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"hypertrophic cardiomyopathy"[MeSH Terms] AND management

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Hypertrophic Obstructive Cardiomyopathy (HOCM)

Definition

HOCM is a subset of hypertrophic cardiomyopathy (HCM) in which LV outflow tract (LVOT) obstruction is present. HCM itself is defined as unexplained left ventricular hypertrophy in the absence of abnormal loading conditions (valve disease, hypertension, or congenital heart defects) sufficient to account for the degree of hypertrophy. Prevalence is 0.2-0.5% worldwide, affecting all racial groups. - Goldman-Cecil Medicine, p. 494

Genetics and Pathogenesis

Inheritance: Autosomal dominant with variable penetrance
Sarcomere mutations account for ~50-60% of cases; over 1400 pathogenic variants identified
Most common genes:
- MYH7 (beta-myosin heavy chain) - most frequently mutated
- MYBPC3 (myosin-binding protein C)
- TNNT2 (troponin T)
- These three genes together account for 70-80% of all HCM cases
All are gain-of-function mutations affecting sarcomeric proteins - this enhances myofilament function, causing myocyte hypercontractility, increased energy use, and net negative energy balance
Contrast with dilated cardiomyopathy (DCM): same genes (e.g., beta-myosin) can be involved, but in DCM the mutations are loss-of-function
Robbins & Kumar Basic Pathology, p. 373-374; Goldman-Cecil Medicine, p. 496

Morphology / Gross Pathology

The key gross and microscopic findings:

Massive myocardial hypertrophy without ventricular dilation (heart is thick-walled, heavy, and hypercontractile)
90% show asymmetric septal hypertrophy (ASH) - disproportionate thickening of the ventricular septum vs. LV free wall
Remaining 10% show concentric hypertrophy
On longitudinal section: ventricular cavity takes on a "banana-like" configuration due to septal compression
Systolic anterior motion (SAM) of the mitral valve - the anterior mitral leaflet contacts the septum during systole, creating a fibrous endocardial plaque in the LVOT
Left atrium is enlarged

Histological triad:

Marked myocyte hypertrophy
Myocyte (and myofiber) disarray (haphazard arrangement)
Interstitial fibrosis

Robbins & Kumar Basic Pathology, p. 373-374

HCM: asymmetric septal hypertrophy (A) showing "banana-shaped" ventricular lumen with the fibrous endocardial plaque (arrow), and (B) histology demonstrating myocyte disarray and interstitial fibrosis

FIG 9.27 - Robbins & Kumar Basic Pathology: (A) Asymmetric septal hypertrophy causing the characteristic "banana-shaped" LV lumen, with fibrous endocardial plaque (arrow). (B) Histology showing myocyte disarray, extreme hypertrophy, branching, and interstitial fibrosis.

Pathophysiology

The obstruction is dynamic, not fixed. Two main mechanisms impair cardiac output:

Mechanism	Effect
Diastolic dysfunction	Myocardium doesn't fully relax after systole → impaired LV filling
LVOT obstruction (SAM of mitral valve)	Dynamic obstruction during systole → reduced effective stroke volume

Combined effect:

Reduced cardiac output
Elevated pulmonary venous pressure
Secondary mitral regurgitation (from SAM)
Myocardial ischemia even without CAD (massive hypertrophy + high LV pressures + compromised intramural arterial blood flow)

Clinical Features

Typically manifests during the postpubertal growth spurt, but can present at any age.

