In the Thick of It

Dr. Martin Maron, director of the HCM Center at Lahey Hospital & Medical Center and national principal investigator of the ACACIA-HCM trial, joins Dr. Florian Rader of the HCM Center at Cedars-Sinai to discuss the trial’s findings on aficamten in symptomatic non-obstructive hypertrophic cardiomyopathy (HCM). The conversation covers the long-standing treatment gap for the roughly half of non-obstructive patients who remain symptomatic on beta blockers or calcium channel blockers, the phase 3 trial design, and its co-primary endpoints of health status (KCCQ) and exercise capacity (peak VO2). Dr. Maron explains why the results are clinically meaningful and reviews secondary outcomes, including improvements in NT-proBNP and measures of diastolic function, along with consistent benefit across pre-specified subgroups such as patients with mid-cavitary obstruction. Additionally, the two discuss safety findings on ejection fraction reductions and heart failure events during dose titration, and how real-world monitoring and titration may look if aficamten is approved for this indication.  

Dr. Rachel J. Lampert, MD, a cardiac electrophysiologist and professor of medicine at Yale School of Medicine, and patient advocate Hannah Keime of HeartCharged join Dr. John Fritzlen to discuss arrhythmias, sudden cardiac death, and life after receiving an implantable cardioverter-defibrillator (ICD) in hypertrophic cardiomyopathy (HCM). The conversation covers how often patients with HCM receive ICDs and device therapy, why shock risk persists for a decade or more after implant, and how clinicians look for precipitants and structural changes before escalating treatment with beta blockers, antiarrhythmics like sotalol, catheter ablation, or cardiac denervation. Dr. Lampert shares findings from the LIVE-HCM study on vigorous exercise and arrhythmia risk, along with a structured approach for safely returning to exercise after a shock. Additionally, Hannah reflects on being shocked both in her sleep and on stage, the emotional weight of living with a device, and how adjustments to her ICD programming shaped her experience. 

Patient advocates Hannah and Bethany Keime from HeartCharged sit down with Dr. John Fritzlen to discuss the long-term journey of living with hypertrophic cardiomyopathy (HCM). The conversation covers the progressive nature of the condition, including the onset of heart failure symptoms, atrial fibrillation, and myocardial remodeling over decades, as well as how advanced diagnostics like cardiopulmonary exercise testing (CPET) help clinicians track subtle declines. Dr. Fritzlen shares tailored approaches for counseling young or newly diagnosed patients, emphasizing the importance of active lifestyle management and proactive treatment strategies like cardiac myosin inhibitors. Additionally, the group addresses the critical clinical and lifestyle factors involved in selecting implantable cardioverter-defibrillators (ICDs), detailing the durability advantages of subcutaneous (S-ICD) and extravascular (EV-ICD) systems for active, younger populations.

Dr. Florian Rader joins Dr. Louise Bjerregaard to discuss a groundbreaking randomized, double-blind, triple-crossover trial that challenges the long-standing "mantra" of using beta blockers as first-line therapy for non-obstructive hypertrophic cardiomyopathy (HCM). Dr. Bjerregaard explains how the study compared bisoprolol, verapamil, and placebo, revealing that bisoprolol actually resulted in a significant reduction in functional capacity and a worsening of patient symptoms as measured by the KCCQ score. The conversation explores why slowing the heart rate may be detrimental to patients with "stiff hearts" who rely on chronotropic competence to maintain cardiac output, and why calcium channel blockers like verapamil might be a more favorable alternative for symptom management. This episode is essential listening for clinicians looking to move beyond expert opinion toward evidence-based, personalized care for their non-obstructive HCM patients.View the results of the trial here: https://www.jacc.org/doi/10.1016/j.jacc.2025.11.028

Dr. John Fritzlen sits down with Dr. Hunain Shiwani to discuss a paradigm shift in diagnosing hypertrophic cardiomyopathy (HCM). For 50 years, the medical community has relied on a static 15mm wall thickness threshold that fails to account for individual body size, age, and biological sex; a bias that often leaves female patients underdiagnosed. Dr. Shiwani details his team’s groundbreaking research using machine learning and cardiac MRI data from the UK Biobank to establish personalized diagnostic thresholds. Discover how these demographic-based indexes can improve clinical accuracy, reduce diagnostic bias, and empower clinicians through tools like the HCM Calculator to provide more equitable care for patients on the margins of traditional criteria.References:HCM Calculator: https://hcmcalculator.com/

