR datasets was minimal; root-mean square difference of 0.008��0.010 and 0.007��0.005�ms (local activation time maps), 0.068��0.063�gs (force-time integral maps), and 0.031��0.026 (CMR LGE signal intensity maps). Following validation, LA-SUMs were used for automatic quantification of post-ablation scar formation using CMR imaging, demonstrating a weak but significant relationship between ablation force-time integral and scar coverage (R 2�=�0.18, P�<�0.0001).The proposed LA-SUM displays an integrated unfold map for multimodal information. The method is applicable to any LA surface, including those derived from imaging and EAM systems. The LA-SUM would facilitate standardization of future research studies involving segmental analysis of the LA.

View details for PubMedID 28884216

View details for PubMedCentralID PMC5633640
Myocardial Deformation Measured by 3-Dimensional Speckle Tracking in Children and Adolescents With Systemic Arterial Hypertension. Hypertension (Dallas, Tex. : 1979) Navarini, S., Bellsham-Revell, H., Chubb, H., Gu, H., Sinha, M. D., Simpson, J. M. 2017; 70 (6): 1142?47
Abstract

Systemic arterial hypertension predisposes children to cardiovascular risk in childhood and adult life. Despite extensive study of left ventricular (LV) hypertrophy, detailed 3-dimensional strain analysis of cardiac function in hypertensive children has not been reported. The aim of this study was to evaluate LV mechanics (strain, twist, and torsion) in young patients with hypertension compared with a healthy control group and assess factors associated with functional measurements. Sixty-three patients (26 hypertension and 37 normotensive) were enrolled (mean age, 14.3 and 11.4 years; 54% men and 41% men, respectively). All children underwent clinical evaluation and echocardiographic examination, including 3-dimensional strain. There was no difference in LV volumes and ejection fraction between the groups. Myocardial deformation was significantly reduced in those with hypertension compared with controls. For hypertensive and normotensive groups, respectively, global longitudinal strain was -15.1�2.3 versus -18.5�1.9 (P<0.0001), global circumferential strain -15.2�3 versus -19.9�3.1 (<0.0001), global radial strain +44.0�11.3 versus 63.4�10.5 (P<0.0001), and global 3-dimensional strain -26.1�3.8 versus -31.5�3.8 (P<0.0001). Basal clockwise rotation, apical counterclockwise rotation, twist, and torsion were not significantly different. After multivariate regression analyses blood pressure, body mass index and LV mass maintained a significant relationship with measures of LV strain. Similar ventricular volumes and ejection fraction were observed in hypertensive and normotensive children, but children with hypertension had significantly lower strain indices. Whether reduced strain might predict future cardiovascular risk merits further longitudinal study.

View details for PubMedID 29084877
Intra-Atrial Conduction Delay Revealed by Multisite Incremental Atrial Pacing is an Independent Marker of Remodeling in Human Atrial Fibrillation. JACC. Clinical electrophysiology Williams, S. E., Linton, N. W., Harrison, J., Chubb, H., Whitaker, J., Gill, J., Rinaldi, C. A., Razavi, R., Niederer, S., Wright, M., O'Neill, M. 2017; 3 (9): 1006?17
Abstract

This study sought to characterize direction-dependent and coupling interval-dependent changes in left atrial conduction and electrogram morphology in uniformly classified patients with paroxysmal atrial fibrillation (AF) and normal bipolar voltage mapping.Although AF classifications are based on arrhythmia duration, the clinical course, and treatment response vary between patients within these groups. Electrophysiological mechanisms responsible for this variability are incompletely described.Intracardiac contact mapping during incremental atrial pacing was used to characterize atrial conduction, activation dispersion, and electrogram morphology in 15 consecutive paroxysmal AF patients undergoing first-time pulmonary vein isolation. Outcome measures were vulnerability to AF induction at electrophysiology study and 2-year follow-up for arrhythmia recurrence.Conduction delay showed a bimodal distribution, occurring at either long (high right atrium pacing: 326�� 13�ms; coronary sinus pacing: 319 � 16 ms) or short (high right atrium pacing: 275 � 11 ms; coronary sinus pacing: 271�� 11�ms) extrastimulus coupling intervals. Arrhythmia recurrence was found only in patients with conduction delay at long extrastimulus coupling intervals, and patients with inducible AF were characterized by increased activation dispersion (activation dispersion time: 168 � 29 ms vs. 136 � 11 ms). Electrogram voltage and duration varied throughout the left atrium, between patients, and with pacing site but were not correlated with AF vulnerability or arrhythmia recurrence.Within the single clinical entity of paroxysmal AF, incremental atrial pacing identified a spectrum of activation patterns correlating with AF vulnerability and arrhythmia recurrence. In contrast, electrogram morphology (characterized by electrogram voltage and duration) was highly variable and not associated with AF vulnerability or recurrence. An improved understanding of the electrical phenotype in AF could lead to improved mechanistic classifications.

