Overview
This lecture covers hypertrophic cardiomyopathy (HCM), including its definition, pathophysiology, diagnosis, management, and recent advances in clinical trials, with a focus on both obstructive and non-obstructive disease.
Definition and Epidemiology
- HCM is defined as left ventricular wall thickness >15 mm without other identifiable cause.
- It is the most common genetic cardiovascular disease and a leading cause of sudden cardiac death (SCD).
- Synonyms include HOCM, IHSS, and asymmetric septal hypertrophy.
Classification and Pathophysiology
- Classified as non-obstructive, obstructive (resting gradient >30 mmHg), or latent (provocable gradient >30 mmHg).
- Pathophysiology involves systolic anterior motion (SAM) of the mitral valve, dynamic LV outflow tract (LVOT) obstruction, and myocardial fibrosis.
- Dynamic obstruction is increased by higher contractility, lower preload, and inversely related to afterload.
Clinical Presentation and Diagnosis
- Many patients are asymptomatic; most common symptom is exertional dyspnea.
- Physical exam may reveal a systolic murmur, bisferiens pulse, and sustained PMI.
- Diagnosis uses EKG (LVH pattern), echocardiography (wall thickness, SAM, MR), cardiac MRI (fibrosis), and sometimes cardiac catheterization.
Genetics & Screening
- HCM is autosomal dominant; mutations usually in myosin, actin, or troponin genes.
- Screening involves EKG and echocardiogram in first-degree relatives, starting in childhood with frequency based on age and risk.
Management
- First-line therapy: beta blockers or non-dihydropyridine calcium channel blockers; disopyramide is an alternative.
- Septal myectomy and alcohol septal ablation are options for symptomatic, refractory cases.
- Alcohol ablation has a higher rate of pacemaker need and heart block than myectomy.
- ICDs are indicated for secondary prevention after SCD; risk-based primary prevention is individualized.
Recent and Ongoing Clinical Trials
- Mavacamten and aficamten (myosin ATPase inhibitors) show reduction in LVOT gradients, symptom improvement, and reversible mild EF decreases (typically 5–10%).
- Major studies: EXPLORER-HCM, VALOR-HCM, REDWOOD-HCM, MAVERICK-HCM (including non-obstructive HCM).
- Extension and real-world registries monitor long-term outcomes.
- New therapies (e.g., transcatheter myotomy/SESAME procedure) are in development.
Special Considerations
- Exercise recommendations are shifting; shared decision-making is emphasized, even for competitive athletes.
- Atrial fibrillation is common and increases risk; rhythm control and anticoagulation are key.
- Pregnancy in HCM is generally well-tolerated; maintain adequate preload and monitor for bradycardia with beta blockers.
- Non-obstructive HCM is harder to treat; ongoing trials are evaluating therapies.
Key Terms & Definitions
- HCM — Hypertrophic Cardiomyopathy: inherited thickening of the heart muscle without other cause.
- LVOT — Left Ventricular Outflow Tract.
- SAM — Systolic Anterior Motion of the mitral valve.
- Myomectomy — Surgical removal of part of the thickened septum.
- ICD — Implantable Cardioverter-Defibrillator.
- Mavacamten/Aficamten — Selective myosin inhibitors for HCM.
- SCD — Sudden Cardiac Death.
Action Items / Next Steps
- Read up on recent clinical trials: EXPLORER-HCM, VALOR-HCM, REDWOOD-HCM.
- Review 2020 HCM guidelines for management pathways.
- Prepare for next week’s grand rounds on mavacamten experiences.
- For pediatric-to-adult HCM patients, obtain and review original operative reports.