#hypertrophic-cardiomyopathy #lvot-obstruction #cardiac-myosin-inhibitors #septal-reduction #atrial-fibrillation

HCM: Management

Definition

Management of hypertrophic cardiomyopathy is governed by three questions asked in order: is there obstruction, is the patient at risk of sudden death, and what is the physiological stage of the disease. Obstruction dictates the pharmacological ladder and the choice of septal reduction; risk dictates the ICD decision and is covered on concepts/HCM-Diagnosis-and-Risk; the stage — hypercontractile, fibrotic or burned out — dictates whether therapy is aimed at relieving a gradient or at treating systolic heart failure. (sources/HCM-NEJM-2025, rating: very high)

Abbreviations: AF, atrial fibrillation; AAD, antiarrhythmic drug; KCCQ-CSS, Kansas City Cardiomyopathy Questionnaire clinical summary score; LAVi, left atrial volume index; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; LVOTO, left ventricular outflow tract obstruction; NYHA, New York Heart Association; SRT, septal reduction therapy; TEE, transoesophageal echocardiography.

Key Concepts

Management by Physiology

The phenotype, not the label, sets the target. The same drug is correct in one row and inert in another.

Stage	Physiology	Therapeutic target	First-line	Escalation
Obstructive, hypercontractile	Systolic anterior motion of the mitral valve with basal septal hypertrophy; dynamic gradient	Relieve the gradient	Non-vasodilating beta-blocker	Calcium-channel blocker → disopyramide → cardiac myosin inhibitor → septal reduction
Nonobstructive, hypercontractile	Diastolic dysfunction, subendocardial ischaemia and microvascular disease with a preserved ejection fraction	Slow remodelling and treat symptoms	Valsartan in early disease (IIb); otherwise standard heart-failure care	No approved pharmacotherapy
Burned out / fibrotic	Cavity dilatation and LVEF <50%	Treat systolic heart failure	Guideline-directed heart-failure therapy	Transplantation or left ventricular assist assessment

(Sources: sources/esc-cmp-2023, rating: very high; sources/HCM-AHA-2024, rating: very high; sources/HCM-NEJM-2025, rating: very high)

LVOT Obstruction: Physiology and Medical Therapy

Definition and threshold. LVOTO is a peak Doppler gradient ≥30 mmHg; the treatment threshold is ≥50 mmHg. Approximately 70% of patients have subaortic muscular obstruction. (sources/esc-cmp-2023, rating: very high; sources/HCM-NEJM-2025, rating: very high)
Obstruction is dynamic and varies inversely with LV volume, worsening with upright posture, Valsalva, exercise and inotropes and improving with increased preload and afterload. It reflects the hypertrophied basal septum together with systolic anterior motion of the mitral valve. This volume-dependence explains most of the drug rules below. (sources/HCM-NEJM-2025)
Stepwise pharmacotherapy runs from a non-vasodilating beta-blocker through verapamil or diltiazem and disopyramide to a cardiac myosin inhibitor; the ESC 2023 and AHA 2024 grades for each step are tabulated side by side on concepts/LVOTO. (sources/esc-cmp-2023; sources/HCM-AHA-2024, rating: very high)
Drugs to avoid. Nitrates, phosphodiesterase-5 inhibitors and digoxin reduce preload or increase contractility and worsen obstruction. (sources/esc-cmp-2023)
Septal reduction is offered for LVOTO ≥50 mmHg with NYHA III–IV symptoms refractory to maximal therapy (Class I); see below. (sources/esc-cmp-2023)

