Hypertrophic cardiomyopathy

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

HCM ranges from an incidental familial phenotype to dynamic obstruction, AF, heart failure and ventricular arrhythmia. Symptoms, obstruction and sudden-death risk are related but must be assessed separately.

Echo establishes thickness and haemodynamics; CMR refines morphology, fibrosis and phenocopies. A three-generation pedigree and genomic counselling connect the individual diagnosis to family care.

Therapy is phenotype-led: symptom control and obstruction reduction, anticoagulation for AF, ICD for selected risk, and advanced HF treatment when systolic or restrictive progression occurs.

Key points

HCM is otherwise-unexplained increased LV wall thickness; first exclude hypertension, aortic stenosis and phenocopies.
LV outflow obstruction is dynamic: measure gradients at rest and with Valsalva; use exercise stress echo when symptoms and resting testing disagree.
A harsh systolic murmur that increases with Valsalva/standing supports dynamic obstruction but absence of a murmur does not exclude HCM.
Sudden-death prevention uses integrated risk, including syncope, family history, wall thickness, LV function, apical aneurysm, rhythm and CMR fibrosis.
AF is often poorly tolerated and materially increases embolic risk; detect it actively and anticoagulate when confirmed.
Offer genetic counselling and testing when it will clarify diagnosis or family management; screen first-degree relatives clinically.
Mavacamten and, from July 2026, NICE-recommended aficamten are specialist options for symptomatic obstructive HCM with mandatory systolic-function surveillance.
Avoid dehydration and unreviewed vasodilators or high-dose diuresis when significant obstruction is present.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Sarcomeric genetic disease

Pathogenic variants in myocardial contractile proteins account for many familial cases and are commonly inherited in an autosomal dominant pattern. Altered force generation and energy use promote hypertrophy, myocyte disarray and fibrosis, with age-dependent expression.

Genotype-negative familial or sporadic HCM

Some clinically convincing HCM has no currently identifiable causal variant. Undiscovered or complex genetic influences may contribute, so a negative panel does not erase phenotypic or family risk.

Non-sarcomeric HCM mimics

Cardiac amyloidosis, Fabry disease and other storage or metabolic disorders can produce increased wall thickness resembling HCM, but they are separate diseases rather than HCM subtypes. Systemic clues matter because treatment, testing and family implications differ.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Sarcomeric dysfunction and remodelling
In sarcomeric HCM, disordered contractile-protein function increases energetic demand and promotes myocyte hypertrophy. Cellular disarray and interstitial fibrosis develop, often with asymmetric but variably distributed left-ventricular thickening.
2
Diastolic dysfunction
The hypertrophied, fibrotic ventricle relaxes poorly and has reduced compliance. Filling therefore requires higher pressure, causing exertional breathlessness, left-atrial enlargement and vulnerability to atrial fibrillation.
3
Dynamic outflow obstruction
In obstructive HCM, septal hypertrophy and systolic anterior motion of the mitral valve narrow the outflow tract and may cause mitral regurgitation. Reduced preload or afterload, or increased contractility, may intensify the dynamic gradient.
4
Myocardial ischaemia
Increased muscle mass and microvascular dysfunction create a supply–demand mismatch even without obstructive coronary disease. Repeated ischaemia contributes to chest pain, fibrosis and impaired ventricular function.
5
Arrhythmic substrate
Disarray, scar and abnormal loading facilitate re-entry and ventricular arrhythmia, while atrial stretch promotes fibrillation. Syncope, ventricular tachycardia and sudden death risk require assessment beyond ejection fraction.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Typical symptoms

Exertional breathlessness, chest pain, palpitations, presyncope or syncope; some patients remain asymptomatic despite marked hypertrophy.

Dynamic obstruction

Symptoms or murmur may worsen with reduced preload or afterload; systolic anterior motion can cause both LVOT obstruction and posteriorly directed MR.

Apical or concealed disease

Deep T-wave inversion, apical aneurysm or focal hypertrophy may be missed on limited echo and requires contrast echo or CMR.

Phenocopy clues

Neuropathy/carpal tunnel, renal disease, angiokeratoma, pre-excitation, conduction disease or syndromic features should redirect testing for amyloid, Fabry or metabolic/storage disease.

Arrhythmic red flagsRed flag

Cardiac syncope, resuscitated arrest, sustained VT, strong young sudden-death history or recurrent non-sustained VT requires prompt inherited-cardiac/EP review.