View details for PubMedID 28966986

View details for PubMedCentralID PMC5612260
Epicardial electroanatomical mapping, radiofrequency ablation, and lesion imaging in the porcine left ventricle under real-time magnetic resonance imaging guidance-an in vivo feasibility study. 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 Mukherjee, R. K., Roujol, S., Chubb, H., Harrison, J., Williams, S., Whitaker, J., O'Neill, L., Silberbauer, J., Neji, R., Schneider, R., Pohl, T., Lloyd, T., O'Neill, M., Razavi, R. 2017
Abstract

Magnetic resonance imaging (MRI) is the gold standard for defining myocardial substrate in 3D and can be used to guide ventricular tachycardia ablation. We describe the feasibility of using a prototype magnetic resonance-guided electrophysiology (MR-EP) system in a pre-clinical model to perform real-time MRI-guided epicardial mapping, ablation, and lesion imaging with active catheter tracking.Experiments were performed in vivo in pigs (n?=?6) using an MR-EP guidance system research prototype (Siemens Healthcare) with an irrigated ablation catheter (Vision-MR, Imricor) and a dedicated electrophysiology recording system (Advantage-MR, Imricor). Following epicardial access, local activation and voltage maps were acquired, and targeted radiofrequency (RF) ablation lesions were delivered. Ablation lesions were visualized in real time during RF delivery using MR-thermometry and dosimetry. Hyper-acute and acute assessment of ablation lesions was also performed using native T1 mapping and late-gadolinium enhancement (LGE), respectively. High-quality epicardial bipolar electrograms were recorded with a signal-to-noise ratio of greater than 10:1 for a signal of 1.5?mV. During epicardial ablation, localized temperature elevation could be visualized with a maximum temperature rise of 35?�C within 2?mm of the catheter tip relative to remote myocardium. Decreased native T1 times were observed (882?�?107?ms) in the lesion core 3-5?min after lesion delivery and relative location of lesions matched well to LGE. There was a good correlation between ablation lesion site on the iCMR platform and autopsy.The MR-EP system was able to successfully acquire epicardial voltage and activation maps in swine, deliver, and visualize ablation lesions, demonstrating feasibility for intraprocedural guidance and real-time assessment of ablation injury.

View details for PubMedID 29294008
Cardiac Electrophysiology Under MRI Guidance: an Emerging Technology. Arrhythmia & electrophysiology review Chubb, H., Williams, S. E., Whitaker, J., Harrison, J. L., Razavi, R., O'Neill, M. 2017; 6 (2): 85?93
Abstract

MR-guidance of electrophysiological (EP) procedures offers the potential for enhanced arrhythmia substrate assessment, improved procedural guidance and real-time assessment of ablation lesion formation. Accurate device tracking techniques, using both active and passive methods, have been developed to offer an interface similar to electroanatomic mapping platforms, and MR-compatible EP equipment continues to be developed. Progress to clinical implementation of these technically complex fields has been relatively slow over the last 10 years, but recent developments have led to successful clinical experience. However, further advances, particularly in harnessing the full imaging potential of CMR, are required to realise the mainstream adoption of this powerful guidance modality.

