CAP Profiles

Bio

Bio

Dr. Maron is Director of Preventive Cardiology. He is board certified in internal medicine, cardiovascular disease, and clinical lipidology. He was an undergraduate at Stanford, received his medical degree from University of Southern California, and completed his residency in internal medicine at UCLA. He completed a cardiology fellowship and a research fellowship in cardiovascular disease epidemiology and prevention at Stanford University as a Robert Wood Johnson Clinical Scholar. He was on the faculty at Vanderbilt for 20 years before returning to Stanford in 2014. His research is focused on primary and secondary prevention of coronary artery disease. He has extensive experience in multicenter clinical trials, serving as a member of the Executive Committee and Chair of the Optimal Medical Therapy Committee for the VA-funded COURAGE trial, and now as the PI and Co-Chair of the NHLBI-funded ISCHEMIA trial, and Co-Chair of the NHLBI-funded ISCHEMIA-CKD trial.

Clinical Focus

  • Cardiovascular Disease
  • Coronary Artery Disease
  • Angina
  • High Cholesterol
  • Familial Hypercholesterolemia
  • Coronary Artery Calcification
  • Primary Prevention
  • Secondary Prevention
  • Chest Pain

Academic Appointments

Professional Education

  • Fellowship: Stanford University Cardiovascular Medicine Fellowship CA
  • Board Certification: American Board of Internal Medicine, Internal Medicine (1984)
  • Residency: Stanford University Hospital -Clinical Excellence Research Center CA
  • Medical Education: Univ Of So Ca - Los Angeles (1981) CA
  • Residency: UCLA Health Sciences CA
  • Internship: UCLA Health Sciences CA
  • Board Certification: American Board of Internal Medicine, Cardiovascular Disease (1991)

Contact

    Fax: (650) 725-1599
  • Cardiovascular Medicine Clinic 300 Pasteur Dr Rm A260 MC 5319 Stanford, CA 94305
    • Tel: (650) 723-6459
    Fax: (650) 724-1444

Links

Research & Scholarship

Current Research and Scholarly Interests

Dr. Maron is the Co-Chair and Principal Investigator of the ISCHEMIA trial, and Co-Chair of the ISCHEMIA-CKD trial. These large, international, NIH-funded studies will determine whether an initial invasive strategy of cardiac catheterization and revascularization plus optimal medical therapy will reduce cardiovascular events in patients with and without chronic kidney disease and at least moderate ischemia compared to an initial conservative strategy of optimal medical therapy alone.

Clinical Trials

  • Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) in Participants With Hyperlipoproteinemia(a) and Cardiovascular Disease Recruiting

    This is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 681257 and to assess the efficacy of different doses and dosing regimens of ISIS 681257 for reduction of plasma Lipoprotein(a) [Lp(a)] levels in participants with hyperlipoproteinemia(a) and established cardiovascular disease (CVD).

    View full details

Teaching

2017-18 Courses

Publications

All Publications

  • Digital Health Interventions for Cardiac Rehabilitation: Systematic Literature Review. Journal of medical Internet research Wongvibulsin, S., Habeos, E. E., Huynh, P. P., Xun, H., Shan, R., Porosnicu Rodriguez, K. A., Wang, J., Gandapur, Y. K., Osuji, N., Shah, L. M., Spaulding, E. M., Hung, G., Knowles, K., Yang, W. E., Marvel, F. A., Levin, E., Maron, D. J., Gordon, N. F., Martin, S. S. 2021; 23 (2): e18773

    Abstract

    BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. Despite strong evidence supporting the benefits of cardiac rehabilitation (CR), over 80% of eligible patients do not participate in CR. Digital health technologies (ie, the delivery of care using the internet, wearable devices, and mobile apps) have the potential to address the challenges associated with traditional facility-based CR programs, but little is known about the comprehensiveness of these interventions to serve as digital approaches to CR. Overall, there is a lack of a systematic evaluation of the current literature on digital interventions for CR.OBJECTIVE: The objective of this systematic literature review is to provide an in-depth analysis of the potential of digital health technologies to address the challenges associated with traditional CR. Through this review, we aim to summarize the current literature on digital interventions for CR, identify the key components of CR that have been successfully addressed through digital interventions, and describe the gaps in research that need to be addressed for sustainable and scalable digital CR interventions.METHODS: Our strategy for identifying the primary literature pertaining to CR with digital solutions (defined as technology employed to deliver remote care beyond the use of the telephone) included a consultation with an expert in the field of digital CR and searches of the PubMed (MEDLINE), Embase, CINAHL, and Cochrane databases for original studies published from January 1990 to October 2018.RESULTS: Our search returned 31 eligible studies, of which 22 were randomized controlled trials. The reviewed CR interventions primarily targeted physical activity counseling (31/31, 100%), baseline assessment (30/31, 97%), and exercise training (27/31, 87%). The most commonly used modalities were smartphones or mobile devices (20/31, 65%), web-based portals (18/31, 58%), and email-SMS (11/31, 35%). Approximately one-third of the studies addressed the CR core components of nutrition counseling, psychological management, and weight management. In contrast, less than a third of the studies addressed other CR core components, including the management of lipids, diabetes, smoking cessation, and blood pressure.CONCLUSIONS: Digital technologies have the potential to increase access and participation in CR by mitigating the challenges associated with traditional, facility-based CR. However, previously evaluated interventions primarily focused on physical activity counseling and exercise training. Thus, further research is required with more comprehensive CR interventions and long-term follow-up to understand the clinical impact of digital interventions.

    View details for DOI 10.2196/18773

    View details for PubMedID 33555259

  • Coronary CT Angiography Followed by Invasive Angiography in Patients With Moderate or Severe Ischemia-Insights From the ISCHEMIA Trial. JACC. Cardiovascular imaging Mancini, G. B., Leipsic, J., Budoff, M. J., Hague, C. J., Min, J. K., Stevens, S. R., Reynolds, H. R., O'Brien, S. M., Shaw, L. J., Manjunath, C. N., Mavromatis, K., Demkow, M., Lopez-Sendon, J. L., Chernavskiy, A. M., Gosselin, G., Schuchlenz, H., Devlin, G. P., Chauhan, A., Bangalore, S., Hochman, J. S., Maron, D. J. 2021

    Abstract

    OBJECTIVES: This study aimed to examine the concordance of coronary computed tomographic angiography (CCTA) assessment of coronary anatomy and invasive coronary angiography (ICA) as the reference standard in patients enrolled in the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA).BACKGROUND: Performance of CCTA compared with ICA has not been assessed in patients with very high burdens of stress-induced ischemia and a high likelihood of anatomically significant coronary artery disease (CAD). A blinded CCTA was performed after enrollment to exclude patients with left main (LM) disease or no obstructive CAD before randomization to an initial conservative or invasive strategy, the latter guided by ICA and optimal revascularization.METHODS: Rates of concordance were calculated on a per-patient basis in patients randomized to the invasive strategy. Anatomic significance was defined as≥50% diameter stenosis (DS) for both modalities. Sensitivity analyses using a threshold of≥70% DS for CCTA or considering only CCTA images of good-to-excellent quality were performed.RESULTS: In 1,728 patients identified by CCTA as having no LM disease ≥50% and at least single-vessel CAD, ICA confirmed 97.1% without LM disease≥50%, 92.2% with at least single-vessel CAD and no LM disease≥50%, and only 4.9% without anatomically significant CAD. Results using a≥70% DS threshold or only CCTA of good-to-excellent quality showed similar overall performance.CONCLUSIONS: CCTA before randomization in ISCHEMIA demonstrated high concordance with subsequent ICA for identification of patients with angiographically significant disease without LM disease.

    View details for DOI 10.1016/j.jcmg.2020.11.012

    View details for PubMedID 33454249

  • Clinical and Quality of Life Outcomes With Chronic Total Occlusion: The ISCHEMIA CTO Substudy Bangalore, S., Mancini, G. B., Leipsic, J., Budoff, M. J., Xu, Y., Anthopolos, R., Dwivedi, A., Spertus, J., Jones, P., Mark, D. B., Hague, C., Min, J. K., Reynolds, H., Elghamaz, A., Nair, R., Mavromatis, K., Gosselin, G., Banerjee, S., Pejkov, H., Lindsay, S., Williams, D. O., Stone, G. W., O'Brien, S. M., Hochman, J. S., Maron, D. J. LIPPINCOTT WILLIAMS & WILKINS. 2020: E477–E478

    View details for Web of Science ID 000598973900032

  • Myocardial Infarction in the ISCHEMIA Trial: Impact of Different Definitions on Incidence, Prognosis, and Treatment Comparisons. Circulation Chaitman, B. R., Alexander, K. P., Cyr, D. D., Berger, J. S., Reynolds, H. R., Bangalore, S., Boden, W. E., Lopes, R. D., Demkow, M., Perna, G. P., Riezebos, R. K., McFalls, E. O., Banerjee, S., Bagai, A., Gosselin, G., O'Brien, S. M., Rockhold, F. W., Waters, D. D., Thygesen, K. A., Stone, G. W., White, H. D., Maron, D. J., Hochman, J. S., ISCHEMIA Research Group 2020

    Abstract

    Background: In ISCHEMIA, an initial invasive strategy did not significantly reduce rates of cardiovascular events or all-cause mortality compared with a conservative strategy in patients with stable ischemic heart disease and moderate/severe myocardial ischemia. The most frequent component of composite cardiovascular endpoints was myocardial infarction. Methods: ISCHEMIA prespecified that the primary and major secondary composite endpoints of the trial be analyzed using two MI definitions. For procedural MI, the primary MI definition used CK-MB as the preferred biomarker whereas the secondary definition used cardiac troponin. Procedural thresholds were >5 times URL for PCI and >10 times for CABG. Procedural MI definitions included (i) a category of elevated biomarker only events with much higher biomarker thresholds (ii) new ST segment depression of ≥ 1mm for the primary and ≥ 0.5 mm for the secondary definition and (iii) new coronary dissections ≥ NHLBI grade 3. We compared MI type, frequency, and prognosis by treatment assignment using both MI definitions. Results: Procedural MI's accounted for 20.1% of all MI events with the primary definition and 40.6% of all MI events with the secondary definition. Four-year MI rates in patients undergoing revascularization were more frequent with the invasive vs conservative strategy using the primary [2.7% vs. 1.1%; adjusted HR 2.98 (95% CI 1.87, 4.73)] and secondary [8.2% vs. 2.0%; adjusted HR 5.04 (95% CI 3.64, 6.97)] MI definitions. Type 1 MI's were less frequent with the invasive vs conservative strategy using the primary [3.40% vs. 6.89%; adjusted HR 0.53 (95% CI 0.41,0.69); p<0.0001], and secondary [3.48% vs 6.89%; adjusted HR 0.53 (95% CI 0.41, 0.69); p<0.0001] definitions. The risk of subsequent cardiovascular death was higher after a type 1 MI compared to no MI using the primary [adjusted HR 3.38 (95% CI 2.03,5.61); p<0.001] or secondary MI definition [adjusted HR 3.52 (2.11, 5.88); p<0.001]. Conclusions: In ISCHEMIA, type 1 MI events using the primary and secondary definitions during 5-year follow-up were more frequent with an initial conservative strategy and associated with subsequent cardiovascular death. Procedural MI rates were greater in the invasive strategy and using the secondary MI definition. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01471522.

    View details for DOI 10.1161/CIRCULATIONAHA.120.047987

    View details for PubMedID 33267610

  • Management of Coronary Disease in Patients with Advanced Kidney Disease Reply NEW ENGLAND JOURNAL OF MEDICINE Bangalore, S., Maron, D. J., Hochman, J. S. 2020; 383 (11): 1091–92

    View details for Web of Science ID 000571807800034

  • Invasive or Conservative Strategy for Stable Coronary Disease REPLY NEW ENGLAND JOURNAL OF MEDICINE Maron, D. J., Hochman, J. S. 2020; 383 (10)

    View details for Web of Science ID 000569841600028

  • Invasive or Conservative Strategy for Stable Coronary Disease. Reply. The New England journal of medicine Antman, E. M., Braunwald, E. 2020; 383 (10): e66

    View details for DOI 10.1056/NEJMc2024008

    View details for PubMedID 32877597

  • Nurse Practitioner-Directed Cardio-Diabetes Pilot Program JNP-JOURNAL FOR NURSE PRACTITIONERS Bryant, E., Janaszek, K., Nejedly, M., Li, E., Bouvier, M., Schroeder, K., Khandelwal, A., Lough, M. E., Lamendola, C., Reisenberg, A., Purewal, S., Maron, D. J. 2020; 16 (8): E123–E128

    View details for DOI 10.1016/j.nurpra.2020.05.009

    View details for Web of Science ID 000566686900008

  • Routine Revascularization versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials. Circulation Bangalore, S., Maron, D. J., Stone, G. W., Hochman, J. S. 2020

    Abstract

    Background: Revascularization is often performed in patients with stable ischemic heart disease (SIHD). However, whether revascularization reduces death and other cardiovascular outcomes is uncertain. Methods: We conducted PUBMED/EMBASE/CENTRAL searches for randomized trials comparing routine revascularization versus an initial conservative strategy in patients with SIHD. The primary outcome was death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), heart failure, stroke, unstable angina and freedom from angina. Trials were stratified by percent stent use and by percent statin use to evaluate outcomes in contemporary trials. Results: Fourteen RCTs that enrolled 14,877 patients followed up for a weighted mean of 4.5 years with 64,678 patient years of follow-up fulfilled our inclusion criteria. Most trials enrolled patients with preserved left ventricular systolic function, low symptom burden and excluded patients with left main disease. Revascularization compared with medical therapy alone was not associated with a reduced risk of death (RR=0.99, 95% CI 0.90-1.09). Trial sequential analysis showed that the cumulative z-curve crossed the futility boundary indicating firm evidence for lack of a 10% or greater reduction in death. Revascularization was associated with a reduced non-procedural MI (RR=0.76, 95% CI 0.67-0.85) but also with increased procedural MI (RR=2.48, 95% CI 1.86-3.31) with no difference in overall MI (RR=0.93, 95% CI 0.83-1.03). A significant reduction in unstable angina (RR=0.64, 95% CI 0.45-0.92) and increase in freedom from angina (RR=1.10, 95% CI 1.05-1.15) was also observed with revascularization. There were no treatment-related differences in the risk of heart failure or stroke. Conclusions: In patients with SIHD, routine revascularization was not associated with improved survival, but was associated with a lower risk of non-procedural MI and unstable angina with greater freedom from angina at the expense of higher rates of procedural MI. Longer-term follow-up of trials is needed to assess whether reduction in these non-fatal spontaneous events improves long-term survival.

    View details for DOI 10.1161/CIRCULATIONAHA.120.048194

    View details for PubMedID 32794407

  • Risk Prediction Tool for Assessing the Probability of Death or Myocardial Infarction in Patients With Stable Coronary Artery Disease. The American journal of cardiology Boden, W. E., Hartigan, P. M., Mancini, J., Teo, K. K., Chaitman, B. R., Maron, D. J., Kostuk, W. J., Hartigan, J. A., Dada, M., Spertus, J. A., Bates, E. R., Weintraub, W. S., COURAGE Trial Investigators 2020

    Abstract

    Several risk scores in acute coronary syndromes are available, but few models exist for stable coronary artery disease to guide decision-making and prognosis. A multivariate model was developed using 23 baseline candidate variables from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Therapy EvaluationTrial (n = 2,287 patients). Discrimination of the model was evaluated by the concordance c-index. The procedure was validated using 100 random half samples. We identified 9 independent predictors of death or myocardial infarction (MI) during a 5-year follow-up. The following predictors and points contributing to the risk score were: heart failure (3), number of diseased coronary arteries (1 for each vessel), diabetes (1), age (1 for each 15 years ≥ age 45), previous revascularization (1), current smoking (1), female (1), previous MI (1), and high-density lipoprotein cholesterol (1: 31 to 40 mg/dL; 2: <30 mg/dL). The risk tool had a potential range from 0 to 15, corresponding to 5-year event rates of 5.8% to 56%. C-indices ranged from 0.67 for the full data set to 0.62 for the validating subsamples. Respective observed versus predicted 5-year event rates for 3 predefined risk strata revealed: 30% had a low-risk score of 0 to 3 (9.3% vs 9.3%, or 1.9%/year); 59% had an intermediate-risk score of 4-6 (18.0% vs 18.1%, or 3.6%/year); and 11% had a high-risk score of 7-11 (36% vs 36.5%, or 7.2%/year). This stable coronary artery disease risk score permitted a prognostic assessment of 5-year probability of death or MI with an approximate 4-fold range in event rates from the lowest (9.3%) to the highest (36%) terciles, thus enabling better clinical practice decisions that allow physicians to tailor the intensity of treatment to the level of risk.

    View details for DOI 10.1016/j.amjcard.2020.05.046

    View details for PubMedID 32654755

  • The Project Baseline Health Study: a step towards a broader mission to map human health NPJ DIGITAL MEDICINE Arges, K., Assimes, T., Bajaj, V., Balu, S., Bashir, M. R., Beskow, L., Blanco, R., Califf, R., Campbell, P., Carin, L., Christian, V., Cousins, S., Das, M., Dockery, M., Douglas, P. S., Dunham, A., Eckstrand, J., Fleischmann, D., Ford, E., Fraulo, E., French, J., Gambhir, S. S., Ginsburg, G. S., Green, R. C., Haddad, F., Hernandez, A., Hernandez, J., Huang, E. S., Jaffe, G., King, D., Koweek, L. H., Langlotz, C., Liao, Y. J., Mahaffey, K. W., Marcom, K., Marks, W. J., Maron, D., McCabe, R., McCall, S., McCue, R., Mega, J., Miller, D., Muhlbaier, L. H., Munshi, R., Newby, L., Pak-Harvey, E., Patrick-Lake, B., Pencina, M., Peterson, E. D., Rodriguez, F., Shore, S., Shah, S., Shipes, S., Sledge, G., Spielman, S., Spitler, R., Schaack, T., Swamy, G., Willemink, M. J., Wong, C. A. 2020; 3 (1): 84

    Abstract

    The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.

    View details for DOI 10.1038/s41746-020-0290-y

    View details for Web of Science ID 000538242900001

    View details for PubMedID 32550652

    View details for PubMedCentralID PMC7275087

  • INCIDENTAL CORONARY ARTERY CALCIFICATION IN NON-GATED CT SCANS Sanders, M., Balla, S., Rodriguez, F., Patel, B., Eng, D., Khandwala, N., Sandhu, A., Maron, D. ELSEVIER SCIENCE INC. 2020: 1806

    View details for Web of Science ID 000522979101793

  • Cardiorespiratory Fitness, Body-Mass Index, and Markers of Insulin Resistance in Apparently Healthy Women and Men. The American journal of medicine Clarke, S. L., Reaven, G. M., Leonard, D., Barlow, C. E., Haskell, W. L., Willis, B. L., DeFina, L., Knowles, J. W., Maron, D. J. 2020

    Abstract

    BACKGROUND: Insulin resistance may be present in healthy adults and is associated poor health outcomes. Obesity is a risk factor for insulin resistance, but most obese adults do not have insulin resistance. Fitness may be protective, but the association between fitness, weight, and insulin resistance has not been studied in a large population of healthy adults.METHODS: A cross-sectional analysis of cardiorespiratory fitness, body-mass index, and markers of insulin resistance was performed. Study participants were enrolled at the Cooper Clinic (Dallas, Texas). The analysis included 19,263 women and 48,433 men with no history of diabetes or cardiovascular disease. Cardiorespiratory fitness was measured using exercise treadmill testing. Impaired fasting glucose (100-125 mg/dL) and elevated fasting triglycerides (≥150 mg/dL) were used as a markers of insulin resistance.RESULTS: Among normal weight individuals, poor fitness was associated with a 2.2 (1.4-3.6; p=0.001) fold higher odds of insulin resistance in women and a 2.8 (2.1-3.6; p<0.001) fold higher odds in men. The impact of fitness remained significant for overweight and obese individuals, with the highest risk group being the unfit obese. Among obese women, the odds ratio for insulin resistance was 11.0 (8.7-13.9; p<0.001) for fit and 20.3 (15.5-26.5; p<0.001) for unfit women. Among obese men, the odds ratio for insulin resistance was 7.4 (6.7-8.2; p<0.001) for fit and 12.9 (11.4-14.6; p<0.001) for unfit men.CONCLUSION: Independent of weight, poor fitness is associated with risk of insulin resistance. Obese individuals, particularly women, may benefit from the greatest absolute risk reduction by achieving moderate fitness.

    View details for DOI 10.1016/j.amjmed.2019.11.031

    View details for PubMedID 31926863

  • Management of Coronary Disease in Patients with Advanced Kidney Disease. The New England journal of medicine Bangalore, S., Maron, D. J., O'Brien, S. M., Fleg, J. L., Kretov, E. I., Briguori, C., Kaul, U., Reynolds, H. R., Mazurek, T., Sidhu, M. S., Berger, J. S., Mathew, R. O., Bockeria, O., Broderick, S., Pracon, R., Herzog, C. A., Huang, Z., Stone, G. W., Boden, W. E., Newman, J. D., Ali, Z. A., Mark, D. B., Spertus, J. A., Alexander, K. P., Chaitman, B. R., Chertow, G. M., Hochman, J. S. 2020

    Abstract

    Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease.We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03).Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

    View details for DOI 10.1056/NEJMoa1915925

    View details for PubMedID 32227756

  • Initial Invasive versus Conservative Management of Stable Ischemic Heart Disease Patients with a History of Heart Failure or Left Ventricular Dysfunction: Insights from the ISCHEMIA Trial. Circulation Lopes, R. D., Alexander, K. P., Stevens, S. R., Reynolds, H. R., Stone, G. W., Pina, I. L., Rockhold, F. W., Elghamaz, A., Lopez-Sendon, J. L., Farsky, P. S., Chernyavskiy, A. M., Diaz, A., Phaneuf, D., DeBelder, M. A., Ma, Y. T., Guzman, L. A., Khouri, M., Sionis, A., Hausenloy, D. J., Doerr, R., Selvanayagam, J. K., Maggioni, A. P., Hochman, J. S., Maron, D. J. 2020

    Abstract

    Background: It is unknown whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in patients with a history of heart failure (HF) or left ventricular dysfunction (LVD) when EF ≥35%, but <45%. Methods: Among 5179 participants randomized into the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA), all of whom had LVEF ≥35%, we compared cardiovascular outcomes by treatment strategy in those with a history of HF or LV dysfunction (HF/LVD) at baseline versus those without HF/LVD. Median followup was 3.2 years. Results: There were 398 (7.7%) participants with HF/LVD at baseline of whom 177 had HF/LVEF>45%, 28 had HF/LVEF 35-45% and 193 had LVEF 35-45% but no prior history of HF. HF/LVD was associated with more comorbidities at baseline, particularly prior myocardial infarction (MI), stroke and hypertension. Compared to those without HF/LVD, those with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal MI, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest; four-year cumulative incidence rate (22.7% vs. 13.8%), cardiovascular death or MI (19.7% vs. 12.3%), and all-cause death or HF (15.0% vs. 6.9%). Those with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% vs. 29.3%, difference in 4-year event rate -12.1%; 95% CI: -22.6, -1.6%), whereas those without HF/LVD did not (13.0% vs. 14.6%, difference in 4-year event rate -1.6%; 95% CI: -3.8%, 0.7%; p-interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and CV mortality when invasive versus conservative strategy associated outcomes were analyzed with LVEF as a continuous variable for those with and without prior HF. Conclusions: ISCHEMIA trial participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35-45%, an initial invasive approach was associated with a better event-free survival. This result should be considered hypothesis generating. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01471522.