Cardiac Myosin Inhibitors

Mechanism. Mavacamten and aficamten reduce actin–myosin cross-bridge formation, lowering contractility and relieving the gradient without vasodilation — the first therapy directed at the sarcomeric abnormality rather than at loading. See entities/Mavacamten and entities/Aficamten.
The two trials point the same way. Aficamten improved peak oxygen consumption by 1.7 ml/kg/min over placebo on background therapy in SEQUOIA-HCM, and in MAPLE-HCM it beat metoprolol monotherapy on every objective endpoint — metoprolol lowered heart rate by 23.4 bpm and moved neither the gradient, NT-proBNP nor LAVi. Trial sizes, gradient responses, washout behaviour and the nonobstructive data are tabulated on concepts/LVOTO. (sources/aficamten-sequoiahcm-nejm-2024, rating: very high; sources/aficamten-maplehcm-nejm-2025, rating: very high)
Dose-limiting effect is systolic dysfunction. Mavacamten produced LVEF <50% in 21.5% versus 1.7% with placebo over 48 weeks in nonobstructive disease, so serial echocardiographic monitoring is mandatory. (sources/mavacamten-odysseyhcm-nejm-2025, rating: very high)
Mavacamten is absolutely contraindicated in pregnancy (Class III: Harm), which converts the decision to start one into a pre-conception surgical decision — see below. (sources/HCM-AHA-2024)

Septal Reduction Therapy

Indication and outcomes. Surgical myectomy and alcohol septal ablation are offered for LVOTO ≥50 mmHg with NYHA III–IV symptoms refractory to maximal medical therapy (Class I). In the SHaRe registry of 10,225 patients, 18% underwent septal reduction — 75% myectomy — with 0.4% thirty-day mortality and 0.6% annual mortality, and repeat reduction more frequent after ablation. Myectomy is durable in experienced hands, including in children. Indications, operative technique, the myectomy-versus-ablation comparison and apical myectomy are on concepts/Septal-Reduction-Therapy. (sources/esc-cmp-2023, rating: very high; sources/HCM-NEJM-2025, rating: very high)
Document the result after the procedure. Post-septal ablation assessment must measure both resting and provoked gradients; a residual provocable gradient ≥50 mmHg indicates an incomplete result. (sources/hemodynamics-circ-2012, rating: high)

Nonobstructive and End-Stage Disease

Nonobstructive HCM is about one third of overt disease, and its long-term mortality does not differ significantly from obstructive disease. Five to ten per cent progress to "burned-out" HCM with cavity dilatation and loss of obstruction, requiring transplantation or left ventricular assist support. (sources/HCM-NEJM-2025, rating: very high)
An LVEF <50% in HCM is not equivalent to an LVEF <50% in other disease. It corresponds physiologically to an LVEF of 35–40% in non-HCM systolic heart failure, and 6–8% of patients present this way. Annual mortality in patients with extensive fibrosis is approximately 2%. (sources/HCM-NEJM-2025)
The physiology dictates the target. Hypercontractile physiology is treated by relieving obstruction; fibrotic physiology is treated as classic heart failure, including consideration of transplantation. (sources/HCM-NEJM-2025)
Valsartan may slow remodelling in early disease (Class IIb, Level B-R; AHA 2024). Eligible patients are ≤45 years with a pathogenic or likely pathogenic sarcomeric variant, mild phenotype (NYHA I–II), maximum wall thickness 13–25 mm, no secondary-prevention ICD and no AF. The recommendation rests on a single trial of 178 patients. (sources/HCM-AHA-2024, rating: very high)
Cardiac myosin inhibition does not work when there is no obstruction. ODYSSEY-HCM randomised 580 symptomatic patients across 201 centres in 22 countries for 48 weeks: mavacamten did not improve peak oxygen consumption (P=0.07) or KCCQ-CSS (P=0.06) versus placebo, despite a geometric mean NT-proBNP ratio of 0.41. LVEF fell below 50% in 21.5% versus 1.7%, and serious heart failure events occurred in 6.6% versus 1.7%. (sources/mavacamten-odysseyhcm-nejm-2025, rating: very high)
The explanatory mechanism: symptoms in nonobstructive disease are driven by diastolic dysfunction, subendocardial ischaemia, reduced LV compliance and microvascular disease, none of which myosin inhibition corrects. No approved pharmacotherapy exists for symptomatic nonobstructive HCM. (sources/mavacamten-odysseyhcm-nejm-2025)