View details for PubMedID 28845235

View details for PubMedCentralID PMC5517375
The role of myocardial wall thickness in atrial arrhythmogenesis EUROPACE Whitaker, J., Rajani, R., Chubb, H., Gabrawi, M., Varela, M., Wright, M., Niederer, S., O'Neill, M. D. 2016; 18 (12): 1758-1772
Abstract

Changes in the structure and electrical behaviour of the left atrium are known to occur with conditions that predispose to atrial fibrillation (AF) and in response to prolonged periods of AF. We review the evidence that changes in myocardial thickness in the left atrium are an important part of this pathological remodelling process. Autopsy studies have demonstrated changes in the thickness of the atrial wall between patients with different clinical histories. Comparison of the reported tissue dimensions from pathological studies provides an indication of normal ranges for atrial wall thickness. Imaging studies, most commonly done using cardiac computed tomography, have demonstrated that these changes may be identified non-invasively. Experimental evidence using isolated tissue preparations, animal models of AF, and computer simulations proves that the three-dimensional tissue structure will be an important determinant of the electrical behaviour of atrial tissue. Accurately identifying the thickness of the atrial may have an important role in the non-invasive assessment of atrial structure. In combination with atrial tissue characterization, a comprehensive assessment of the atrial dimensions may allow prediction of atrial electrophysiological behaviour and in the future, guide radiofrequency delivery in regions based on their tissue thickness.

View details for DOI 10.1093/europace/euw014

View details for Web of Science ID 000392745700003

View details for PubMedID 27247007
Slow Conduction in the Border Zones of Patchy Fibrosis Stabilizes the Drivers for Atrial Fibrillation: Insights from Multi-Scale Human Atrial Modeling FRONTIERS IN PHYSIOLOGY Morgan, R., Colman, M. A., Chubb, H., Seemann, G., Aslanidi, O. V. 2016; 7
Abstract

Introduction: The genesis of atrial fibrillation (AF) and success of AF ablation therapy have been strongly linked with atrial fibrosis. Increasing evidence suggests that patient-specific distributions of fibrosis may determine the locations of electrical drivers (rotors) sustaining AF, but the underlying mechanisms are incompletely understood. This study aims to elucidate a missing mechanistic link between patient-specific fibrosis distributions and AF drivers. Methods: 3D atrial models integrated human atrial geometry, rule-based fiber orientation, region-specific electrophysiology, and AF-induced ionic remodeling. A novel detailed model for an atrial fibroblast was developed, and effects of myocyte-fibroblast (M-F) coupling were explored at single-cell, 1D tissue and 3D atria levels. Left atrial LGE MRI datasets from 3 chronic AF patients were segmented to provide the patient-specific distributions of fibrosis. The data was non-linearly registered and mapped to the 3D atria model. Six distinctive fibrosis levels (0-healthy tissue, 5-dense fibrosis) were identified based on LGE MRI intensity and modeled as progressively increasing M-F coupling and decreasing atrial tissue coupling. Uniform 3D atrial model with diffuse (level 2) fibrosis was considered for comparison. Results: In single cells and tissue, the largest effect of atrial M-F coupling was on the myocyte resting membrane potential, leading to partial inactivation of sodium current and reduction of conduction velocity (CV). In the 3D atria, further to the M-F coupling, effects of fibrosis on tissue coupling greatly reduce atrial CV. AF was initiated by fast pacing in each 3D model with either uniform or patient-specific fibrosis. High variation in fibrosis distributions between the models resulted in varying complexity of AF, with several drivers emerging. In the diffuse fibrosis models, waves randomly meandered through the atria, whereas in each the patient-specific models, rotors stabilized in fibrotic regions. The rotors propagated slowly around the border zones of patchy fibrosis (levels 3-4), failing to spread into inner areas of dense fibrosis. Conclusion: Rotors stabilize in the border zones of patchy fibrosis in 3D atria, where slow conduction enable the development of circuits within relatively small regions. Our results can provide a mechanistic explanation for the clinical efficacy of ablation around fibrotic regions.