    View details for DOI 10.1161/CIRCULATIONAHA.120.050304

    View details for PubMedID 32862662

  • Primary Prevention Trial Designs Using Coronary Imaging: A National Heart, Lung, and Blood Institute Workshop. JACC. Cardiovascular imaging Greenland, P., Michos, E. D., Redmond, N., Fine, L. J., Alexander, K. P., Ambrosius, W. T., Bibbins-Domingo, K., Blaha, M. J., Blankstein, R., Fortmann, S. P., Khera, A., Lloyd-Jones, D. M., Maron, D. J., Min, J. K., Muhlestein, J. B., Nasir, K., Sterling, M. R., Thanassoulis, G. 2020

    Abstract

    Coronary artery calcium (CAC) is considered a useful test for enhancing risk assessment in the primary prevention setting. Clinical trials are under consideration. The National Heart, Lung, and Blood Institute convened a multidisciplinary working group on August 26 to 27, 2019, in Bethesda, Maryland, to review available evidence and consider the appropriateness of conducting further research on coronary artery calcium (CAC) testing, or other coronary imaging studies, as a way of informing decisions for primary preventive treatments for cardiovascular disease. The working group concluded that additional evidence to support current guideline recommendations for use of CAC in middle-age adults is very likely to come from currently ongoing trials in that age group, and a new trial is not likely to be timely or cost effective. The current trials will not, however, address the role of CAC testing in younger adults or older adults, who are also not addressed in existing guidelines, nor will existing trials address the potential benefit of an opportunistic screening strategy made feasible by the application of artificial intelligence. Innovative trial designs for testing the value of CAC across the lifespan were strongly considered and represent important opportunities for additional research, particularly those that leverage existing trials or other real-world data streams including clinical computed tomography scans. Sex and racial/ethnic disparities in cardiovascular disease morbidity and mortality, and inclusion of diverse participants in future CAC trials, particularly those based in the United States, would enhance the potential impact of these studies.

    View details for DOI 10.1016/j.jcmg.2020.06.042

    View details for PubMedID 32950442

  • Management of Coronary Disease in Patients with Advanced Kidney Disease. Reply. The New England journal of medicine Bangalore, S., Maron, D. J., Hochman, J. S. 2020; 383 (11): 1091–92

    View details for DOI 10.1056/NEJMc2024023

    View details for PubMedID 32905690

  • Under-Reporting and Under-Representation of Racial/Ethnic Minorities in Major Atrial Fibrillation Clinical Trials. JACC. Clinical electrophysiology Sarraju, A., Maron, D. J., Rodriguez, F. 2020; 6 (6): 739–41

    View details for DOI 10.1016/j.jacep.2020.03.001

    View details for PubMedID 32553226

  • The Project Baseline Health Study: a step towards a broader mission to map human health. NPJ digital medicine Arges, K., Assimes, T., Bajaj, V., Balu, S., Bashir, M. R., Beskow, L., Blanco, R., Califf, R., Campbell, P., Carin, L., Christian, V., Cousins, S., Das, M., Dockery, M., Douglas, P. S., Dunham, A., Eckstrand, J., Fleischmann, D., Ford, E., Fraulo, E., French, J., Gambhir, S. S., Ginsburg, G. S., Green, R. C., Haddad, F., Hernandez, A., Hernandez, J., Huang, E. S., Jaffe, G., King, D., Koweek, L. H., Langlotz, C., Liao, Y. J., Mahaffey, K. W., Marcom, K., Marks, W. J., Maron, D., McCabe, R., McCall, S., McCue, R., Mega, J., Miller, D., Muhlbaier, L. H., Munshi, R., Newby, L. K., Pak-Harvey, E., Patrick-Lake, B., Pencina, M., Peterson, E. D., Rodriguez, F., Shore, S., Shah, S., Shipes, S., Sledge, G., Spielman, S., Spitler, R., Schaack, T., Swamy, G., Willemink, M. J., Wong, C. A. 2020; 3 (1): 84

    Abstract

    The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.

    View details for DOI 10.1038/s41746-020-0290-y

    View details for PubMedID 33597683

  • Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia: Secondary Analysis of the ISCHEMIA Randomized Clinical Trial. JAMA cardiology Reynolds, H. R., Shaw, L. J., Min, J. K., Spertus, J. A., Chaitman, B. R., Berman, D. S., Picard, M. H., Kwong, R. Y., Bairey-Merz, C. N., Cyr, D. D., Lopes, R. D., Lopez-Sendon, J. L., Held, C., Szwed, H., Senior, R., Gosselin, G., Nair, R. G., Elghamaz, A., Bockeria, O., Chen, J., Chernyavskiy, A. M., Bhargava, B., Newman, J. D., Hinic, S. B., Jaroch, J., Hoye, A., Berger, J., Boden, W. E., O'Brien, S. M., Maron, D. J., Hochman, J. S. 2020

    Abstract

    While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization.To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants.This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018.CCTA and angina assessment.Sex differences in stress test, CCTA findings, and symptom severity.Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76).Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease.ClinicalTrials.gov Identifier: NCT01471522.

    View details for DOI 10.1001/jamacardio.2020.0822

    View details for PubMedID 32227128

  • Health-Status Outcomes with Invasive or Conservative Care in Coronary Disease. The New England journal of medicine Spertus, J. A., Jones, P. G., Maron, D. J., O'Brien, S. M., Reynolds, H. R., Rosenberg, Y., Stone, G. W., Harrell, F. E., Boden, W. E., Weintraub, W. S., Baloch, K., Mavromatis, K., Diaz, A., Gosselin, G., Newman, J. D., Mavromichalis, S., Alexander, K. P., Cohen, D. J., Bangalore, S., Hochman, J. S., Mark, D. B. 2020

    Abstract

    In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients.We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency.At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina).In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

    View details for DOI 10.1056/NEJMoa1916370

    View details for PubMedID 32227753

  • Initial Invasive or Conservative Strategy for Stable Coronary Disease. The New England journal of medicine Maron, D. J., Hochman, J. S., Reynolds, H. R., Bangalore, S., O'Brien, S. M., Boden, W. E., Chaitman, B. R., Senior, R., López-Sendón, J., Alexander, K. P., Lopes, R. D., Shaw, L. J., Berger, J. S., Newman, J. D., Sidhu, M. S., Goodman, S. G., Ruzyllo, W., Gosselin, G., Maggioni, A. P., White, H. D., Bhargava, B., Min, J. K., Mancini, G. B., Berman, D. S., Picard, M. H., Kwong, R. Y., Ali, Z. A., Mark, D. B., Spertus, J. A., Krishnan, M. N., Elghamaz, A., Moorthy, N., Hueb, W. A., Demkow, M., Mavromatis, K., Bockeria, O., Peteiro, J., Miller, T. D., Szwed, H., Doerr, R., Keltai, M., Selvanayagam, J. B., Steg, P. G., Held, C., Kohsaka, S., Mavromichalis, S., Kirby, R., Jeffries, N. O., Harrell, F. E., Rockhold, F. W., Broderick, S., Ferguson, T. B., Williams, D. O., Harrington, R. A., Stone, G. W., Rosenberg, Y. 2020

    Abstract

    Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

    View details for DOI 10.1056/NEJMoa1915922

    View details for PubMedID 32227755

  • Health Status after Invasive or Conservative Care in Coronary and Advanced Kidney Disease. The New England journal of medicine Spertus, J. A., Jones, P. G., Maron, D. J., Mark, D. B., O'Brien, S. M., Fleg, J. L., Reynolds, H. R., Stone, G. W., Sidhu, M. S., Chaitman, B. R., Chertow, G. M., Hochman, J. S., Bangalore, S. 2020

    Abstract

    In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status.We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy.Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, -0.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, -2.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, -1.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, -2.2 to 3.4).Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy. (Funded by the National Heart, Lung, and Blood Institute; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

    View details for DOI 10.1056/NEJMoa1916374

    View details for PubMedID 32227754

  • Baseline Predictors of Low-Density Lipoprotein Cholesterol and Systolic Blood Pressure Goal Attainment After 1 Year in the ISCHEMIA Trial. Circulation. Cardiovascular quality and outcomes Newman, J. D., Alexander, K. P., Gu, X., O'Brien, S. M., Boden, W. E., Govindan, S. C., Senior, R., Moorthy, N., Rezende, P. C., Demkow, M., Lopez-Sendon, J. L., Bockeria, O., Pandit, N., Gosselin, G., Stone, P. H., Spertus, J. A., Stone, G. W., Fleg, J. L., Hochman, J. S., Maron, D. J. 2019; 12 (11): e006002

    Abstract

    BACKGROUND: Risk factor control is the cornerstone of managing stable ischemic heart disease but is often not achieved. Predictors of risk factor control in a randomized clinical trial have not been described.METHODS AND RESULTS: The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) randomized individuals with at least moderate inducible ischemia and obstructive coronary artery disease to an initial invasive or conservative strategy in addition to optimal medical therapy. The primary aim of this analysis was to determine predictors of meeting trial goals for LDL-C (low-density lipoprotein cholesterol, goal <70 mg/dL) or systolic blood pressure (SBP, goal <140 mmHg) at 1 year post-randomization. We included all randomized participants in the ISCHEMIA trial with baseline and 1-year LDL-C and SBP values by January 28, 2019. Among the 3984 ISCHEMIA participants (78% of 5179 randomized) with available data, 35% were at goal for LDL-C, and 65% were at goal for SBP at baseline. At 1 year, the percent at goal increased to 52% for LDL-C and 75% for SBP. Adjusted odds of 1-year LDL-C goal attainment were greater with older age (odds ratio [OR], 1.11 [95% CI, 1.03-1.20] per 10 years), lower baseline LDL-C (OR, 1.19 [95% CI, 1.17-1.22] per 10 mg/dL), high-intensity statin use (OR, 1.30 [95% CI, 1.12-1.51]), nonwhite race (OR, 1.32 [95% CI, 1.07-1.63]), and North American enrollment compared with other regions (OR, 1.32 [95% CI, 1.06-1.66]). Women were less likely than men to achieve 1-year LDL-C goal (OR, 0.68 [95% CI, 0.58-0.80]). Adjusted odds of 1-year SBP goal attainment were greater with lower baseline SBP (OR, 1.27 [95% CI, 1.22-1.33] per 10 mmHg) and with North American enrollment (OR, 1.35 [95% CI, 1.04-1.76]).CONCLUSIONS: In ISCHEMIA, older age, male sex, high-intensity statin use, lower baseline LDL-C, and North American location predicted 1-year LDL-C goal attainment, whereas lower baseline SBP and North American location predicted 1-year SBP goal attainment. Future studies should examine the effects of sex disparities, international practice patterns, and provider behavior on risk factor control.

    View details for DOI 10.1161/CIRCOUTCOMES.119.006002

    View details for PubMedID 31718297

  • Preventive Cardiology as a Subspecialty of Cardiovascular Medicine JACC Council Perspectives JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Shapiro, M. D., Maron, D. J., Morris, P. B., Kosiborod, M., Sandesara, P. B., Virani, S. S., Khera, A., Ballantyne, C. M., Baum, S. J., Sperling, L. S., Bhatt, D. L., Fazio, S. 2019; 74 (15): 1928–42

    View details for Web of Science ID 000489157600012

  • Controversies in Diagnostic Imaging of Patients With Suspected Stable and Acute Chest Pain Syndromes. JACC. Cardiovascular imaging Shaw, L. J., Blankstein, R., Brown, D. L., Dhruva, S. S., Douglas, P. S., Genders, T. S., Gibbons, R. J., Greenwood, J. P., Kwong, R., Leipsic, J., Mahmarian, J. J., Maron, D., Nagel, E., Nicol, E., Nieman, K., Pellikka, P. A., Redberg, R. F., Weir-McCall, J., Williams, M. C., Chandrasekhar, Y. 2019; 12 (7 Pt 1): 1254–78

    Abstract

    There has been a tremendous growth quantity of high-quality imaging evidence in the area of acute and stable ischemic heart disease (SIHD). A number of recent comparative effectiveness trials have spurned significant controversies in the field of cardiovascular imaging. The result of this evidence is that many health care policies and national guidelines have undergone significant revisions. With all of this evidence, many challenges remain and the optimal evaluation strategy for evaluation of patients presenting with chest pain remains ill-defined. This paper enlisted the guidance of numerous experts in the field of cardiovascular imaging to garner their perspective on available imaging research in chest pain syndromes. Each of these vignettes represent editorial perspectives and diverse opinions as to which, if any, shouldbethe primary test in the evaluation of stable chest pain. These perspectives are not meant to be all inclusive but to highlight many of the commonly discussed controversies in the evaluation of chest pain symptoms. Theseperspectives are presented as a pre-amble to an upcoming American College of Cardiology/American Heart Association clinical practice guideline that is undergoing revision from the previous report published in 2012. Theevidence has changed considerably since the 2012SIHD guideline, and the current perspectives represent thediversity of availableevidence as to the optimal imagingstrategy for evaluation of the symptomatic patient.

    View details for DOI 10.1016/j.jcmg.2019.05.009

    View details for PubMedID 31272608

  • Studies Evaluating Statin Adherence and Outcome Should Adjust for Smoking Persistence and Antiplatelet Treatment Discontinuation-Reply. JAMA cardiology Rodriguez, F., Maron, D. J., Heidenreich, P. A. 2019

    View details for DOI 10.1001/jamacardio.2019.1969

    View details for PubMedID 31241723

  • Lifestyle, Glycosylated Hemoglobin A1c, and Survival Among Patients With Stable Ischemic Heart Disease and Diabetes JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Mancini, G., Maron, D. J., Hartigan, P. M., Spertus, J. A., Kostuk, W. J., Berman, D. S., Teo, K. K., Weintraub, W. S., Boden, W. E., COURAGE Trial Res Grp 2019; 73 (16): 2049–58

    View details for DOI 10.1016/j.jacc.2018.11.067

    View details for Web of Science ID 000465129200007

  • ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 appropriate use criteria for coronary revascularization in patients with stable ischemic heart disease JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Patel, M. R., Calhoon, J. H., Dehmer, G. J., Grantham, J., Maddox, T. M., Maron, D. J., Smith, P. K., Wolk, M. J., Blankenship, J. C., Bove, A. A., Bradley, S. M., Dean, L. S., Duffy, P. L., Ferguson, T., Grover, F. L., Guyton, R. A., Hlatky, M. A., Lazar, H. L., Rigolin, V. H., Rose, G. A., Shemin, R. J., Tamis-Holland, J. E., Tommaso, C. L., Wann, L., Wong, J. B., Doherty, J. U., Bailey, S. R., Bhave, N. M., Brown, A. S., Daugherty, S. L., Desai, M. Y., Duvernoy, C. S., Gillam, L. D., Hendel, R. C., Kramer, C. M., Lindsay, B. D., Manning, W. J., Sachdeva, R., Winchester, D. E., Allen, J. M. 2019; 157 (3): E131–E161

    View details for DOI 10.1016/j.jtcvs.2018.11.027

    View details for Web of Science ID 000458822000017

  • Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial. JAMA cardiology Hochman, J. S., Reynolds, H. R., Bangalore, S., O'Brien, S. M., Alexander, K. P., Senior, R., Boden, W. E., Stone, G. W., Goodman, S. G., Lopes, R. D., Lopez-Sendon, J., White, H. D., Maggioni, A. P., Shaw, L. J., Min, J. K., Picard, M. H., Berman, D. S., Chaitman, B. R., Mark, D. B., Spertus, J. A., Cyr, D. D., Bhargava, B., Ruzyllo, W., Wander, G. S., Chernyavskiy, A. M., Rosenberg, Y. D., Maron, D. J., ISCHEMIA Research Group 2019

    Abstract

    Importance: It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia.Objective: To describe baseline characteristics of participants enrolled and randomized in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial and to evaluate whether qualification by stress imaging or nonimaging exercise tolerance test (ETT) influenced risk profiles.Design, Setting, and Participants: The ISCHEMIA trial recruited patients with SIHD with moderate or severe ischemia on stress testing. Blinded coronary computed tomography angiography was performed in most participants and reviewed by a core laboratory to exclude left main stenosis of at least 50% or no obstructive coronary artery disease (CAD) (<50% for imaging stress test and <70% for ETT). The study included 341 enrolling sites (320 randomizing) in 38 countries and patients with SIHD and moderate or severe ischemia on stress testing. Data presented were extracted on December 17, 2018.Main Outcomes and Measures: Enrolled, excluded, and randomized participants' baseline characteristics. No clinical outcomes are reported.Results: A total of 8518 patients were enrolled, and 5179 were randomized. Common reasons for exclusion were core laboratory determination of insufficient ischemia, unprotected left main stenosis of at least 50%, or no stenosis that met study obstructive CAD criteria on study coronary computed tomography angiography. Randomized participants had a median age of 64 years, with 1168 women (22.6%), 1726 nonwhite participants (33.7%), 748 Hispanic participants (15.5%), 2122 with diabetes (41.0%), and 4643 with a history of angina (89.7%). Among the 3909 participants randomized after stress imaging, core laboratory assessment of ischemia severity (in 3901 participants) was severe in 1748 (44.8%), moderate in 1600 (41.0%), mild in 317 (8.1%) and none or uninterpretable in 236 (6.0%), Among the 1270 participants who were randomized after nonimaging ETT, core laboratory determination of ischemia severity (in 1266 participants) was severe (an eligibility criterion) in 1051 (83.0%), moderate in 101 (8.0%), mild in 34 (2.7%) and none or uninterpretable in 80 (6.3%). Among the 3912 of 5179 randomized participants who underwent coronary computed tomography angiography, 79.0% had multivessel CAD (n=2679 of 3390) and 86.8% had left anterior descending (LAD) stenosis (n=3190 of 3677) (proximal in 46.8% [n=1749 of 3739]). Participants undergoing ETT had greater frequency of 3-vessel CAD, LAD, and proximal LAD stenosis than participants undergoing stress imaging.Conclusions and Relevance: The ISCHEMIA trial randomized an SIHD population with moderate or severe ischemia on stress testing, of whom most had multivessel CAD.Trial Registration: ClinicalTrials.gov Identifier: NCT01471522.

    View details for PubMedID 30810700

  • Effect of Coronary Anatomy and Myocardial Ischemia on Long-Term Survival in Patients with Stable Ischemic Heart Disease. Circulation. Cardiovascular quality and outcomes Weintraub, W. S., Hartigan, P. M., Mancini, G. B., Teo, K. K., Maron, D. J., Spertus, J. A., Chaitman, B. R., Shaw, L. J., Berman, D., Boden, W. E. 2019; 12 (2): e005079

    Abstract

    Background The severity of coronary artery disease (CAD) and of ischemia are evaluated to guide therapy, but their relative prognostic importance remains uncertain. Accordingly, we sought to clarify their association with long-term survival in the COURAGE trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation). Methods and Results Survival data from after the original trial period ended was obtained at 15 Veterans Affairs sites and 13 of 18 United States non-Veterans Affairs sites. Date of death was obtained from the Veterans Affairs system-wide Corporate Data Warehouse and the National Death Index. Of the original 2287 patients in COURAGE, 1370 (60%) had both stress perfusion imaging and quantitative coronary angiography available, with extended survival evaluated in 767 subjects. Survival was calculated by the Kaplan-Meier method, and a Cox proportional-hazards model adjusted for baseline differences. There were 369 all-cause deaths during a median follow-up of 7.9 years (range, 0-15 years). The number of coronary arteries diseased predicted survival (HR, 1.25; 95% CI, 1.09-1.43), whereas severity of ischemia did not (HR, 0.99; 95% CI, 0.80-1.22). Percutaneous coronary intervention did not offer a survival advantage over optimal medical therapy (HR, 0.95; 95% CI, 0.77-1.16) and there was no interaction between therapeutic strategy and number of coronary arteries diseased or severity of ischemia. In fully adjusted models, the number of coronary arteries diseased was not associated with increased mortality. Conclusions In univariate analysis, the number of coronary arteries diseased predicted long-term mortality, but severity of ischemia did not. Adjusted for baseline variables, neither assessment approach predicted mortality. Overall, there was no survival benefit from percutaneous coronary intervention in any subset defined by either angiographic or ischemic severity. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00007657.

    View details for PubMedID 30773025

  • Effect of Coronary Anatomy and Myocardial Ischemia on Long-Term Survival in Patients with Stable Ischemic Heart Disease CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Weintraub, W. S., Hartigan, P. M., Mancini, G., Teo, K. K., Maron, D. J., Spertus, J. A., Chaitman, B. R., Shaw, L. J., Berman, D., Boden, W. E., COURAGE Trial Investigators 2019; 12 (2)

    View details for DOI 10.1161/CIRCOUTCOMES.118.005079

    View details for Web of Science ID 000458997000008

  • Association of Statin Adherence With Mortality in Patients With Atherosclerotic Cardiovascular Disease. JAMA cardiology Rodriguez, F., Maron, D. J., Knowles, J. W., Virani, S. S., Lin, S., Heidenreich, P. A. 2019

    Abstract

    Statins decrease mortality in those with atherosclerotic cardiovascular disease (ASCVD), but statin adherence remains suboptimal.To determine the association between statin adherence and mortality in patients with ASCVD who have stable statin prescriptions.This retrospective cohort analysis included patients who were between ages 21 and 85 years and had 1 or more International Classification of Diseases, Ninth Revision, Clinical Modification codes for ASCVD on 2 or more dates in the previous 2 years without intensity changes to their statin prescription who were treated within the Veterans Affairs Health System between January 1, 2013, and April 2014.Statin adherence was defined by the medication possession ratio (MPR). Adherence levels were categorized as an MPR of less than 50%, 50% to 69%, 70% to 89%, and 90% or greater. For dichotomous analyses, adherence was defined as an MPR of 80% or greater.The primary outcome was death of all causes adjusted for demographic and clinical characteristics, as well as adherence to other cardiac medications.Of 347 104 eligible adults with ASCVD who had stable statin prescriptions, 5472 (1.6%) were women, 284 150 (81.9%) were white, 36 208 (10.4%) were African American, 16 323 (4.7%) were Hispanic, 4093 (1.2%) were Pacific Islander, 1293 (0.4%) were Native American, 1145 (0.3%) were Asian, and 1794 (0.5%) were other races. Patients taking moderate-intensity statin therapy were more adherent than patients taking high-intensity statin therapy (odds ratio [OR], 1.18; 95% CI, 1.16-1.20). Women were less adherent (OR, 0.89; 95% CI, 0.84-0.94), as were minority groups. Younger and older patients were less likely to be adherent compared with adults aged 65 to 74 years. During a mean (SD) of 2.9 (0.8) years of follow-up, there were 85 930 deaths (24.8%). Compared with the most adherent patients (MPR ≥ 90%), patients with an MPR of less than 50% had a hazard ratio (HR; adjusted for clinical characteristics and adherence to other cardiac medications) of 1.30 (95% CI, 1.27-1.34), those with an MPR of 50% to 69% had an HR of 1.21 (95% CI, 1.18-1.24), and those with an MPR of 70% to 89% had an HR of 1.08 (95% CI, 1.06-1.09).Using a national sample of Veterans Affairs patients with ASCVD, we found that a low adherence to statin therapy was associated with a greater risk of dying. Women, minorities, younger adults, and older adults were less likely to adhere to statins. Our findings underscore the importance of finding methods to improve adherence.

    View details for PubMedID 30758506

  • Coronary CT Angiography and Subsequent Risk of Myocardial Infarction. The New England journal of medicine Sandhu, A. T., Maron, D. J. 2019; 380 (3): 299

    View details for PubMedID 30653281

  • Coronary artery calcium testing: A call for universal coverage. Preventive medicine reports Naghavi, M., Maron, D. J., Kloner, R. A., Berman, D. S., Budoff, M., Superko, H. R., Shah, P. K. 2019; 15: 100879

    Abstract

    Heart attacks kill more Americans than all cancers combined. Fatal heart attack victims have no symptoms until minutes before they die, hence early detection of high-risk asymptomatic individuals is needed. Even though heart attacks kill and cost more than cancers, as a nation we spend over 20 times more on screening for asymptomatic cancer than for asymptomatic atherosclerotic cardiovascular disease (ASCVD), the underlying cause of heart attacks. Currently, payers only cover screening for risk factors of ASCVD such as blood pressure and blood cholesterol. This approach tends to miss high-risk and over-treat low-risk individuals. Although treadmill stress testing with ECG is not indicated for ASCVD detection in asymptomatic individuals, it is done often, and frequently leads to misleading conclusions or unnecessary downstream diagnostic procedures. For example, former President Clinton had passed his treadmill stress tests for several years during his presidential annual checkup but had a heart attack shortly after his presidency. This common practice is a waste of our limited resources. Instead, a more accurate risk assessment using coronary artery calcium (CAC) testing is available; and has just been adopted by ACC/AHA guidelines, however payers do not cover it. CAC is measured non-invasively with a 5-minute CT-scan of the heart, and costs less than $200, whereas cancer screening with colonoscopy and mammography costs over $3000. There is an opportunity to save lives and dollars if CAC testing is covered for appropriately selected individuals. Texas has already passed HB1290 to mandate CAC coverage. Other states must step up and take actions.

