About This Page
This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Autosomal dominant mutations in sarcomeric proteins (beta-myosin heavy chain, myosin-binding protein C most common)
- Most common cause of sudden cardiac death (SCD) in young athletes (<35 years)
- Murmur: crescendo-decrescendo systolic at LLSB, increases with Valsalva and standing (decreased preload), decreases with squatting and leg elevation (increased preload)
- Diagnosis: echo showing wall thickness >=15 mm (or >=13 mm with family history) without another cause
- SCD risk stratification determines ICD candidacy. Beta-blockers are first-line for symptoms. Mavacamten (cardiac myosin inhibitor) for obstructive HCM
Overview
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease, affecting ~1 in 500 people. It is caused by autosomal dominant mutations in sarcomeric proteins, most commonly beta-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3). The hallmark is asymmetric left ventricular hypertrophy, typically involving the interventricular septum, that is not explained by loading conditions (e.g., HTN, aortic stenosis). Approximately 70% of patients have dynamic LVOT obstruction at rest or with provocation (obstructive HCM). The 2020 ACC/AHA HCM Guideline emphasizes shared decision-making, SCD risk assessment, and novel therapies.
Epidemiology
Prevalence ~1 in 500 (0.2%). Equal sex distribution but men are diagnosed more often. HCM is the most common cause of SCD in athletes <35 and in young people overall. Annual SCD risk varies widely (~0.5-1%/year overall, but much higher in high-risk subgroups). Most patients have a normal lifespan with appropriate management. HCM can present at any age but is most commonly diagnosed in adolescence/young adulthood or incidentally in middle age.
Clinical Features
Symptoms
Exertional dyspnea (most common symptom — diastolic dysfunction + LVOT obstruction)
Exertional syncope or presyncope (LVOT obstruction with exercise, arrhythmia)
Exertional chest pain (increased myocardial demand, small vessel disease)
Palpitations (AF occurs in ~20-25%, also PVCs/NSVT)
Sudden cardiac death as first presentation (especially in young athletes)
Many patients are asymptomatic (diagnosed on family screening or incidental echo)
Signs
Harsh crescendo-decrescendo systolic murmur at LLSB (dynamic LVOT obstruction + MR)
Murmur INCREASES with: Valsalva (strain phase), standing, dehydration, post-PVC beats — anything that decreases preload or increases contractility
Murmur DECREASES with: squatting, leg elevation, passive leg raise, hand grip — anything that increases preload or afterload
Bifid (bisferiens) carotid pulse: brisk upstroke then mid-systolic dip (from obstruction) then second peak
S4 gallop (non-compliant, hypertrophied ventricle)
Laterally displaced PMI with sustained, forceful impulse
Investigations
First-line
Transthoracic echocardiogramDiagnostic: LV wall thickness >=15 mm (>=13 mm with positive family history) without another cause. Look for asymmetric septal hypertrophy, systolic anterior motion (SAM) of mitral valve, dynamic LVOT gradient (>=30 mmHg at rest = obstructive; provocation with Valsalva may unmask latent obstruction), mitral regurgitation (from SAM), diastolic dysfunction, LA enlargement
ECGAbnormal in ~95%: LVH with strain, deep narrow Q waves in lateral/inferior leads (septal hypertrophy — "dagger" Q waves), LAE, T-wave inversions. Giant T-wave inversions in mid-precordial leads suggest apical HCM (Yamaguchi variant)
Second-line
Cardiac MRIGold standard for morphology. Late gadolinium enhancement (LGE) identifies fibrosis/scar — extent of LGE correlates with SCD risk and is used in risk stratification
Ambulatory ECG (Holter 24-48h)Detect NSVT (runs of >=3 beats at >=120 bpm) — NSVT is a risk factor for SCD
Exercise stress testingAssess functional capacity, provoke latent LVOT obstruction, assess BP response (failure to augment SBP by >=20 mmHg = abnormal — SCD risk factor)
Specialist
Genetic testingRecommended for index patient to enable cascade screening of first-degree relatives. Pathogenic variant identified in ~30-60%