View details for DOI 10.3359/fphys.2016.00474

View details for Web of Science ID 000386093900001

View details for PubMedID 27826248

View details for PubMedCentralID PMC5079097
Implantable cardioverter-defibrillators in congenital heart disease. Herzschrittmachertherapie & Elektrophysiologie Chubb, H., Rosenthal, E. 2016; 27 (2): 95-103
Abstract

Implantable cardioverter-defibrillators (ICD) have an important role in reducing sudden cardiac death in patients with congenital heart disease (CHD); however, the benefit of ICDs needs to be weighed up against both short-term and long-term adverse effects, which are difficult to evaluate in the heterogeneous CHD population. A tailored approach, taking into account risk stratification and patient-specific factors, is needed to select the most appropriate strategy. This review discusses primary and secondary ICD indications, implantation approaches and long-term follow-up. Recent publications have shed light on the concerns of system longevity, lead extractions, inappropriate shocks and impact on the quality of life. All of these factors require consideration prior to commitment to this long-term treatment strategy.

View details for DOI 10.1007/s00399-016-0437-3

View details for PubMedID 27250725

View details for PubMedCentralID PMC4894938
Personalized models of human atrial electrophysiology derived from endocardial electrograms. IEEE transactions on bio-medical engineering Corrado, C., Whitaker, J., Chubb, H., Williams, S., Wright, M., Gill, J., O'Neill, M., Niederer, S. 2016
Abstract

Computational models represent a novel framework for understanding the mechanisms behind atrial fibrillation (AF) and offer a pathway for personalizing and optimizing treatment. The characterization of local electrophysiological properties across the atria during procedures remains a challenge. The aim of this work is to characterize the regional properties of the human atrium from multielectrode catheter measurements.We propose a novel method that characterizes regional electrophysiology properties by fitting parameters of an ionic model to conduction velocity and effective refractory period restitution curves obtained by a s1-s2 pacing protocol applied through a multielectrode catheter. Using an in-silico dataset we demonstrate that the fitting method can constrain parameters with a mean error of 21.9 � 16.1% and can replicate conduction velocity and effective refractory curves not used in the original fitting with a relative error of 4.4 � 6.9%.We demonstrate this parameter estimation approach on five clinical datasets recorded from AF patients. Recordings and parametrization took approx. 5 and 6 min, respectively. Models fitted restitution curves with an error of ~ 5% and identify a unique parameter set. Tissue properties were predicted using a two-dimensional atrial tissue sheet model. Spiral wave stability in each case was predicted using tissue simulations, identifying distinct stable (2/5), meandering and breaking up (2/5), and unstable self-terminating (1/5) spiral tip patterns for different cases.We have developed and demonstrated a robust and rapid approach for personalizing local ionic models from a clinically tractable.

View details for DOI 10.1109/TBME.2016.2574619

View details for PubMedID 28207381
Pacing and Defibrillators in Complex Congenital Heart Disease. Arrhythmia & electrophysiology review Chubb, H., O'Neill, M., Rosenthal, E. 2016; 5 (1): 57-64
Abstract

Device therapy in the complex congenital heart disease (CHD) population is a challenging field. There is a myriad of devices available, but none designed specifically for the CHD patient group, and a scarcity of prospective studies to guide best practice. Baseline cardiac anatomy, prior surgical and interventional procedures, existing tachyarrhythmias and the requirement for future intervention all play a substantial role in decision making. For both pacing systems and implantable cardioverter defibrillators, numerous factors impact on the merits of system location (endovascular versus non-endovascular), lead positioning, device selection and device programming. For those with Fontan circulation and following the atrial switch procedure there are also very specific considerations regarding access and potential complications. This review discusses the published guidelines, device indications and the best available evidence for guidance of device implantation in the complex CHD population.

View details for DOI 10.15420/aer.2016.2.3

View details for PubMedID 27403295

View details for PubMedCentralID PMC4939312
Twenty-Seven Years Experience With Transvenous Pacemaker Implantation in Children Weighing < 10 kg CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Konta, L., Chubb, M. H., Bostock, J., Rogers, J., Rosenthal, E. 2016; 9 (2)
Abstract