    View details for DOI 10.1016/j.pmedr.2019.100879

    View details for PubMedID 31193256

    View details for PubMedCentralID PMC6525277

  • The Comparative Effect of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on 10-Year and Lifetime Atherosclerotic Cardiovascular Disease Risk. Obesity surgery Raygor, V., Garcia, L., Maron, D. J., Morton, J. M. 2019

    Abstract

    Bariatric surgery reduces atherosclerotic cardiovascular disease (ASCVD) risk. However, the comparative effect of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on 10-year and lifetime ASCVD risk, as defined by the American College of Cardiology/American Heart Association (ACC/AHA), remains unknown.Using the ACC/AHA ASCVD risk estimator, 10-year and lifetime ASCVD risks were calculated before and 1 year after bariatric surgery for patients aged 40-78 who underwent RYGB or SG at an academic medical center in California between 2003 and 2015. Change in risk was calculated by taking the difference between 1-year and baseline risk. Statistical analyses included the Wilcoxon signed rank test, Mann-Whitney U test, Quade's test, and multiple logistic regression.There were 536 patients (mean age 52 ± 10 years, 20% male), of whom 438 underwent RYGB and 98 underwent SG. Patients undergoing RYGB were predominately female (82% vs 71%, p = 0.021) and had higher baseline BMIs (44.4 ± 8.4 vs 41.9 ± 8.0, p < 0.001) than patients undergoing SG. Compared with baseline, 10-year and lifetime ASCVD risks were significantly lower 1 year after surgery (aggregate of RYGB and SG, 4.2 ± 6.0% vs. 2.2 ± 3.5%, p < 0.001; 50 ± 11% vs. 39 ± 12%, p < 0.001, respectively). Patients who underwent RYGB had greater reductions in 10-year and lifetime ASCVD risks from baseline to 1 year after surgery than patients who underwent SG (1.7 ± 3.5% vs. 0.8 ± 2.4%, p < 0.001; 11 ± 23% vs. 0 ± 12%, p < 0.001, respectively).Although RYGB and SG significantly lower 10-year and lifetime cardiovascular disease risks by 1 year after surgery, patients who undergo RYGB may experience greater cardiovascular risk reduction relative to counterparts who undergo SG.

    View details for DOI 10.1007/s11695-019-03948-8

    View details for PubMedID 31115847

  • Lifestyle, Glycosylated Hemoglobin A1c, and Survival Among Patients With Stable Ischemic Heart Disease and Diabetes. Journal of the American College of Cardiology Mancini, G. B., Maron, D. J., Hartigan, P. M., Spertus, J. A., Kostuk, W. J., Berman, D. S., Teo, K. K., Weintraub, W. S., Boden, W. E. 2019; 73 (16): 2049–58

    Abstract

    The importance of glycosylated hemoglobin A1c (A1c) control as part of comprehensive risk factor management in patients with stable ischemic heart disease (SIHD) and diabetes mellitus (DM) is controversial.The purpose of this study was to determine whether a greater number of controlled risk factors at 1 year, including A1c, affects survival in patients with DM and SIHD.Of 690 patients with DM followed in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 592 (86%) had complete ascertainment of 7 pre-specified risk factors at baseline and after 1 year: systolic blood pressure, low-density lipoprotein cholesterol, nonsmoking, physical activity, diet adherence, body mass index, and A1c. The primary outcome measure was mortality beyond 1 year after randomization.During a mean follow-up of 7.0 ± 4.2 years beyond 1 year after randomization, 186 subjects died (31.4% overall, 4.5%/year). The greater the number of risk factors controlled at 1 year, the higher the probability of survival (unadjusted log rank p = 0.002). Compared with 0 to 1 controlled risk factors, attaining 3 to 7 goals predicted progressively lower mortality (hazard ratio for control of 6 or 7 risk factors was 0.13; 95% confidence interval: 0.05 to 0.40). Importantly, only 10.3% of subjects achieved control of 6 or 7 risk factors. In multivariate analysis, the strongest predictors of improved survival were no smoking, regular physical activity, dietary adherence, and A1c <7%.In this high-risk subset of SIHD patients with DM, the number of controlled risk factors, particularly lifestyle behaviors and A1c, were associated with improved survival. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).

    View details for PubMedID 31023428

  • Preventive Cardiology as a Subspecialty of Cardiovascular Medicine: JACC Council Perspectives. Journal of the American College of Cardiology Shapiro, M. D., Maron, D. J., Morris, P. B., Kosiborod, M., Sandesara, P. B., Virani, S. S., Khera, A., Ballantyne, C. M., Baum, S. J., Sperling, L. S., Bhatt, D. L., Fazio, S. 2019; 74 (15): 1926–42

    Abstract

    Although significant progress has been made to reduce the global burden of cardiovascular disease, efforts have focused primarily on treatment of manifest disease rather than on prevention of events. An enormous opportunity exists to transition focus from intervention to providing equal attention to prevention of cardiovascular disease. The nascent specialty of "preventive cardiology" is emerging from the background of long-established services such as lipid, diabetes, hypertension, and general cardiology clinics. It is incumbent on the cardiology community to invest in cardiovascular prevention because past gains are threatened with the rising tide of obesity and diabetes. Now is the time to establish a dedicated preventive cardiology subspecialty to train the clinicians of the future. This American College of Cardiology Council Perspective aims to define the need for preventive cardiology as a unique subspecialty, broaches controversies, provides a structure for future training and education, and identifies possible paths forward to professional certification.

    View details for DOI 10.1016/j.jacc.2019.08.1016

    View details for PubMedID 31601373

  • Cost-effectiveness of on-pump and off-pump coronary artery bypass grafting for patients with coronary artery disease: Results from the MASS III trial INTERNATIONAL JOURNAL OF CARDIOLOGY Scudeler, T., Hueb, W. A., Farkouh, M. E., Maron, D. J., de Soarez, P., Campolina, A., Takiuti, M., Rezende, P., Godoy, L., Hueb, A., Lima, E., Garzillo, C., Franchini Ramires, J., Kalil Filho, R. 2018; 273: 63–68

    Abstract

    Recent trials have reported similar clinical outcomes between on-pump and off-pump coronary artery bypass graft (CABG). However, long-term cost-effectiveness of these strategies is unknown.A prespecified economic study was performed based on the MASS III trial. Costs were estimated for all patients based on observed healthcare resource usage over a 5-year follow-up. Health state utilities were evaluated with the SF-6D questionnaire. Cost-effectiveness was assessed as cost per quality-adjusted life-year (QALY) gained using a Markov model. Probabilistic sensitivity analysis with the Monte-Carlo simulation and cost-effectiveness acceptability curve were used to address uncertainty.Quality of life improved significantly in both groups during follow-up compared with baseline. At 5 years, when comparing on-pump and off-pump CABG groups, no differences were found in cumulative life-years (4.851 and 4.766 years, P = .319) and QALY gained (4.150 and 4.105 QALYs, P = .332). Mean cost in US dollars per patient during the trial did not differ significantly between the on-pump and off-pump groups ($5890.29 and $5674.75, respectively, P = .409). Over a lifetime horizon, the incremental cost-effectiveness ratio of on-pump versus off-pump CABG was $12,576 per QALY gained, which is above the suggested cost-effectiveness threshold range (from $3210 to 10,122). In the sensitivity analysis, the probability that on-pump CABG is cost-effective compared to off-pump surgery for a willingness-to-pay threshold of $3212 per QALY gained was <1%. For the $10,122 per QALY threshold, the same probability was 35%.This decision-analytic model suggests that on-pump CABG is not cost-effective when compared to off-pump CABG from a public health system perspective.

    View details for PubMedID 30158068

  • ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate Use Criteria for Coronary Revascularization in Patients With Stable Ischemic Heart Disease (vol 24, pg 1759, 2017) JOURNAL OF NUCLEAR CARDIOLOGY Patel, M. R., Calhoon, J. H., Dehmer, G. J., Grantham, J., Maddox, T. M., Maron, D. J., Smith, P. K. 2018; 25 (6): 2191–92

    Abstract

    To more clearly reflect the relationship between iFR (instantaneous wave-free ratio) and FFR (fractional flow reserve), this Correction document highlights the following changes to the original document published in the Journal of Nuclear Cardiology; the version available at JACC [1] has been updated to reflect the changes, with JACC's Correction document available at [2].

    View details for PubMedID 29748874

  • Healthy Behavior, Risk Factor Control, and Survival in the COURAGE Trial. Journal of the American College of Cardiology Maron, D. J., Mancini, G. B., Hartigan, P. M., Spertus, J. A., Sedlis, S. P., Kostuk, W. J., Berman, D. S., Teo, K. K., Weintraub, W. S., Boden, W. E., COURAGE Trial Group 2018; 72 (19): 2297–2305

    Abstract

    BACKGROUND: Individual risk factor control improves survival in patients with stable ischemic heart disease (SIHD). It is uncertain if multiple risk factor control further extends survival.OBJECTIVES: This study determined whether a greater number of risk factors at goal predicted improved survival in SIHD patients.METHODS: Of 2,287 participants in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 2,102 (92%) had complete ascertainment of 6 pre-specified risk factors: systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, diet, and body mass index. Participants received interventions to control these risk factors. The outcome measure was mortality.RESULTS: During a mean follow-up of 6.8 years, 473 (22.5%) subjects died. In univariate analysis, the greater the number of risk factors controlled, the higher the probability of survival (unadjusted log rank: p< 0.001). In multivariate analysis, the strongest predictors at 1 year of improved survival were being a nonsmoker, regular physical activity, having a systolic blood pressure<130mmHg, and following the American Heart Association Step 2 diet. Baseline risk factor values and evidence-based medications did not independently predict survival once risk factor control at 1 year was included in the model. Having 4 to 6 risk factors compared with 0 to 1 risk factor at goal predicted lower mortality (hazard ratios for 4 and 6 controlled risk factors: 0.64; 95% confidence interval: 0.41 to 0.98, and 0.27; 95% confidence interval: 0.09 to 0.79, respectively).CONCLUSIONS: The greater the number of risk factors in control, the higher the probability of survival in patients with SIHD. More effective strategies are needed to achieve comprehensive risk factor control, including healthy behaviors. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657).

    View details for PubMedID 30384885

  • International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease (ISCHEMIA-CKD): Rationale and design AMERICAN HEART JOURNAL Bangalore, S., Maron, D. J., Fleg, J. L., O'Brien, S. M., Herzog, C. A., Stone, G. W., Mark, D. B., Spertus, J. A., Alexander, K. P., Sidhu, M. S., Chertow, G. M., Boden, W. E., Hochman, J. S., ISCHEMIA-CKD Res Grp 2018; 205: 42–52

    Abstract

    Patients with chronic kidney disease (CKD) and stable ischemic heart disease are at markedly increased risk of cardiovascular events. Prior trials comparing a strategy of optimal medical therapy (OMT) with or without revascularization have largely excluded patients with advanced CKD. Whether a routine invasive approach when compared with a conservative strategy is beneficial in such patients is unknown.ISCHEMIA-CKD is a National Heart, Lung, and Blood Institute-funded randomized trial designed to determine the comparative effectiveness of an initial invasive strategy (cardiac catheterization and optimal revascularization [percutaneous coronary intervention or coronary artery bypass graft surgery, if suitable] plus OMT) versus a conservative strategy (OMT alone, with cardiac catheterization and revascularization [percutaneous coronary intervention or coronary artery bypass graft surgery, if suitable] reserved for failure of OMT) on long-term clinical outcomes in 777 patients with advanced CKD (defined as those with estimated glomerular filtration rate <30 mL/min/1.73m2 or on dialysis) and moderate or severe ischemia on stress testing. Participants were randomized in a 1:1 fashion to the invasive or a conservative strategy. The primary end point is a composite of death or nonfatal myocardial infarction. Major secondary endpoints are a composite of death, nonfatal myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest; angina control; and disease-specific quality of life. Safety outcomes such as initiation of maintenance dialysis and a composite of initiation of maintenance dialysis or death will be reported. The trial is projected to have 80% power to detect a 22% to 24% reduction in the primary composite end point with the invasive strategy when compared with the conservative strategy.ISCHEMIA-CKD will determine whether an initial invasive management strategy improves clinical outcomes when added to OMT in patients with advanced CKD and stable ischemic heart disease.

    View details for PubMedID 30172098

  • Planning and Conducting the ISCHEMIA Trial: Setting the Record Straight CIRCULATION Maron, D. J., Harrington, R. A., Hochman, J. S. 2018; 138 (14): 1384–86

    View details for DOI 10.1161/CIRCULATIONAHA.118.036904

    View details for Web of Science ID 000446002500002

  • Frequency of Statin Use in Patients With Low-Density Lipoprotein Cholesterol ≥190 mg/dl from the Veterans Affairs Health System. The American journal of cardiology Rodriguez, F., Knowles, J. W., Maron, D. J., Virani, S. S., Heidenreich, P. A. 2018

    Abstract

    Patients with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dl have severe hypercholesterolemia and are at markedly increased risk for adverse cardiovascular events. This study sought to examine the prevalence and treatment of patients with uncontrolled severe hypercholesterolemia in the Veterans Affairs (VA) Health System. The study population was comprised of VA outpatients ≥21 years of age without atherosclerotic disease or diabetes mellitus and an index LDL-C ≥190 mg/dl during April 2011 to March 2014. Patients needed to have filled medications at the VA within the past 6 months. Patient and facility-level predictors of statin use, high-intensity statin use, and statin intensification were analyzed using multivariate logistic regressions. There were a total of 63,576 patients meeting inclusion criteria, including 8,553 (13.5%) women and 26,879 (29.0%) nonwhite patients. The mean (±S.D.) age was 55 (±13) years and the mean of the most recent LDL-C values was 207 ± 22 mg/dl. Only 52% of all eligible patients were on any statin therapy and 9.7% received high-intensity statin therapy. High-intensity statin use increased from 8.6% in 2011 to 13.6% in 2014 (p < 0.001). In adjusted analysis, patients <35 or >75 years of age were less likely to be on a statin (p < 0.001). Women were less likely to be treated than men, odds ratio = 0.88; 95% confidence interval (0.83, 0.92). Similar patterns were observed for predictors of high-intensity statin use and statin intensification. In conclusion, only half of high-risk VA patients with uncontrolled severe hypercholesterolemia were treated with statins and a small minority was on high-intensity statin therapy.

    View details for PubMedID 30055758

  • ISCHEMIA: Establishing the Primary End Point CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Bangalore, S., Maron, D. J., Reynolds, H. R., Stone, G. W., O'Brien, S. M., Alexander, K. P., Hochman, J. S. 2018; 11 (5): e004791

    View details for PubMedID 29752391

    View details for PubMedCentralID PMC5967873

  • Predicting the Benefits of Percutaneous Coronary Intervention on 1-Year Angina and Quality of Life in Stable Ischemic Heart Disease: Risk Models From the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Zhang, Z., Jones, P., Weintraub, W. S., Mancini, G., Sedlis, S., Maron, D. J., Teo, K., Hartigan, P., Kostuk, W., Berman, D., Boden, W. E., Spertus, J. A. 2018; 11 (5): e003971

    Abstract

    Percutaneous coronary intervention (PCI) is a therapy to reduce angina and improve quality of life in patients with stable ischemic heart disease. However, it is unclear whether the quality of life after PCI is more dependent on the PCI or other patient-related factors. To address this question, we created models to predict angina and quality of life 1 year after PCI and medical therapy.Using data from the 2287 stable ischemic heart disease patients randomized in the COURAGE trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) to PCI plus optimal medical therapy (OMT) versus OMT alone, we built prediction models for 1-year Seattle Angina Questionnaire angina frequency, physical limitation, and quality of life scores, both as continuous outcomes and categorized by clinically desirable states, using multivariable techniques. Although most patients improved regardless of treatment, marked variability was observed in Seattle Angina Questionnaire scores 1 year after randomization. Adding PCI conferred a greater mean improvement (about 2 points) in Seattle Angina Questionnaire scores that were not affected by patient characteristics (P values for all interactions >0.05). The proportion of patients free of angina or having very good/excellent physical limitation (physical function) or quality of life at 1 year was 57%, 58%, 66% with PCI+OMT and 50%, 55%, 59% with OMT alone group, respectively. However, other characteristics, such as baseline symptoms, age, diabetes mellitus, and the magnitude of myocardium subtended by narrowed coronary arteries were as, or more, important than revascularization in predicting symptoms (partial R2=0.07 versus 0.29, 0.03 versus 0.22, and 0.05 versus 0.24 in the domain of angina frequency, physical limitation, and quality of life, respectively). There was modest/good discrimination of the models (C statistic=0.72-0.82) and excellent calibration (coefficients of determination for predicted versus observed deciles=0.83-0.97).The health status outcomes of stable ischemic heart disease patients treated by OMT+PCI versus OMT alone can be predicted with modest accuracy. Angina and quality of life at 1 year is improved by PCI but is more strongly associated with other patient characteristics.URL: https://www.clinicaltrials.gov. Unique identifier: NCT00007657.

    View details for PubMedID 29752388

  • Methodological Issues in "Dietary Patterns and Long-Term Survival" Reply AMERICAN JOURNAL OF MEDICINE Leonard, D., Shah, N. S., Barlow, C. E., DeFina, L. F., Willis, B. L., Maron, D. J. 2018; 131 (5): E211

    View details for PubMedID 29673492

  • International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial: Rationale and design. American heart journal ISCHEMIA Trial Research Group, Maron, D. J., Hochman, J. S., O'Brien, S. M., Reynolds, H. R., Boden, W. E., Stone, G. W., Bangalore, S., Spertus, J. A., Mark, D. B., Alexander, K. P., Shaw, L., Berger, J. S., Ferguson, T. B., Williams, D. O., Harrington, R. A., Rosenberg, Y. 2018; 201: 124–35

    Abstract

    BACKGROUND: Prior trials comparing a strategy of optimal medical therapy with or without revascularization have not shown that revascularization reduces cardiovascular events in patients with stable ischemic heart disease (SIHD). However, those trials only included participants in whom coronary anatomy was known prior to randomization and did not include sufficient numbers of participants with significant ischemia. It remains unknown whether a routine invasive approach offers incremental value over a conservative approach with catheterization reserved for failure of medical therapy in patients with moderate or severe ischemia.METHODS: The ISCHEMIA trial is a National Heart, Lung, and Blood Institute supported trial, designed to compare an initial invasive or conservative treatment strategy for managing SIHD patients with moderate or severe ischemia on stress testing. Five thousand one-hundred seventy-nine participants have been randomized. Key exclusion criteria included estimated glomerular filtration rate (eGFR) <30 mL/min, recent myocardial infarction (MI), left ventricular ejection fraction <35%, left main stenosis >50%, or unacceptable angina at baseline. Most enrolled participants with normal renal function first underwent blinded coronary computed tomography angiography (CCTA) to exclude those with left main coronary artery disease (CAD) and without obstructive CAD. All randomized participants receive secondary prevention that includes lifestyle advice and pharmacologic interventions referred to as optimal medical therapy (OMT). Participants randomized to the invasive strategy underwent routine cardiac catheterization followed by revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, when feasible, as selected by the local Heart Team to achieve optimal revascularization. Participants randomized to the conservative strategy undergo cardiac catheterization only for failure of OMT. The primary endpoint is a composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest. Assuming the primary endpoint will occur in 16% of the conservative group within 4 years, estimated power exceeds 80% to detect an 18.5% reduction in the primary endpoint. Major secondary endpoints include the composite of CV death and nonfatal MI, net clinical benefit (primary and secondary endpoints combined with stroke), angina-related symptoms and disease-specific quality of life, as well as a cost-effectiveness assessment in North American participants. Ancillary studies of patients with advanced chronic kidney disease and those with documented ischemia and non-obstructive coronary artery disease are being conducted concurrently.CONCLUSIONS: ISCHEMIA will provide new scientific evidence regarding whether an invasive management strategy improves clinical outcomes when added to optimal medical therapy in patients with SIHD and moderate or severe ischemia.

    View details for PubMedID 29778671

  • Letter by Hochman and Maron Regarding Article, "'Faith Healing' and 'Subtraction Anxiety' in Unblinded Trials of Procedures: Lessons From DEFER and FAME-2 for End Points in the ISCHEMIA Trial." Circulation. Cardiovascular quality and outcomes Hochman, J. S., Maron, D. J. 2018; 11 (4): e004742

    View details for PubMedID 29636347

  • Dietary Patterns and Long-Term Survival: A Retrospective Study of Healthy Primary Care Patients AMERICAN JOURNAL OF MEDICINE Shah, N. S., Leonard, D., Finley, C. E., Rodriguez, F., Sarraju, A., Barlow, C. E., DeFina, L. F., Willis, B. L., Haskell, W. L., Maron, D. J. 2018; 131 (1): 48–55

    View details for DOI 10.1016/j.amjmed.2017.08.010

    View details for Web of Science ID 000417605300030

  • Association of Educational Attainment and Cardiovascular Risk in Hispanic Individuals: Findings From the Cooper Center Longitudinal Study. JAMA cardiology Rodriguez, F., Leonard, D., DeFina, L., Barlow, C. E., Willis, B. L., Haskell, W. L., Maron, D. J. 2018

    Abstract

    Hispanic individuals are the fastest growing ethnic group in the United States and face lower socioeconomic status compared with non-Hispanic white (NHW) individuals. However, Hispanic individuals tend to experience better health outcomes than expected, a phenomenon known as the Hispanic paradox. Little is known about how higher socioeconomic status is associated with Hispanic cardiovascular risk factor burden and outcomes.To determine cardiovascular risk and outcomes among highly educated Hispanic vs NHW individuals in a preventive medicine clinic.Retrospective cohort analysis of participants from the Cooper Center Longitudinal Study who underwent preventive medical examinations at the Cooper Clinic in Dallas, Texas, from October 1972 to November 2017. Analysis began April 2018.Ethnicity, self-defined as Hispanic or NHW.Prevalence of major metabolic risk factors and cardiorespiratory fitness were compared, as were changes among participants with at least 2 visits. Ethnic differences adjusted for age, examination year, and educational attainment were estimated using regression models. Age-matched comparisons of coronary artery calcium scores were performed. All-cause mortality was summarized using the Kaplan-Meier method.This study included 1351 Hispanic and 43 736 NHW participants aged 20 to 80 years, body mass index between 18.5 and 50.0, and were not missing key cardiometabolic or fitness variables. Both Hispanic and NHW participants had high educational attainment, with a mean of more than 15 years of total education. Hispanic women and men had a higher prevalence of metabolic syndrome (71 of 518 [13.1%] vs 1477 of 13 732 [10.8%] for women and 255 of 833 [30.6%] vs 7902 of 30 004 [26.3%] for men, respectively). Although Hispanic individuals were twice as likely to have diabetes, there was no difference in calculated 10-year atherosclerotic cardiovascular disease risk scores by ethnicity. Both Hispanic and NWH individuals experienced a statistically significant worsening in cardiometabolic parameters during follow-up, although this was not statistically significantly different between groups. In age-matched analyses, there were no significant differences in the prevalence of coronary artery calcium scores between Hispanic and NWH individuals. During a mean (SD) follow-up of 12.9 (7.5) years, there was no difference in mortality between Hispanic and NHW individuals.Hispanic and NHW men and women with high educational attainment had similar atherosclerotic cardiovascular disease risk, subclinical coronary atherosclerosis, and mortality during follow-up. These findings do not support the Hispanic paradox in a highly educated Hispanic population.