Unstable AFRed flag

Fast AF can sharply reduce filling and output; hypotension, ischaemia, pulmonary oedema or syncope requires immediate cardioversion assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
12-lead ECG and ambulatory monitoringFirst step
Why
Detect hypertrophy patterns, pre-excitation, AF and ventricular arrhythmia.
Interpretation and limitations
ECG abnormalities may precede imaging; choose monitoring duration according to symptoms and AF/VT suspicion.
02
Comprehensive TTE
Why
Measure maximal wall thickness, chambers, systolic/diastolic function, SAM/MR and LVOT gradient.
Interpretation and limitations
Record gradients at rest and with Valsalva; a peak instantaneous gradient of at least 30 mmHg defines obstruction, while 50 mmHg commonly marks the haemodynamic threshold for invasive treatment consideration in symptomatic disease.
03
Exercise stress echocardiography
Why
Reveal provocable obstruction and link symptoms to physiology.
Interpretation and limitations
Use physiological exercise when resting/Valsalva gradient is below 50 mmHg but exertional symptoms persist; do not provoke with dehydration.
04
CMR
Why
Define distribution of hypertrophy, apical aneurysm, LV function and late gadolinium enhancement.
Interpretation and limitations
Extensive fibrosis and adverse morphology contribute to risk; CMR also helps identify infiltrative or storage phenocopies.
05
Formal sudden-death risk assessment
Why
Guide shared ICD decisions.
Interpretation and limitations
Combine validated risk estimation with clinical modifiers; neither one wall measurement nor LVEF alone is sufficient.
06
Genetic counselling/testing
Why
Establish a molecular diagnosis and enable cascade testing.
Interpretation and limitations
Cascade-test pathogenic/likely pathogenic variants; retain phenotype surveillance when testing is negative but familial risk remains.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Hypertensive heart disease

Longstanding hypertension commonly causes concentric hypertrophy. A clear pressure history, more uniform wall thickening and possible regression with sustained pressure control may favour hypertensive remodelling, although both conditions can coexist.

Aortic stenosis

Fixed valvular obstruction produces pressure-overload hypertrophy and exertional symptoms. Calcified restricted cusps and a valve-level Doppler gradient distinguish it from dynamic subvalvular obstruction.

Athlete’s heart

Intensive training can cause physiological hypertrophy, usually with proportionate cavity enlargement and preserved relaxation. Physiological proportions, absence of pathological scar and change with detraining when assessed favour adaptation; disproportionate wall thickening, a pathogenic variant or a convincing family history supports HCM.

Amyloidosis or storage disease

These are distinct HCM mimics, not forms of sarcomeric HCM. Relative voltage–wall-thickness discordance, neuropathy, carpal tunnel, renal or skin features, and disease-specific CMR, laboratory or genetic findings may direct the appropriate pathway.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DiagnosisUnexplained LV hypertrophyFirst stepIncreased wall thickness not fully explained by loading.

1Confirm measurements and history; quantify hypertension and exclude aortic stenosis, athlete remodelling and technical artefact.
2Obtain ECG, comprehensive echo with provocation and CMR; look deliberately for phenocopy and extracardiac clues.
3Build a three-generation pedigree and refer for inherited-cardiac genetic counselling/testing when appropriate.
4At diagnosis, assess symptoms, AF, ventricular arrhythmia, sudden-death risk and exercise/pregnancy needs rather than deferring these to later follow-up.

02ObstructionSymptomatic obstructive HCMSymptoms attributable to LVOTO despite general measures.

1Avoid hypovolaemia and review drugs that reduce preload/afterload; start a non-vasodilating beta-blocker and titrate to symptoms and tolerance.
2If ineffective or not tolerated, a specialist may use verapamil/diltiazem or disopyramide according to gradient, BP, conduction and interaction profile.
3For eligible NYHA II-III disease, discuss a NICE-approved myosin inhibitor: mavacamten under TA913 or aficamten under TA1181, with mandated echo and interaction safeguards.
4If severe symptoms and gradient persist despite maximum tolerated medical therapy, refer to an experienced HCM centre for surgical myectomy or alcohol septal ablation selection.

03RhythmAF and sudden-death preventionDocumented AF, syncope or ventricular-risk markers.

1If AF is haemodynamically unstable, perform urgent synchronised cardioversion; otherwise prioritise rhythm/rate strategy because loss of atrial contribution may be poorly tolerated.
2Anticoagulate confirmed AF unless contraindicated; usual CHA2DS2-VASc thresholds underestimate the HCM-specific embolic concern.
3Integrate syncope, family history, maximum thickness, LA size, LVOTO, LVEF, apical aneurysm, non-sustained VT and CMR scar in ICD discussion.
4After shared decision, implant an ICD for accepted secondary prevention and selected primary prevention; an ICD does not treat obstruction or HF.

04FamilyRelatives and life planningConfirmed or suspected HCM.

