Cardiology · Cardiomyopathy

Hypertrophic Cardiomyopathy

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Hypertrophic cardiomyopathy is an autosomal dominant disorder caused by mutations in sarcomere proteins, most commonly beta-myosin heavy chain.

Confidence:
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The physical exam reveals a harsh systolic crescendo-decrescendo murmur at the left sternal border that does not radiate to the carotids.

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The murmur intensity increases with maneuvers that decrease preload, such as Valsalva maneuver or standing up.

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The murmur intensity decreases with maneuvers that increase preload or afterload, such as squatting, handgrip, or passive leg raise.

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Patients often present with exertional syncope, angina, or dyspnea due to left ventricular outflow tract (LVOT) obstruction and diastolic dysfunction.

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First-line medical therapy for symptomatic patients is beta-blockers or non-dihydropyridine calcium channel blockers to improve diastolic filling and reduce outflow obstruction.

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Implantable cardioverter-defibrillator (ICD) placement is the definitive management for patients at high risk of sudden cardiac death.

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Vignette unlocked

A 22-year-old male college athlete presents to the clinic for a sports physical. He reports occasional lightheadedness during intense basketball games but denies chest pain or palpitations. On physical exam, a harsh systolic murmur is heard at the left sternal border. The murmur increases in intensity when the patient performs a Valsalva maneuver and decreases when he squats. His family history is significant for a paternal uncle who died suddenly at age 30.

What is the most likely diagnosis?

+Reveal answer

Hypertrophic cardiomyopathy

The vignette describes the classic dynamic murmur of hypertrophic cardiomyopathy, which increases with decreased preload (Valsalva) and decreases with increased preload (squatting), consistent with LVOT obstruction.

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Etiology / Epidemiology

Autosomal dominant genetic disorder of sarcomere proteins. Among the most common identifiable structural causes of sudden cardiac death in young athletes (ranked first in the US National Registry [Maron, 2009] but third in NCAA data [Petek, 2024]).

Clinical Manifestations

Dyspnea and syncope. Systolic murmur that increases with Valsalva; pulsus bisferiens.

Diagnosis

Echocardiogram showing maximal LV wall thickness ≥15 mm in any segment (≥13 mm if a first-degree relative is affected or genotype is positive).

Treatment

Beta-blockers are first-line. Avoid nitrates, diuretics, and digoxin.

Prognosis

Risk of ventricular arrhythmias. Annual ICD evaluation for high-risk patients.

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Epidemiology & Etiology

Inherited as an autosomal dominant trait involving mutations in genes encoding cardiac sarcomere proteins. It is among the most common identifiable causes of sudden cardiac death in young, otherwise healthy athletes: the US National Registry of Sudden Death in Athletes (Maron et al., 2009) ranked HCM first (about one-third of confirmed cardiovascular deaths), whereas a 20-year NCAA study (Petek et al., 2024) ranked it third (12.7%) behind autopsy-negative sudden unexplained death and idiopathic left ventricular hypertrophy; the 2025 AHA/ACC sports-participation scientific statement notes that autopsy-negative sudden cardiac death is likely the most common cause under age 35. Prevalence is approximately 1 in 500 in the general population.

Pertinent Anatomy

Characterized by asymmetric septal hypertrophy leading to left ventricular outflow tract (LVOT) obstruction. The anterior leaflet of the mitral valve is pulled toward the septum during systole, known as systolic anterior motion (SAM).

Pathophysiology

Hypertrophy causes diastolic dysfunction and impaired filling. LVOT obstruction worsens with decreased preload or increased contractility. This creates a dynamic pressure gradient that results in the classic crescendo-decrescendo murmur.

Clinical Manifestations

Patients present with exertional dyspnea, angina, or syncope. The systolic murmur intensity increases with Valsalva maneuver or standing, and decreases with squatting. Red flags include syncope, family history of sudden death, and non-sustained ventricular tachycardia on Holter monitor.

Diagnosis

The Echocardiogram is the first-line diagnostic test, revealing maximal left ventricular wall thickness ≥15 mm in any segment in the absence of another identifiable cause, or ≥13 mm in first-degree relatives of an affected patient and in genotype-positive individuals. Genetic testing is recommended for family screening. Cardiac MRI is useful for assessing myocardial fibrosis and extent of hypertrophy.

Treatment

Beta-blockers (e.g., metoprolol) are the first-line therapy to reduce heart rate and contractility. Avoid nitrates, diuretics, and digoxin as these decrease preload or increase contractility, worsening LVOT obstruction. Surgical septal myectomy or alcohol septal ablation is reserved for refractory symptoms.

Prognosis

Patients have an increased risk of ventricular arrhythmias and sudden cardiac death, although most are at low risk with contemporary risk stratification and management. An implantable cardioverter-defibrillator (ICD) is recommended for high-risk patients. Regular monitoring with serial echocardiograms is recommended to assess disease progression.

Differential Diagnosis

Aortic Stenosis: murmur intensity decreases with Valsalva

Athlete's Heart: physiological hypertrophy, no diastolic dysfunction

Hypertensive Heart Disease: concentric hypertrophy, not asymmetric

Mitral Valve Prolapse: mid-systolic click

Dilated Cardiomyopathy: systolic dysfunction, thin walls