Hypertrophic Cardiomyopathy
Asymmetric septal hypertrophy (≥ 15 mm) not explained by loading conditions. Autosomal dominant. The #1 cause of sudden cardiac death in young athletes. Know the LVOT obstruction physiology -it drives everything.
🔍 Overview
LVOT Obstruction -The Core Physiology
~70% of HCM patients have dynamic LVOT obstruction (gradient ≥ 30 mmHg at rest or with provocation). The thickened septum narrows the outflow tract → high-velocity flow → Venturi effect pulls the anterior mitral leaflet toward the septum (SAM = systolic anterior motion) → further obstruction + mitral regurgitation.
What WORSENS obstruction
- ↓ Preload -dehydration, Valsalva, standing, diuretics (smaller LV cavity → septum and MV closer together)
- ↓ Afterload -vasodilators, exercise-induced vasodilation
- ↑ Contractility -exercise, inotropes, digoxin, catecholamines
What IMPROVES obstruction
- ↑ Preload -IV fluids, leg elevation, squatting
- ↑ Afterload -phenylephrine (alpha agonist)
- ↓ Contractility / HR -beta-blockers, verapamil
Avoid in HCM: nitrates, diuretics, digoxin, ACEi/ARBs (drop preload/afterload → worsen obstruction), dobutamine/milrinone (increase contractility → worsen obstruction). If hypotensive → IV fluids + phenylephrine. NOT vasopressors that increase contractility.
Clinical Features
- Murmur: harsh crescendo-decrescendo systolic murmur at LLSB. Louder with Valsalva and standing (decreased preload). Softer with squatting (increased preload). This is the opposite of most murmurs.
- Symptoms: exertional dyspnea, syncope (especially exertional -red flag), chest pain, palpitations
- ECG: LVH, deep septal Q waves (V1–V3, "dagger" Q waves), T-wave inversions
- Echo (diagnostic): septal wall thickness ≥ 15 mm, SAM of mitral valve, LVOT gradient, MR
🚨 Management
Medical Therapy
| Drug | Role | Notes |
|---|---|---|
| Beta-blocker (non-vasodilating) 1ST LINE | ↓ HR, ↓ contractility, ↑ diastolic filling time | Metoprolol or propranolol preferred. Titrate to resting HR 60–65. Do NOT use carvedilol (vasodilating properties worsen obstruction). |
| Verapamil (Calan) 2ND LINE | ↓ HR, ↓ contractility, improves diastolic relaxation | If BB intolerant. Avoid in severe resting obstruction (gradient > 100 mmHg) -vasodilatory effect may worsen hemodynamics. |
| Disopyramide ADD-ON | Negative inotrope (Class Ia antiarrhythmic) | Added to BB for refractory symptoms. Must combine with BB (disopyramide alone → reflex tachycardia from anticholinergic effects). |
| Mavacamten (Camzyos) BREAKTHROUGH | Cardiac myosin inhibitor. Directly reduces contractility by decreasing myosin-actin cross-bridge formation. | EXPLORER-HCM, 2020: reduced LVOT gradient from 74 → 12 mmHg. Improved symptoms and exercise capacity. First targeted therapy for HCM. Requires REMS program (risk of excessive EF reduction). |
Invasive Therapy (Refractory Symptoms)
- Septal myectomy (Morrow procedure) -surgical resection of hypertrophied septum. Gold standard for refractory obstructive HCM. Success rate > 95%. Mortality < 1% at experienced centers.
- Alcohol septal ablation -ethanol injection into septal perforator artery → controlled MI of hypertrophied septum. Alternative for high surgical risk. Higher rates of heart block (10–20%) and need for permanent pacemaker.
Sudden Cardiac Death Risk -ICD Criteria
HCM is the #1 cause of sudden cardiac death in young athletes. Risk stratify ALL HCM patients.
