What are the typical symptoms and management of hypertrophic cardiomyopathy (HCM)?

Clinical Presentation of Hypertrophic Cardiomyopathy

Most patients with HCM are asymptomatic and will achieve normal life expectancy, but when symptomatic, they typically present with exertional dyspnea, chest pain, palpitations, dizziness, presyncope, or syncope—symptoms that occur despite preserved systolic function. 1

Symptom Profile

Common Presenting Symptoms

The most frequently reported symptoms in patients with HCM include:

• Exertional dyspnea (shortness of breath): The most common symptom, occurring in approximately 89% of symptomatic patients, particularly with physical activity 2
• Chest pain (angina pectoris): Present in 70% of symptomatic patients, often occurring with exertion even in the absence of coronary artery disease 2
• Palpitations: Reported in 81% of symptomatic patients, often described as fluttering or rapid heartbeat 2
• Fatigue/tiredness: Affects 89% of symptomatic patients and represents a major limitation to daily activities 2
• Dizziness and lightheadedness: Occurs in 89% of symptomatic patients 2
• Syncope or presyncope: Less common but clinically significant, particularly concerning for sudden cardiac death risk 1

Pathophysiologic Mechanisms

These symptoms arise from multiple interrelated mechanisms:

• Diastolic dysfunction: Impaired ventricular relaxation and increased chamber stiffness lead to elevated left atrial and LV end-diastolic pressures, causing pulmonary congestion and reduced cardiac output 1
• Left ventricular outflow tract obstruction (LVOTO): Present in approximately 70% of HCM patients (obstructive HCM), caused by systolic anterior motion (SAM) of the mitral valve with mitral-septal contact 1, 3
• Myocardial ischemia: Results from supply-demand mismatch due to myocardial hypertrophy, microvascular dysfunction, impaired coronary flow reserve, and increased intracavitary pressures 1
• Mitral regurgitation: Secondary to SAM or primary leaflet abnormalities contributes to symptom burden 1
• Atrial fibrillation: Associated with progressive heart failure symptoms and increased thromboembolic risk 1

Clinical Heterogeneity

Asymptomatic Patients

A large proportion of patients presenting with HCM are asymptomatic and most will achieve normal life expectancy 1. However, sudden cardiac death can occur unpredictably in asymptomatic patients, particularly those younger than 35 years of age, including competitive athletes 1.

Age-Related Presentations

• Older patients: Characteristically show relatively mild degrees of left ventricular hypertrophy and may not experience severe symptoms, though some develop large resting subaortic gradients 1
• Younger patients: May present with more severe phenotypes or remain asymptomatic until sudden cardiac death occurs 1

Disease Progression Pathways

When HCM results in significant complications, there are three relatively discrete pathways 1:

1. Sudden cardiac death: Due to ventricular tachyarrhythmias, most commonly in asymptomatic patients ≤35 years of age 1
2. Progressive heart failure: Characterized by exertional dyspnea with or without chest pain 1
3. Atrial fibrillation: Associated with various degrees of heart failure and increased risk of systemic thromboembolism and stroke 1

Initial Management Approach

Symptomatic Patients

Beta-blockers are the first-line pharmacologic therapy for symptomatic HCM due to their negative inotropic effects and ability to attenuate tachycardia, which prolongs diastolic filling. 1, 4

For patients who cannot tolerate or do not respond to beta-blockers:

• Calcium channel blockers (verapamil or diltiazem) provide effective symptomatic relief through similar negative inotropic and rate-lowering effects 1, 4
• Critical caveat: Both verapamil and diltiazem should be used cautiously in patients with severe outflow tract obstruction, elevated pulmonary artery wedge pressure, and low systemic blood pressure, as decreased blood pressure can trigger increased outflow obstruction and precipitate pulmonary edema 1
• Avoid dihydropyridine calcium channel blockers (e.g., nifedipine) in patients with obstructive physiology as their vasodilatory effects aggravate outflow obstruction 1

For refractory symptoms despite beta-blockers and calcium channel blockers:

• Disopyramide may be added for patients with obstructive HCM 1, 4
• Cardiac myosin inhibitors (mavacamten) represent a newer targeted therapy option 4, 5
• Septal reduction therapy (surgical myectomy or alcohol septal ablation) for drug-refractory heart failure caused by LVOTO 1, 4

Asymptomatic Patients

Essential management includes 1, 4:

• Patient and family education about the disease process
• Screening of first-degree relatives
• Avoiding particularly strenuous activity or competitive athletics 4
• Risk stratification for sudden cardiac death regardless of symptom status 1
• Maintaining healthy body mass index, avoiding dehydration and excess alcohol, smoking cessation 4

Important Clinical Pitfalls

• Dynamic nature of obstruction: LVOTO gradients vary with heart rate, blood pressure, volume status, activity, medications, food, and alcohol intake—provocative maneuvers (standing, Valsalva, exercise) are essential if minimal gradients are observed at rest 1, 4
• Vasodilator use: ACE inhibitors and vasodilators can worsen LVOTO and should be avoided in patients with resting or provocable obstruction 1, 4
• Aggressive diuresis: Can decrease preload and augment LVOTO 4
• Coronary artery disease exclusion: Must exclude CAD in HCM patients with angina pectoris, as concomitant severe coronary atherosclerosis exacerbates ischemia and is associated with poorer prognosis 1