Hypertrophic cardiomyopathy is the most common inherited cardiac disease (prevalence ~1 in 200–500), characterized by left ventricular hypertrophy (typically asymmetric septal thickening) in the absence of another loading condition, with dynamic left ventricular outflow tract obstruction (LVOTO) present in ~50–75% of patients. [1-3] It is an autosomal dominant disorder caused by sarcomeric gene mutations and is a leading cause of sudden cardiac death (SCD) in young people. [1][4]
1. History
- Exertional symptoms: dyspnea on exertion, exercise intolerance, fatigue — the hallmark complaints [3][5]
- Chest pain: anginal-type, often exertional; due to microvascular ischemia and increased myocardial oxygen demand
- Syncope/presyncope: particularly with exertion or postural changes — a red flag for SCD risk [4][6]
- Palpitations: may indicate atrial fibrillation (present in >50% over time) or ventricular arrhythmias [2-3]
- Timing and triggers: symptoms worsen with dehydration, Valsalva, standing, post-prandial states, exercise, and heat — all reduce preload and worsen LVOTO [6]
- Severity/progression: assess NYHA functional class; use cardiopulmonary exercise testing if uncertain [6]
- Important negatives: many patients are asymptomatic and diagnosed incidentally via murmur, abnormal ECG, or family screening [3][5]
2. Alarm Features
- Syncope (especially exertional or recurrent unexplained) — major SCD risk factor [4][6]
- Cardiac arrest or sustained ventricular tachycardia — secondary prevention ICD indication [6-7]
- Family history of HCM-related sudden death in a close relative [4][6]
- Acute hypotension in obstructive HCM — a medical urgency requiring immediate volume resuscitation and vasoconstrictors (phenylephrine); avoid inotropes [8]
- New-onset heart failure symptoms (orthopnea, PND, edema) — may indicate progression to end-stage/burned-out HCM with LVEF <50% [2]
- Rapid atrial fibrillation — poorly tolerated due to loss of atrial kick and shortened diastolic filling
3. Medications
First-line (symptomatic obstructive HCM)
- Beta-blockers (e.g., metoprolol succinate) — first-line; titrate to resting heart rate suppression [8]
- Non-dihydropyridine calcium channel blockers (verapamil, diltiazem) — alternative if beta-blockers not tolerated; do not combine with beta-blockers (risk of excessive bradycardia/hypotension) [3][6]
Second-line / escalation
- Disopyramide — potent negative inotrope; must be combined with an AV nodal blocker (beta-blocker or CCB) to prevent AF with rapid conduction [3][8]
- Mavacamten (Camzyos) — first-in-class cardiac myosin inhibitor; FDA-approved for symptomatic NYHA II–III obstructive HCM; requires REMS program with serial LVEF monitoring (do not initiate if LVEF <55%; interrupt if LVEF <50%) [8-10]
- Aficamten (Myqorzo) — next-in-class cardiac myosin inhibitor; FDA-approved for symptomatic obstructive HCM [9][11]
Contraindicated / avoid in obstructive HCM
- Vasodilators (nitroglycerin, nifedipine, amlodipine, ACE inhibitors, ARBs)
- High-dose diuretics
- Positive inotropes (dobutamine, dopamine, milrinone)
- Digoxin
- Stimulant medications (ADHD stimulants)
- β-agonists [6][8]
Drug interactions with mavacamten: Contraindicated with strong CYP2C19 inhibitors and moderate-to-strong CYP2C19/CYP3A4 inducers [10]
4. Diet
- Maintain adequate hydration — dehydration reduces preload and worsens LVOTO [6][12]
- Avoid excessive alcohol — can cause vasodilation and dehydration; also increases AF risk [6]
- Avoid excessive caffeine [6]
- Maintain healthy body weight [6]
- No specific dietary restrictions beyond standard cardiovascular health recommendations
5. Review of Systems
- Cardiovascular: chest pain, dyspnea, palpitations, syncope/presyncope, orthopnea, lower extremity edema
- Neurological: lightheadedness, dizziness, near-syncope (especially positional or exertional)
- Pulmonary: exertional dyspnea, paroxysmal nocturnal dyspnea
- Constitutional: exercise intolerance, fatigue
- Musculoskeletal/systemic: screen for features of phenocopies (e.g., Fabry disease — neuropathic pain, angiokeratomas; Noonan syndrome — dysmorphic features; Danon disease — skeletal myopathy) [8]