Cardiac catheterizationRarely needed. May assess LVOT gradient invasively (Brockenbrough-Braunwald-Morrow sign: post-PVC beat shows increased gradient and decreased pulse pressure)
Management
2020 ACC/AHA Guideline for HCM1
SCD risk stratification (determines ICD)
- Major risk factors: prior cardiac arrest/sustained VT, family history of SCD from HCM, unexplained syncope, massive LVH (>=30 mm), NSVT on Holter, abnormal BP response to exercise
- Additional: extensive LGE on MRI (>=15% of LV mass), LV apical aneurysm, LVEF <50%
- ICD recommended if: prior arrest/sustained VT (Class I), or >=1 major risk factor with shared decision-making (Class IIa)
- Use the AHA/ACC HCM SCD risk calculator or ESC HCM Risk-SCD model
2
Symptom management — obstructive HCM
- First-line: non-vasodilating beta-blocker (propranolol, nadolol, metoprolol) — slows HR, prolongs diastolic filling, reduces LVOT gradient
- Second-line: verapamil or diltiazem if beta-blocker intolerant (use cautiously if severe obstruction)
- Disopyramide: add to beta-blocker for refractory obstruction (negative inotrope, reduces gradient)
- Mavacamten (cardiac myosin inhibitor): FDA-approved 2022 for symptomatic obstructive HCM. EXPLORER-HCM trial showed significant improvement in symptoms and gradient. Monitor LVEF (hold if <50%)
- Avoid: vasodilators (ACEi/ARB in obstruction), high-dose diuretics, digoxin, nifedipine — all worsen LVOT gradient
3
Septal reduction therapy (refractory symptoms)
- Surgical septal myectomy (Morrow procedure): gold standard for drug-refractory obstructive HCM — resects the basal septum, success >95%, operative mortality <1% at experienced centers
- Alcohol septal ablation: catheter-based alternative for patients who are not surgical candidates — inject ethanol into septal perforator artery to create controlled septal MI. Higher rate of heart block requiring pacemaker (~10-20%)
4
General measures
- Avoid competitive/intense sports (2020 guideline: shared decision-making for mild/non-obstructive HCM with low-moderate intensity recreational exercise allowed)
- Screen first-degree relatives: echo + ECG (clinical) or genetic testing if pathogenic variant identified in proband
- Anticoagulation for AF (CHA2DS2-VASc >=1 warrants anticoagulation in HCM — lower threshold than typical AF)
- Hydration: avoid dehydration (worsens obstruction)
Complications
- Sudden cardiac death: From VT/VF, especially during exertion — most feared complication
- Atrial fibrillation: Occurs in 20-25%; poorly tolerated (loss of atrial kick in stiff ventricle); high stroke risk even with low CHA2DS2-VASc
- Heart failure: Progressive diastolic dysfunction; ~5% develop "burned-out" HCM with systolic failure (LVEF <50%)
- Infective endocarditis: Especially with LVOT obstruction and MR (though routine prophylaxis not recommended)
- LV apical aneurysm: Present in ~2-5%, high risk of VT and thromboembolism
USMLE Step 2 CK Exam Tips
- 1HCM murmur maneuvers: Valsalva and standing INCREASE the murmur (less preload = smaller LV = more obstruction). Squatting DECREASES it. This is the OPPOSITE of most other murmurs
- 2Young athlete with exertional syncope or sudden death = HCM until proven otherwise
- 3The most common cause of SCD in athletes <35 is HCM. In athletes >35 it is CAD
- 4Do NOT give vasodilators, digoxin, or high-dose diuretics in obstructive HCM — all worsen the gradient
- 5Mavacamten is a new high-yield drug for Step 2 CK — cardiac myosin inhibitor for obstructive HCM (EXPLORER-HCM trial)
- 6If an HCM question asks about screening: offer echo + ECG to all first-degree relatives, or genetic testing if mutation known
- 7ECG finding: deep narrow Q waves in lateral leads ("septal Q waves") = septal hypertrophy, not prior MI
- 8Brockenbrough sign: post-PVC beat in HCM shows increased LVOT gradient with decreased pulse pressure (opposite of normal)
practicetest your knowledge on hypertrophic cardiomyopathyApply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — cardiovascular and beyond.
open q-bank