- ICD indicated (secondary prevention): prior cardiac arrest, sustained VT
- ICD considered (primary prevention) if ≥ 1 major risk factor:
| Risk Factor | Details |
|---|---|
| Family history of SCD | 1st degree relative with SCD from HCM (especially < 50 yo) |
| Massive LVH | Max wall thickness ≥ 30 mm |
| Unexplained syncope | Recent (< 6 months), especially exertional |
| NSVT | Non-sustained VT on Holter (≥ 3 beats at ≥ 120 bpm) |
| Abnormal BP response to exercise | Failure of SBP to rise ≥ 20 mmHg with exercise (especially age < 40) |
| Extensive LGE on MRI | ≥ 15% LGE → significant fibrosis → arrhythmia substrate |
| LV apical aneurysm | Independent risk for VT |
🧪 Workup
Workup
- Echo -wall thickness, LVOT gradient, SAM
- 48h Holter -NSVT for SCD
- Exercise stress -hypotension
- Cardiac MRI -fibrosis, apical HCM
- Genetic testing
- Family echo -first-degree relatives
📋 On Rounds
Why does the HCM murmur get louder with Valsalva?
Valsalva decreases venous return (preload) → smaller LV cavity → the hypertrophied septum and anterior mitral leaflet are now closer together → more SAM → greater LVOT obstruction → louder murmur. This is the opposite of AS (fixed obstruction -murmur gets softer with decreased preload because less blood crosses the valve). The dynamic nature of the obstruction is the key concept -anything that makes the ventricle smaller worsens HCM obstruction.
What is mavacamten and why is it a breakthrough?
Mavacamten is a first-in-class cardiac myosin inhibitor -it directly reduces the number of myosin-actin cross-bridges that form during systole, reducing contractility at the sarcomere level. EXPLORER-HCM, 2020 showed it reduced resting LVOT gradient from 74 to 12 mmHg (vs 4 mmHg reduction with placebo). This is the first drug that targets the root cause of HCM (excess contractility) rather than compensating for it with negative chronotropy (BB)
Why are vasodilators, diuretics, and digoxin dangerous in obstructive HCM?
In obstructive HCM, the septum narrows the LVOT and the anterior mitral leaflet is pulled into the outflow tract during systole (SAM = systolic anterior motion). Vasodilators (ACEi, ARBs, nitrates, dihydropyridine CCBs) → reduce afterload → less resistance to outflow → LVOT gradient INCREASES → worsens obstruction. Diuretics → reduce preload → smaller LV cavity → septum and mitral leaflet are closer together → obstruction worsens.
Clinical Examples
📋 Case 1, Symptomatic Obstructive HCM
Patient: 48M with exertional dyspnea and near-syncope when climbing stairs. Systolic murmur that increases with Valsalva. Echo: septal thickness 24 mm, LVOT gradient 72 mmHg at rest, SAM of MV with moderate MR. EF 70%.
Key findings: Obstructive HCM (resting gradient > 30 mmHg) with NYHA II-III symptoms. SAM causes dynamic LVOT obstruction + MR. Gradient worsens with decreased preload (Valsalva, dehydration, standing).
Management:
- Metoprolol succinate 50 mg → titrate to 200 mg daily (first-line, slows HR, increases filling time, reduces gradient)
- If beta-blocker inadequate: add disopyramide 100 mg QID (negative inotrope, reduces LVOT gradient)
- Mavacamten 5 mg daily if refractory to above EXPLORER-HCM, 2020
- AVOID: vasodilators (ACEi, nitrates), diuretics (reduce preload → worsen obstruction), digoxin (positive inotrope)
- If refractory to all medical therapy: septal myectomy (surgical, gold standard) or alcohol septal ablation
Teaching point: In HCM, everything that reduces preload or increases contractility worsens obstruction. The hemodynamic goal is the opposite of HFrEF, increase preload, decrease contractility, slow HR.
📋 Case 2, Sudden Cardiac Death Risk Stratification
Patient: 22M diagnosed with HCM on screening echo after his brother died suddenly during basketball at age 19. Septal thickness 30 mm, no resting LVOT obstruction, EF 65%. Asymptomatic. Holter: 3-beat run of NSVT.
Key findings: Multiple SCD risk factors: family history of SCD, massive LVH (≥ 30 mm), NSVT on Holter. HCM is the #1 cause of SCD in young athletes.
Management:
- ICD implantation recommended, ≥ 1 major risk factor for SCD in HCM warrants primary prevention ICD
- SCD risk factors: family hx SCD, syncope, NSVT, max wall thickness ≥ 30 mm, abnormal BP response to exercise
- No competitive sports (AHA/ACC Class III recommendation for HCM with any risk factor)
- Cardiac MRI with LGE, extent of fibrosis is an emerging risk predictor
- Screen all first-degree relatives with echo + ECG (genetic counseling, consider genetic testing)
Teaching point: The decision to place an ICD in HCM requires only ONE major risk factor. This is different from HFrEF (where EF ≤ 35% is the threshold). A 22-year-old with massive LVH + family SCD + NSVT has a very high SCD risk.