    View details for PubMedID 30566183

  • Planning and Conducting the ISCHEMIA Trial. Circulation Maron, D. J., Harrington, R. A., Hochman, J. S. 2018; 138 (14): 1384–86

    View details for PubMedID 30354348

    View details for PubMedCentralID PMC6205757

  • ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate Use Criteria for Coronary Revascularization in Patients With Stable Ischemic Heart Disease JOURNAL OF NUCLEAR CARDIOLOGY Patel, M. R., Calhoon, J. H., Dehmer, G. J., Grantham, J., Maddox, T. M., Maron, D. J., Smith, P. K., Wolk, M. J., Dehmer, G. J., Smith, P. K., Blankenship, J. C., Bove, A. A., Bradley, S. M., Dean, L. S., Duffy, P. L., Ferguson, T., Grover, F. L., Guyton, R. A., Hlatky, M. A., Lazar, H. L., Rigolin, V. H., Rose, G. A., Shemin, R. J., Tamis-Holland, J. E., Tommaso, C. L., Wann, L., Wong, J. B., Doherty, J. U., Dehmer, G. J., Bailey, S. R., Bhave, N. M., Brown, A. S., Daugherty, S. L., Desai, M. Y., Duvernoy, C. S., Gillam, L. D., Hendel, R. C., Kramer, C. M., Lindsay, B. D., Manning, W. J., Sachdeva, R., Wann, L., Winchester, D. E., Wolk, M. J., Allen, J. M., Chazal, R. A., Jacobovitz, S., Oetgen, W. J., Allen, J. M., Velasquez, M., Scholtz, A., Calhoon, J. H., Dehmer, G. J., Grantham, J., Maddox, T. M., Maron, D. J., Smith, P. K., Wolk, M. J., Blankenship, J. C., Bove, A. A., Bradley, S. M., Dean, L. S., Duffy, P. L., Ferguson, T., Grover, F. L., Guyton, R. A., Hlatky, M. A., Lazar, H. L., Rigolin, V. H., Rose, G. A., Shemin, R. J., Tamis-Holland, J. E., Tommaso, C. L., Wann, L., Wong, J. B., Anderson, J. L., Blankenship, J. C., Brinker, J. A., Costea, A. I., Denktas, A. E., Klein, L. W., Kushner, F. G., Levine, G. N., Maron, D., McClurken, J. B., Piana, R. N., Spertus, J. A., Stainback, R. F., Stoler, R. C., Villines, T. C., Wiener, D. H., Bailey, S. R., Bhave, N., Brown, A. S., Daugherty, S. L., Dehmer, G. J., Desai, M. Y., Doherty, J. U., Duvernoy, C., Gillam, L. D., Hendel, R. C., Kramer, C. M., Lindsay, B. D., Manning, W. J., Sachdeva, R., Wann, L., Winchester, D. E., Allen, J. M., Amer Coll Cardiology 2017; 24 (5): 1759–92

    Abstract

    The American College of Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, and American Association for Thoracic Surgery, along with key specialty and subspecialty societies, have completed a 2-part revision of the appropriate use criteria (AUC) for coronary revascularization. In prior coronary revascularization AUC documents, indications for revascularization in acute coronary syndromes and stable ischemic heart disease (SIHD) were combined into 1 document. To address the expanding clinical indications for coronary revascularization, and to align the subject matter with the most current American College of Cardiology/American Heart Association guidelines, the new AUC for coronary artery revascularization were separated into 2 documents addressing SIHD and acute coronary syndromes individually. This document presents the AUC for SIHD.Clinical scenarios were developed to mimic patient presentations encountered in everyday practice. These scenarios included information on symptom status; risk level as assessed by noninvasive testing; coronary disease burden; and, in some scenarios, fractional flow reserve testing, presence or absence of diabetes, and SYNTAX score. This update provides a reassessment of clinical scenarios that the writing group felt were affected by significant changes in the medical literature or gaps from prior criteria. The methodology used in this update is similar to the initial document but employs the recent modifications in the methods for developing AUC, most notably, alterations in the nomenclature for appropriate use categorization.A separate, independent rating panel scored the clinical scenarios on a scale of 1 to 9. Scores of 7 to 9 indicate that revascularization is considered appropriate for the clinical scenario presented. Scores of 1 to 3 indicate that revascularization is considered rarely appropriate for the clinical scenario, whereas scores in the mid-range of 4 to 6 indicate that coronary revascularization may be appropriate for the clinical scenario.As seen with the prior coronary revascularization AUC, revascularization in clinical scenarios with high symptom burden, high-risk features, and high coronary disease burden, as well as in patients receiving antianginal therapy, are deemed appropriate. Additionally, scenarios assessing the appropriateness of revascularization before kidney transplantation or transcatheter valve therapy are now rated. The primary objective of the AUC is to provide a framework for the assessment of practice patterns that will hopefully improve physician decision making.

    View details for PubMedID 28608183

  • Relationship between simple markers of insulin resistance and coronary artery calcification JOURNAL OF CLINICAL LIPIDOLOGY Reaven, G. M., Knowles, J. W., Leonard, D., Barlow, C. E., Willis, B. L., Haskell, W. L., Maron, D. J. 2017; 11 (4): 1007–12

    Abstract

    Insulin resistance in apparently healthy persons is associated with a cluster of metabolic abnormalities that promote coronary atherosclerosis. Identifying these individuals before manifest disease would provide useful clinical information.We hypothesized that combining 2 simple markers of insulin resistance, prediabetes (PreDM) and triglyceride (TG) concentration ≥150 mg/dL, would identify apparently healthy persons with adverse cardiometabolic risk profiles and increased coronary artery calcium (CAC) compared with those with neither or only 1 abnormality.A cross-sectional analysis was performed using data from 25,886 apparently healthy individuals (18,453 men and 7433 women) evaluated at the Cooper Clinic from 1998 to 2015. Participants were divided into those with a normal fasting glucose concentrations (<100 mg/dL = normal fasting glucose) or PreDM (fasting plasma glucose ≥100 and <126 mg/dL) and further subdivided into those with a plasma TG concentration <150 or ≥150 mg/dL. These 4 groups were compared on the basis of multiple coronary artery disease risk factors and the presence of CAC determined during their evaluation.Participants with PreDM and a TG concentration ≥150 mg/dL had a significantly more adverse coronary artery disease risk profile than individuals with either abnormality or only 1 abnormality (PreDM or TG concentration ≥150 mg/dL). Furthermore, the odds of detectable CAC were higher in participants with PreDM and a TG ≥ 150 mg/dL than in participants with neither or only 1 abnormality.The presence of 2 markers of insulin resistance, PreDM and TG concentration ≥150 mg/dL, is associated with increased cardiometabolic risk and detectable CAC within a population of apparently healthy individuals.

    View details for PubMedID 28652190

  • Use of troponin assay 99th percentile as the decision level for myocardial infarction diagnosis AMERICAN HEART JOURNAL Bagai, A., Alexander, K. P., Berger, J. S., Senior, R., Sajeev, C., Pracon, R., Mavromatis, K., Luis Lopez-Sendon, J., Gosselin, G., Diaz, A., Perna, G., Drozdz, J., Humen, D., Petrauskiene, B., Cheema, A. N., Phaneuf, D., Banerjee, S., Miller, T. D., Kedev, S., Schuchlenz, H., Stone, G. W., Goodman, S. G., Mahaffey, K. W., Jaffe, A. S., Rosenberg, Y. D., Bangalore, S., Newby, L., Maron, D. J., Hochman, J. S., Chaitman, B. R. 2017; 190: 135–39

    Abstract

    The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known.We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute-sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial. Each hospital laboratory's troponin assay manufacturer and model, the recommended assay's 99th percentile upper reference limit (URL) from the manufacturer's package insert, and the troponin concentration used locally as the decision level to diagnose myocardial infarction were ascertained.Twenty-one unique troponin assays from 9 manufacturers were used by the surveyed hospital laboratories. The ratio of the troponin concentration used locally to diagnose myocardial infarction to the assay manufacturer-determined 99th percentile URL was <1 at 19 (6.6%) laboratories, equal to 1 at 91 (31.6%) laboratories, >1 to ≤5 at 101 (35.1%) laboratories, >5 to ≤10 at 34 (11.8%) laboratories, and >10 at 43 (14.9%) laboratories. The variability in troponin decision level for myocardial infarction relative to the assay 99th percentile URL was present for laboratories in and outside of the United States, as well as for high- and standard-sensitivity assays.There is substantial hospital-level variation in the troponin threshold used to diagnose myocardial infarction; only one-third of hospital laboratories currently follow the Universal Definition of Myocardial Infarction consensus recommendation for use of troponin concentration at the 99th percentile of a normal reference population as the decision level to diagnose myocardial infarction. This variability across laboratories has important implications for both the diagnosis of myocardial infarction in clinical practice as well as adjudication of myocardial infarction in clinical trials.

    View details for PubMedID 28760208

  • ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate Use Criteria for Coronary Revascularization in Patients With Stable Ischemic Heart Disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Patel, M. R., Calhoon, J. H., Dehmer, G. J., Grantham, J. A., Maddox, T. M., Maron, D. J., Smith, P. K., Wolk, M. J., Dehmer, G. J., Blankenship, J. C., Bove, A. A., Bradley, S. M., Dean, L. S., Duffy, P. L., Ferguson, T. B., Grover, F. L., Guyton, R. A., Hlatky, M. A., Lazar, H. L., Rigolin, V. H., Rose, G. A., Shemin, R. J., Tamis-Holland, J. E., Tommaso, C. L., Wann, L. S., Wong, J. B., Doherty, J. U., Dehmer, G. J., Bailey, S. R., Bhave, N. M., Brown, A. S., Daugherty, S. L., Desai, M. Y., Duvernoy, C. S., Gillam, L. D., Hendel, R. C., Kramer, C. M., Lindsay, B. D., Manning, W. J., Patel, M. R., Sachdeva, R., Wann, L. S., Winchester, D. E., Allen, J. M., Chazal, R. A., Jacobovitz, S., Oetgen, W. J., White, L., Velasquez, M., Scholtz, A., Anderson, J. L., Brinker, J. A., Costea, A. I., Denktas, A. E., Klein, L. W., Kushner, F. G., Levine, G. N., Maron, D. J., McClurken, J. B., Piana, R. N., Spertus, J. A., Stainback, R. F., Stoler, R. C., Villines, T. C., Wiener, D. H. 2017; 69 (17): 2212-2241

    View details for DOI 10.1016/j.jacc.2017.02.001

    View details for Web of Science ID 000399988700013

  • ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate Use Criteria for Coronary Revascularization in Patients With Stable Ischemic Heart Disease: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons. Journal of the American College of Cardiology Patel, M. R., Calhoon, J. H., Dehmer, G. J., Grantham, J. A., Maddox, T. M., Maron, D. J., Smith, P. K. 2017; 69 (17): 2212-2241

    View details for DOI 10.1016/j.jacc.2017.02.001

    View details for PubMedID 28291663

  • Intensity of Statin Treatment and Mortality-Reply. JAMA cardiology Rodriguez, F., Maron, D. J., Heidenreich, P. A. 2017

    View details for DOI 10.1001/jamacardio.2017.0549

    View details for PubMedID 28445560

  • ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2016 Appropriate Use Criteria for Coronary Revascularization in Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and the Society of Thoracic Surgeons. Journal of the American College of Cardiology Patel, M. R., Calhoon, J. H., Dehmer, G. J., Grantham, J. A., Maddox, T. M., Maron, D. J., Smith, P. K. 2017; 69 (5): 570-591

    View details for DOI 10.1016/j.jacc.2016.10.034

    View details for PubMedID 28012615

  • Association Between Intensity of Statin Therapy and Mortality in Patients With Atherosclerotic Cardiovascular Disease. JAMA cardiology Rodriguez, F., Maron, D. J., Knowles, J. W., Virani, S. S., Lin, S., Heidenreich, P. A. 2017; 2 (1): 47-54

    Abstract

    High-intensity statin therapy is recommended for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Nevertheless, statin therapy in general, and high-intensity statin therapy in particular, is underused in patients with established ASCVD.To determine the association between all-cause mortality and intensity of statin therapy in the Veterans Affairs health care system.A retrospective cohort analysis was conducted of patients aged 21 to 84 years with ASCVD treated in the Veterans Affairs health care system from April 1, 2013, to April 1, 2014. Patients who were included had 1 or more International Classification of Diseases, Ninth Revision codes for ASCVD on 2 or more different dates in the prior 2 years.Intensity of statin therapy was defined by the 2013 American College of Cardiology/American Heart Association guidelines, and use was defined as a filled prescription in the prior 6 months. Patients were excluded if they were taking a higher statin dose in the prior 5 years.The primary outcome was death from all causes adjusted for the propensity to receive high-intensity statins.The study sample included 509 766 eligible adults with ASCVD at baseline (mean [SD] age, 68.5 [8.8] years; 499 598 men and 10 168 women), including 150 928 (29.6%) receiving high-intensity statin therapy, 232 293 (45.6%) receiving moderate-intensity statin therapy, 33 920 (6.7%) receiving low-intensity statin therapy, and 92 625 (18.2%) receiving no statins. During a mean follow-up of 492 days, there was a graded association between intensity of statin therapy and mortality, with 1-year mortality rates of 4.0% (5103 of 126 139) for those receiving high-intensity statin therapy, 4.8% (9703 of 200 709) for those receiving moderate-intensity statin therapy, 5.7% (1632 of 28 765) for those receiving low-intensity statin therapy, and 6.6% (4868 of 73 728) for those receiving no statin (P < .001). After adjusting for the propensity to receive high-intensity statins, the hazard ratio for mortality was 0.91 (95% CI, 0.88-0.93) for those receiving high- vs moderate-intensity statins. The magnitude of benefit of high- vs moderate-intensity statins was similar, for an incident cohort hazard ratio of 0.93 (95% CI, 0.85-1.01). For patients aged 76 to 84 years, the hazard ratio was 0.91 (95% CI, 0.87-0.95). Patients treated with maximal doses of high-intensity statins had lower mortality (hazard ratio, 0.90; 95% CI, 0.87-0.94) compared with those receiving submaximal doses.We found a graded association between intensity of statin therapy and mortality in a national sample of patients with ASCVD. High-intensity statins were associated with a small but significant survival advantage compared with moderate-intensity statins, even among older adults. Maximal doses of high-intensity statins were associated with a further survival benefit.

    View details for DOI 10.1001/jamacardio.2016.4052

    View details for PubMedID 27829091

  • Preventive Interventions After Coronary Artery Calcium Scanning: Seeing is Believing. JACC. Cardiovascular imaging Maron, D. J. 2017; 10 (8): 843–44

    View details for PubMedID 28797403

  • Using Absolute Event Rates to See What Works in Cardiovascular Medicine. Journal of the American College of Cardiology Bittl, J. A., Maron, D. J. 2017; 70 (11): 1376–78

    View details for PubMedID 28882236

  • Using Commercial Programs for Lifestyle Intervention: Not Reinventing the Wheel. Journal of the American College of Cardiology Maron, D. J., Sandhu, A. T. 2017; 70 (3): 328–30

    View details for PubMedID 28705313

  • Dietary Patterns and Long-Term Survival: a Retrospective Study of Healthy Primary Care Patients. The American journal of medicine Shah, N. S., Leonard, D., Finley, C. E., Rodriguez, F., Sarraju, A., Barlow, C. E., DeFina, L. F., Willis, B. L., Haskell, W. L., Maron, D. J. 2017

    Abstract

    Dietary patterns are related to mortality in selected populations with comorbidities. We studied whether dietary patterns are associated with long-term survival in a middle-aged, healthy population.In this observational cohort study at the Cooper Clinic preventive medicine center (Dallas, Texas), a volunteer sample of 11,376 men and women with no history of myocardial infarction or stroke completed a baseline dietary assessment between 1987-1999 and were observed for an average of 18 years. Proportional hazard regressions, including a tree-augmented model, were used to assess the association of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern, Mediterranean dietary pattern, and individual dietary components with mortality. The primary outcome was death from all causes. The secondary outcome was death from cardiovascular disease.Mean baseline age was 47 years. Each quintile increase in the DASH diet score was associated with a 6% lower adjusted risk for all-cause mortality (P<0.02). The Mediterranean diet was not independently associated with all-cause or cardiovascular mortality. Solid fats and added sugars were the most predictive of mortality. Individuals who consumed >34% of their daily calories as solid fats had the highest risk for all-cause mortality.The DASH dietary pattern was associated with significantly lower all-cause mortality over nearly two decades of follow-up in a middle-aged, generally healthy population. Added solid fat and added sugar intake were the most predictive of all-cause mortality. These results suggest that promotion of a healthy dietary pattern should begin in middle age, before the development of comorbid risk factors.

    View details for PubMedID 28860032

  • Risk Estimates for Atherosclerotic Cardiovascular Disease in Adults With Congenital Heart Disease AMERICAN JOURNAL OF CARDIOLOGY Lui, G. K., Rogers, I. S., Ding, V. Y., Hedlin, H. K., MacMillen, K., Maron, D. J., Sillman, C., Romfh, A., Dade, T. C., Haeffele, C., Grady, S. R., McElhinney, D. B., Murphy, D. J., Fernandes, S. M. 2017; 119 (1): 112-118

    Abstract

    The adult with congenital heart disease (CHD) is at risk of developing atherosclerotic cardiovascular disease (ASCVD). We performed a cross-sectional study to describe established ASCVD risk factors and estimate 10-year and lifetime risk of ASCVD in adults over age 18 with CHD of moderate or great complexity using 3 validated risk assessment tools-the Framingham Study Cardiovascular Disease Risk Assessment, the Reynolds Risk Score, and the ASCVD Risk Estimator. We obtained extensive clinical and survey data on 178 enrolled patients, with average age 37.1 ± 12.6 years, 51% men. At least 1 modifiable ASCVD risk factor was present in 70%; the 2 most common were overweight/obesity (53%) and systemic hypertension (24%). Laboratory data were available in 103 of the 178 patients. Abnormal levels of glycated hemoglobin, high-sensitivity C-reactive protein, and high-density lipoprotein were each found in around 30% of patients. The 10-year ASCVD predicted risk using all 3 tools was relatively low (i.e., at least 90% of patients <10% risk), yet the median estimated lifetime risk was 36%. In conclusion, ASCVD risk factors are prevalent in adults with CHD. The risk estimation tools suggest that this population is particularly vulnerable to ASCVD with aging and should undergo guideline-based screening and management of modifiable risk factors.

    View details for DOI 10.1016/j.amjcard.2016.09.023

    View details for PubMedID 28247847

  • Use of high-intensity statins for patients with atherosclerotic cardiovascular disease in the Veterans Affairs Health System: Practice impact of the new cholesterol guidelines AMERICAN HEART JOURNAL Rodriguez, F., Lin, S., Maron, D. J., Knowles, J. W., Virani, S. S., Heidenreich, P. A. 2016; 182: 97-102

    Abstract

    The November 2013 American College of Cardiology/American Heart Association cholesterol guidelines recommend the use of high-intensity statins for patients with atherosclerotic cardiovascular disease (ASCVD). We sought to determine how these guidelines are being adopted at the Veterans Affairs (VA) Health System and identify treatment gaps.We examined administrative data from the VA 12 months prior to the index dates of April 1, 2013, and after April 1, 2014, to identify patients ≤75 years of age with ≥2 codes for ASCVD. We identified those on high-intensity statin therapy (atorvastatin 40 mg or 80 mg, rosuvastatin 20 mg or 40 mg, and simvastatin 80 mg) during the 6 months after the index date.The study sample included 331,927 and 326,759 eligible adults with ASCVD before and after the release of the new guidelines, respectively. Overall, high-intensity statin use increased from 28% to 35% after guideline release. High-intensity statin use was lowest in Hispanics and Native Americans, although all groups showed an increase over time. Among those on low- or moderate-intensity statin therapy, 15.6% were intensified to a high-intensity statin after guideline release. Groups less likely to undergo statin intensification were older adults (odds ratio=0.78 for each 10-year increase, 95% CI 0.76-0.81), women (odds ratio=0.86, 95% CI 0.75-0.99), and certain minority groups. Academic teaching hospitals and hospitals on the West Coast were more likely to intensify statins after release of the new guidelines.High-intensity statin use increased in the VA following release of the American College of Cardiology/American Heart Association cholesterol treatment guidelines, although disparities persist for certain patient groups including older adults, women, and certain minority groups.

    View details for DOI 10.1016/j.ahj.2016.09.007

    View details for Web of Science ID 000389136600012

    View details for PubMedID 27914506

  • Can Cardiac Conduction System Disease Be Prevented? JAMA internal medicine Narayan, S. M., Baykaner, T., Maron, D. J. 2016; 176 (8): 1093-1094

    View details for DOI 10.1001/jamainternmed.2016.2863

    View details for PubMedID 27367299

  • Optimal medical therapy with or without percutaneous coronary intervention in women with stable coronary disease: A pre-specified subset analysis of the Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation (COURAGE) trial AMERICAN HEART JOURNAL Acharjee, S., Teo, K. K., Jacobs, A. K., Hartigan, P. M., Barn, K., Gosselin, G., Tanguay, J., Maron, D. J., Kostuk, W. J., Chaitman, B. R., Mancini, G. B., Spertus, J. A., Dada, M. R., Bates, E. R., Booth, D. C., Weintraub, W. S., O'Rourke, R. A., Boden, W. E. 2016; 173: 108-117

    Abstract

    To determine whether sex-based differences exist in clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in patients with stable coronary artery disease.A prior pre-specified unadjusted analysis from COURAGE showed that women randomized to PCI had a lower rate of death or myocardial infarction during a median 4.6-year follow-up with a trend for interaction with respect to sex.We analyzed outcomes in 338 women (15%) and 1949 men (85%) randomized to PCI plus OMT versus OMT alone after adjustment for relevant baseline characteristics.There was no difference in treatment effect by sex for the primary end point (death or myocardial infarction; HR, 0.89; 95% CI, 0.77-1.03 for women and HR, 1.02, 95% CI 0.96-1.10 for men; P for interaction = .07). Although the event rate was low, a trend for interaction by sex was nonetheless noted for hospitalization for heart failure, with only women, but not men, assigned to PCI experiencing significantly fewer events as compared to their counterparts receiving OMT alone (HR, 0.59; 95% CI, 0.40-0.84, P < .001 for women and HR, 0.86; 95% CI, 0.74-1.01, P = .47 for men; P for interaction = .02). Both sexes randomized to PCI experienced significantly reduced need for subsequent revascularization (HR, 0.72; 95% CI, 0.62-0.83, P < .001 for women; HR, 0.84; 95% CI, 0.79-0.89, P < .001 for men; P for interaction = .02) with evidence of a sex-based differential treatment effect.In this adjusted analysis of the COURAGE trial, there were no significant differences in treatment effect on major outcomes between men and women. However, women assigned to PCI demonstrated a greater benefit as compared to men, with a reduction in heart failure hospitalization and need for future revascularization. These exploratory observations require further prospective study.

    View details for DOI 10.1016/j.ahj.2015.07.020

    View details for PubMedID 26920603

  • Medical Therapy With Versus Without Revascularization in Stable Patients With Moderate and Severe Ischemia The Case for Community Equipoise JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Stone, G. W., Hochman, J. S., Williams, D. O., Boden, W. E., Ferguson, T. B., Harrington, R. A., Maron, D. J. 2016; 67 (1): 81-99

    View details for DOI 10.1016/j.jacc.2015.09.056

    View details for Web of Science ID 000367520500013

  • Conservative versus invasive stable ischemic heart disease management strategies: what do we plan to learn from the ISCHEMIA trial? Future cardiology Cheng-Torres, K. A., Desai, K. P., Sidhu, M. S., Maron, D. J., Boden, W. E. 2016; 12 (1): 35-44

    Abstract

    Over the past decade, landmark randomized clinical trials comparing initial management strategies in stable ischemic heart disease (SIHD) have demonstrated no significant reduction in 'hard' end points (all-cause mortality, cardiac death or myocardial infarction) with one strategy versus another. The main advantage derived from early revascularization is improved short-term quality of life. Nonetheless, questions remain regarding how best to manage SIHD patients, such as whether a high-risk subgroup can be identified that may experience a survival or myocardial infarction benefit from early revascularization, and if not, when should diagnostic catheterization and revascularization be performed. The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial is designed to address these questions by randomizing SIHD patients with at least moderate ischemia to an initial conservative strategy of optimal medical therapy or an initial invasive strategy of optimal medical therapy plus cardiac catheterization and revascularization.