Epicardial pacemaker implantation is the favored approach in children weighing <10 kg in many units. The high incidence of premature failure and fractures with earlier epicardial leads led our unit to undertake transvenous pacemaker implantation in neonates and infants from 1987. To date there have been no long-term follow-up reports of what is for many a controversial strategy.Between 1987 and 2003, 37 neonates and infants-median age 6.7 months (1 day to 3 years) and median weight 4.6 kg (2.7-10 kg)-had a permanent transvenous pacing system implanted. Pacing leads were placed into the right ventricular apex/outflow tract through a subclavian vein puncture with a redundant loop in the atrium. Three patients were lost to follow-up, 4 patients died from complications of cardiac surgery, and 2 patients had their system removed. At long-term follow-up in 28 patients at a median of 17.2 (range, 11.2-27.4) years, 10 patients have a single chamber ventricular pacemaker, 14 a dual chamber pacemaker, 3 a biventricular pacemaker, and 1 has a single chamber implantable cardioverter defibrillator. Subclavian vein patency was assessed in 26 patients. The overall subclavian vein occlusion rate was 10 of 13 (77%) <5 kg and 2 of 13 (15%) >5 kg during long-term follow-up. After a median of 14.3 (range, 13.4-17.6) years of pacing, 7 patients continue with their original lead.Transvenous pacing in infants <10 kg results in encouraging short- and long-term clinical outcomes. Subclavian vein occlusion remains an important complication, occurring predominantly in those weighing <5 kg.

View details for DOI 10.1161/CIRCEP.115.003422

View details for Web of Science ID 000370344000001

View details for PubMedID 26857908
Look Before You Leap Optimizing Outcomes of Atrial Fibrillation Ablation JACC-CARDIOVASCULAR IMAGING O'Neill, M. D., Chubb, H. 2016; 9 (2): 149-151
View details for DOI 10.1016/j.jcmg.2015.10.014

View details for Web of Science ID 000370304900009

View details for PubMedID 26777219
Predicting spiral wave stability by personalised electrophysiology models Predicting spiral wave stability by personalized electrophysiology models Corrado, C., Whitaker, J., Chubb, H., Williams, S., Gill, J., O'Neill, M., Neiderer, S. 2016
View details for DOI 10.23919/CIC.2016.7868721
Fetal aortic valve stenosis: a critique of case selection criteria for fetal intervention PRENATAL DIAGNOSIS Hunter, L. E., Chubb, H., Miller, O., Sharland, G., Simpson, J. M. 2015; 35 (12): 1176-1181
Abstract

Selection of fetuses with aortic stenosis (AS) for prenatal intervention has been influenced by published scoring systems. This study aimed to test these scoring systems by retrospective application to consecutive cases of fetal AS.Retrospective analysis of the echocardiographic findings of 31 consecutive fetuses with AS evaluated at a tertiary fetal cardiology centre. Published 'eHLHS' scores and threshold scores were applied to the group and compared to postnatal management, in terms of biventricular repair versus single ventricle palliation.Thirty-one fetuses were identified with AS, and eHLHS was identified in 17 at the initial echocardiogram. No fetus with a full eHLHS score (3/3 or 4/4) achieved a biventricular repair. Three fetuses had a favourable threshold score (?4), one of whom had a successful biventricular outcome. Seven fetuses had an unfavourable threshold score (<4) and underwent a univentricular pathway.The eHLHS score is a reliable predictor for the progression to HLHS at term. The score identifies those who would achieve a biventricular repair postnatally without prenatal intervention. A minority of fetuses with favourable threshold scores may achieve a biventricular repair postnatally without prenatal intervention, but eHLHS and an unfavourable threshold score (<4) predict a single ventricle pathway postnatally.

