Hypertrophic cardiomyopathy (HCM)

A 23-year-old male presents to the emergency department after a syncopal episode during a football match. He reports intermittent exertional chest pain, palpitations, and progressive shortness of breath over the past several months. He denies any history of hypertension or valvular disease. His father died suddenly at the age of 35. On physical examination, a harsh crescendo–decrescendo systolic murmur is heard best at the left lower sternal border. The murmur increases with Valsalva maneuver and standing and decreases with squatting and handgrip. A fourth heart sound (S4) is present. Electrocardiography shows left ventricular hypertrophy with deep, narrow (“dagger-like”) Q waves in the inferior and lateral leads. Transthoracic echocardiography demonstrates asymmetric septal hypertrophy with a maximal wall thickness of 18 mm, systolic anterior motion (SAM) of the mitral valve, and a resting left ventricular outflow tract (LVOT) gradient of 60 mmHg. Cardiac MRI shows patchy late gadolinium enhancement. Diagnosis?

Diagnosis is Hypertrophic cardiomyopathy (HCM) with obstructive LVOT physiology and high risk of sudden cardiac death.

1. Definition

Hypertrophic cardiomyopathy is an autosomal dominant disorder caused by mutations in sarcomeric proteins, characterized by unexplained left ventricular hypertrophy, dynamic LVOT obstruction, diastolic dysfunction, myocardial ischemia, and increased risk of arrhythmias and sudden cardiac death.

2. Etiology

1. Autosomal dominant inheritance with variable penetrance
2. Sarcomeric mutations (~60%):
• β-myosin heavy chain (MYH7)
• Myosin-binding protein C (MYBPC3)
3. Sporadic/nonfamilial cases (~40%)
4. Rare mutations involving thin filament proteins

3. Pathophysiology

1. Asymmetric septal hypertrophy leads to reduced LV cavity size
2. Diastolic dysfunction due to impaired relaxation and increased stiffness
3. Dynamic LVOT obstruction:
• Caused by septal hypertrophy + systolic anterior motion (SAM) of mitral valve
• May be present at rest or only with provocation (e.g., exercise, Valsalva)
• Gradient ≥30 mmHg is significant; ≥50 mmHg indicates intervention
4. Mitral regurgitation due to SAM
5. Myocardial ischemia due to microvascular dysfunction
6. Arrhythmias:
• Atrial fibrillation (most common)
• Ventricular tachycardia → ventricular fibrillation → sudden cardiac death
7. Autonomic dysfunction:
• Abnormal blood pressure response to exercise

4. Clinical Features

4.1 Classic Features

1. Dyspnea
2. Angina
3. Exertional syncope
4. Sudden cardiac death (especially in young athletes)

4.2 Additional Features

1. Palpitations
2. Fatigue
3. Family history of sudden cardiac death
4. Symptoms worsened by dehydration or exertion

5. Physical Examination

1. Harsh systolic murmur at left lower sternal border
2. Murmur characteristics:
• ↑ with ↓ preload (Valsalva, standing)
• ↓ with ↑ preload (squatting)
• ↓ with ↑ afterload (handgrip)
3. Pulsus bisferiens
4. S4 heart sound
5. Apical holosystolic murmur (mitral regurgitation)

6. Diagnosis

6.1 Electrocardiography

1. Left ventricular hypertrophy
2. Deep, narrow (“dagger-like”) Q waves in inferior and lateral leads
3. T-wave inversions
4. Arrhythmias (AF, VT)

6.2 Imaging

1. Echocardiography (gold standard):
• LV wall thickness ≥15 mm
• 13–14 mm may be diagnostic with family history or ECG abnormalities
• Asymmetric septal hypertrophy
• Systolic anterior motion (SAM) of mitral valve (highly specific)
• LVOT gradient ≥30 mmHg
2. Cardiac MRI:
• Detects fibrosis (late gadolinium enhancement)
• Helps risk stratification

6.3 Additional Evaluation

1. Holter monitoring (detects NSVT)
2. Exercise testing (assesses BP response and LVOT gradient)
3. Genetic testing and family screening

7. Management

7.1 General Measures

1. Screen first-degree relatives
2. Avoid dehydration and maintain adequate preload
3. Avoid competitive sports (shared decision-making recommended)
4. Avoid drugs that reduce preload or afterload

7.2 Medical Therapy

1. Beta-blockers (first-line)
2. Non-dihydropyridine calcium channel blockers (verapamil, diltiazem)
3. Disopyramide (for refractory obstructive HCM)
4. Mavacamten (for symptomatic obstructive HCM, NYHA class II–III)

7.3 Drugs to Avoid

1. Nitrates and vasodilators
2. ACE inhibitors/ARBs (in obstructive HCM, may worsen LVOT obstruction)
3. Positive inotropes (e.g., dobutamine)
4. Excess diuretics

7.4 ICD Indications

1. Prior cardiac arrest or sustained VT
2. Family history of sudden cardiac death
3. Unexplained syncope
4. LV wall thickness >30 mm
5. Non-sustained VT on Holter
6. Extensive fibrosis (late gadolinium enhancement on MRI)
7. Abnormal blood pressure response to exercise
8. Apical aneurysm (if present)

7.5 Surgical Management

Indications: Symptomatic patients with LVOT gradient ≥50 mmHg despite optimal medical therapy

1. Septal myectomy (gold standard)
2. Alcohol septal ablation

8. Key Clinical Insight

Young patient with exertional syncope + family history of sudden death = hypertrophic cardiomyopathy until proven otherwise

9. Exam Level Pearls

1. Young athlete with exertional syncope and family history → classic HCM
2. Murmur increases with Valsalva (key differentiator from aortic stenosis)
3. LVOT obstruction is dynamic and preload-dependent
4. Most common cause of sudden cardiac death in young athletes
5. Most common cause of death = ventricular arrhythmia (VT → VF)
6. Echocardiography is the diagnostic modality of choice