    View details for DOI 10.2217/fca.15.57

    View details for PubMedID 26696561

  • Treatment of Patients With Stable Ischemic Heart Disease--Reply. JAMA Bangalore, S., Maron, D. J., Hochman, J. S. 2016; 315 (17): 1905–6

    View details for PubMedID 27139072

  • Effect of Baseline Exercise Capacity on Outcomes in Patients With Stable Coronary Heart Disease (A Post Hoc Analysis of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation Trial) AMERICAN JOURNAL OF CARDIOLOGY Padala, S. K., Sidhu, M. S., Hartigan, P. M., Maron, D. J., Teo, K. K., Sperms, J. A., Mancini, G. B., Sedlis, S. P., Chaitman, B. R., Heller, G. V., Weintraub, W. S., Boden, W. E. 2015; 116 (10): 1509-1515

    View details for DOI 10.1016/j.amjcard.2015.08.012

    View details for PubMedID 26410604

  • Effect of PCI on Long-Term Survival in Patients with Stable Ischemic Heart Disease NEW ENGLAND JOURNAL OF MEDICINE Sedlis, S. P., Hartigan, P. M., Teo, K. K., Maron, D. J., Spertus, J. A., Mancini, G. B., Kostuk, W., Chaitman, B. R., Berman, D., Lorin, J. D., Dada, M., Weintraub, W. S., Boden, W. E. 2015; 373 (20): 1937-1946

    View details for DOI 10.1056/NEJMoa1505532

    View details for Web of Science ID 000364445500008

    View details for PubMedID 26559572

  • Evidence-Based Management of Stable Ischemic Heart Disease Challenges and Confusion JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Bangalore, S., Maron, D. J., Hochman, J. S. 2015; 314 (18): 1917-1918

    View details for Web of Science ID 000364490700011

    View details for PubMedID 26547460

  • Identification of Emergency Department Patients With Acute Heart Failure at Low Risk for 30-Day Adverse Events: The STRATIFY Decision Tool. JACC. Heart failure Collins, S. P., Jenkins, C. A., Harrell, F. E., Liu, D., Miller, K. F., Lindsell, C. J., Naftilan, A. J., McPherson, J. A., Maron, D. J., Sawyer, D. B., Weintraub, N. L., Fermann, G. J., Roll, S. K., Sperling, M., Storrow, A. B. 2015; 3 (10): 737-747

    View details for DOI 10.1016/j.jchf.2015.05.007

    View details for PubMedID 26449993

  • Accelerated atherosclerosis in patients with chronic inflammatory rheumatologic conditions. International journal of clinical rheumatology Hong, J., Maron, D. J., Shirai, T., Weyand, C. M. 2015; 10 (5): 365-381

    Abstract

    Atherosclerosis is a complex inflammatory disease involving aberrant immune and tissue healing responses, which begins with endothelial dysfunction and ends with plaque development, instability and rupture. The increased risk for coronary artery disease in patients with rheumatologic diseases highlights how aberrancy in the innate and adaptive immune system may be central to development of both disease states and that atherosclerosis may be on a spectrum of immune-mediated conditions. Recognition of the tight association between chronic inflammatory disease and complications of atherosclerosis will impact the understanding of underlying pathogenic mechanisms and change diagnostic and therapeutic approaches in patients with rheumatologic syndromes as well as patients with coronary artery disease. In this review, we provide a summary of the role of the immune system in atherosclerosis, discuss the proposed mechanisms of accelerated atherosclerosis seen in association with rheumatologic diseases, evaluate the effect of immunosuppression on atherosclerosis and provide updates on available risk assessment tools, biomarkers and imaging modalities.

    View details for PubMedID 27042216

  • Why Optimal Medical Therapy Should Be a Universal Standard of Care JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Maron, D. J., Boden, W. E. 2015; 66 (7): 774-776

    View details for DOI 10.1016/j.jacc.2015.06.018

    View details for Web of Science ID 000359952900002

    View details for PubMedID 26271058

    View details for PubMedCentralID PMC4695209

  • Validation of the Appropriate Use Criteria for Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease (from the COURAGE Trial) AMERICAN JOURNAL OF CARDIOLOGY Bradley, S. M., Chan, P. S., Hartigan, P. M., Nallamothu, B. K., Weintraub, W. S., Sedlis, S. P., Dada, M., Maron, D. J., Kostuk, W. J., Berman, D. S., Teo, K. K., Mancini, G. B., Boden, W. E., Spertus, J. A. 2015; 116 (2): 167-173

    Abstract

    Establishing the validity of appropriate use criteria (AUC) for percutaneous coronary intervention (PCI) in the setting of stable ischemic heart disease can support their adoption for quality improvement. We conducted a post hoc analysis of 2,287 Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial patients with stable ischemic heart disease randomized to PCI with optimal medical therapy (OMT) or OMT alone. Within appropriateness categories, we compared rates of death, myocardial infarction, revascularization subsequent to initial therapy, and angina-specific health status as determined by the Seattle Angina Questionnaire in patients randomized to PCI + OMT to those randomized to OMT alone. A total of 1,987 patients (87.9%) were mapped to the 2012 publication of the AUC, with 1,334 (67.1%) classified as appropriate, 551 (27.7%) uncertain, and 102 (5.1%) as inappropriate. There were no significant differences between PCI and OMT alone in the rate of mortality and myocardial infarction by appropriateness classification. Rates of revascularization were significantly lower in patients initially receiving PCI + OMT who were classified as appropriate (hazard ratio 0.65; 95% confidence interval 0.53 to 0.80; p <0.001) or uncertain (hazard ratio 0.49; 95% confidence interval 0.32 to 0.76; p = 0.001). Furthermore, among patients classified as appropriate by the AUC, Seattle Angina Questionnaire scores at 1 month were better in the PCI-treated group compared with the medical therapy group (80 ± 23 vs 75 ± 24 for angina frequency, 73 ± 24 vs 68 ± 24 for physical limitations, and 68 ± 23 vs 60 ± 24 for quality of life; all p <0.01), with differences generally persisting through 12 months. In contrast, health status scores were similar throughout the first year of follow-up in PCI + OMT patients compared with OMT alone in patients classified as uncertain or inappropriate. In conclusion, these findings support the validity of the AUC in efforts to improve health care quality through optimal use of PCI.

    View details for DOI 10.1016/j.amjcard.2015.03.057

    View details for Web of Science ID 000357548100001

    View details for PubMedID 25960375

  • Primary Prevention of Heart Failure in Older Adults. JACC. Heart failure Maron, D. J., Hunt, S. A. 2015; 3 (7): 529-530

    View details for DOI 10.1016/j.jchf.2015.04.004

    View details for PubMedID 26160367

  • Reply to Letters Regarding Article, "Prognostic Value of Fasting Versus Nonfasting Low-Density Lipoprotein Cholesterol Levels on Long-Term Mortality: Insight From the National Health and Nutrition Examination Survey III (NHANES-III)". Circulation Doran, B., Guo, Y., Xu, J., Weintraub, H., Mora, S., Maron, D. J., Bangalore, S. 2015; 131 (19)

    View details for DOI 10.1161/CIRCULATIONAHA.114.014177

    View details for PubMedID 25964286

  • Prognostic Value of Fasting Versus Nonfasting Low-Density Lipoprotein Cholesterol Levels on Long-Term Mortality: Insight From the National Health and Nutrition Examination Survey III (NHANES-III). Circulation Doran, B., Guo, Y., Xu, J., Weintraub, H., Mora, S., Maron, D. J., Bangalore, S. 2014; 130 (7): 546-553

    Abstract

    National and international guidelines recommend fasting lipid panel measurement for risk stratification of patients for prevention of cardiovascular events. However, the prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol (LDL-C) is uncertain.Patients enrolled in the National Health and Nutrition Examination Survey III (NHANES-III), a nationally representative cross-sectional survey performed from 1988 to 1994, were stratified on the basis of fasting status (≥8 or <8 hours) and followed for a mean of 14.0 (±0.22) years. Propensity score matching was used to assemble fasting and nonfasting cohorts with similar baseline characteristics. The risk of outcomes as a function of LDL-C and fasting status was assessed with the use of receiver operating characteristic curves and bootstrapping methods. The interaction between fasting status and LDL-C was assessed with Cox proportional hazards modeling. Primary outcome was all-cause mortality. Secondary outcome was cardiovascular mortality. One-to-one matching based on propensity score yielded 4299 pairs of fasting and nonfasting individuals. For the primary outcome, fasting LDL-C yielded prognostic value similar to that for nonfasting LDL-C (C statistic=0.59 [95% confidence interval, 0.57-0.61] versus 0.58 [95% confidence interval, 0.56-0.60]; P=0.73), and LDL-C by fasting status interaction term in the Cox proportional hazards model was not significant (Pinteraction=0.11). Similar results were seen for the secondary outcome (fasting versus nonfasting C statistic=0.62 [95% confidence interval, 0.60-0.66] versus 0.62 [95% confidence interval, 0.60-0.66]; P=0.96; Pinteraction=0.34).Nonfasting LDL-C has prognostic value similar to that of fasting LDL-C. National and international agencies should consider reevaluating the recommendation that patients fast before obtaining a lipid panel.

    View details for DOI 10.1161/CIRCULATIONAHA.114.010001

    View details for PubMedID 25015340

  • Trial to Assess Chelation Therapy (TACT) and equipoise: When evidence conflicts with beliefs. American heart journal Maron, D. J., Hlatky, M. A. 2014; 168 (1): 4-5

    View details for DOI 10.1016/j.ahj.2014.03.008

    View details for PubMedID 24952853

  • Comparative definitions for moderate-severe ischemia in stress nuclear, echocardiography, and magnetic resonance imaging. JACC. Cardiovascular imaging Shaw, L. J., Berman, D. S., Picard, M. H., Friedrich, M. G., Kwong, R. Y., Stone, G. W., Senior, R., Min, J. K., Hachamovitch, R., Scherrer-Crosbie, M., Mieres, J. H., Marwick, T. H., Phillips, L. M., Chaudhry, F. A., Pellikka, P. A., Slomka, P., Arai, A. E., Iskandrian, A. E., Bateman, T. M., Heller, G. V., Miller, T. D., Nagel, E., Goyal, A., Borges-Neto, S., Boden, W. E., Reynolds, H. R., Hochman, J. S., Maron, D. J., Douglas, P. S. 2014; 7 (6): 593-604

    Abstract

    The lack of standardized reporting of the magnitude of ischemia on noninvasive imaging contributes to variability in translating the severity of ischemia across stress imaging modalities. We identified the risk of coronary artery disease (CAD) death or myocardial infarction (MI) associated with ≥10% ischemic myocardium on stress nuclear imaging as the risk threshold for stress echocardiography and cardiac magnetic resonance. A narrative review revealed that ≥10% ischemic myocardium on stress nuclear imaging was associated with a median rate of CAD death or MI of 4.9%/year (interquartile range: 3.75% to 5.3%). For stress echocardiography, ≥3 newly dysfunctional segments portend a median rate of CAD death or MI of 4.5%/year (interquartile range: 3.8% to 5.9%). Although imprecisely delineated, moderate-severe ischemia on cardiac magnetic resonance may be indicated by ≥4 of 32 stress perfusion defects or ≥3 dobutamine-induced dysfunctional segments. Risk-based thresholds can define equivalent amounts of ischemia across the stress imaging modalities, which will help to translate a common understanding of patient risk on which to guide subsequent management decisions.

    View details for DOI 10.1016/j.jcmg.2013.10.021

    View details for PubMedID 24925328

    View details for PubMedCentralID PMC4128344

  • As REGARDS treatment goal attainment compared with COURAGE: the perfect should not be the enemy of the good. Journal of the American College of Cardiology Maron, D. J., Boden, W. E. 2014; 63 (16): 1634-1635

    View details for DOI 10.1016/j.jacc.2014.01.047

    View details for PubMedID 24583302

  • Predicting Outcome in the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) Coronary Anatomy Versus Ischemia JACC-CARDIOVASCULAR INTERVENTIONS Mancini, G. B., Hartigan, P. M., Shaw, L. J., Berman, D. S., Hayes, S. W., Bates, E. R., Maron, D. J., Teo, K., Sedlis, S. P., Chaitman, B. R., Weintraub, W. S., Spertus, J. A., Kostuk, W. J., Dada, M., Booth, D. C., Boden, W. E. 2014; 7 (2): 195-201

    Abstract

    The aim of this study was to determine the relative utility of anatomic and ischemic burden of coronary artery disease for predicting outcomes.Both anatomic burden and ischemic burden of coronary artery disease determine patient prognosis and influence myocardial revascularization decisions. When both measures are available, their relative utility for prognostication and management choice is controversial.A total of 621 patients enrolled in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial with baseline quantitative nuclear single-photon emission computed tomography (SPECT) and quantitative coronary angiography were studied. Several multiple regression models were constructed to determine independent predictors of the endpoint of death, myocardial infarction (MI) (excluding periprocedural MI) and non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Ischemic burden during stress SPECT, anatomic burden derived from angiography, left ventricular ejection fraction, and assignment to either optimal medical therapy (OMT) + percutaneous coronary intervention (PCI) or OMT alone were analyzed.In nonadjusted and adjusted regression models, anatomic burden and left ventricular ejection fraction were consistent predictors of death, MI, and NSTE-ACS, whereas ischemic burden and treatment assignment were not. There was a marginal (p = 0.03) effect of the interaction term of anatomic and ischemic burden for the prediction of clinical outcome, but separately or in combination, neither anatomy nor ischemia interacted with therapeutic strategy to predict outcome.In a cohort of patients treated with OMT, anatomic burden was a consistent predictor of death, MI, and NSTE-ACS, whereas ischemic burden was not. Importantly, neither determination, even in combination, identified a patient profile benefiting preferentially from an invasive therapeutic strategy. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657).

    View details for DOI 10.1016/j.jcin.2013.10.017

    View details for Web of Science ID 000331719900020

    View details for PubMedID 24440015

  • Machine learning for risk prediction of acute coronary syndrome. AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium Vanhouten, J. P., Starmer, J. M., Lorenzi, N. M., Maron, D. J., Lasko, T. A. 2014; 2014: 1940-1949

    Abstract

    Acute coronary syndrome (ACS) accounts for 1.36 million hospitalizations and billions of dollars in costs in the United States alone. A major challenge to diagnosing and treating patients with suspected ACS is the significant symptom overlap between patients with and without ACS. There is a high cost to over- and under-treatment. Guidelines recommend early risk stratification of patients, but many tools lack sufficient accuracy for use in clinical practice. Prognostic indices often misrepresent clinical populations and rely on curated data. We used random forest and elastic net on 20,078 deidentified records with significant missing and noisy values to develop models that outperform existing ACS risk prediction tools. We found that the random forest (AUC = 0.848) significantly outperformed elastic net (AUC=0.818), ridge regression (AUC = 0.810), and the TIMI (AUC = 0.745) and GRACE (AUC = 0.623) scores. Our findings show that random forest applied to noisy and sparse data can perform on par with previously developed scoring metrics.

    View details for PubMedID 25954467

  • Health Status and Quality of Life in Patients With Stable Coronary Artery Disease and Chronic Kidney Disease Treated With Optimal Medical Therapy or Percutaneous Coronary Intervention (Post Hoc Findings from the COURAGE Trial) AMERICAN JOURNAL OF CARDIOLOGY Sedlis, S. P., Jurkovitz, C. T., Hartigan, P. M., Kolm, P., Goldfarb, D. S., Lorin, J. D., Dada, M., Maron, D. J., Spertus, J. A., Mancini, G. B., Teo, K. K., Boden, W. E., Weintraub, W. S. 2013; 112 (11): 1703-1708

    Abstract

    Chronic kidney disease (CKD) is an important clinical co-morbidity that increases the risk of death and myocardial infarction in patients with coronary artery disease (CAD) even when treated with guideline-directed therapies. It is unknown, however, whether CKD influences the effects of CAD treatments on patients' health status, their symptoms, function, and quality of life. We performed a post hoc analysis of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study to compare health status in patients with stable CAD with and without CKD defined as a glomerular filtration rate of <60 ml/min/1.73 m(2) randomized to either percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) or OMT alone. Health status was measured at baseline, 1, 3, 6, 12, 24, and 36 months of follow-up with the Seattle Angina Questionnaire in 310 patients with CKD and 1,719 patients without CKD. Linear mixed-effects models were used to analyze Seattle Angina Questionnaire scores longitudinally. Mean scores for angina-related quality of life, angina frequency, and physical limitation domains improved from baseline values in both patients with and without CKD and plateaued. Early improvement (1 to 6 months) was more common in patients treated with PCI plus OMT than with OMT alone in both patients with and without CKD. Treatment satisfaction scores were high at baseline in all groups and did not change significantly over time. In conclusion, although CKD is an important determinant of event-free survival in patients with stable CAD, it neither precludes satisfactory treatment of angina with PCI plus OMT or OMT alone nor is it associated with an unsatisfactory quality of life.

    View details for DOI 10.1016/j.amjcard.2013.07.034

    View details for Web of Science ID 000327685900001

    View details for PubMedID 24011740

  • Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA JOURNAL OF NUCLEAR CARDIOLOGY Phillips, L. M., Hachamovitch, R., Berman, D. S., Iskandrian, A. E., Min, J. K., Picard, M. H., Kwong, R. Y., Friedrich, M. G., Scherrer-Crosbie, M., Hayes, S. W., Sharir, T., Gosselin, G., Mazzanti, M., Senior, R., Beanlands, R., Smanio, P., Goyal, A., Al-Mallah, M., Reynolds, H., Stone, G. W., Maron, D. J., Shaw, L. J. 2013; 20 (6): 969-975

    Abstract

    There is a preponderance of evidence that, in the setting of an acute coronary syndrome, an invasive approach using coronary revascularization has a morbidity and mortality benefit. However, recent stable ischemic heart disease (SIHD) randomized clinical trials testing whether the addition of coronary revascularization to guideline-directed medical therapy (GDMT) reduces death or major cardiovascular events have been negative. Based on the evidence from these trials, the primary role of GDMT as a front line medical management approach has been clearly defined in the recent SIHD clinical practice guideline; the role of prompt revascularization is less precisely defined. Based on data from observational studies, it has been hypothesized that there is a level of ischemia above which a revascularization strategy might result in benefit regarding cardiovascular events. However, eligibility for recent negative trials in SIHD has mandated at most minimal standards for ischemia. An ongoing randomized trial evaluating the effectiveness of randomization of patients to coronary angiography and revascularization as compared to no coronary angiography and GDMT in patients with moderate-severe ischemia will formally test this hypothesis. The current review will highlight the available evidence including a review of the published and ongoing SIHD trials.

    View details for DOI 10.1007/s12350-013-9773-4

    View details for Web of Science ID 000327858600005

    View details for PubMedID 23963599

  • Low Levels of High-Density Lipoprotein Cholesterol and Increased Risk of Cardiovascular Events in Stable Ischemic Heart Disease Patients A Post-Hoc Analysis From the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Acharjee, S., Boden, W. E., Hartigan, P. M., Teo, K. K., Maron, D. J., Sedlis, S. P., Kostuk, W., Spertus, J. A., Dada, M., Chaitman, B. R., Mancini, G. B., Weintraub, W. S. 2013; 62 (20): 1826-1833

    Abstract

    This study sought to assess the independent effect of high-density lipoprotein-cholesterol (HDL-C) level on cardiovascular risk in patients with stable ischemic heart disease (SIHD) who were receiving optimal medical therapy (OMT).Although low HDL-C level is a powerful and independent predictor of cardiovascular risk, recent data suggest that this may not apply when low-density lipoprotein-cholesterol (LDL-C) is reduced to optimal levels using intensive statin therapy.We performed a post-hoc analysis in 2,193 men and women with SIHD from the COURAGE trial. The primary outcome measure was the composite of death from any cause or nonfatal myocardial infarction (MI). The independent association between HDL-C levels measured after 6 months on OMT and the rate of cardiovascular events after 4 years was assessed. Similar analyses were performed separately in subjects with LDL-C levels below 70 mg/dl (1.8 mmol/l).In the overall population, the rate of death/MI was 33% lower in the highest HDL-C quartile as compared with the lowest quartile, with quartile of HDL-C being a significant, independent predictor of death/MI (p = 0.05), but with no interaction for LDL-C category (p = 0.40). Among subjects with LDL-C levels <70 mg/dl, those in the highest quintile of HDL-C had a 65% relative risk reduction in death or MI as compared with the lowest quintile, with HDL-C quintile demonstrating a significant, inverse predictive effect (p = 0.02).In this post-hoc analysis, patients with SIHD continued to experience incremental cardiovascular risk associated with low HDL-C levels despite OMT during long-term follow-up. This relationship persisted and appeared more prominent even when LDL-C was reduced to optimal levels with intensive dyslipidemic therapy. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).

    View details for DOI 10.1016/j.jacc.2013.07.051

    View details for Web of Science ID 000326574400003

    View details for PubMedID 23973693

  • Prognostic importance of coronary anatomy and left ventricular ejection fraction despite optimal therapy: Assessment of residual risk in the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation Trial AMERICAN HEART JOURNAL Mancini, G. B., Hartigan, P. M., Bates, E. R., Chaitman, B. R., Sedlis, S. P., Maron, D. J., Kostuk, W. J., Spertus, J. A., Teo, K. K., Dada, M., Knudtson, M., Berman, D. S., Booth, D. C., Boden, W. E., Weintraub, W. S. 2013; 166 (3): 481-487

    Abstract

    It is unknown if baseline angiographic findings can be used to estimate residual risk of patients with chronic stable angina treated with both optimal medical therapy (OMT) and protocol-assigned or symptom-driven percutaneous coronary intervention (PCI).Death, myocardial infarction (MI), and hospitalization for non-ST-segment elevation acute coronary syndrome were adjudicated in 2,275 COURAGE patients. The number of vessels diseased (VD) was defined as the number of major coronary arteries with ≥50% diameter stenosis. Proximal left anterior descending, either isolated or in combination with other disease, was also evaluated. Depressed left ventricular ejection fraction (LVEF) was defined as ≤50%. Cox regression analyses included these anatomical factors as well as interaction terms for initial treatment assignment (OMT or OMT + PCI).Percutaneous coronary intervention and proximal left anterior descending did not influence any outcome. Death was predicted by low LVEF (hazard ratio [HR] 1.86, CI 1.34-2.59, P < .001) and VD (HR 1.45, CI 1.20-1.75, P < .001). Myocardial infarction and non-ST-segment elevation acute coronary syndrome were predicted only by VD (HR 1.53, CI 1.30-1.81 and HR 1.24, CI 1.06-1.44, P = .007, respectively).In spite of OMT and irrespective of protocol-assigned or clinically driven PCI, LVEF and angiographic burden of disease at baseline retain prognostic power and reflect residual risk for secondary ischemic events.

    View details for DOI 10.1016/j.ahj.2013.07.007

    View details for Web of Science ID 000324163600022

    View details for PubMedID 24016497

  • Frequency, Predictors, and Consequences of Crossing Over to Revascularization Within 12 Months of Randomization to Optimal Medical Therapy in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Spertus, J. A., Maron, D. J., Cohen, D. J., Kolm, P., Hartigan, P., Weintraub, W. S., Berman, D. S., Teo, K. K., Shaw, L. J., Sedlis, S. P., Knudtson, M., Aslan, M., Dada, M., Boden, W. E., Mancini, G. B. 2013; 6 (4): 409-418

    Abstract

    In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, some patients with stable ischemic heart disease randomized to optimal medical therapy (OMT) crossed over to early revascularization. The predictors and outcomes of patients who crossed over from OMT to revascularization are unknown.We compared characteristics of OMT patients who did and did not undergo revascularization within 12 months and created a Cox regression model to identify predictors of early revascularization. Patients' health status was measured with the Seattle Angina Questionnaire. To quantify the potential consequences of initiating OMT without percutaneous coronary intervention, we compared the outcomes of crossover patients with a matched cohort randomized to immediate percutaneous coronary intervention. Among 1148 patients randomized to OMT, 185 (16.1%) underwent early revascularization. Patient characteristics independently associated with early revascularization were worse baseline Seattle Angina Questionnaire scores and healthcare system. Among 156 OMT patients undergoing early revascularization matched to 156 patients randomized to percutaneous coronary intervention, rates of mortality (hazard ratio=0.51 [0.13-2.1]) and nonfatal myocardial infarction (hazard ratio=1.9 [0.75-4.6]) were similar, as were 1-year Seattle Angina Questionnaire scores. OMT patients, however, experienced worse health status over the initial year of treatment and more unstable angina admissions (hazard ratio=2.8 [1.1-7.5]).Among COURAGE patients assigned to OMT alone, patients' angina, dissatisfaction with their current treatment, and, to a lesser extent, their health system were associated with early revascularization. Because early crossover was not associated with an increase in irreversible ischemic events or impaired 12-month health status, these findings support an initial trial of OMT in stable ischemic heart disease with close follow-up of the most symptomatic patients.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00007657.