Dr. James MacNamara welcomes Dr. Milind Desai from the Cleveland Clinic to dissect the results and implications of the ODYSSEY trial, the largest study ever conducted in hypertrophic cardiomyopathy (HCM). The trial investigated the use of mavacamten in patients with non-obstructive HCM, a population with significant unmet medical needs. While the study did not reach statistical significance for its primary endpoints of KCCQ score and peak VO2, Dr. Desai highlights a powerful "rowing in the same direction" effect seen in secondary data. This includes a 53% reduction in cardiac biomarkers (BNP and troponin) and favorable cardiac remodeling observed on echocardiography. The conversation explores why a strong placebo effect may have impacted the results and identifies a specific "sweet spot" responder group: patients with an ejection fraction above 65% and no history of atrial tachyarrhythmias.References:ODYSSEY Subgroup Analysis: https://www.jacc.org/doi/10.1016/j.jacc.2025.12.092ODYSSEY Exploratory Analyses: https://www.jacc.org/doi/10.1016/j.jacc.2025.12.092ODYSSEY-HCM Trial: https://www.nejm.org/doi/full/10.1056/NEJMoa2505927

In this episode of In the Thick of It, Dr. John Fritzlen joins leading electrophysiologist Dr. Mark Link and Hannah and Bethany from Heart Charged to discuss the critical role of implantable cardioverter-defibrillators (ICDs) in managing hypertrophic cardiomyopathy. The group navigates the complex clinical landscape of ICD indications, including the importance of MRI findings and specific risk factors like non-sustained ventricular tachycardia (NSVT). Dr. Link provides an expert comparison of transvenous, subcutaneous (S-ICD), and the latest extravascular (EV-ICD) technologies, focusing on device durability and suitability for active patients. Throughout the conversation, the "Bionic Babes" of Heart Charged offer invaluable patient perspectives on life with a defibrillator, the necessity of shared decision-making, and the evolving guidelines that now encourage vigorous exercise for those living with the condition.

In this episode of In the Thick of It, Dr. Floridian Rader and Dr. Ahmad Masri discuss the transformative results of the MAPLE trial, a head-to-head study comparing aficamten—a cardiac myosin inhibitor—to metoprolol in patients with symptomatic obstructive hypertrophic cardiomyopathy1. The trial utilized a rigorous "double-dummy" design to ensure blinding while testing both medications at therapeutic doses2. Dr. Masri highlights unexpected findings, including the significant reduction in peak $VO_2$ and the worsening of cardiac biomarkers like NT-proBNP in the metoprolol group3. The conversation explores how these results challenge decades of reliance on beta-blockers as a first-line therapy and demonstrate the efficacy of aficamten as a potent upfront monotherapy for improving patient function and cardiac remodeling4.

In this episode of In the Thick of It, Dr. Madeline Smoot talks with Dr. Alex McNamara to discuss the complexities of managing refractory symptoms in patients with hypertrophic cardiomyopathy (HCM). The conversation highlights the distinction between obstructive and non-obstructive symptoms, emphasizing the importance of provocative testing—such as cardiopulmonary exercise testing (CPET) and gold-directed Valsalva maneuvers—to unmask "labile" obstruction that resting echoes might miss. They explore the evolving role of cardiac myosin inhibitors and the potential impact of GLP-1 agonists on obesity-related symptom burden. Additionally, Dr. McNamara provides insights into identifying red flags beyond obstruction, including primary mitral valve disease and the early stages of restrictive or "burnt-out" HCM.

In this episode of In the Thick of It, genetic counselor Matthew Thomas sits down with Dr. Roddy Walsh and Dr. Juan Pablo Ochoa to discuss their groundbreaking research on the genetic architecture of Hypertrophic Cardiomyopathy (HCM). The conversation centers on "Intermediate Effect Variants" (IEVs)—genetic markers that fall between rare, high-impact Mendelian mutations and common, low-impact polygenic risk factors. By utilizing a massive dataset of over 20,000 patients and robust ancestry-matched controls, the researchers demonstrate how these variants contribute to disease severity, age of onset, and wall thickness. This episode explores the practical implications for clinical genetic testing, the necessity of diverse genomic data, and how these findings are shifting the field toward a more quantitative and comprehensive understanding of HCM risk.References: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.074529