1Offer first-degree relatives ECG and cardiac imaging through an inherited-cardiac service; repeat at age- and family-appropriate intervals because penetrance is variable.
2Use cascade testing only for a causal pathogenic family variant; a negative result can change surveillance only after expert variant review.
3Give individualised exercise advice and pre-pregnancy assessment; new exertional syncope or palpitations prompts earlier reassessment.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Specialist cardiac-myosin inhibitor for eligible symptomatic NYHA II-III obstructive HCM under NICE TA913.

Mavacamten

CYP2C19 poor metaboliser or phenotype pending: start 2.5 mg orally once daily, maximum 5 mg; other phenotypes: start 5 mg once daily, maximum 15 mg, with SmPC-directed echo titration.

Do not start if LVEF is below 55%; interrupt if LVEF falls below 50%. Genotype CYP2C19, check every new prescription including OTC CYP2C19/CYP3A4 interactions, and avoid in pregnancy; effective contraception is required during treatment and for 6 months after.

Specialist cardiac-myosin inhibitor for eligible adults with symptomatic NYHA II-III obstructive HCM under NICE TA1181, added to optimised standard care or used alone when standard care is contraindicated.

Aficamten

Start 5 mg orally once daily; consider 10 mg once daily when the Valsalva LVOT gradient is at least 100 mmHg. Increase by 5 mg at intervals of 2-8 weeks to a maximum 20 mg once daily, guided by LVEF and Valsalva LVOT gradient.

Do not initiate or up-titrate if LVEF is below 55%. If LVEF is 40 to below 50%, reduce by 5 mg (interrupt for 7 days if already taking 5 mg); if LVEF is below 40%, interrupt for at least 7 days, with label-directed echo before resumption. Check every prescription for CYP2C9/CYP2D6/CYP3A interactions and use effective contraception during treatment; pregnancy requires expert benefit-risk review.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Sudden cardiac death

Fibrosis and myocyte disarray can support malignant ventricular arrhythmia. Risk is shaped by syncope, family history, rhythm findings, wall thickness, ventricular function, apical aneurysm and CMR scar.

Atrial fibrillation and embolic stroke

High filling pressure enlarges the left atrium and promotes atrial fibrillation, which is often poorly tolerated. Blood stasis produces important embolic risk requiring prompt detection and management.

Heart failure

Diastolic stiffness, obstruction and mitral regurgitation can cause pulmonary congestion despite preserved ejection fraction. Some patients later develop restrictive physiology or systolic impairment with advanced symptoms.

Syncope from outflow obstruction

Dynamic obstruction may sharply limit forward output during exertion or reduced preload, causing presyncope or syncope. Because arrhythmia can present similarly, every concerning episode needs integrated assessment.

Apical aneurysm and ventricular thrombus

Regional wall stress, ischaemia and scar may create an apical aneurysm with akinetic blood stasis. This adds ventricular-arrhythmia and systemic-embolism risk even when global ejection fraction remains preserved.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

At each review record exertional symptoms, syncope, chest pain, pulse/BP and congestion; an abrupt change triggers early imaging/rhythm assessment.
Repeat ambulatory ECG at phenotype-appropriate intervals and whenever palpitations or syncope changes.
Recalculate sudden-death risk when clinical, echo, CMR or family information changes.
For myosin inhibitors, use product-specific echo timing: mavacamten requires early LVOT/LVEF checks; aficamten requires echo 2-8 weeks after initiation, dose adjustment or interruption. Once stable, assess at least 6-monthly with LVEF at least 55%, or 3-monthly if LVEF is 50 to below 55%.
Review every prescription and OTC medicine for myosin-inhibitor interactions before starting, stopping or changing the dose.
Track first-degree-relative screening and revisit pregnancy and exercise counselling.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Gradient is dynamic

A low resting gradient does not exclude clinically important exercise-provoked obstruction.

MR may be part of LVOTO

SAM-related MR can improve when obstruction is treated; distinguish it from primary mitral disease before choosing intervention.

Wall thickness is not the whole risk score

Scar, apical aneurysm, LV systolic impairment and ventricular arrhythmia can modify an ICD decision.

New 2026 option

NICE TA1181 recommends aficamten as add-on to optimised standard care, or alone when standard care is contraindicated; NHS England implementation was specified within 30 days of final guidance.

Myosin inhibitors can cause systolic failure

Symptomatic benefit never removes the need for echo, interaction and pregnancy safeguards.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing HCM from hypertrophy without excluding hypertension, aortic stenosis or a phenocopy.
02
Using only a resting LVOT gradient in an exertion-limited patient.
03
Reassuring after syncope because LVEF is preserved.
04
Applying ordinary AF stroke thresholds without recognising HCM-specific embolic risk.
05
Starting or changing mavacamten with no CYP interaction check or scheduled echo.