    View details for DOI 10.1161/CIRCOUTCOMES.113.000139

    View details for Web of Science ID 000321898000008

    View details for PubMedID 23838107

  • Impact of Adding Ezetimibe to Statin to Achieve Low-Density Lipoprotein Cholesterol Goal (from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE] Trial) AMERICAN JOURNAL OF CARDIOLOGY Maron, D. J., Hartigan, P. M., Neff, D. R., Weintraub, W. S., Boden, W. E. 2013; 111 (11): 1557-1562

    Abstract

    In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study, a revascularization strategy trial with optimal medical therapy in both arms, the low-density lipoprotein (LDL) cholesterol goal was 60 to 85 mg/dl; this was revised to <70 mg/dl in 2004. COURAGE patients (n = 2,287) were titrated with increasing statin doses to achieve the initial LDL cholesterol goal using a prespecified protocol. Ezetimibe was not available when study enrollment began in 1999 but became available after approval in 2003. After maximizing statin dose, ezetimibe was added to reach the LDL cholesterol goal in 34% of patients (n = 734). Median baseline LDL cholesterol was higher in patients who received ezetimibe than in those who did not (109 vs 96 mg/dl). At baseline, 18% of patients who would later receive ezetimibe had LDL cholesterol <85 mg/dl, and 8% had LDL cholesterol <70 mg/dl. On maximum tolerated statin (with or without other lipid-lowering drugs), 40% had LDL cholesterol <85 mg/dl and 23% had LDL cholesterol <70 mg/dl before starting ezetimibe. At the final study visit, 68% of ezetimibe patients achieved LDL cholesterol <85 mg/dl, and 46% achieved LDL cholesterol <70 mg/dl. Using Cox regression analysis, the most significant factors associated with achieving LDL cholesterol goals were lower baseline LDL cholesterol, average statin dose, and ezetimibe use. In conclusion, after maximizing statin dose, the addition of ezetimibe results in a substantial increase in the percentage of patients who reach LDL cholesterol goal, a key component of optimal medical therapy.

    View details for DOI 10.1016/j.amjcard.2013.02.005

    View details for Web of Science ID 000319892100004

    View details for PubMedID 23538020

  • Risk Factor Control for Coronary Artery Disease Secondary Prevention in Large Randomized Trials JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Farkouh, M. E., Boden, W. E., Bittner, V., Muratov, V., Hartigan, P., Ogdie, M., Bertolet, M., Mathewkutty, S., Teo, K., Maron, D. J., Sethi, S. S., Domanski, M., Frye, R. L., Fuster, V. 2013; 61 (15): 1607-1615

    Abstract

    This study evaluated data from 3 federally funded trials that focused on optimal medical therapy to determine if formalized attempts at risk factor control within clinical trials are effective in achieving guideline-driven treatment goals for diabetic patients with coronary artery disease (CAD).Despite clear evidence of benefit for CAD secondary prevention, the level of risk factor control in clinical practice has been disappointing.We obtained data from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) diabetes subgroup, (n = 766 of 2,287), the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial (n = 2,368), and the FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900) to evaluate the proportion of patients achieving guideline-based, protocol-driven treatment targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking cessation, and hemoglobin A1c. The primary outcome measure was the proportion of diabetic CAD patients meeting all 4 pre-specified targets at 1 year after enrollment.The pooled data include 5,034 diabetic patients. The percentages of patients achieving the 1-year low-density lipoprotein cholesterol targets compared with baseline increased from 55% to 77% in COURAGE, from 59% to 75% in BARI 2D, and from 34% to 42% in FREEDOM. Although similar improved trends were seen for systolic blood pressure, glycemic control, and smoking cessation, only 18% of the COURAGE diabetes subgroup, 23% of BARI 2D patients, and 8% of FREEDOM patients met all 4 pre-specified treatment targets at 1 year of follow-up.A significant proportion of diabetic CAD patients fail to achieve pre-specified targets for 4 major modifiable cardiovascular risk factors in clinical trials. We conclude that fundamentally new thinking is needed to explore approaches to achieve optimal secondary prevention treatment goals. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657) (Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D]; NCT00006305) (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).

    View details for DOI 10.1016/j.jacc.2013.01.044

    View details for Web of Science ID 000317192700007

    View details for PubMedID 23500281

  • Revascularization for Silent Ischemia? Another Piece of the Puzzle JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Maron, D. J., Hochman, J. S. 2013; 61 (15): 1624-1625

    View details for DOI 10.1016/j.jacc.2013.01.046

    View details for Web of Science ID 000317192700009

    View details for PubMedID 23500294

  • In Mildly Symptomatic Patients, Should an Invasive Strategy with Catheterization and Revascularization Be Routinely Undertaken? In Mildly Symptomatic Patients, an Invasive Strategy with Catheterization and Revascularization Should Not Be Routinely Undertaken CIRCULATION-CARDIOVASCULAR INTERVENTIONS Maron, D. J., Ting, H. H. 2013; 6 (1): 114-121

    View details for DOI 10.1161/CIRCINTERVENTIONS.112.973438

    View details for Web of Science ID 000330360900024

    View details for PubMedID 23424271

  • Galectin 3 complements BNP in risk stratification in acute heart failure BIOMARKERS Fermann, G. J., Lindsell, C. J., Storrow, A. B., Hart, K., Sperling, M., Roll, S., Weintraub, N. L., Miller, K. F., Maron, D. J., Naftilan, A. J., McPherson, J. A., Sawyer, D. B., Christenson, R., Collins, S. P. 2012; 17 (8): 706-713

    Abstract

    Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure.Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial.Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide.In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events.

    View details for DOI 10.3109/1354750X.2012.719037

    View details for Web of Science ID 000311681100003

    View details for PubMedID 22998064

  • Clinical pathway: helicopter scene STEMI protocol to facilitate long-distance transfer for primary PCI. Critical pathways in cardiology Huang, R. L., Thomassee, E. J., Park, J. Y., Scott, C., Maron, D. J., Fredi, J. L. 2012; 11 (4): 193-198

    Abstract

    The latest American College of Cardiology/American Heart Association guidelines recommend primary percutaneous coronary intervention (PCI) in acute ST-elevation myocardial infarction (STEMI) patients within 90 minutes from presentation to the emergency room. For interhospital transfers, the most recent PCI guidelines recommend first medical contact-to-device times ≤120 minutes. Although PCI-capable hospitals have improved door-to-balloon times, many patients present to non-PCI-capable facilities and have been excluded from national quality measures.In our acute myocardial infarction network, not only do we enable non-PCI hospitals to transfer STEMI patients but empower outside emergency medical services (EMS) to activate the catheterization laboratory team with a burst page and transfer STEMI patients directly from the scene. Data on patient characteristics, outcomes, and time elements were collected for "scene STEMI" patients who circumvented outlying rural non-PCI hospitals and are presented in this case series.From December 2007 to November 2010, 22 STEMI patients with higher than average acuity were transported by helicopter directly to our medical center for primary PCI. Median distance from the scene to our medical center was 47 miles [25th to 75th interquartile range (IQR) = 39-71 miles]. Median EMS-to-balloon time was 120 minutes (IQR = 111-134 minutes). There were no false activations by EMS. In comparison, our median time for interhospital STEMI transfers (N = 335) was 145 minutes (IQR = 121-186 minutes) from 2007 to 2009.In our single-center experience, 22 scene STEMI patients were diagnosed and appropriately triaged by EMS to our center for primary PCI. Our data show feasibility of an EMS-activated STEMI network over long distances with good reperfusion times.

    View details for DOI 10.1097/HPC.0b013e318261c995

    View details for PubMedID 23149361

  • Risk stratification in acute heart failure: Rationale and design of the STRATIFY and DECIDE studies AMERICAN HEART JOURNAL Collins, S. P., Lindsell, C. J., Jenkins, C. A., Harrell, F. E., Fermann, G. J., Miller, K. F., Roll, S. N., Sperling, M. I., Maron, D. J., Naftilan, A. J., McPherson, J. A., Weintraub, N. L., Sawyer, D. B., Storrow, A. B. 2012; 164 (6): 825-834

    Abstract

    A critical challenge for physicians facing patients presenting with signs and symptoms of acute heart failure (AHF) is how and where to best manage them. Currently, most patients evaluated for AHF are admitted to the hospital, yet not all warrant inpatient care. Up to 50% of admissions could be potentially avoided and many admitted patients could be discharged after a short period of observation and treatment. Methods for identifying patients that can be sent home early are lacking. Improving the physician's ability to identify and safely manage low-risk patients is essential to avoiding unnecessary use of hospital beds.Two studies (STRATIFY and DECIDE) have been funded by the National Heart Lung and Blood Institute with the goal of developing prediction rules to facilitate early decision making in AHF. Using prospectively gathered evaluation and treatment data from the acute setting (STRATIFY) and early inpatient stay (DECIDE), rules will be generated to predict risk for death and serious complications. Subsequent studies will be designed to test the external validity, utility, generalizability and cost-effectiveness of these prediction rules in different acute care environments representing racially and socioeconomically diverse patient populations.A major innovation is prediction of 5-day as well as 30-day outcomes, overcoming the limitation that 30-day outcomes are highly dependent on unpredictable, post-visit patient and provider behavior. A novel aspect of the proposed project is the use of a comprehensive cardiology review to correctly assign post-treatment outcomes to the acute presentation.Finally, a rigorous analysis plan has been developed to construct the prediction rules that will maximally extract both the statistical and clinical properties of every data element. Upon completion of this study we will subsequently externally test the prediction rules in a heterogeneous patient cohort.

    View details for DOI 10.1016/j.ahj.2012.07.033

    View details for Web of Science ID 000311634500009

    View details for PubMedID 23194482

  • A comparison of criterion standard methods to diagnose acute heart failure. Congestive heart failure (Greenwich, Conn.) Collins, S. P., Lindsell, C. J., Yealy, D. M., Maron, D. J., Naftilan, A. J., McPherson, J. A., Storrow, A. B. 2012; 18 (5): 262-271

    Abstract

    The authors sought to compare and contrast the clinical criterion standards currently used in a cohort of emergency department (ED) patients to diagnose acute heart failure syndromes (AHFS). In a prospective observational study of patients with signs and symptoms of AHFS, 3 criterion standards were examined: (1) the treating ED physician's diagnosis; (2) the hospital discharge diagnosis; and (3) a diagnosis based on medical record review by a panel of cardiologists. Using Cohen's kappa (κ) coefficient, the authors assessed agreement and then compared the different standards by repeatedly setting one as the criterion standard and the other two as index tests. A total of 483 patients were enrolled. Across all criterion standards, patients with AHFS were more likely to have a history of AHFS, congestion on physical examination and chest radiography, and elevated natriuretic peptide levels than those without AHFS. The standards agreed well (cardiology review vs hospital discharge diagnosis, κ=0.74; cardiology review vs ED diagnosis, κ=0.66; ED diagnosis vs hospital discharge diagnosis κ=0.59). Each method had similar sensitivity but differing specificities. Different criterion standards identify different patients from among those being evaluated for AHFS. Researchers should consider this when choosing between the various criterion standard approaches when evaluating new index tests.

    View details for DOI 10.1111/j.1751-7133.2012.00288.x

    View details for PubMedID 22994440

  • Baseline stress myocardial perfusion imaging results and outcomes in patients with stable ischemic heart disease randomized to optimal medical therapy with or without percutaneous coronary intervention AMERICAN HEART JOURNAL Shaw, L. J., Weintraub, W. S., Maron, D. J., Hartigan, P. M., Hachamovitch, R., Min, J. K., Dada, M., Mancini, G. B., Hayes, S. W., O'Rourke, R. A., Spertus, J. A., Kostuk, W., Gosselin, G., Chaitman, B. R., Knudtson, M., Friedman, J., Slomka, P., Germano, G., Bates, E. R., Teo, K. K., Boden, W. E., Berman, D. S. 2012; 164 (2): 243-250

    Abstract

    The COURAGE trial reported similar clinical outcomes for patients with stable ischemic heart disease (SIHD) receiving optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). The current post hoc substudy analysis examined the relationship between baseline stress myocardial ischemia and clinical outcomes based on randomized treatment assignment.A total of 1,381 randomized patients (OMT n = 699, PCI + OMT n = 682) underwent baseline stress myocardial perfusion single-photon emission computed tomographic imaging. Site investigators interpreted the extent of ischemia by the number of ischemic segments using a 6-segment myocardial model. Patients were divided into those with no to mild (<3 ischemic segments) and moderate to severe ischemia (≥ 3 ischemic segments). Cox proportional hazards models were calculated to assess time to the primary end point of death or myocardial infarction.At baseline, moderate to severe ischemia occurred in more than one-quarter of patients (n = 468), and the incidence was comparable in both treatment groups (P = .36). The primary end point, death or myocardial infarction, was similar in the OMT and PCI + OMT treatment groups for no to mild (18% and 19%, P = .92) and moderate to severe ischemia (19% and 22%, P = .53, interaction P value = .65). There was no gradient increase in events for the overall cohort with the extent of ischemia.From the COURAGE trial post hoc substudy, the extent of site-defined ischemia did not predict adverse events and did not alter treatment effectiveness. Currently, evidence supports equipoise as to whether the extent and severity of ischemia impact on therapeutic effectiveness.

    View details for DOI 10.1016/j.ahj.2012.05.018

    View details for Web of Science ID 000307673700018

    View details for PubMedID 22877811

  • Relationship between Uric Acid Levels and Diagnostic and Prognostic Outcomes in Acute Heart Failure. The open biomarkers journal Henry-Okafor, Q., Collins, S. P., Jenkins, C. A., Miller, K. F., Maron, D. J., Naftilan, A. J., Weintraub, N., Fermann, G. J., McPherson, J., Menon, S., Sawyer, D. B., Storrow, A. B. 2012; 5: 9-15

    Abstract

    We evaluated the association of plasma uric acid alone and in combination with b-type natriuretic peptide (BNP) for emergency department (ED) diagnosis and 30-day prognosis in patients evaluated for acute heart failure (AHF).We prospectively enrolled 322 adult ED patients with suspected AHF. Wilcoxon rank sum test, multivariable logistic regression and likelihood ratio (LR) tests were used for statistical analyses.Uric acid's diagnostic utility was poor and failed to show significant associations with 30-day clinical outcomes. Uric acid also did not add significantly to BNP results.Among ED patients with suspected AHF, uric acid has poor diagnostic and prognostic utility.

    View details for PubMedID 24058387

  • Therapeutic procedures for coronary vasospasm-induced polymorphic ventricular tachycardia. Therapeutic advances in cardiovascular disease Dresen, W. F., Wells, Q. S., Maron, D. J., McPherson, J. A. 2012; 6 (3): 115-121

    Abstract

    Coronary vasospasm is an unusual cause of angina and myocardial ischemia, with the potential to provoke acute myocardial infarction, malignant cardiac arrhythmias, and sudden cardiac death. The diagnosis is largely clinical and requires a high index of suspicion. Provocation studies are rarely performed due to the risks of the procedure and the relatively low incidence of disease. A subset of patients does not respond to conventional medical therapy and a paucity of evidence exists to guide therapy. While generally believed a multifocal phenomenon, there have been reports of successful treatment of focal, refractory vasospasm with coronary stent implantation. Furthermore, consideration of an implantable cardioverter defibrillator is warranted when vasospasm is complicated by lethal ventricular arrhythmias.

    View details for DOI 10.1177/1753944712446303

    View details for PubMedID 22547691

  • Soluble ST2 as a Diagnostic and Prognostic Marker for Acute Heart Failure Syndromes. The open biomarkers journal Henry-Okafor, Q., Collins, S. P., Jenkins, C. A., Miller, K. F., Maron, D. J., Naftilan, A. J., Weintraub, N., Fermann, G. J., McPherson, J., Menon, S., Sawyer, D. B., Storrow, A. B. 2012; 2012 (5): 1-8

    Abstract

    OBJECTIVES: We investigated the association of sST2 with diagnostic and prognostic outcomes and assessed whether it aids B-natriuretic peptide (BNP) in diagnosing and predicting outcomes in emergency department (ED) patients with suspected AHFS. METHODS: We recruited patients who presented to the ED of 3 tertiary hospitals with signs or symptoms of AHFS and met modified Framingham criteria for AHFS. Outcome measures were a final diagnosis of AHFS and 5-and 30-day adverse events. RESULTS: In the 295 subjects with sST2 available, the median sST2 was 0.20 ng/ml (IQR=0.10, 0.34). Although unadjusted analyses indicated sST2 was significantly associated with the diagnosis of AHFS (p=0.02), this was not so in the adjusted analysis (p=0.33). Moderately low diagnostic utility was noted with an AUC of 0.62 (95% CI=0.56, 0.69). Similar sST2 test characteristics were seen when BNP was restricted between 100 and 500 pg/ml. While sST2 was associated with AHFS readmission at 30-days (p=0.04), in the adjusted analyses it was not associated with adverse events. CONCLUSION: In patients with signs or symptoms of AHFS, unadjusted analyses indicated that sST2 was significantly associated with the diagnosis of AHFS and with 30-day AHFS recidivism. However, the associations did not carry over to adjusted analyses, and sST2 did not add significant information with regard to explaining the diagnostic and prognostic variability of BNP.

    View details for PubMedID 23439880

  • Effectiveness of Percutaneous Coronary Intervention in Patients With Silent Myocardial Ischemia (Post Hoc Analysis of the COURAGE Trial) AMERICAN JOURNAL OF CARDIOLOGY Gosselin, G., Teo, K. K., Tanguay, J., Gokhale, R., Hartigan, P. M., Maron, D. J., Gupta, V., Mancini, G. B., Bates, E. R., Chaitman, B. R., Spertus, J. A., Kostuk, W. J., Dada, M., Sedlis, S. P., Berman, D. S., Shaw, L. J., O'Rourke, R. A., Weintraub, W. S., Boden, W. E. 2012; 109 (7): 954-959

    Abstract

    Previous studies have suggested that percutaneous coronary intervention (PCI) decreases long-term mortality in patients with silent myocardial ischemia (SMI), but whether PCI specifically decreases mortality when added to intensive medical therapy is unknown. We performed a post hoc analysis of clinical outcomes in patients in the COURAGE trial based on the presence or absence of anginal symptoms at baseline. Asymptomatic patients were classified as having SMI by electrocardiographic ischemia at rest or reversible stress perfusion imaging (exercise-induced or pharmacologic). Study end points included the composite primary end point (death or myocardial infarction [MI]); individual end points of death, MI, and hospitalization for acute coronary syndrome; and need for revascularization. Of 2,280 patients 12% (n = 283) had SMI and 88% were symptomatic (n = 1,997). There were no between-group differences in age, gender, cardiac risk factors, previous MI or revascularization, extent of angiographic disease, or ischemia by electrocardiogram or imaging. Compared to symptomatic patients, those with SMI had fewer subsequent revascularizations (16% vs 27%, p <0.001) regardless of treatment assignment and fewer hospitalizations for acute coronary syndrome (7% vs 12%, p <0.04). No significant differences in outcomes were observed between the 2 treatment groups, although there was a trend toward fewer deaths in the PCI group (n = 7, 5%) compared to the optimal medical therapy (OMT) group (n = 16, 11%, p = 0.12). In conclusion, addition of PCI to OMT did not decrease nonfatal cardiac events in patients with SMI but showed a trend toward fewer deaths. Although underpowered, given similar outcomes in other small studies, these findings suggest the need for an adequately powered trial of revascularization versus OMT in SMI patients.

    View details for DOI 10.1016/j.amjcard.2011.11.023

    View details for Web of Science ID 000302111400005

    View details for PubMedID 22445578

  • Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages INTERNATIONAL JOURNAL OF NANOMEDICINE Yu, S. S., Lau, C. M., Thomas, S. N., Jerome, W. G., Maron, D. J., Dickerson, J. H., Hubbell, J. A., Giorgio, T. D. 2012; 7: 799-813

    Abstract

    The assessment of macrophage response to nanoparticles is a central component in the evaluation of new nanoparticle designs for future in vivo application. This work investigates which feature, nanoparticle size or charge, is more predictive of non-specific uptake of nanoparticles by macrophages. This was investigated by synthesizing a library of polymer-coated iron oxide micelles, spanning a range of 30-100 nm in diameter and -23 mV to +9 mV, and measuring internalization into macrophages in vitro. Nanoparticle size and charge both contributed towards non-specific uptake, but within the ranges investigated, size appears to be a more dominant predictor of uptake. Based on these results, a protease-responsive nanoparticle was synthesized, displaying a matrix metalloproteinase-9 (MMP-9)-cleavable polymeric corona. These nanoparticles are able to respond to MMP-9 activity through the shedding of 10-20 nm of hydrodynamic diameter. This MMP-9-triggered decrease in nanoparticle size also led to up to a six-fold decrease in nanoparticle internalization by macrophages and is observable by T(2)-weighted magnetic resonance imaging. These findings guide the design of imaging or therapeutic nanoparticles for in vivo targeting of macrophage activity in pathologic states.

    View details for DOI 10.2147/IJN.S28531

    View details for Web of Science ID 000302716500001

    View details for PubMedID 22359457

  • Is cardiac catheterization necessary before initial management of patients with stable ischemic heart disease? Results from a Web-based survey of cardiologists AMERICAN HEART JOURNAL Maron, D. J., Stone, G. W., Berman, D. S., Mancini, G. B., Scott, T. A., Byrne, D. W., Harrell, F. E., Shaw, L. J., Hachamovitch, R., Boden, W. E., Weintraub, W. S., Spertus, J. A. 2011; 162 (6): 1034-U124

    Abstract

    It is unknown whether preconceived beliefs regarding the need for cardiac catheterization and revascularization in patients with stable ischemic heart disease (SIHD) would preclude a study randomizing patients with significant ischemia to a conservative strategy. Given the widespread practice of performing revascularization in patients with SIHD, we assessed the feasibility of conducting a randomized trial comparing initial invasive and conservative strategies in patients with SIHD and moderate or severe ischemia.An online survey to cardiologists queried their willingness to enroll a sample patient with frequent stable angina, >10% myocardial ischemia, and normal ejection fraction into a randomized trial with a 50% chance of being conservatively managed without cardiac catheterization.Among 499 respondents, 57% (95% CI 53%-62%) were willing to enroll the patient. Among 207 cardiologists unwilling to enroll, 55% (95% CI 48%-61%) would be willing if they knew the patient did not have very high-risk features on stress imaging, yielding a total of 80% (95% CI 76%-83%) of cardiologists willing to enroll. No differences were observed among different types of cardiologists (interventional, invasive/noninterventional, and noninvasive). Seventy-one percent (95% CI 67%-75%) were more likely to try initial medical therapy after the publication of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial results.Most surveyed cardiologists were willing to enroll SIHD patients with at least moderate ischemia into a trial with an initial noninvasive strategy arm. These findings support the feasibility of planning a large-scale trial to test the role of cardiac catheterization and revascularization in the initial management of SIHD patients with moderate or severe ischemia.

