HOCM Memory Palace: Murmur Maneuvers, SAM & Treatment

Hypertrophic cardiomyopathy (HCM) is left ventricular hypertrophy that cannot be explained by loading conditions or infiltrative disease, often caused by an autosomal dominant sarcomere gene variant (most often MYH7 or MYBPC3), and diagnosed in adults by a wall thickness of 15 mm or more. About two-thirds of patients have dynamic left ventricular outflow tract (LVOT) obstruction, the "HOCM" picture, from a thick basal septum plus systolic anterior motion (SAM) of the mitral valve. The resulting systolic murmur at the left sternal border gets louder with Valsalva or standing and softer with squatting, passive leg raise or handgrip, and HCM is a classic cause of sudden cardiac death in young athletes. Under the 2024 AHA/ACC guideline, symptomatic obstruction is treated with a non-vasodilating beta-blocker first, then verapamil or diltiazem, then a cardiac myosin inhibitor (mavacamten, or aficamten, FDA-approved in December 2025), disopyramide or septal reduction therapy.

The memory palace: the crowded gym with the bouncing door

Picture a high school gym hosting a charity sprint, with one narrow exit half blocked by a bulging wall and a curtain that keeps getting sucked into the doorway. Walk through it station by station.

Station 1: Family photo wall (genetics and screening)

• HCM is the most common monogenic cardiac disorder, affecting about 1 in 500 people (Merck gives 1 in 200 to 1 in 500 adults).
• Inheritance is usually autosomal dominant with incomplete penetrance (a few cases are autosomal recessive): each child of an affected parent has a 50% chance of inheriting the variant, but not every carrier develops hypertrophy (see the autosomal dominant memory palace).
• MYH7 (beta-myosin heavy chain) and MYBPC3 (myosin-binding protein C) are the most common genes. Genetic testing finds a pathogenic variant in only about 35% of patients with clinical HCM.
• Testing should include genes for phenocopies such as Fabry disease and the RASopathies.
• Family screening (2024 guideline): genetic counseling; cascade testing of first-degree relatives only if a pathogenic variant is found; echo screening of relatives every 1-2 years in children and every 3-5 years in adults.

Station 2: Overgrown wall (the hypertrophy)

• Microscopy shows myocyte hypertrophy, myocyte disarray and interstitial fibrosis.
• The usual pattern is asymmetric hypertrophy of the basal interventricular septum; apical HCM is more common in people of Asian descent.
• Diagnostic threshold: maximal LV wall thickness ≥15 mm on echo or MRI with no other cause, or ≥13 mm in someone with a family history of HCM or a pathogenic variant.
• The stiff ventricle fills poorly: high filling pressures cause exertional dyspnea, and atrial contraction against it gives an S4 (HFpEF-like physiology). Angina can occur with normal coronaries (microvascular dysfunction, high oxygen demand).

Station 3: Floppy curtain (SAM and obstruction)

• Abnormal flow in the thick ventricle pushes the often elongated anterior mitral leaflet into the outflow tract in systole (SAM), narrowing the LVOT and causing posteriorly directed mitral regurgitation.
• Obstructive HCM means a peak LVOT gradient ≥30 mm Hg at rest or with provocation. Gradients ≥50 mm Hg are generally enough to cause symptoms; septal reduction therapy is for a gradient ≥50 mm Hg with severe symptoms (usually NYHA class III-IV) despite medical therapy.
• The obstruction is dynamic: lower preload, lower afterload or stronger contraction worsens it.

Station 4: Banging door (the murmur and maneuvers)

Merck describes a dynamic, late-peaking systolic murmur best heard at the left sternal border in the 3rd or 4th intercostal space. A separate apical murmur of mitral regurgitation may be present, and the carotid upstroke is brisk with a bifid peak (unlike the weak, slow-rising pulsus parvus et tardus of aortic stenosis).

Rule: a smaller ventricle makes the HOCM murmur louder.

Vasodilators also make the HOCM murmur louder. The opposite responses to Valsalva and squatting separate HOCM from aortic stenosis, which is heard at the upper sternal borders and radiates to the carotids; other lesions are in the heart murmurs table.

Station 5: Collapsing sprinter (symptoms, sudden death and AF)

• Dyspnea, angina-like chest pain, palpitations and syncope, often exertional; many patients have no symptoms.
• Exertional syncope (obstruction or arrhythmia) is an important sudden-death risk marker.
• Sudden cardiac death: a relatively common cause of sudden death in young athletes (Merck); StatPearls calls it the most common identifiable cause in healthy people under 35 in the US. With modern care, the yearly rate is under 0.5%.
• Atrial fibrillation is common and poorly tolerated (a stiff ventricle depends on the atrial kick). The 2024 guideline recommends anticoagulation regardless of CHA2DS2-VASc score, with a DOAC first line (see atrial fibrillation).

Station 6: Camera room (diagnosis)

• Transthoracic echo first: wall thickness, SAM, mitral regurgitation and the LVOT gradient. If the resting gradient is under 50 mm Hg, provoke it (Valsalva, then exercise echo if needed).
• Cardiac MRI measures thickness precisely and shows apical aneurysms and late gadolinium enhancement (fibrosis) for sudden-death risk.
• ECG: LVH with repolarization changes (deep T-wave inversions, ST depression), Q waves and left atrial enlargement, plus 24-48 hours of ambulatory monitoring.
• Athlete's heart vs HCM: training can thicken the wall to 12-15 mm; HCM has a smaller LV cavity, and ECG, cardiac MRI, exercise capacity and regression with detraining separate them.