6. Collateral History and Family History
- Three-generation family history is recommended as part of initial evaluation (Class I recommendation) [8]
- Ask specifically about: relatives with HCM, unexplained sudden death (especially <50 years), heart failure, ICD placement, cardiac transplantation [5][8]
- Family history of SCD in a close relative is a major risk factor for ICD consideration [4][6]
- Genetic counseling by a counselor versed in cardiac genetics is highly recommended before genetic testing [3]
- Genetic variants found in only 30–60% of patients; 8+ genes implicated [3]
- All first-degree relatives require screening with ECG and echocardiography [7-8]
7. Risk Factors
- Autosomal dominant inheritance — sarcomeric gene mutations (MYH7, MYBPC3 most common) [1-2]
- Family history of HCM or sudden cardiac death
- Young age — higher SCD risk in younger patients [4][8]
- Massive LVH (wall thickness ≥30 mm) [4][6]
- LV apical aneurysm with regional scarring [4][6]
- Extensive late gadolinium enhancement on CMR (>15–20% of LV mass) [12-13]
- LVEF <50% (end-stage progression) [4][12]
- NSVT on ambulatory monitoring [6]
- Unexplained syncope [4][6]
- Abnormal blood pressure response to exercise [7]
8. Differential Diagnosis
- Athlete's heart — physiologic LVH; typically concentric, wall thickness rarely >13 mm, normal diastolic function, regression with deconditioning [8]
- Hypertensive heart disease — concentric LVH; wall thickness rarely >20 mm; history of uncontrolled hypertension [12]
- Aortic stenosis — fixed obstruction (not dynamic); crescendo-decrescendo murmur radiating to carotids; does NOT increase with Valsalva
- Cardiac amyloidosis — infiltrative; biventricular thickening, diastolic dysfunction, low voltage on ECG despite thick walls; consider in older patients [8][12]
- Fabry disease — X-linked; concentric LVH, neuropathic pain, renal dysfunction, angiokeratomas; check alpha-galactosidase A [8]
- Glycogen storage diseases (Pompe, Danon) — consider in young patients with massive hypertrophy [8]
- RASopathies (Noonan syndrome) — in infants/children with dysmorphic features [8]
- Mitochondrial cardiomyopathy — multisystem involvement
9. Past Medical History
- Prior episodes of syncope, presyncope, or cardiac arrest
- Known arrhythmias (AF, VT, NSVT)
- Prior septal reduction therapy (myectomy or alcohol septal ablation)
- ICD placement history
- Heart failure history and NYHA class trajectory
- Comorbidities that affect management: hypertension (complicates medication choices), coronary artery disease, renal disease
- Pregnancy history (HCM generally well-tolerated but requires specialized management) [14]
- Surgical history relevant to anesthesia planning (avoid general anesthesia pitfalls — see below)
10. Physical Exam
Vital signs
- Blood pressure may be normal; hypotension is a danger sign [8]
- Heart rate: may be normal or tachycardic
Key findings
- Harsh crescendo-decrescendo systolic murmur at left lower sternal border/apex [8][15]
- Increases with Valsalva, standing, dehydration (decreased preload)
- Decreases with squatting, passive leg raise (increased preload/afterload)
- Murmur of mitral regurgitation at apex — posteriorly directed jet from SAM [8]
- Prominent apical impulse (sustained, laterally displaced) [8]
- Abnormal carotid pulse — brisk upstroke with bisferiens quality ("spike and dome") [8]
- S4 gallop (due to decreased compliance) [8]
- Patients without LVOTO may have a normal exam [8]
Dynamic maneuvers (critical for ED/clinic)
- Valsalva → increases murmur (decreases preload)
- Squat-to-stand → increases murmur (decreases preload)
- Squatting → decreases murmur (increases preload and afterload)
11. Lab Studies
- BNP / NT-proBNP — elevated in symptomatic HCM; useful for monitoring and prognostication [16]
- Troponin — may be chronically mildly elevated due to myocardial ischemia/fibrosis; acute elevation raises concern for ACS or myocardial injury [16]
- Basic metabolic panel — assess renal function (relevant for medication dosing and contrast use)