    View details for DOI 10.1016/j.ahj.2011.09.001

    View details for Web of Science ID 000298033300011

    View details for PubMedID 22137077

  • Angiographic Disease Progression and Residual Risk of Cardiovascular Events While on Optimal Medical Therapy Observations From the COURAGE Trial CIRCULATION-CARDIOVASCULAR INTERVENTIONS Mancini, G. B., Hartigan, P. M., Bates, E. R., Sedlis, S. P., Maron, D. J., Spertus, J. A., Berman, D. S., Kostuk, W. J., Shaw, L. J., Weintraub, W. S., Teo, K. K., Dada, M., Chaitman, B. R., O'Rourke, R. A., Boden, W. E. 2011; 4 (6): 545-552

    Abstract

    The extent to which recurrent events in patients with stable coronary artery disease is attributable to progression of an index lesion originally ≥50% diameter stenosis (DS) but not revascularized or originally <50% DS is unknown during optimal medical therapy (OMT).In the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 205 patients assigned to OMT plus percutaneous coronary intervention (PCI) and 284 patients assigned to OMT only had symptom-driven angiograms suitable for analysis. Percentages of patients in the OMT+PCI and OMT-only cohorts with index lesions originally <50% DS were 30% and 32%, respectively; 20% and 68% had index lesions originally ≥50% DS. In both groups, index lesions originally <50% or ≥50% DS represented <4% and <25% of all such lesions, respectively. The only angiographic predictor of myocardial infarction or acute coronary syndrome was the number of lesions originally ≥50% DS that had not been revascularized (odds ratio, 1.15; confidence limits, 1.01-1.31; P<0.04).Lesions originally <50% DS were index lesions in one third of patients referred for symptom-driven repeat angiography, but represented <4% of all such lesions. Nonrevascularized lesions originally ≥50% DS were more often index lesions in OMT-only patients, but still represented a minority (<25%) of all such lesions. These findings underscore the need for improved therapies to arrest plaque progression and reliable strategies for selecting stenoses warranting PCI.

    View details for DOI 10.1161/CIRCINTERVENTIONS.110.960062

    View details for Web of Science ID 000300549500005

    View details for PubMedID 22045968

  • Impact of Metabolic Syndrome and Diabetes on Prognosis and Outcomes With Early Percutaneous Coronary Intervention in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) Trial JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Maron, D. J., Boden, W. E., Spertus, J. A., Hartigan, P. M., Mancini, G. B., Sedlis, S. P., Kostuk, W. J., Chaitman, B. R., Shaw, L. J., Berman, D. S., Dada, M., Teo, K. K., Weintraub, W. S., O'Rourke, R. A. 2011; 58 (2): 131-137

    Abstract

    Our purpose was to clarify the clinical utility of identifying metabolic syndrome (MetS) in patients with coronary artery disease (CAD).It is uncertain whether MetS influences prognosis in patients with CAD and whether the risk associated with MetS exceeds the risk associated with the sum of its individual components.In a post hoc analysis, we compared the incidence of death or myocardial infarction (MI) in stable CAD patients in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial according to the presence (+) or absence (-) of MetS and diabetes: Group A, -MetS/-diabetes; Group B, +MetS/-diabetes; Group C, -MetS/+diabetes; and Group D, +MetS/+diabetes. We explored which MetS components best predicted adverse outcomes and whether MetS had independent prognostic significance beyond its individual components.Of 2,248 patients, 61% had MetS and 34% diabetes. Risk for death or MI increased from Group A (14%) to Group D (25%, p < 0.001). Hypertension (hazard ratio [HR]: 1.30; 95% confidence interval [CI]: 0.98 to 1.71; p = 0.07), low high-density lipoprotein cholesterol (HR: 1.26; 95% CI: 1.03 to 1.55; p = 0.03), and elevated glucose (HR: 1.17; 95% CI: 0.96 to 1.47; p = 0.11) most strongly predicted death or MI. MetS was associated with an increased risk of death or MI (unadjusted HR: 1.41; 95% CI: 1.15 to 1.73; p = 0.001). However, after adjusting for its individual components, MetS was no longer significantly associated with outcome (HR: 1.15; 95% CI: 0.79 to 1.68; p = 0.46). Allocation to initial percutaneous coronary intervention did not affect the incidence of death or MI within any group.Among stable CAD patients in the COURAGE trial, the presence of MetS identified increased risk for death or MI, but MetS did not have independent prognostic significance after adjusting for its constituent components. The addition of early percutaneous coronary intervention to optimal medical therapy did not significantly reduce the risk of death or MI regardless of MetS or diabetes status. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657).

    View details for DOI 10.1016/j.jacc.2011.02.046

    View details for Web of Science ID 000292189300006

    View details for PubMedID 21718908

  • The Cost-Effectiveness of Percutaneous Coronary Intervention as a Function of Angina Severity in Patients With Stable Angina CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Zhang, Z., Kolm, P., Boden, W. E., Hartigan, P. M., Maron, D. J., Spertus, J. A., O'Rourke, R. A., Shaw, L. J., Sedlis, S. P., Mancini, G. B., Berman, D. S., Dada, M., Teo, K. K., Weintraub, W. S. 2011; 4 (2): 172-U72

    Abstract

    The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial compared percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) to OMT alone in reducing the risk of cardiovascular events in 2287 patients with stable coronary disease. We examined the cost-effectiveness of PCI as a function of angina severity at the time of randomization.Angina severity was assessed with the Seattle Angina Questionnaire (SAQ). Patients were grouped into tertiles based on the distribution of baseline scores such that higher tertiles represented better health status. Clinically significant improvement from baseline within individual patients was defined as score increases of >8 for physical limitation, >20 for angina frequency, and >16 for quality-of-life domains. The incremental cost-effectiveness ratio for PCI was calculated as the difference in costs divided by the difference in proportion of patients with clinically significant improvement. Improvement in angina severity was significantly greater for PCI patients in the lowest and middle tertiles. The number of patients needed to treat was much larger for the highest tertile. The added in-trial cost of PCI ranged from $7300 to $13 000. Incremental cost-effectiveness ratios ranged from $80 000 to $330 000 for the lowest and middle tertiles and from $520 000 to >$3 million for the highest tertile for 1 additional patient to achieve significant clinical improvement in health status.The incremental cost of PCI to provide meaningful clinical benefit above that achieved by OMT alone was lower for patients with severe angina than for those with mild or no angina. However, it is uncertain that at any level of angina severity that PCI as an initial strategy would achieve a socially acceptable cost threshold. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00007657.

    View details for DOI 10.1161/CIRCOUTCOMES.110.940502

    View details for Web of Science ID 000288372200008

    View details for PubMedID 21304091

  • Is Optimal Medical Therapy as Used in the COURAGE Trial Feasible for Widespread Use? Current treatment options in cardiovascular medicine Maron, D. J., Boden, W. E., Weintraub, W. S., Calfas, K. J., O'Rourke, R. A. 2011; 13 (1): 16-25

    Abstract

    Medical therapy is the foundation upon which all treatment for patients with stable coronary artery disease (CAD) is based, regardless of whether revascularization is performed. Although professional societies recommend comprehensive lifestyle and pharmacologic interventions with specific risk factor targets, in practice this does not usually occur. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial tested multiple simultaneous lifestyle and pharmacologic interventions (referred to as "optimal medical therapy" [OMT]) with or without percutaneous coronary intervention (PCI) in patients with stable CAD. Nurse case managers were trained to counsel patients according to protocols designed to achieve predefined lifestyle and risk factor goals. Medications were provided at no cost to patients. Adherence to lifestyle and medication prescription was very high and resulted in significant improvement in risk factor targets. COURAGE found no benefit from the addition of PCI to OMT in the primary outcome of death or myocardial infarction. OMT as delivered in COURAGE has been praised but it has also been criticized as not achievable in "real world" clinical practice. The authors, all COURAGE investigators, believe that the delivery of OMT in COURAGE represents a viable model for secondary prevention that can be translated to real practice, but acknowledge that it is difficult to do so in our fee-for-service health care system. New models of team-based healthcare to achieve evidence-based treatment targets and improved clinical outcomes are needed. Successful translation of COURAGE OMT to everyday practice will require a health care system that rewards quality of care.

    View details for DOI 10.1007/s11936-010-0104-7

    View details for PubMedID 21120640

  • Do Major Cardiovascular Outcomes in Patients With Stable Ischemic Heart Disease in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation Trial Differ by Healthcare System? CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Chaitman, B. R., Hartigan, P. M., Booth, D. C., Teo, K. K., Mancini, G. B., Kostuk, W. J., Spertus, J. A., Maron, D. J., Dada, M., O'Rourke, R. A., Weintraub, W. S., Berman, D. S., Shaw, L. J., Boden, W. E. 2010; 3 (5): 476-483

    Abstract

    The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial enrolled patients from 3 distinct healthcare systems (HCSs) in North America. The primary aim of this study was to determine whether there is a treatment difference in cardiovascular outcomes by HCS.The study population included 968 patients from the US Department of Veterans Affairs (VA), 386 from the US non-VA, and 931 from Canada with different comorbidities and prognoses. The primary outcome was all-cause mortality or nonfatal myocardial infarction (MI) during the median 4.6-year follow-up. Baseline demographics were similar between percutaneous coronary intervention and optimal medical therapy treatment groups within each HCS. After follow-up, the primary end point of total mortality and nonfatal MI was not statistically significant between percutaneous coronary intervention and optimal medical therapy, regardless of HCS: VA, 22.3% versus 21.9% (hazard ratio, 1.05; 95% CI, 0.80-1.38; P=0.95); US non-VA, 15.8% versus 21.8% (hazard ratio, 0.70; 95% CI, 0.43-1.12; P=0.24); Canadian HCS, 17.3% versus 13.5% (hazard ratio, 1.30; 95% CI, 0.93-1.83; P=0.17). The interaction between HCSs and treatment was not statistically significant. Long-term mortality was significantly higher in the VA system as a result of significantly greater comorbidity and worse left ventricular function.In the COURAGE trial, addition of percutaneous coronary intervention to optimal medical therapy did not improve 5-year survival or reduce MI or other major adverse cardiovascular events regardless of whether patients were Canadian or American or US veterans or non-veterans. Outcome differences were largely explained by differences in baseline characteristics known to affect long-term prognosis.

    View details for DOI 10.1161/CIRCOUTCOMES.109.901579

    View details for Web of Science ID 000284262100008

    View details for PubMedID 20664026

  • Having It Both Ways JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Bittl, J. A., Maron, D. J. 2010; 55 (9): 865-866

    View details for DOI 10.1016/j.jacc.2009.11.027

    View details for Web of Science ID 000274865100003

    View details for PubMedID 20045277

  • Optimal Medical Therapy With or Without Percutaneous Coronary Intervention for Patients With Stable Coronary Artery Disease and Chronic Kidney Disease AMERICAN JOURNAL OF CARDIOLOGY Sedlis, S. P., Jurkovitz, C. T., Hartigan, P. M., Goldfarb, D. S., Lorin, J. D., Dada, M., Maron, D. J., Spertus, J. A., Mancini, G. B., Teo, K. K., O'Rourke, R. A., Boden, W. E., Weintraub, W. S. 2009; 104 (12): 1647-1653

    Abstract

    Chronic kidney disease (CKD) is a risk factor for poor outcomes in patients with coronary artery disease (CAD), but it is unknown whether CKD influences the efficacy of alternative CAD treatment strategies. Thus, we compared outcomes in stable CAD patients with and without CKD randomized to percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) or OMT alone in a post hoc analysis of the 2,287 patient COURAGE study. At baseline, 320 patients (14%) had CKD defined as a glomerular filtration rate of <60 mL/min/1.73 m(2), as estimated by the abbreviated 4-variable Modification of Diet in Renal Disease equation. The patients with CKD were older (68 +/- 9 vs 61 +/- 10 years; p <0.001) and more often had diabetes mellitus (42% vs 33%; p = 0.002), hypertension (81% vs 65%; p <0.03), heart failure (13% vs 3.4%; p <001), and three-vessel CAD (37% vs 29%, p = 0.01). After adjustment for these differences, CKD remained an independent predictor of death or nonfatal myocardial infarction (hazard ratio 1.48, 95% confidence interval 1.15 to 1.90). PCI had no effect on these outcomes. Furthermore, at 36 months, a similar percentage of patients with CKD treated with OMT (70%) and PCI plus OMT (76%) were angina free compared to patients without CKD. In conclusion, CKD is an important determinant of clinical outcomes in patients with stable CAD, regardless of the treatment strategy. Although PCI did not reduce the risk of death or myocardial infarction when added to OMT for patients with CKD, it also was not associated with worse outcomes in this high-risk group.

    View details for DOI 10.1016/j.amjcard.2009.07.043

    View details for Web of Science ID 000278137800008

    View details for PubMedID 19962469

  • Impact of an Initial Strategy of Medical Therapy Without Percutaneous Coronary Intervention in High-Risk Patients From the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) Trial AMERICAN JOURNAL OF CARDIOLOGY Maron, D. J., Spertus, J. A., Mancini, G. B., Hartigan, P. M., Sedlis, S. P., Bates, E. R., Kostuk, W. J., Dada, M., Berman, D. S., Shaw, L. J., Chaitman, B. R., Teo, K. K., O'Rourke, R. A., Weintraub, W. S., Boden, W. E. 2009; 104 (8): 1055-1062

    Abstract

    We explored the safety and quality-of-life consequences of treating patients with stable coronary disease and high-risk features initially with optimal medical therapy (OMT) alone compared to OMT plus percutaneous coronary intervention. This was a post hoc analysis of Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial patients. We defined high risk as the onset of Canadian Cardiovascular Society class III angina within 2 months or stabilized acute coronary syndrome within 2 weeks of enrollment. The primary end point was death or myocardial infarction after 4.6 years. Of the 2,287 patients enrolled in the COURAGE trial, 264 (12%) were high risk and had a relative risk of 1.56 for death or myocardial infarction (p = 0.0008) compared to those with non-high-risk features. A total of 35 primary events occurred in the OMT group and 32 in the percutaneous coronary intervention plus OMT group (hazard ratio 1.11, 95% confidence interval 0.69 to 1.79; p = 0.68). No significant difference was found in the prevalence of angina between the 2 groups at 1 year. During the first year of follow-up, 30% of the OMT patients crossed over to the revascularization group. In conclusion, an initial strategy of OMT alone for high-risk patients in the COURAGE trial did not result in increased death or myocardial infarction at 4.6 years or worse angina at 1 year, but it was associated with a high rate of crossover to revascularization.

    View details for DOI 10.1016/j.amjcard.2009.05.056

    View details for Web of Science ID 000270864600009

    View details for PubMedID 19801024

  • Optimal Medical Therapy With or Without Percutaneous Coronary Intervention in Older Patients With Stable Coronary Disease A Pre-Specified Subset Analysis of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) Trial JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Teo, K. K., Sedlis, S. P., Boden, W. E., O'Rourke, R. A., Maron, D. J., Hartigan, P. M., Dada, M., Gupta, V., Spertus, J. A., Kostuk, W. J., Berman, D. S., Shaw, L. J., Chaitman, B. R., Mancini, G. B., Weintraub, W. S. 2009; 54 (14): 1303-1308

    Abstract

    Our aim was to access clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in older patients with stable coronary artery disease (CAD).While older patients with CAD are at increased risk for cardiac events compared with younger patients, it is unclear whether PCI may mitigate this risk more effectively than OMT alone or, alternatively, may be associated with more complications.We conducted a pre-specified analysis of outcomes in stable CAD patients stratified by age and randomized to PCI+OMT or OMT alone in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial.A total of 1,381 patients (60%) were <65 years of age (mean 56+/-6 years) and 904 patients (40%) were >or=65 years of age (mean 72+/-5 years). Achieved treatment targets for blood pressure, low-density lipoprotein cholesterol, adherence to diet and exercise, and angina-free status did not differ by age or treatment assignment. Among older patients, there was a 2- to 3-fold higher death rate, but similar rates of myocardial infarction, stroke, and major cardiac events compared with younger patients. The addition of PCI to OMT did not improve or worsen clinical outcomes in patients>or=65 years of age during a median 4.6 year follow-up.These data support adherence to American College of Cardiology/American Heart Association clinical practice guidelines that advocate OMT as an appropriate initial management strategy, regardless of age. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657).

    View details for DOI 10.1016/j.jacc.2009.07.013

    View details for Web of Science ID 000270082700013

    View details for PubMedID 19778673

  • Impact of Optimal Medical Therapy With or Without Percutaneous Coronary Intervention on Long-Term Cardiovascular End Points in Patients With Stable Coronary Artery Disease (from the COURAGE Trial) AMERICAN JOURNAL OF CARDIOLOGY Boden, W. E., O'Rourke, R. A., Teo, K. K., Maron, D. J., Hartigan, P. M., Sedlis, S. P., Dada, M., Labedi, M., Spertus, J. A., Kostuk, W. J., Berman, D. S., Shaw, L. J., Chaitman, B. R., Mancini, G. B., Weintraub, W. S. 2009; 104 (1): 1-4

    Abstract

    The main results of the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial revealed no significant differences in the primary end point of all-cause mortality or nonfatal myocardial infarction [MI] or major secondary end points (composites of death/MI/stroke; hospitalization for acute coronary syndromes [ACSs]) during a median 4.6-year follow-up in 2,287 patients with stable coronary artery disease randomized to optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). We sought to assess the impact of PCI when added to OMT on major prespecified tertiary cardiovascular outcomes (time to first event), namely cardiac death and composites of cardiac death/MI, cardiac death/MI/hospitalization for ACS, cardiac death/MI/stroke, MI/stroke, or cardiac death/MI/ACS/stroke, during study follow-up. There were no significant differences between treatment arms for the composite of cardiac death or MI (15% in PCI + OMT group vs 14.2% in OMT group, hazard ratio 1.07, 95% confidence interval 0.86 to 1.33, p = 0.62) or in any of the major prespecified composite cardiovascular events during long-term follow-up, even after excluding periprocedural MI as an outcome of interest. Overall, cause-specific cardiovascular outcomes paralleled closely the primary and secondary composite outcomes of the trial as a whole. In conclusion, compared with an initial management strategy of OMT alone, addition of PCI did not decrease the incidence of major cardiovascular outcomes including cardiac death or the composite of cardiac death/MI/ACS/stroke in patients with stable coronary artery disease.

    View details for DOI 10.1016/j.amjcard.2009.02.059

    View details for Web of Science ID 000267895100001

    View details for PubMedID 19576311

  • Quantitative Results of Baseline Angiography and Percutaneous Coronary Intervention in the COURAGE Trial CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Mancini, G. B., Bates, E. R., Maron, D. J., Hartigan, P., Dada, M., Gosselin, G., Kostuk, W., Sedlis, S. P., Shaw, L. J., Berman, D. S., Berger, P. B., Spertus, J., Mavromatis, K., Knudtson, M., Chaitman, B. R., O'Rourke, R. A., Weintraub, W. S., Teo, K., Boden, W. E. 2009; 2 (4): 320-U97

    Abstract

    COURAGE compared outcomes in stable coronary patients randomized to optimal medical therapy plus percutaneous coronary intervention (PCI) versus optimal medical therapy alone.Angiographic data were analyzed by treatment arm, health care system (Veterans Administration, US non-Veterans Administration, Canada), and gender. Veterans Administration patients had higher prevalence of coronary artery bypass graft surgery and left ventricular ejection fraction < or =50%. Men had worse diameter stenosis of the most severe lesion, higher prevalence of prior coronary artery bypass graft surgery, lower left ventricular ejection fraction, and more 3-vessel disease that included a proximal left anterior descending lesion (P<0.0001 for all comparisons versus women). Failure to cross rate (3%) and visual angiographic success of stent procedures (97%) were similar to contemporary practice in the National Cardiovascular Data Registry. Quantitative angiographic PCI success was 93% (residual lesion <50% in-segment) and 82% (<20% in-stent), with only minor nonsignificant differences among health care systems and genders. Event rates were higher in patients with higher jeopardy scores and more severe vessel disease, but rates were similar irrespective of treatment strategy. Within the PCI plus optimal medical therapy arm, complete revascularization was associated with a trend toward lower rate of death or nonfatal myocardial infarction. Complete revascularization was similar between genders and among health care systems.PCI success and completeness of revascularization did not differ significantly by health care system or gender and were similar to contemporary practice. Angiographic burden of disease affected overall event rates but not response to an initial strategy of PCI plus optimal medical therapy or optimal medical therapy alone.

    View details for DOI 10.1161/CIRCOUTCOMES.108.830091

    View details for Web of Science ID 000276074200007

    View details for PubMedID 20031857

  • Health-Risk Appraisal With or Without Disease Management for Worksite Cardiovascular Risk Reduction JOURNAL OF CARDIOVASCULAR NURSING Maron, D. J., Forbes, B. L., Groves, J. R., Dietrich, M. S., Sells, P., Digenio, A. G. 2008; 23 (6): 513-518

    Abstract

    Worksite health promotion programs use health risk appraisal (HRA) surveys to identify employees at increased risk, then provide a range of interventions to encourage high-risk individuals to improve their health. Our objective was to determine how the intensity of intervention after HRA affected cardiovascular risk after 1 year, comparing individual follow-up counseling with environmental supports.133 employees of Vanderbilt University with cardiovascular risk factors were randomly assigned to worksite HRA plus targeted disease management (DM group) or HRA plus information about worksite health promotion programs (HRA group). The DM group received longitudinal individualized counseling for risk reduction, whereas the HRA group members received one feedback session about their risk factors and information about free worksite health promotion programs. The main outcome measure was the difference between groups in the change in average Framingham risk score from baseline to 1 year.There was no significant baseline difference between groups in the Framingham risk score. Among DM participants, the mean (SD) Framingham risk score decreased by 22.6%; among HRA participants, the mean score rose by 4.3% (P = .017 for the difference between groups).In this study of employees with cardiovascular risk factors, HRA followed by individual counseling was more effective than providing information about free worksite health promotion programs.

    View details for Web of Science ID 000260533500010

    View details for PubMedID 18953215

  • Cost-Effectiveness of Percutaneous Coronary Intervention in Optimally Treated Stable Coronary Patients CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Weintraub, W. S., Boden, W. E., Zhang, Z., Kolm, P., Zhang, Z., Spertus, J. A., Hartigan, P., Veledar, E., Jurkovitz, C., Bowen, J., Maron, D. J., O'Rourke, R., Dada, M., Teo, K. K., Goeree, R., Barnett, P. G. 2008; 1 (1): 12-U33

    Abstract

    The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluations) trial compared the effect of percutaneous coronary intervention (PCI) plus optimal medical therapy with optimal medical therapy alone on cardiovascular events in 2287 patients with stable coronary disease. After 4.6 years, there was no difference in the primary end point of death or myocardial infarction, although PCI improved quality of life. The present study evaluated the relative cost and cost-effectiveness of PCI in the COURAGE trial.Resource use was assessed by diagnosis-related group for hospitalizations and by current procedural terminology code for outpatient visits and tests and then converted to costs by use of 2004 Medicare payments. Medication costs were assessed with the Red Book average wholesale price. Life expectancy beyond the trial was estimated from Framingham survival data. Utilities were assessed by the standard gamble method. The incremental cost-effectiveness ratio was expressed as cost per life-year and cost per quality-adjusted life-year gained. The added cost of PCI was approximately $10,000, without significant gain in life-years or quality-adjusted life-years. The incremental cost-effectiveness ratio varied from just over $168,000 to just under $300,000 per life-year or quality-adjusted life-year gained with PCI. A large minority of the distributions found that medical therapy alone offered better outcome at lower cost. The costs per patient for a significant improvement in angina frequency, physical limitation, and quality of life were $154,580, $112,876, and $124,233, respectively.The COURAGE trial did not find the addition of PCI to optimal medical therapy to be a cost-effective initial management strategy for symptomatic, chronic coronary artery disease.

    View details for DOI 10.1161/CIRCOUTCOMES.108.798462

    View details for Web of Science ID 000207504300005

    View details for PubMedID 20031783

  • Reducing post-myocardial infarction mortality in the elderly JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Boden, W. E., Maron, D. J. 2008; 51 (13): 1255-1257

    View details for DOI 10.1016/j.jacc.2008.01.004

    View details for Web of Science ID 000254637000003

    View details for PubMedID 18371554

  • Using COURAGE to treat angina. Medscape journal of medicine Maron, D. J. 2008; 10 (12): 286-?