📋 Case 3, HCM with Atrial Fibrillation
Patient: 56F with known HCM, presents with palpitations and dyspnea. HR 148 irregularly irregular, BP 88/60. Echo: LVOT gradient now 95 mmHg (was 35 at baseline). New moderate MR.
Key findings: Afib with rapid ventricular response in HCM, hemodynamic emergency. Loss of atrial kick + fast HR → decreased filling time → dramatically increased LVOT gradient → hypotension.
Management:
- IV phenylephrine for hypotension (pure alpha agonist, increases afterload without increasing contractility, reduces gradient)
- IV metoprolol for rate control (do NOT use diltiazem or verapamil acutely if hypotensive)
- If hemodynamically unstable: emergent synchronized cardioversion
- Long-term anticoagulation, ALL HCM patients with Afib need anticoagulation regardless of CHA₂DS₂-VASc score
- Consider amiodarone or catheter ablation for rhythm control (Afib recurrence is poorly tolerated in HCM)
Teaching point: Afib in HCM is a medical emergency. Unlike the general population, ALL HCM patients with Afib require anticoagulation, the stroke risk is markedly elevated regardless of CHA₂DS₂-VASc score.
📣 Sample Presentation
One-Liner
"Ms. Washington is a 34-year-old referred after a murmur was found on sports physical. Echo shows septal thickness 22 mm, LVOT gradient 65 mmHg at rest, SAM of mitral valve. Asymptomatic."
Key Points to Cover on Rounds
Known HCM with obstruction (resting gradient 65). Currently asymptomatic, NYHA class I. SCD risk assessment: no FH of SCD, no unexplained syncope, no NSVT on Holter, max wall thickness 22 mm (risk factor), no exercise hypotension. ICD discussion: intermediate risk based on wall thickness -shared decision-making. Started metoprolol 25 mg BID. Avoid dehydration, vasodilators, digoxin. Activity: no competitive sports.
💊 Medications
Key Medications -Hypertrophic Cardiomyopathy
The governing principle: anything that shrinks the ventricle or speeds it up makes obstruction worse. In obstructive HCM the gradient rises when preload or afterload falls, or when contractility rises. That single idea explains every drug choice and every drug to avoid below.
| Drug | Dose | Role | Watch for |
|---|---|---|---|
| Metoprolol / bisoprolol 1ST LINE | Titrate to symptoms and heart rate | First line for symptomatic obstruction. Slows the heart, so diastole is longer and filling is better, and reduces contractility so the gradient falls. | Bradycardia, fatigue, bronchospasm. Titrate to symptoms, not to a target gradient. |
| Verapamil | 120 to 480 mg daily | Alternative when beta-blockers are not tolerated. Improves diastolic relaxation. | Dangerous in severe obstruction with hypotension or a very high gradient, where its vasodilatory effect can precipitate collapse. Avoid in decompensated patients. |
| Disopyramide | Titrated, usually with a beta-blocker | Added for refractory obstruction before considering septal reduction. | Potent negative inotrope, which is the point. QT prolongation and marked anticholinergic effects (dry mouth, urinary retention). Pair with an AV nodal blocker as it can accelerate AV conduction in AF. |
| Mavacamten (Camzyos) CARDIAC MYOSIN INHIBITOR | Start 5 mg daily, titrate among 2.5, 5, 10 and 15 mg by echo | Reduces excessive actin-myosin cross-bridging, lowering the gradient and improving symptoms in obstructive HCM EXPLORER-HCM, 2020. | Dispensed only through a REMS program because it can reduce LVEF and precipitate heart failure. Echo-guided titration is mandatory; hold the drug if LVEF falls below 50%. Numerous CYP interactions. |
| Anticoagulation | DOAC or warfarin | Any atrial fibrillation in HCM warrants anticoagulation, irrespective of the CHA2DS2-VASc score. | HCM confers a stroke risk that the usual score underestimates, so the score is not used to decide here. |
Avoid in obstructive HCM: dihydropyridine calcium blockers (amlodipine, nifedipine) and nitrates, which drop afterload and preload; aggressive diuresis, which drops preload; and digoxin or other inotropes, which raise contractility. Each one widens the gradient. Treat hypotension in obstructive HCM with fluids and phenylephrine, never with an inotrope.