Atrial Fibrillation

Anticoagulation is mandatory for all patients with clinical AF, independent of CHA₂DS₂-VASc (Class I, Level B-NR). Strokes occur in patients with a score of zero, so the score cannot be used to withhold therapy. See concepts/NOAC-AF-Management. (sources/HCM-AHA-2024, rating: very high)
AF affects about one quarter of symptomatic patients, and CHA₂DS₂-VASc does not identify those at high risk of death. (sources/HCM-NEJM-2025, rating: very high)
Rhythm control is preferred over rate control because AF is poorly tolerated in a stiff, preload-dependent ventricle. Antiarrhythmics are sotalol, dofetilide or amiodarone, followed by catheter ablation. (sources/HCM-AHA-2024; sources/HCM-NEJM-2025)
Extended ambulatory monitoring for AF screening is Class I, upgraded from IIa, performed annually in high-risk patients identified by the HCM-AF score or by risk factors. (sources/HCM-AHA-2024)
Ablation outcome depends on genotype. In a single-centre retrospective comparison of 27 patients, MYBPC3- or MYH7-positive patients had more left atrial fibrosis on electroanatomical mapping (12.3% abnormal voltage versus 5.7%) despite similar atrial pressures. Freedom from AF at 12 months was similar — about 75% versus 73% — but gene-positive patients required more procedures (1.67 versus 1.20; P=0.03), all remained on antiarrhythmic drugs, and fibrosis progressed at redo procedures. See concepts/HCM-Atrial-Myopathy and concepts/Catheter-Ablation-AF. (sources/MYBPC3-MYH7-JACCEP-2024, rating: medium)

Pregnancy and Preconception Planning

Mavacamten is absolutely contraindicated in pregnancy (Class III: Harm; AHA 2024). Pregnant patients should be managed at a comprehensive HCM centre. (sources/HCM-AHA-2024, rating: very high)
HCM is generally well tolerated. Maternal mortality is 0.2%, with no difference between obstructive and nonobstructive disease in ROPAC. A 2025 propensity-matched analysis found no difference in 10-year all-cause mortality between parous and nulliparous women, and in earlier data covering 127 women and 271 pregnancies fewer than 10% had symptom exacerbation. (sources/cmp-pregnancy-jaccadv-2026, rating: medium; sources/HCM-AHA-2024)
Risk concentrates in three settings: severe hypertrophy, a resting or provocable gradient above 100 mmHg, and a personal or family history of severe arrhythmia. These patients need individualised delivery planning rather than general reassurance. (sources/cmp-pregnancy-jaccadv-2026)
The myosin inhibitor contraindication converts a pharmacological decision into a surgical one. Where LVOTO is severe enough that a myosin inhibitor would otherwise be started, myectomy should be performed before pregnancy — a pre-conception indication driven partly by teratogenicity rather than by a change in the myectomy criteria. See concepts/Pregnancy-in-Genetic-Cardiomyopathy.
Haemodynamic principle. Pregnancy increases blood volume and stroke volume, mildly dilates the LV and can lower the dynamic gradient — but reduced preload, tachycardia or excessive vasodilation worsen obstruction. Avoid hypovolaemia and Valsalva, and do not diurese aggressively.
Intrapartum management. Treat hypotension promptly with phenylephrine, a pure alpha agonist that avoids tachycardia, together with volume to maintain preload. In severe LVOTO an assisted second stage — labour to full dilatation, labour down, then instrumental delivery without maternal pushing — avoids the haemodynamic cost of prolonged Valsalva. Neuraxial anaesthesia is preferred for most patients. (sources/cmp-pregnancy-jaccadv-2026)
If LVOTO is uncorrected, beta-blockers or calcium channel blockers are used where LVEF is normal. Beta-blockers remain first-line for arrhythmia; amiodarone is reserved for life-threatening arrhythmia as a single dose.
Risk scores are inadequate. HCM is mWHO class II–III. CARPREG II recognises LVOTO and ventricular dysfunction as adverse predictors but contains no HCM-specific variables validated in pregnancy cohorts, and neither tool accounts for genotype. See concepts/mWHO-Classification. (sources/cmp-pregnancy-jaccadv-2026)

