Overview
This lecture reviews hypertrophic cardiomyopathy (HCM), focusing on its diagnosis, pathophysiology, management, and new therapies including novel myosin inhibitors.
Case Presentations & HCM Phenotypes
- HCM presents with variable phenotypes, including apical and asymmetric septal hypertrophy and non-obstructive vs. obstructive forms.
- Key symptoms: exertional dyspnea, heart failure signs, fatigue, arrhythmia, and syncope.
- Severity ranges from mild symptoms to advanced heart failure and end-stage disease.
Pathophysiology & Diagnosis
- HCM is a genetic disorder, most commonly due to mutations in myosin binding protein C and beta myosin heavy chain.
- Characterized by left ventricular hypertrophy (>15 mm wall thickness, or >13 mm with family history) with no other apparent cause.
- Obstructive HCM defined by LV outflow tract (LVOT) gradient ≥30 mmHg.
- Clinical features include diastolic dysfunction, mitral regurgitation, arrhythmias, and microvascular angina.
- Diagnosis relies on echocardiography (main), MRI (for unclear cases or fibrosis assessment), and rarely, cardiac catheterization.
Management & Guidelines
- First-line therapies: beta blockers and non-dihydropyridine calcium channel blockers to reduce symptoms.
- Disopyramide can be added if symptoms persist (caution for arrhythmia risk).
- Septal reduction therapy (surgery or alcohol ablation) reserved for refractory cases, mainly at experienced centers.
- Non-obstructive HCM management options remain limited.
- Monitoring includes frequent echocardiograms for gradient and ejection fraction (EF) assessment.
Emerging Therapies: Myosin Inhibitors
- Mavacamten: a selective, reversible cardiac myosin inhibitor that reduces LVOT gradients, improves symptoms, and is FDA-approved for obstructive HCM.
- Clinical trials (PIONEER, EXPLORER, VALOR) show significant improvements in exercise capacity, symptoms, gradient reduction, and quality of life.
- Main adverse effect: reversible drop in EF; requires regular monitoring.
- Ongoing studies evaluate long-term safety and use in non-obstructive HCM.
- Aficamten: a newer, short-half-life myosin inhibitor under clinical study.
Key Terms & Definitions
- Hypertrophic Cardiomyopathy (HCM) — genetic cardiac disorder with left ventricular hypertrophy not explained by other causes.
- LVOT Gradient — pressure difference across the left ventricular outflow tract, defines obstructive HCM.
- Mavacamten — allosteric, reversible myosin ATPase inhibitor for obstructive HCM.
- Septal Reduction Therapy — surgical or catheter-based procedure to decrease septal thickness and reduce LVOT obstruction.
Action Items / Next Steps
- Review HCM guideline-directed therapy algorithms.
- Monitor patients on myosin inhibitors with serial echocardiograms at initiation and regular intervals.
- Read latest ACC/AHA guidelines for HCM management.
- For further learning, watch Dr. Byland’s Grand Rounds on HCM (as referenced).