- Thyroid function — exclude thyrotoxicosis as cause of symptoms
- CBC — rule out anemia exacerbating symptoms
- Genetic testing — recommended after genetic counseling; identifies sarcomeric mutations in 30–60% [3][8]
- Alpha-galactosidase A — if Fabry disease suspected [8]
- Serum/urine protein electrophoresis — if amyloidosis suspected
12. Imaging
First-line
- Transthoracic echocardiography (TTE) — diagnostic cornerstone [3][8][12]
- LV wall thickness ≥15 mm (≥13 mm with family history or positive genotype) [1][3]
- Assess LVOT gradient at rest and with provocative maneuvers
- SAM of the mitral valve, mitral regurgitation, diastolic dysfunction
- Exercise stress echocardiography if resting gradient <50 mmHg — to unmask latent obstruction [8][17]
Gold standard / advanced
- Cardiac MRI (CMR) — superior for wall thickness measurement, apical variants, and late gadolinium enhancement (LGE) quantification for fibrosis/SCD risk stratification [12-13]
- Recommended at initial evaluation; repeat every 3–5 years [5]
- LGE >15–20% of LV mass = extensive fibrosis → increased SCD risk [12-13]
- Identifies LV apical aneurysm [6]
When imaging is unnecessary
13. Special Tests
- Ambulatory ECG monitoring (24–48 hr Holter or ≥2-week wireless patch) — detect NSVT and paroxysmal AF; part of SCD risk stratification; repeat every 1–3 years [5]
- Cardiopulmonary exercise testing (CPET) — assess functional capacity, peak VO₂, blood pressure response to exercise [6][17]
- Exercise stress echocardiography — provoke latent LVOT obstruction when resting gradient <50 mmHg [8][17]
- Genetic testing — after pretest genetic counseling; identifies pathogenic sarcomeric variants [3][8]
- HCM Risk-SCD Calculator (ESC model) — estimates 5-year SCD risk using age, wall thickness, LA diameter, LVOT gradient, family history of SCD, NSVT, and syncope; useful for shared decision-making but should not be the sole criterion for ICD decisions [6][12-13]
The AHA/ACC 2024 guidelines recommend the ICD assessment algorithm shown below:
14. ECG
ECG is abnormal in up to 95% of HCM patients and is the most sensitive routine screening test. [1][12][15]
Common findings
- LVH voltage criteria (large R waves in lateral leads, deep S waves in V1–V2)
- Prominent Q waves — typically in inferior (II, III, aVF) and lateral leads (I, aVL, V5–V6); represent septal hypertrophy, not infarction [15][18]
- ST-segment depression and T-wave inversions — repolarization abnormalities [15]
- Giant T-wave inversions in precordial leads — suggestive of apical HCM variant [15]
- Left axis deviation [15][18]
- P-wave abnormalities (left atrial enlargement) [15]
- Atrial fibrillation — found in >50% over time on ambulatory monitoring [3]
- NSVT on Holter — SCD risk marker [6]
Dangerous patterns
- Sustained VT or VF — immediate ICD indication [6-7]
- Rapid AF — poorly tolerated; urgent rate control needed
- A normal ECG does not exclude HCM (5–10% have normal ECG) [12][15]
15. Assessment
- HCM is classified as obstructive (resting or provocable LVOT gradient ≥30 mmHg; hemodynamically significant ≥50 mmHg) or nonobstructive [2][12]
- Most patients have a favorable prognosis with modern management, compatible with normal longevity [5]
- Annual SCD risk is approximately 0.5–1% overall; substantially lower in patients without risk markers [4][13]
- Atypical presentations: apical HCM (giant T-wave inversions, apical aneurysm risk), midventricular obstruction, end-stage/burned-out HCM (LVEF <50%, LV dilation) [2][4]
- Complications: SCD, AF with stroke risk, progressive heart failure, infective endocarditis (rare), end-stage HCM requiring transplant [2][4]
16. Treatment Plan
The 2020 AHA/ACC guideline management algorithm for symptomatic obstructive HCM is shown below:
Initial stabilization (ED setting)
- Acute hypotension/hemodynamic compromise: IV fluids (volume resuscitation), IV phenylephrine (pure alpha-agonist to increase afterload), IV beta-blocker if tachycardic; avoid dobutamine, milrinone, vasodilators [8-9]
- Rapid AF: rate control with IV beta-blocker or IV diltiazem; avoid digoxin; anticoagulation is strongly recommended for all HCM patients with AF regardless of CHA₂DS₂-VASc score [2]