⚡ Summary
Summary
One Principle Explains Everything
Anything that shrinks the ventricle or speeds it up makes the obstruction worse. The gradient rises when preload falls, when afterload falls, or when contractility rises. Every drug rule, every murmur maneuver and every hemodynamic instruction on this page follows from that one sentence.
Define It
Asymmetric septal hypertrophy of 15 mm or more, not explained by loading conditions. Autosomal dominant, from sarcomere protein mutations. It is the leading cause of sudden cardiac death in young athletes, and it can be entirely asymptomatic until that event.
The Murmur Behaves Backwards
The systolic murmur increases with Valsalva and on standing (both reduce preload) and decreases with squatting and handgrip (which increase preload and afterload). Aortic stenosis does the opposite, and that is the bedside discriminator between the two.
The Drugs to Avoid
Nitrates, diuretics in excess, dihydropyridine calcium channel blockers, ACE inhibitors and ARBs all drop preload or afterload and worsen the gradient. Digoxin, dobutamine and milrinone raise contractility and worsen it too. These are the standard drugs for other cardiac disease, which is what makes this so easy to get wrong.
Treat Hypotension Backwards From Instinct
Give IV fluid and phenylephrine. Do not give inotropes: a pure alpha agonist raises afterload and relieves the obstruction, whereas an inotrope worsens it and can precipitate arrest. This is the reverse of almost every other shock algorithm.
Medical Therapy Slows and Fills
Beta blockers first line, which slow the heart and allow diastolic filling. Verapamil as an alternative, though with caution in severe obstruction or high filling pressures. Disopyramide for its negative inotropy in refractory symptoms. Mavacamten, a cardiac myosin inhibitor, reduces the gradient and symptoms in obstructive disease (EXPLORER-HCM) and requires echocardiographic monitoring of the ejection fraction.
Invasive Options for Refractory Symptoms
Septal myectomy is the gold standard in experienced centers, with excellent durability. Alcohol septal ablation for poor surgical candidates, at the cost of a heart block risk requiring a pacemaker. These treat symptoms, not sudden death risk, so an ICD decision is made separately.
Risk Stratify Every Patient for Sudden Death
Family history of sudden cardiac death, unexplained syncope, massive hypertrophy of 30 mm or more, non-sustained ventricular tachycardia on monitoring, and an abnormal blood pressure response to exercise. Add extensive late gadolinium enhancement on MRI and apical aneurysm as modifiers. Screen first-degree relatives with ECG and echocardiography, and discuss genetic testing, since the disease is inherited and the index case is often found through a relative.
📄 One Pager
Text version
Cardiology · One Pager
Hypertrophic Cardiomyopathy
Wall ≥ 15mm. Obstruction worsened by dehydration + vasodilators. BB first-line. Mavacamten = new. SCD risk stratification in all patients.
Diagnosis
- LV wall thickness ≥ 15mm (any segment) not explained by loading conditions
- Autosomal dominant (screen first-degree relatives)
- LVOT obstruction: gradient ≥ 30 mmHg at rest or provocation
- SAM of mitral valve on echo
Management
- Beta-blocker first-line (reduce HR → improve filling time → reduce obstruction)
- Verapamil second-line (if BB-intolerant)
- Disopyramide for refractory obstruction
- Mavacamten (cardiac myosin inhibitor) EXPLORER-HCM, 2020
- Septal myectomy or alcohol septal ablation if refractory to meds
SCD Risk Assessment
- FH sudden cardiac death < 50 years
- Unexplained syncope
- Non-sustained VT on Holter
- Max wall thickness ≥ 30mm
- Exercise hypotension
- ICD implantation based on risk score (≥ 1 major risk factor → discuss ICD)
Key Drugs
Metoprolol50-200 mg BID
Verapamil120-480 mg/day
Disopyramide100-200 mg TID
Mavacamten5-15 mg daily
Pitfalls
- Vasodilators (ACEi, nitrates) → worsen obstruction
- Diuretics → reduce preload → worsen obstruction
- Digoxin → increases contractility → worsen obstruction
- Dehydration → worse obstruction
- No competitive sports
Related Topics
ACS OverviewAortic DissectionAortic StenosisArrhythmiasAtrial FibrillationCardiac Tamponade