View details for DOI 10.1002/pd.4661

View details for Web of Science ID 000368442000003

View details for PubMedID 26223202
The Effect of Contact Force in Atrial Radiofrequency Ablation: Electroanatomical, CMR and Histological Assessment in a Chronic Porcine Model Journal of the American College of Cardiology: Clinical Electrophysiology Williams, S., Harrison, J., Chubb, H., Bloch, L., Andersen, N., Dam, H., Karim, R., Whitaker, J., Gill, J., Cooklin, M., Rinaldi, A., Rhode, K., Wright, M., Schaeffter, T., Kim, W., Jensen, H., Razavi, R., O'Neill, M. 2015; 1 (5): 421-431
View details for DOI 10.1016/j.jacep.2015.06.003
The Effect of Contact Force in Atrial Radiofrequency�Ablation: Electroanatomical, Cardiovascular Magnetic Resonance, and�Histological Assessment in a Chronic�Porcine Model. JACC. Clinical electrophysiology Williams, S. E., Harrison, J., Chubb, H., Bloch, L. �., Andersen, N. P., Dam, H., Karim, R., Whitaker, J., Gill, J., Cooklin, M., Rinaldi, C. A., Rhode, K., Wright, M., Schaeffter, T., Kim, W. Y., Jensen, H., Razavi, R., O'Neill, M. D. 2015; 1 (5): 421?31
Abstract

This study sought to determine the effect of contact force (CF) on atrial lesion size, quality, and transmurality by using a chronic porcine model of radiofrequency ablation.CF is a major determinant of ventricular lesion formation, but uncertainty exists regarding the most appropriate CF parameters to safely achieve permanent, transmural lesions in the atria.Intercaval linear ablation (30 W, 42�C, 17 ml/min irrigation) was performed in 8 G�ttingen minipigs by using a force-sensing catheter with CF >20 g (high force) or�<10 g (low force) at alternate ends of the line, separated by an intentional gap. Voltage mapping and cardiovascular magnetic resonance (CMR) imaging were performed pre-ablation, immediately after ablation, and at 2 months' post-procedure. Lesions were sectioned orthogonal to the axis of ablation to assess transmurality.Mean CF was 22.6 � 11.4 g and 7.8 � 4.0 g in the high and low CF regions. Acute tissue edema was greater with high CF, both caudally (7.0 mm vs. 4.6 mm; p�= 0.016) and cranially (6.9 mm vs. 4.6 mm; p�= 0.038). There was no difference in chronic lesion size (voltage mapping) or volume (late gadolinium enhancement CMR) between high and low CF regions. There was no difference in scar density (assessed by low-voltage criteria and late gadolinium enhancement signal intensity) or histological transmurality between high and low CF regions.Although high CF (>20 g) resulted in more acute tissue edema than low CF (<10 g), chronically there�was no difference in lesion size, quality, or transmurality. Appropriate CF targets for atrial ablation may be lower�than previously thought.

View details for PubMedID 29759471
Personalization of Atrial Electrophysiology Models from Decapolar Catheter Measurements Corrado, C., Williams, S., Chubb, H., O'Neill, M., Niederer, S. A., VanAssen, H., Bovendeerd, P., Delhaas, T. SPRINGER-VERLAG BERLIN. 2015: 21?28
View details for DOI 10.1007/978-3-319-20309-6_3

View details for Web of Science ID 000364538500003
Left Atrial Segmentation from 3D Respiratory- and ECG-gated Magnetic Resonance Angiography Karim, R., Chubb, H., Staab, W., Aziz, S., Housden, R., O'Neill, M., Razavi, R., Rhode, K., VanAssen, H., Bovendeerd, P., Delhaas, T. SPRINGER-VERLAG BERLIN. 2015: 155?63
View details for DOI 10.1007/978-3-319-20309-6_18

View details for Web of Science ID 000364538500018
Advances in CMR of Post-ablation Atrial Injury Curr Cardiovasc Imaging Rep Harrison, J. L., Whitaker, J., Chubb, H., Williams, S., Wright, M., Razavi, R., O'Neill, M. 2015; 8 (22): 22-28
View details for DOI 10.1007/s12410-015-9336-y
Pathophysiology and Management of Arrhythmias Associated with Atrial Septal Defect and Patent Foramen Ovale. Arrhythmia & electrophysiology review Chubb, H., Whitaker, J., Williams, S. E., Head, C. E., Chung, N. A., Wright, M. J., O'Neill, M. 2014; 3 (3): 168-172
Abstract

Atrial septal defects (ASDs) are among the most common of congenital heart defects and are frequently associated with atrial arrhythmias. Atrial and ventricular geometrical remodelling secondary to the intracardiac shunt promotes evolution of the electrical substrate, predisposing the patient to atrial fibrillation and other arrhythmias. Closure of an ASD reduces the immediate and long-term prevalence of atrial arrhythmias, but the evidence suggests that patients remain at an increased long-term risk in comparison with the normal population. The closure technique itself and its timing impacts future arrhythmia risk profile while subsequent transseptal access following surgical or device closure is complicated. Newer techniques combined with increased experience will help to alleviate some of the difficulties associated with optimal management of arrhythmias in these patients.

