Hypertrophic Cardiomyopathy (HOCM)

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]

• 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]

• 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

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]

• 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

• 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]

• 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]

• 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]

• 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

• 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)

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)

• 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

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

• [5]

• 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:

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]

• 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]

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]

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]

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]

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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.

5. Diagnosis and Evaluation of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review. — Maron BJ, Desai MY, Nishimura RA, et al. Journal of the American College of Cardiology. 2022.

6. Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review. — Maron BJ, Desai MY, Nishimura RA, et al. Journal of the American College of Cardiology. 2022.

7. 2017 AHA/­ACC/­HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/­American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. — Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. Heart Rhythm. 2018.

8. 2024 AHA/­ACC/­AMSSM/­HRS/­PACES/­SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/­American College of Cardiology Joint Committee on Clinical Practice Guidelines. — Ommen SR, Ho CY, Asif IM, et al. Journal of the American College of Cardiology. 2024.

9. FDA Orange Book. — FDA Orange Book. 2026.

10. FDA Drug Label. — Updated date: 2025-04-17. Food and Drug Administration.

11. Mavacamten and Aficamten in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Trials. — Fahim M, Eldawud D, Wahadneh O, et al. The American Journal of Cardiology. 2026.

12. Hypertrophic Cardiomyopathy: A Practical Approach to Guideline Directed Management. — Ommen SR, Semsarian C. Lancet. 2021.

13. Recommendations for Multimodality Cardiovascular Imaging of Patients With Hypertrophic Cardiomyopathy: An Update From the American Society of Echocardiography, in Collaboration With the American Society of Nuclear Cardiology, the Society for Cardiovascular Magnetic Resonance, and the Society of Cardiovascular Computed Tomography. — Nagueh SF, Phelan D, Abraham T, et al. Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2022.

14. EJHF Expert Consensus Statement on the Diagnosis and Management of Hypertrophic Cardiomyopathy. — Meder B, Coats CJ, Leinwand LA, et al. European Journal of Heart Failure. 2026.

15. Hypertrophic Obstructive Cardiomyopathy. — Veselka J, Anavekar NS, Charron P. Lancet. 2017.

16. Effects of Mavacamten on Cardiac Biomarkers in Nonobstructive Hypertrophic Cardiomyopathy: Insights From the ODYSSEY-HCM Trial. — Desai MY, Olivotto I, Abraham T, et al. Journal of the American College of Cardiology. 2025.

17. Exercise Testing to Unmask Latent LVOT Obstruction in a Highly Symptomatic Patient With Hypertrophic Cardiomyopathy. — Husaini M, Bach RG, Cresci S. Journal of the American College of Cardiology. 2024.

18. Sudden Death in the Young: Information for the Primary Care Provider. — Erickson CC, Salerno JC, Berger S, et al. Pediatrics. 2021.

19. 2020 AHA/­ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/­American Heart Association Joint Committee on Clinical Practice Guidelines. — Ommen SR, Mital S, Burke MA, et al. Journal of the American College of Cardiology. 2020.

20. 2020 AHA/­ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: Executive Summary: A Report of the American College of Cardiology/­American Heart Association Joint Committee on Clinical Practice Guidelines. — Ommen SR, Mital S, Burke MA, et al. Journal of the American College of Cardiology. 2020.