Exercise and Competitive Sport

AHA 2024 reversed the default. Universal restriction from vigorous activity or competitive sport is not indicated for most patients (Class III: No Benefit). Vigorous recreational activity is reasonable after annual expert evaluation (Class IIa), and competitive sport may be considered by HCM-experienced providers (Class IIb). (sources/HCM-AHA-2024, rating: very high)
ESC 2023 individualises instead. High-intensity exercise and competitive sport are discouraged in high-risk patients, while genotype-positive, phenotype-negative patients without symptoms or risk factors may participate. ESC 2022 allows high-intensity exercise in asymptomatic adults without risk markers as Class IIb. See concepts/HCM-Exercise. (sources/esc-cmp-2023, rating: very high; sources/VA-SCD-ESC-2022, rating: very high)
The 2025 sports statement separates genotype from phenotype. Genotype-positive, phenotype-negative athletes can compete, since low arrhythmic risk is well established. Clinical HCM makes competitive sport reasonable to consider after comprehensive expert assessment with shared decision-making, supported by LIVE-HCM — which found no increase in malignant ventricular arrhythmia in HCM patients exercising vigorously — and by multicentre registry data showing low breakthrough event rates. (sources/competitive-sports-aha-2025, rating: very high)
An ICD should not be implanted solely to enable sport. Inappropriate shock risk is about 5% per year and device-related complication risk about 4% per year. Athletes who stop competing should be told that recreational activity remains important for health and longevity. See concepts/Sports-Cardiology-SDM. (sources/competitive-sports-aha-2025)

Perioperative Care

Four factors constitute a Class 3 Harm in obstructive HCM during non-cardiac surgery, and each has a defined substitute. (sources/periop-aha-2024, rating: very high)

Factor	Mechanism	What to do instead
Inotropic agents (dobutamine, milrinone)	Raise contractility, which empties the cavity and worsens systolic anterior motion	Phenylephrine or norepinephrine — vasopressors are preferred to inotropes, which are contraindicated
Tachycardia	Shortens diastole and reduces filling	Control the rate; avoid chronotropes
Excessive preload reduction	A low-volume ventricle obstructs more	Intravenous fluid to hold preload; avoid aggressive diuresis
Peripheral vasodilation	Falling afterload increases the gradient	Vasoconstrictors; avoid spinal or epidural anaesthesia, which produces abrupt sympatholytic vasodilation

Intraoperative TEE is reasonable (Class 2a) in haemodynamically unstable patients and for unexplained intraoperative deterioration, allowing real-time assessment of obstruction severity and volume status. (sources/periop-aha-2024)
See concepts/Perioperative-Cardiovascular-Assessment.

Cardiometabolic Comorbidity

Obesity, hypertension, diabetes and obstructive sleep apnoea are highly prevalent in HCM and worsen prognosis. Intensive modification is a core component of management rather than an optional adjunct. (sources/HCM-AHA-2024, rating: very high)

Emerging Therapies

Gene-targeted approaches are entering early trials: CRISPR correction of MYH7, siRNA silencing and MYBPC3 replacement in phase 1b, with proteomic profiling of kinase and hypoxia-inducible pathways and AI detection of gene-positive, phenotype-negative disease as parallel strategies. (sources/HCM-NEJM-2025, rating: very high)