Station 7: Coach's playbook (treatment, 2024 AHA/ACC)

Symptomatic obstructive HCM, step by step:

1. Non-vasodilating beta-blocker (eg, metoprolol).
2. Verapamil or diltiazem if a beta-blocker fails or is not tolerated. Avoid verapamil with severe dyspnea at rest, hypotension or a resting gradient above 100 mm Hg.
3. Persistent symptoms: add a cardiac myosin inhibitor (adults), add disopyramide, or refer for septal reduction therapy (severe symptoms, usually NYHA III-IV, with a gradient ≥50 mm Hg).

Other branches:

• Nonobstructive HCM: beta-blockers or nondihydropyridine calcium channel blockers; cautious diuretics for congestion.
• LVEF below 50%: stop myosin inhibitors, start standard HFrEF therapy, and consider transplant for advanced disease.
• ICD: after cardiac arrest or sustained ventricular arrhythmia, and for primary prevention in high-risk patients. Major risk markers (2024 guideline): sudden death likely from HCM in a first-degree or close relative aged 50 or younger, massive LV hypertrophy ≥30 mm in any segment, recent unexplained syncope suspected to be arrhythmic, LV apical aneurysm and LVEF under 50%; nonsustained VT and extensive late gadolinium enhancement add to the risk; reassess every 1-2 years. Genotype-positive, phenotype-negative relatives do not get a primary-prevention ICD.
• Exercise: mild-to-moderate recreational exercise is encouraged; competitive sports are a shared decision with an HCM expert, not a blanket ban.

Station 8: Banned list (what worsens obstruction)

• Vasodilators: dihydropyridine calcium channel blockers (amlodipine, nifedipine), nitrates, and ACE inhibitors or ARBs when obstruction is significant.
• Volume depletion: high-dose diuretics, dehydration.
• Positive inotropes such as dopamine and dobutamine.
• Everyday triggers: large meals and alcohol.

Practice question

A 22-year-old college basketball player nearly faints during a sprint drill. He has had exertional chest tightness for months, and an uncle died suddenly at age 30. Blood pressure is 118/72 mm Hg. A harsh, late-peaking systolic murmur is heard at the left lower sternal border; it becomes louder when he stands up from a squat. Echocardiography shows a 21-mm interventricular septum, systolic anterior motion of the mitral valve, an LVEF of 70% and a peak LVOT gradient of 72 mm Hg with Valsalva. Which is the most appropriate initial drug therapy for his symptoms?

A. Amlodipine

B. Furosemide

C. Mavacamten

D. Metoprolol

E. Isosorbide mononitrate

Answer: D. Metoprolol. A non-vasodilating beta-blocker is first-line for symptomatic obstructive HCM: it slows the heart, lengthens diastolic filling (a bigger ventricle, less obstruction) and reduces contractility.

• A: amlodipine is a dihydropyridine vasodilator; lowering afterload and preload worsens the gradient. Only the non-dihydropyridines (verapamil, diltiazem) are used, as second line.
• B: diuretics shrink the ventricle and worsen obstruction; high-dose diuretics are on the avoid list.
• C: myosin inhibitors are for symptoms that persist despite a beta-blocker or calcium channel blocker, and they need echo monitoring through a REMS program.
• E: nitrates drop preload, which makes the murmur louder and can provoke syncope.

He also needs sudden-death risk stratification (his uncle's sudden death at 30 is a major risk marker if it was likely due to HCM, and true exertional syncope would be another) and family screening.

Key takeaways

• HCM is autosomal dominant sarcomere disease (MYH7, MYBPC3), about 1 in 500; wall thickness ≥15 mm (≥13 mm with family history or a variant).
• HOCM: thick basal septum plus SAM, a dynamic LVOT gradient ≥30 mm Hg, and mitral regurgitation.
• Murmur louder with Valsalva or standing, softer with squatting, leg raise or handgrip: the reverse of aortic stenosis for Valsalva and squatting.
• Classic cause of sudden death in young athletes; exertional syncope is a red flag.
• Treatment ladder: non-vasodilating beta-blocker, then verapamil or diltiazem, then a myosin inhibitor (mavacamten; aficamten since December 2025), disopyramide or septal reduction.
• Avoid vasodilators, nitrates, dihydropyridines, high-dose diuretics and inotropes.
• Echo first; ICD for high risk; screen first-degree relatives.

Sources

• 2024 AHA/ACC/Multisociety Hypertrophic Cardiomyopathy Guideline: Key Points — American College of Cardiology (2024)
• 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Hypertrophic Cardiomyopathy Guideline: Pocket Guide — Guideline Central (2024)
• Hypertrophic Cardiomyopathy — Merck Manual Professional Edition (2026)
• Hypertrophic Cardiomyopathy — StatPearls, NCBI Bookshelf (2024)
• Nonsyndromic hypertrophic cardiomyopathy — MedlinePlus Genetics (2026)
• CAMZYOS (mavacamten) prescribing information — DailyMed (2025)
• MYQORZO (aficamten) prescribing information — DailyMed (2025)
• Novel Drug Approvals for 2025 (Myqorzo, approved 12/19/2025) — U.S. Food and Drug Administration
• Cytokinetics Announces FDA Approval of MYQORZO (aficamten) — Cytokinetics (2025)
• NORPACE (disopyramide) prescribing information — DailyMed (2023)
• Aortic Stenosis — Merck Manual Professional Edition (2025)