    View details for PubMedID 19242592

  • Does late PCI improve clinical outcome and survival in patients with arterial occlusion after MI? NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE Maron, D. J. 2007; 4 (5): 250-251

    View details for DOI 10.1038/ncpcardio0856

    View details for Web of Science ID 000245972100008

    View details for PubMedID 17375052

  • The evolving pattern of symptomatic coronary artery disease in the United States and Canada: Baseline characteristics of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial AMERICAN JOURNAL OF CARDIOLOGY Boden, W. E., O'Rourke, R. A., Teo, K. K., Hartigan, P. M., Maron, D. J., Kostuk, W., Knudtson, M., Dada, M., Casperson, P., Harris, C. L., Spertus, J. A., Shaw, L., Chaitman, B. R., Mancini, J., Berman, D. S., Gau, G., Weintraub, W. S. 2007; 99 (2): 208-212

    Abstract

    Major improvements in medical therapy and percutaneous coronary intervention for coronary artery disease (CAD) have emerged during the previous 2 decades, but no randomized trial in patients with stable CAD has been powered to compare these 2 strategies for the hard clinical end points of death or myocardial infarction (MI), and previous studies have not evaluated the effect of coronary stents and intensive medical therapy on cardiac events during long-term follow-up. Between 1999 and 2004, 2,287 patients with documented myocardial ischemia and angiographically confirmed CAD were randomized to the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial, with a principal hypothesis that a strategy of percutaneous coronary intervention plus intensive, guideline-driven medical therapy would be superior to a strategy of intensive medical therapy alone. The primary end point was a composite of all-cause mortality or acute MI (time to first event) during a 2.5- to 7-year (median 5) follow-up. Baseline characteristics were a mean age of 62 +/- 5 years, 85% men, and 86% Caucasian. Mean duration of angina before randomization was 26 months (average 10 episodes/week), and 29% of patients were smokers, 67% had hypertension, 38% had previous MI, 71% had dyslipidemia, 34% had diabetes, 27% had previous revascularization, and 69% had multivessel CAD. Approximately 55% of patients met established criteria for the metabolic syndrome. In conclusion, baseline characteristics of the COURAGE trial study population indicate a highly symptomatic group of patients with CAD who have a significant duration and frequency of antecedent angina pectoris and a high prevalence of cardiac risk factors.

    View details for DOI 10.1016/j.amjcard.2006.07.082

    View details for Web of Science ID 000243545900012

    View details for PubMedID 17223420

  • Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424 JOURNAL OF NUCLEAR CARDIOLOGY Shaw, L. J., Heller, G. V., Casperson, P., Miranda-Peats, R., Slornka, P., Friedman, J., Hayes, S. W., Schwartz, R., Weintraub, W. S., Maron, D. J., Dada, M., King, S., Teo, K., Hartigan, P., Boden, W. E., O'Rourke, R. A., Berman, D. S. 2006; 13 (5): 685-698

    Abstract

    Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial.The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n = 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients' ischemic burdens.The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease.

    View details for DOI 10.1016/j.nuclcard.2006.06.134

    View details for Web of Science ID 000240320900014

    View details for PubMedID 16945749

  • Design and rationale of the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial: Veterans Affairs Cooperative Studies Program no. 424 AMERICAN HEART JOURNAL Boden, W. E., O'Rourke, R. A., Teo, K. K., Hartigan, P. M., Maron, D. J., Kostuk, W., Knudtson, M., Dada, M., Casperson, P., Harris, C. L., Spertus, J. A., Shaw, L., Chaitman, B. R., Mancini, J., Berman, D. S., Weintraub, W. S. 2006; 151 (6): 1173-1179

    Abstract

    Major improvements in medical therapy and percutaneous coronary intervention (PCI) for coronary heart disease have occurred during the past decade, but no randomized trial has compared these 2 strategies for the "hard" clinical end points of death or myocardial infarction nor have earlier studies incorporated the use of coronary stents and aggressive multifaceted medical therapy during long-term follow-up.The COURAGE trial is a multicenter study of patients with documented myocardial ischemia and angiographically confirmed single or multivessel coronary artery disease who are randomized to a strategy of PCI plus intensive medical therapy or intensive medical therapy alone. Medical therapy in both groups is guideline-driven and includes: aspirin, clopidogrel, simvastatin (low-density lipoprotein cholesterol target 60-85 mg/dL), long-acting metoprolol and/or amlodipine, lisinopril or losartan, and long-acting nitrates, as well as lifestyle interventions. The primary end point is a composite of all-cause mortality or acute myocardial infarction, and there will be 85% power to detect an absolute 4.6% (relative 22%) difference between strategies. The principal hypothesis is that PCI plus aggressive medical therapy (projected event rate 16.4%) will be superior to aggressive medical therapy alone (projected event rate 21%) during a 2.5- to 7-year (median of 5 years) follow-up.COURAGE is the largest prospective randomized trial of PCI versus intensive medical therapy to date and will define the incremental benefits of PCI in the setting of contemporary optimal medical therapy for chronic coronary heart disease. A total of 2287 patients have been enrolled, and follow-up will conclude in June 2006.

    View details for DOI 10.1016/j.ahj.2005.08.015

    View details for Web of Science ID 000238614600004

    View details for PubMedID 16781214

  • Ethnic differences in achievement of cholesterol treatment goals JOURNAL OF GENERAL INTERNAL MEDICINE Clark, L. T., Maki, K. C., Galant, R., Maron, D. J., Pearson, T. A., Davidson, M. H. 2006; 21 (4): 320-326

    View details for DOI 10.1111/j.1525-1497.2006.00349.x

    View details for Web of Science ID 000237117200007

  • Ethnic differences in achievement of cholesterol treatment goals. Results from the National Cholesterol Education Program Evaluation Project Utilizing Novel E-Technology II. Journal of general internal medicine Clark, L. T., Maki, K. C., Galant, R., Maron, D. J., Pearson, T. A., Davidson, M. H. 2006; 21 (4): 320-326

    Abstract

    African Americans (AA) have the highest coronary heart disease mortality rate of any ethnic group in the United States. Data from the National Cholesterol Education Program Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II survey were used to assess ethnic differences in low-density lipoprotein cholesterol (LDL-C) goal achievement.NEPTUNE II surveyed patients with treated dyslipidemia to assess achievement of treatment goals established by the Adult Treatment Panel III of the National Cholesterol Education Program. United States physicians working in primary care or relevant subspecialties enrolled 10 to 20 consecutive patients (May to September 2003), and patient data were recorded in Personal Digital Assistants and uploaded to a central database via the internet.Among 4,885 patients receiving treatment for dyslipidemia, 79.7% were non-Hispanic white (NHW) and 8.4% were AA. Non-Hispanic white and AA patients had significantly different frequencies of treatment success, with 69.0% and 53.7%, respectively, having achieved their LDL-C goal (P<.001). African-American patients were more likely to be in the highest risk category, and less likely to be using lipid drug therapy, taking high-efficacy statins, and receiving care from a subspecialist, but the difference in goal achievement remained significant (P<.001) after adjustment for these and other predictors of treatment success.The frequency of treatment success in dyslipidemia management was significantly lower in AA than NHW patients. Additional research is needed to elucidate reasons for this disparity and to evaluate strategies for improving goal achievement among AA patients receiving therapy for dyslipidemia.

    View details for PubMedID 16686806

  • Results of the National Cholesterol Education (NCEP) Program Evaluation Project Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations AMERICAN JOURNAL OF CARDIOLOGY Davidson, M. H., Maki, K. C., Pearson, T. A., Pasternak, R. C., Deedwania, P. C., McKenney, J. M., Fonarow, G. C., Maron, D. J., Ansell, B. J., Clark, L. T., Ballantyne, C. M. 2005; 96 (4): 556-563

    Abstract

    The most recent national survey of compliance with the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) guidelines was completed before ATP III and showed significant underachievement of low-density lipoprotein (LDL) cholesterol goals. The NCEP Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II was a national survey conducted in 2003. Of the 4,885 patients, 67% achieved their LDL cholesterol treatment goal, including 89%, 76%, and 57%, respectively, in the 0 or 1 risk factor, > or = 2 risk factors or coronary heart disease (CHD), and CHD risk equivalent categories. The percentage with triglyceride concentrations > or = 200 mg/dl (2.25 mmol/L) in each risk category who achieved their LDL cholesterol and non-high-density lipoprotein cholesterol goals was 64%, 52%, and 27%, respectively. Patients with diabetes (55%) and other CHD risk equivalents (40%) were less likely to have achieved their LDL cholesterol targets than those with CHD (62%). Of the 1,447 patients with cardiovascular disease, 75% could be classified as very high risk according to the new July 2004 NCEP Writing Group recommendations, and 17.8% of those at very high risk had an LDL cholesterol level of <70 mg/dl (<1.81 mmol/L). In conclusion, these results suggest improved lipid management compared with previous surveys. The largest treatment gaps were found for features new to ATP III as of July 2004, including goal achievement for patients with CHD risk equivalents and for non-high-density lipoprotein cholesterol targets. Most of those (75%) with cardiovascular disease in NEPTUNE II would be considered very high risk and candidates for aggressive therapy to reach the new optional treatment goals.

    View details for DOI 10.1016/j.amjcard.2005.04.019

    View details for Web of Science ID 000231255100017

    View details for PubMedID 16098311

  • Can pravastatin lower coronary event rate if HDL and LDL cholesterol are at low levels? NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE Maron, D. J. 2004; 1 (1): 18-19

    View details for DOI 10.1038/ncpcardio0006

    View details for Web of Science ID 000202931500007

    View details for PubMedID 16265253

  • Flavonoids for reduction of atherosclerotic risk. Current atherosclerosis reports Maron, D. J. 2004; 6 (1): 73-78

    Abstract

    Flavonoids are polyphenolic compounds found in fruits, vegetables, and beverages derived from plants. Foods thought historically by many societies to have healing properties--cocoa, red wine, and tea--are particularly rich in flavonoids. A majority of prospective cohort studies demonstrate a significant inverse association between flavonoid consumption and cardiovascular risk. Short-term studies demonstrate numerous plausible mechanisms by which flavonoids may confer cardiovascular protection: they inhibit low-density lipoprotein oxidation, reduce thrombosis, improve endothelial function, and reduce inflammation. No long-term, randomized, controlled trials of flavonoids with hard clinical endpoints have been conducted. Although there are no recommended daily intake goals for flavonoids, the data presented provide additional rationale to eat a diet containing a variety of flavonoid-rich foods and beverages.

    View details for PubMedID 14662111

  • Cholesterol-lowering effect of a theaflavin-enriched green tea extract - A randomized controlled trial ARCHIVES OF INTERNAL MEDICINE Maron, D. J., Lu, G. P., Cai, N. S., Wu, Z. G., Li, Y. H., Chen, H., Zhu, J. Q., Jin, X. J., Wouters, B. C., Zhao, J. 2003; 163 (12): 1448-1453

    Abstract

    Tea consumption has been associated with decreased cardiovascular risk, but potential mechanisms of benefit are ill-defined. While epidemiologic studies suggest that drinking multiple cups of tea per day lowers low-density lipoprotein cholesterol (LDL-C), previous trials of tea drinking and administration of green tea extract have failed to show any impact on lipids and lipoproteins in humans. Our objective was to study the impact of a theaflavin-enriched green tea extract on the lipids and lipoproteins of subjects with mild to moderate hypercholesterolemia.Double-blind, randomized, placebo-controlled, parallel-group trial set in outpatient clinics in 6 urban hospitals in China. A total of 240 men and women 18 years or older on a low-fat diet with mild to moderate hypercholesterolemia were randomly assigned to receive a daily capsule containing theaflavin-enriched green tea extract (375 mg) or placebo for 12 weeks. Main outcome measures were mean percentage changes in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglyceride levels compared with baseline.After 12 weeks, the mean +/- SEM changes from baseline in total cholesterol, LDL-C, HDL-C, and triglyceride levels were -11.3% +/- 0.9% (P =.01), -16.4% +/- 1.1% (P =.01), 2.3% +/- 2.1% (P =.27), and 2.6% +/- 3.5% (P =.47), respectively, in the tea extract group. The mean levels of total cholesterol, LDL-C, HDL-C, and triglycerides did not change significantly in the placebo group. No significant adverse events were observed.The theaflavin-enriched green tea extract we studied is an effective adjunct to a low-saturated-fat diet to reduce LDL-C in hypercholesterolemic adults and is well tolerated.

    View details for Web of Science ID 000183705400009

    View details for PubMedID 12824094

  • Postexercise protein intake enhances whole-body and leg protein accretion in humans MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Levenhagen, D. K., Carr, C., Carlson, M. G., Maron, D. J., Borel, M. J., Flakoll, P. J. 2002; 34 (5): 828-837

    Abstract

    Exercise increases the use of amino acids for glucose production and stimulates the oxidation of amino acids and other substrates to provide ATP for muscular contraction, and thus the availability of amino acids and energy for postexercise muscle protein synthesis may be limiting. The purpose of this study was to determine the potential of postexercise nutrient intake to enhance the recovery of whole-body and skeletal muscle protein homeostasis in humans.Primed-continuous infusions of L-[1-13C]leucine and L-[ring-2H5]phenylalanine were initiated in the antecubital vein and blood was sampled from a femoral vein and a heated (arterialized) hand vein. Each study consisted of a 30-min basal, a 60-min exercise (bicycle at 60% VO2max), and a 180-min recovery period. Five men and five women were studied three times with an oral supplement administered immediately following exercise in random order: NO = 0, 0, 0; SUPP = 0, 8, 3; or SUPP+PRO = 10, 8, 3 g of protein, carbohydrate, and lipid, respectively.Compared to NO, SUPP did not alter leg or whole-body protein homeostasis during the recovery period. In contrast, SUPP+PRO increased plasma essential amino acids 33%, leg fractional extraction of phenylalanine 4-fold, leg uptake of glucose 3.5-fold, and leg and whole-body protein synthesis 6-fold and 15%, respectively. Whereas postexercise intake of either NO or SUPP resulted in a net leg release of essential amino acids and net loss of whole-body and leg protein, SUPP+PRO resulted in a net leg uptake of essential amino acids and net whole-body and leg protein gain.These findings suggest that the availability of amino acids is more important than the availability of energy for postexercise repair and synthesis of muscle proteins.

    View details for Web of Science ID 000175402700016

    View details for PubMedID 11984302

  • Postexercise nutrient intake timing in humans is critical to recovery of leg glucose and protein homeostasis AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM Levenhagen, D. K., Gresham, J. D., Carlson, M. G., Maron, D. J., Borel, M. J., Flakoll, P. J. 2001; 280 (6): E982-E993

    Abstract

    Although the importance of postexercise nutrient ingestion timing has been investigated for glycogen metabolism, little is known about similar effects for protein dynamics. Each subject (n = 10) was studied twice, with the same oral supplement (10 g protein, 8 g carbohydrate, 3 g fat) being administered either immediately (EARLY) or 3 h (LATE) after 60 min of moderate-intensity exercise. Leg blood flow and circulating concentrations of glucose, amino acids, and insulin were similar for EARLY and LATE. Leg glucose uptake and whole body glucose utilization (D-[6,6-2H(2)]glucose) were stimulated threefold and 44%, respectively, for EARLY vs. LATE. Although essential and nonessential amino acids were taken up by the leg in EARLY, they were released in LATE. Although proteolysis was unaffected, leg (L-[ring-2H(5)]phenylalanine) and whole body (L-[1-13C]leucine) protein synthesis were elevated threefold and 12%, respectively, for EARLY vs. LATE, resulting in a net gain of leg and whole body protein. Therefore, similar to carbohydrate homeostasis, EARLY postexercise ingestion of a nutrient supplement enhances accretion of whole body and leg protein, suggesting a common mechanism of exercise-induced insulin action.

    View details for Web of Science ID 000168809700016

    View details for PubMedID 11350780

  • The epidemiology of low levels of high-density lipoproteins cholesterol in patients with and without coronary artery disease AMERICAN JOURNAL OF CARDIOLOGY Maron, D. J. 2000; 86 (12A): 11L-14L

    Abstract

    Low levels of high-density lipoprotein cholesterol (HDL-C), and elevated total cholesterol-to-HDL-C ratios are independently associated with increased risk of coronary artery disease. In observational studies, every 1-mg/dL increment in HDL-C is associated with a 2% decreased risk of coronary artery disease in men and 3% decreased risk in women. On average, HDL-C levels are lower in men than in women, and are lower in whites than in blacks. Low HDL-C has also been found to be linked to higher risk of ischemic stroke, degree of carotid atherosclerosis, increased atherosclerotic progression as measured by coronary arteriography, higher coronary mortality among people with cardiovascular disease, and the development of coronary artery disease among patients with diabetes mellitus.

    View details for Web of Science ID 000166228700003

    View details for PubMedID 11374848

  • Percutaneous coronary intervention versus medical therapy for coronary heart disease. Current atherosclerosis reports Maron, D. J. 2000; 2 (4): 290-296

    Abstract

    Medical therapy reduces myocardial infarction and death in patients with stable coronary heart disease (CHD). In contrast, there is little evidence available to evaluate the impact of percutaneous coronary intervention (PCI) on hard endpoints in such patients. Four randomized, controlled trials have compared PCI with medical therapy. These studies have demonstrated that PCI results in an improvement in angina and exercise tolerance compared with medical therapy, but they also suggest that medical therapy may be preferable to PCI with respect to the risk of cardiac events. Interpretation of these studies has been limited by small sample size, exclusion of high-risk subjects, no or reduced use of stents, lack of a cost- effectiveness evaluation, and absence of risk factor intervention (except for Atorvastatin versus Revascularization Treatment, which used aggressive low-density lipoprotein lowering with atorvastatin in the medical group only). The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial will permit better definition of the role of PCI in the treatment of stable or recently stabilized patients with CHD.

    View details for PubMedID 11122756

  • Self-reported cardiac risk factors in emergency department nurses and paramedics. Prehospital and disaster medicine BARRETT, T. W., Norton, V. C., Busam, M., Boyd, J., Maron, D. J., Slovis, C. M. 2000; 15 (2): 14-17

    Abstract

    Our objective was to assess the prevalence of cardiac risk factors in a sample of urban paramedics and emergency department (ED) nurses.We asked 175 paramedics and ED nurses working at a busy, urban ED to complete a cardiovascular risk assessment. The survey asked subjects to report smoking history, diet, exercise habits, weight, stress levels, medication use, history of hypertension or cardiac disease, family history of cardiovascular disease (CVD), and cholesterol level (if known).129 of 175 surveys were returned (74% return rate) by 85 paramedics and 44 nurses. The percentages of paramedics and nurses at high or very high risk for cardiac disease were 48% and 41%, respectively. Forty-one percent of female respondents and 46% of male respondents were at high or very high risk. Cigarette smoking was reported in 19% of the paramedics and 14% of the nurses. The percentages of paramedics and nurses who reported hypertension were 13% and 11%, respectively. High cholesterol was reported in 31% of paramedics and 16% of nurses.Forty-eight percent of paramedics and 41% of ED nurses at this center are at high or very high risk for cardiovascular disease, by self-report. Efforts should be made to better educate and intervene in this population of health-care providers in order to reduce their cardiac risk.

    View details for PubMedID 11183456

  • Current perspectives on statins CIRCULATION Maron, D. J., Fazio, S., Linton, M. F. 2000; 101 (2): 207-213

    Abstract

    Statins (HMG-CoA reductase inhibitors) are used widely for the treatment of hypercholesterolemia. They inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering drugs, and lower triglyceride levels in hypertriglyceridemic patients. Statins are well tolerated and have an excellent safety record. Clinical trials in patients with and without coronary heart disease and with and without high cholesterol have demonstrated consistently that statins reduce the relative risk of major coronary events by approximately 30% and produce a greater absolute benefit in patients with higher baseline risk. Proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function, plaque architecture and stability, thrombosis, and inflammation. Mechanisms independent of LDL lowering may play an important role in the clinical benefits conferred by these drugs and may ultimately broaden their indication from lipid-lowering to antiatherogenic agents.

    View details for Web of Science ID 000084821700024

    View details for PubMedID 10637210

  • Nonlipid primary and secondary prevention strategies for coronary heart disease CLINICAL CARDIOLOGY Maron, D. J. 1996; 19 (5): 419-423

    Abstract

    Widespread application of proven primary and secondary preventive strategies for coronary heart disease would result in substantial savings of life and health care dollars. Proven strategies (excluding lipid therapy) include quitting smoking, treating hypertension, physical activity, aspirin therapy, and appropriate use of anticoagulants, beta blockers, and angiotensin-converting enzyme inhibitors in survivors of myocardial infarction. Estrogen replacement therapy is currently under clinical investigation. Avoidance of obesity and tight control of diabetes are prudent interventions as yet unproved by clinical trials. Unfortunately, preventive strategies are frequently underutilized. The greatest challenge for preventive cardiology is to put into practice what we already know to prevent the development and progression of atherosclerosis.

    View details for Web of Science ID A1996UH68300015

    View details for PubMedID 8723603

  • SATURATED FAT INTAKE AND INSULIN RESISTANCE IN MEN WITH CORONARY-ARTERY DISEASE CIRCULATION Maron, D. J., Fair, J. M., Haskell, W. L. 1991; 84 (5): 2020-2027

    Abstract

    To determine whether there is an association between diet and plasma insulin concentration that is independent of obesity, we studied the relation of dietary composition and caloric intake to obesity and plasma insulin concentrations in 215 nondiabetic men aged 32-74 years with angiographically proven coronary artery disease.After adjusting for age, the intake of saturated fatty acids and cholesterol were positively correlated (p less than 0.05) with body mass index (r = 0.18, r = 0.16), waist-to-hip circumference ratio (r = 0.21, r = 0.22), and fasting insulin (r = 0.26, r = 0.23). Carbohydrate intake was negatively correlated with body mass index (r = -0.21), waist-to-hip ratio (r = -0.21), and fasting insulin (r = -0.16). Intake of monounsaturated fatty acids did not correlate significantly with body mass index or waist-to-hip circumference ratio but did correlate positively with fasting insulin (r = 0.24). Intake of dietary calories was negatively correlated with body mass index (r = -0.15). In multivariate analysis, intake of saturated fatty acids was significantly related to elevated fasting insulin concentration independently of body mass index.These cross-sectional findings in nondiabetic men with coronary artery disease suggest that increased consumption of saturated fatty acids is associated independently with higher fasting insulin concentrations.

    View details for Web of Science ID A1991GN52200015

    View details for PubMedID 1934376

  • DEPRESSIVE SYMPTOMS AND SUBSTANCE USE AMONG ADOLESCENT BINGE EATERS AND PURGERS - A DEFINED POPULATION STUDY AMERICAN JOURNAL OF PUBLIC HEALTH Killen, J. D., Taylor, C. B., Telch, M. J., Robinson, T. N., Maron, D. J., Saylor, K. E. 1987; 77 (12): 1539-1541

    Abstract

    We surveyed 646 tenth grade females in Northern California to assess the prevalence of binge eating and purging behaviors. Of these, 10.3 per cent met study criteria for bulimia and an additional 10.4 per cent reported purging behaviors for weight control. Bulimics and purgers were heavier, had greater triceps and subscapular skinfold thicknesses, and reported higher rates of drunkenness, marijuana use, cigarette use, and greater levels of depressive symptomatology.

    View details for Web of Science ID A1987K958400013

    View details for PubMedID 3674255

  • PREVENTIVE MEDICINE IN PRACTICE - THE STATE OF THE ART WESTERN JOURNAL OF MEDICINE Maron, D. J. 1981; 134 (4): 367-372

    Abstract

    Primary and secondary prevention, as opposed to tertiary prevention, is the logical approach to attack today's leading causes of premature death. To apply preventive medicine in their practices, physicians may use a number of tools. The traditional annual examination should be abandoned in favor of periodic screening of asymptomatic patients according to age and sex. Screening should be done on a case-finding basis, facilitated by use of a longitudinal screening flow sheet and evaluated by use of a retrospective audit. An age-sex register can help identify which patients belong to a high-risk group. Health hazard appraisal is a tool for estimating a patient's risk before and after prescribed preventive intervention, and may stimulate patient risk factor reduction-as may other behavior modification techniques. In many cases these tools can be applied by paramedical personnel. Further research is needed to gauge the effects of these techniques on risk, morbidity and mortality.

    View details for Web of Science ID A1981LM98100032

    View details for PubMedID 7245742

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