- VT/VF/cardiac arrest: standard ACLS; defibrillation; avoid isoproterenol
Chronic pharmacological management (obstructive HCM)
- Step 1: Beta-blocker (titrate to symptom relief and heart rate suppression) [8]
- Step 2: Verapamil or diltiazem (if beta-blocker intolerant/ineffective) [8]
- Step 3 (refractory symptoms): Mavacamten (5 mg daily starting dose, max 15 mg; requires REMS, serial LVEF monitoring) or aficamten or disopyramide (with AV nodal blocker) [3][8-10]
- Avoid vasodilators, high-dose diuretics, positive inotropes [6][8]
Septal reduction therapy (refractory to medical therapy)
- Surgical myectomy — gold standard; preferred when concomitant cardiac surgery needed [19-20]
- Alcohol septal ablation — alternative for non-surgical candidates [19-20]
- Should be performed at experienced, high-volume HCM centers [3][8]
SCD prevention
- Secondary prevention ICD: all survivors of cardiac arrest or sustained VT [6-7]
- Primary prevention ICD: consider with ≥1 major risk factor (massive LVH ≥30 mm, family history of SCD, unexplained syncope, NSVT, extensive LGE, apical aneurysm, LVEF <50%) [4][6][8]
- SCD risk is low in patients >60 years; ICD generally discouraged in this age group unless specific high-risk features [4][8]
17. Disposition
Admit if
- Syncope (especially exertional or unexplained) — requires telemetry monitoring and SCD risk assessment
- Acute hemodynamic compromise / hypotension
- New-onset rapid atrial fibrillation with hemodynamic instability
- Sustained VT, VF, or cardiac arrest
- Acute heart failure symptoms
- New diagnosis with concerning features (massive LVH, NSVT on initial monitoring)
Observation
- New-onset AF, hemodynamically stable, requiring rate control optimization
- Presyncope with unclear etiology pending workup
Discharge criteria
- Hemodynamically stable, asymptomatic or at baseline symptoms
- Known HCM with stable presentation and no new risk factors
- Adequate follow-up arranged with cardiology/HCM center
Specialist consultation triggers
- All newly diagnosed HCM patients should be referred to a comprehensive HCM center [3][5]
- Cardiology/electrophysiology for SCD risk stratification and ICD discussion
- Cardiac surgery for septal myectomy evaluation
- Genetics for counseling and testing [3][8]
18. Follow-Up / Return Precautions
Follow-up timing
- Annual clinical evaluation with echocardiogram and 12-lead ECG [5]
- Ambulatory ECG monitoring every 1–3 years (or sooner if arrhythmia symptoms) [5]
- Cardiac MRI every 3–5 years (or sooner if clinical concern for progression) [5]
- SCD risk reassessment every 1–3 years or with any change in clinical profile [5][8]
- First-degree relative screening: ECG + echo at diagnosis; repeat every 1–2 years (children) or 3–5 years (adults) [8]
Return precautions — instruct patients to seek immediate care for:
- Syncope or near-syncope, especially with exertion
- Sustained palpitations or racing heartbeat
- New or worsening chest pain
- Progressive dyspnea or exercise intolerance
- Lightheadedness or dizziness with position changes
Patient counseling
- HCM is a treatable disease compatible with normal longevity in most patients [5]
- Maintain adequate hydration; avoid dehydration, excessive alcohol, and excessive caffeine [6]
- Exercise: newer data support an individualized approach rather than blanket restriction; shared decision-making with cardiology is essential [2][12]
- Avoid stimulant drugs and performance-enhancing substances
- Inform all healthcare providers (especially anesthesiologists) of HCM diagnosis — anesthetic management requires avoidance of vasodilators and maintenance of preload/afterload [8]
- Genetic counseling for family planning and relative screening [3][8]
References
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3. Diagnosis and Management of Hypertrophic Cardiomyopathy: Updated Guidelines From the ACC/AHA. — Leggit JC, Whitaker D. American Family Physician. 2022.
4. Hypertrophic Cardiomyopathy. — Braunwald E. The New England Journal of Medicine. 2025.
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