View details for DOI 10.15420/aer.2014.3.3.168

View details for PubMedID 26835086

View details for PubMedCentralID PMC4711537
Correlation of Echocardiographic and Angiographic Measurements of the Pulmonary Valve Annulus in Pulmonary Stenosis CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Chubb, H., Ward, A., Worme, A., Qureshi, S. A., Rosenthal, E., Krasemann, T. 2014; 84 (2): 192-196
Abstract

The pulmonary valve (PV) annulus is routinely measured angiographically in PV stenosis prior to balloon dilation. We sought to establish whether this radiation exposure is justified, or whether echocardiographic measurements prior to the procedure are sufficient to guide balloon selection.Previous studies have found a strong correlation between echocardiographic and angiographic measurements of the PV annulus. However, error of measurement and its implication for procedural practice has not been explored.A total of 90 procedures in 84 patients were analyzed, at a median age 7.6 months (range 1 day to 14.2 years). The contemporaneous echocardiographic and angiographic measurements were recorded, and the original echocardiograms were re-measured in the 72 available cases by two independent reviewers.There was a good correlation between the two measurement methods (R(2) ?=?0.87). However, the echocardiographic PV measurements were smaller on average, with a significant variation in that discrepancy (mean ratio 0.941 (�0.16)). There was no significant reduction in error if extreme measurements (PV annulus z-score <-3) were excluded (P?=?0.09), or if the reviewed echocardiographic measurements were used (P?=?0.58).There is an unacceptable discrepancy between the measurement techniques: 95% of patients are predicted to have an echocardiographic measurement error between -37% and +26%. Therefore, there is no correction factor that could be employed to allow safe selection of balloon size, and balloon pulmonary valvoplasty without angiographic PV measurement cannot be advocated.

View details for DOI 10.1002/ccd.25450

View details for Web of Science ID 000340554200005

View details for PubMedID 24549968
Brugada Phenocopy with a Flecainide Overdose: A Pharmacological Dose Effect? JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Chubb, H., Cooklin, M., Rosenthal, E. 2014; 25 (5): 547-548
View details for DOI 10.1111/jce.12335

View details for Web of Science ID 000335003500018

View details for PubMedID 24303843
Quantification of Error in the Calculation of Z Scores in Neonates JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Chubb, H., Simpson, J. M. 2014; 27 (4): 449-451
View details for DOI 10.1016/j.echo.2014.01.010

View details for Web of Science ID 000334315700013

View details for PubMedID 24680605
"About Brugada Phenocopy": Brugada Phenocopy with a Flecainide Overdose: A Pharmacological Dose Effect? JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Chubb, H., Cooklin, M., Rosenthal, E. 2014; 25 (3): E1
View details for DOI 10.1111/jce.12373

View details for Web of Science ID 000332161400001

View details for PubMedID 24451005
Highlights of the 6th World Congress in Paediatric Cardiology and Cardiac Surgery. Future cardiology Hayes, N., Chubb, H., Narayan, S., Qureshi, S. 2013; 9 (3): 309-312
Abstract

The 6th World Congress in Paediatric Cardiology and Cardiac Surgery took place in Cape Town, South Africa, in February 2013. The congress is the largest meeting in the field of congenital and paediatric heart disease and attracts a global audience of specialists with the aim of sharing the latest multidisciplinary developments in research and clinical practice. The congress was commended as a huge success and this article aims to give a general flavor of the diverse meeting through detailing a few specific highlights from the various tracks.