Symptoms:

Exertional dyspnea (most common)
Angina (ischemia without obstructive CAD)
Syncope / pre-syncope (often exertional)
Palpitations

Cardinal sign: Harsh systolic ejection murmur at the LLSB/apex

Murmur behavior (dynamic obstruction):

Maneuver	Effect on murmur	Mechanism
Valsalva (straining phase) / standing	↑ murmur	Decreased preload → more obstruction
Squatting / passive leg raise	↓ murmur	Increased preload → less obstruction
Exercise	↑ murmur	Increased inotropy + decreased afterload

Major Complications

Sudden cardiac death (SCD) - HCM is the leading cause of SCD in athletes under 35 years old (responsible for ~1/3 of cases)
Atrial fibrillation with mural thrombus formation and thromboembolic stroke
Ventricular fibrillation
Infective endocarditis of the mitral valve
Congestive heart failure (late)
4-6% incidence of sudden death in children and adolescents specifically

Robbins & Kumar, p. 374; Harriet Lane Handbook, p. 248

Drugs That Worsen HOCM (Contraindicated / Use with Caution)

HOCM is a preload-dependent lesion. These agents worsen LVOT obstruction:

Drug Class	Mechanism of Harm
Diuretics	Volume depletion → decreased preload
Vasodilators (nitrates, ACE inhibitors)	Decreased preload and afterload
Positive inotropes (digoxin, dopamine)	Increased contractility → decreased LV end-diastolic volume
Tachycardia (e.g., from atropine, dehydration)	Less filling time → worsened obstruction

Frameworks for Internal Medicine, p. 319

Diagnosis

Echo (cornerstone): Asymmetric septal hypertrophy (septal/posterior wall ratio >1.3-1.5), SAM of the mitral valve, LVOT gradient (resting ≥30 mmHg, or provoked ≥50 mmHg = significant obstruction)
ECG: LV hypertrophy, deep Q waves (especially inferior and lateral leads), ST/T changes
Genetic testing: Recommended when a diagnostic phenotype is present; valuable for cascade screening of family members
Cardiac MRI: Detects fibrosis (late gadolinium enhancement) - marker of SCD risk

Management

Medical (mainstay)

Beta-blockers (first-line) - reduce heart rate, decrease inotropy, improve diastolic filling
Calcium channel blockers (verapamil or diltiazem) - negative inotropes; alternative to beta-blockers
Disopyramide - negative inotrope + antiarrhythmic; often combined with a beta-blocker for LVOT obstruction
Mavacamten (myosin inhibitor) - novel agent; reduces LVOT obstruction; first-in-class cardiac myosin inhibitor
Avoid: diuretics, vasodilators, digoxin, inotropes

Rate/Rhythm Control for AF in HCM

Preferred: disopyramide + beta-blocker, OR verapamil/diltiazem for rate control, OR amiodarone alone
Anticoagulation for AF (stroke prevention)

Invasive / Procedural

Septal myectomy (Morrow procedure) - surgical resection of the hypertrophied septum; gold standard for drug-refractory symptomatic LVOT obstruction
Alcohol septal ablation - catheter-based injection of alcohol into the first septal perforator → controlled septal infarction; reduces obstruction; used in surgical candidates and pre-transplant HOCM patients
ICD (implantable cardioverter-defibrillator) - for SCD prevention in high-risk patients

Lifestyle

Moderate restriction of physical activity (avoid competitive sports)
Maintain adequate hydration (preload protection)

Pediatric-Specific

Negative inotropes (beta-blocker or CCB) for symptom control
ICD if at increased risk for SCD
Myectomy if symptomatic with subaortic obstruction
Harriet Lane Handbook, p. 248; Goldman-Cecil Medicine; Robbins & Kumar, p. 374

Key Distinguishing Features vs. Other Cardiomyopathies

Feature	HCM/HOCM	DCM	RCM
Wall thickness	Increased	Normal/thin	Normal (may increase)
Cavity size	Small	Dilated	Normal/small
Systolic function	Normal/hyperdynamic	Reduced	Normal
Diastolic function	Impaired (stiff)	Impaired	Severely impaired (stiff)
Genetics	Gain-of-function sarcomere	Loss-of-function sarcomere	Variable

Summary: HOCM is the obstructive form of HCM, caused by gain-of-function sarcomere mutations, characterized by asymmetric septal hypertrophy + dynamic LVOT obstruction from SAM of the mitral valve. Management hinges on negative inotropes, avoidance of preload-reducing agents, and septal reduction procedures for refractory cases. It is the leading cause of sudden cardiac death in young athletes.

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