Contradictions / Open Questions

Beta-blockers are Class I first-line yet inferior on every objective endpoint. Both AHA 2024 and ESC 2023 make beta-blockade step 1 and place myosin inhibitors at step 3 or 4. MAPLE-HCM then showed aficamten monotherapy beating metoprolol monotherapy on peak oxygen consumption, gradient, NT-proBNP and LAVi, while metoprolol improved nothing despite a 23.4 bpm heart-rate fall. No guideline has been revised, and the trial compared against a beta-blocker rather than against disopyramide, so the ordering of steps 3 and 4 remains untested. (sources/aficamten-maplehcm-nejm-2025, rating: very high)
The biomarker–clinical dissociation in nonobstructive disease. ODYSSEY-HCM achieved a 59% NT-proBNP reduction with no improvement in either primary clinical endpoint, whereas in obstructive trials the biomarker and clinical endpoints moved together. NT-proBNP reduction reflects wall stress and filling pressures and does not address the diastolic, ischaemic and microvascular contributors that dominate symptoms without obstruction. The assumption that a biomarker signal predicts clinical benefit is not transferable between the two phenotypes. (sources/mavacamten-odysseyhcm-nejm-2025, rating: very high)
Myosin inhibitor safety at the population level is unquantified. LVEF fell below 50% in 21.5% of mavacamten-treated patients in ODYSSEY-HCM against 1.7% on placebo, and serious heart failure events tripled. In obstructive disease the same mechanism is the therapeutic one, so the margin between gradient relief and systolic dysfunction is narrow and entirely dependent on adherence to serial imaging. No trial is powered to detect the rare harm. (sources/mavacamten-odysseyhcm-nejm-2025)
The guideline offers a weak recommendation in the population where the mechanism has failed. AHA 2024 gives valsartan Class IIb for early nonobstructive disease on one 178-patient trial, while ODYSSEY-HCM showed the more targeted contractility-lowering strategy does not work in the same phenotype. Clinicians are therefore asked to accept a modest, single-trial remodelling claim in a disease where the definitive trial was negative. (sources/HCM-AHA-2024, rating: very high; sources/mavacamten-odysseyhcm-nejm-2025, rating: very high)
Myectomy durability versus ablation invasiveness is unresolved. Registry data show repeat septal reduction is more frequent after alcohol ablation, but no randomised comparison exists, and the less invasive option remains attractive in patients at surgical risk. The choice is being made on observational registry data with unmeasured confounding by baseline surgical risk. (sources/HCM-NEJM-2025, rating: very high)
Exercise advice depends on geography. AHA 2024 states that universal restriction is not indicated (Class III: No Benefit) and allows competitive sport after expert assessment, while ESC 2023 continues to discourage high-intensity and competitive sport in high-risk patients. Neither position rests on randomised data, so an identical patient receives opposite advice depending on which guideline their physician follows. (sources/HCM-AHA-2024; sources/esc-cmp-2023)
Genotype-positive AF ablation achieves the same freedom from AF at a higher procedural cost. Eventual rhythm outcome was similar at 12 months, but gene-positive patients required more procedures, remained on antiarrhythmic drugs and showed progressive fibrosis at redo. This argues that atrial myopathy in sarcomeric disease is progressive rather than a fixed substrate, and that a single successful ablation in a genotype-positive patient may not be durable — though the comparison is 12 patients against 15 in one centre. (sources/MYBPC3-MYH7-JACCEP-2024, rating: medium)
Pregnancy risk tools do not model HCM. mWHO places HCM at class II–III and CARPREG II counts LVOTO and ventricular dysfunction as adverse predictors, yet neither contains HCM-specific variables validated in pregnancy cohorts nor accounts for genotype — the same genotype the AF literature shows determines atrial substrate. Pre-conception counselling is therefore extrapolated rather than predicted. (sources/cmp-pregnancy-jaccadv-2026, rating: medium)

Connections

Part of entities/HCM — the parent overview
Genetics and phenotypes — concepts/HCM-Genetics-and-Phenotypes
Diagnosis and SCD risk — concepts/HCM-Diagnosis-and-Risk
The mechanism behind obstruction and systolic failure — concepts/HCM-Mechanism
Outflow tract obstruction — concepts/LVOTO
Septal reduction — concepts/Septal-Reduction-Therapy
Myosin inhibitors — entities/Mavacamten and entities/Aficamten
Risk calculator — concepts/HCM-Risk-SCD
AF and atrial substrate — concepts/NOAC-AF-Management, concepts/HCM-Atrial-Myopathy and concepts/Catheter-Ablation-AF
Pregnancy and exercise — concepts/Pregnancy-in-Genetic-Cardiomyopathy, concepts/mWHO-Classification, concepts/HCM-Exercise and concepts/Sports-Cardiology-SDM
Perioperative management — concepts/Perioperative-Cardiovascular-Assessment
Phenocopies that must be excluded before treating as HCM — entities/Anderson-Fabry-Disease and entities/ATTR-Amyloidosis
Drug index — Drug-index