View details for DOI 10.2217/fca.13.25

View details for PubMedID 23668735
Systolic and Diastolic Ventricular Function Assessed by Tissue Doppler Imaging in Children with Chronic Kidney Disease ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Simpson, J. M., Rawlins, D., Mathur, S., Chubb, H., Sinha, M. D. 2013; 30 (3): 331-337
Abstract

Chronic kidney disease (CKD) is associated with elevated cardiovascular risk even during childhood. Tissue Doppler is a sensitive technique for the assessment of ventricular dysfunction with relatively little data available in children with CKD. We report a prospective cross-sectional echocardiographic study at a tertiary center. Forty-nine patients with median (range) age 11.2 years (6.9-17.9), weight 39.6 kg (23.6-99.7) and height 146 cm (122-185). Thirty-one patients were male. Median duration of follow-up for CKD was 7.1 years (range 0.13-16.9). Patients were in CKD stage 3 (n = 37) or 4 (n = 12). Mitral valve E-wave, A-wave, and E/A ratio showed mean (SD) z-scores of 0.08 (0.93), 0.12 (0.82) and -0.13 (0.84), respectively. Tissue Doppler imaging (TDI) at the lateral mitral valve annulus showed e', a', s', and E/e' z-scores mean (SD) -1.10 (0.76), -0.29 (0.92), -1.2 (0.7), and 0.86 (1.1), respectively. There was a significant negative correlation of e' and s' z-score with patient age. E/e' ratio correlated positively with patient age. Blood pressure, left ventricular mass, and relative wall thickness did not correlate with tissue Doppler measurements. The e' and s' velocities correlated significantly with each other, suggesting an interaction of systolic and diastolic dysfunction. Children with CKD may have abnormalities of systolic and diastolic ventricular function on TDI, which are not evident on blood pool Doppler. The tissue Doppler results are consistent with worsening ventricular function in older patients.

View details for DOI 10.1111/echo.12015

View details for Web of Science ID 000315694000025

View details for PubMedID 23167909
Pulmonary Atresia with Intact Ventricular Septum Paediatric Cardiovascular Medicine Chubb, H., Daubeney, P. edited by Moller, J., Hoffman, J. Wiley-Blackwell. 2012; 2nd
Clinical scenario: an unusual case of heart failure. Timely topics in medicine. Cardiovascular diseases Chubb, H., Kaski, D. 2007; 11: E9-?
View details for PubMedID 17473900
Heart and heart-lung transplantation for idiopathic restrictive cardiomyopathy in children HEART Fenton, M. J., Chubb, H., McMahon, A. M., Rees, P., ELLIOTT, M. J., Burch, M. 2006; 92 (1): 85-89
Abstract

To review the outcome of cardiac transplantation for restrictive cardiomyopathy (RCM) in children and to assess the ability of new strategies to modulate the effects of high pulmonary vascular resistance.Retrospective case note analysis of all patients receiving a transplant for RCM.18 children with RCM referred for transplantation assessment to Great Ormond Street Hospital, London.Eight boys and 10 girls were referred for assessment. Median age at presentation was 5.0 (mean (SD) 6.1 (4.0)) years. Fourteen orthotopic and two heterotopic transplantations were performed and two patients were referred for heart-lung transplantation. Mean duration from diagnosis to transplantation was 3.3 (3.0) years. Three patients with haemodynamic decompensation before transplantation had increased morbidity in the postoperative period. No patients died while awaiting a transplant. Three patients died in the first year after transplantation, one within 30 days. Five patients received pre-transplantation prostacyclin for a mean duration of 57 (18) days. Transpulmonary gradient was reduced in four of the patients. Mean transpulmonary gradient was 27 (9.8) mm Hg before and 17 (6.7) mm Hg after treatment with prostacyclin (p < 0.05).Most children with RCM require transplantation within four years of diagnosis. Referral for transplantation assessment should precede haemodynamic decompensation. Increase of pulmonary vascular resistance is a variable problem but can be modulated with pre-transplantation prostacyclin. With these strategies, orthotopic transplantation is possible in the majority of cases.

View details for DOI 10.1136/hrt.2004.049502

View details for Web of Science ID 000234061000031

View details for PubMedID 16365357

View details for PubMedCentralID PMC1860993

Henry Chubb

Clinical Assistant Professor, Pediatrics - Cardiology

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