Hypertrophic Cardiomyopathy (HCM)

📋 Key Information Summary

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Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease (prevalence ~1:500), caused predominantly by sarcomeric protein gene variants with autosomal dominant inheritance and variable penetrance.
Diagnosis requires demonstration of unexplained left ventricular hypertrophy (wall thickness ≥15 mm, or ≥13 mm in genotype-positive relatives) on echocardiography or cardiac MRI, after exclusion of alternative causes.
Cardiac MRI (CMR) with late gadolinium enhancement (LGE) is essential for risk stratification — LGE burden ≥15% of LV mass is an independent predictor of sudden cardiac death (SCD).
Genetic testing with a comprehensive HCM panel should be offered to all patients with confirmed HCM; cascade screening of first-degree relatives is mandatory once a pathogenic variant is identified.
Left ventricular outflow tract (LVOT) obstruction (resting gradient ≥30 mmHg or provoked ≥50 mmHg) drives symptoms and is the primary therapeutic target.
First-line medical therapy for obstructive HCM is beta-blockers (metoprolol, atenolol); disopyramide (PBS Authority Required) is added as adjunctive therapy for refractory obstruction.
Mavacamten (Kardiozine®), a first-in-class cardiac myosin inhibitor, is PBS-listed (Authority Required) for symptomatic obstructive HCM refractory to conventional therapy — requires regular echocardiographic monitoring of LVEF.
Septal reduction therapy (surgical myectomy or alcohol septal ablation) is indicated when maximal medical therapy fails to control symptoms (NYHA Class III–IV).
SCD risk stratification uses the AHA/ESC risk calculator integrating family history of SCD, unexplained syncope, maximal LV wall thickness ≥30 mm, LVOT gradient, LGE on CMR, and non-sustained VT on Holter.
ICD implantation is recommended for high-risk patients (5-year SCD risk ≥6% or ≥1 major risk factor) and should be considered for intermediate-risk patients after shared decision-making.
Competitive sport is generally contraindicated for patients with HCM per AHA/ACC/ESC guidelines; moderate-intensity recreational exercise is permissible with individualised assessment.
Pregnancy in HCM requires multidisciplinary planning; most women with non-obstructive HCM tolerate pregnancy well, but those with significant obstruction or prior SCD require close cardiology and obstetric co-management.
Aboriginal and Torres Strait Islander peoples face delayed diagnosis due to geographic barriers and limited access to advanced cardiac imaging; culturally appropriate screening programmes are essential.

Introduction & Australian Epidemiology

Hypertrophic cardiomyopathy (HCM) is a primary cardiac disorder characterised by unexplained myocardial hypertrophy, typically involving the interventricular septum, with a non-dilated, hyperdynamic left ventricle. It is the most common inherited cardiovascular disease, with an estimated prevalence of 1 in 500 in the general population based on echocardiographic screening studies. Genetic studies suggest the true prevalence may be higher, as many carriers of pathogenic sarcomeric variants remain undiagnosed due to incomplete and age-dependent penetrance.

In Australia, HCM is estimated to affect approximately 50,000 individuals, though a significant proportion remain undiagnosed. The condition is the most common cause of sudden cardiac death (SCD) in young people and competitive athletes, accounting for up to one-third of exercise-related SCD in individuals aged <35 years. Australian data from the National Coronial Information System and state-based registries confirm HCM as a leading aetiology in autopsy-positive sudden cardiac arrest in the young.

The natural history of HCM is highly variable. Many patients remain asymptomatic or mildly symptomatic throughout life, while a subset develops progressive heart failure due to diastolic dysfunction, LVOT obstruction, or the development of an end-stage hypokinetic ("burnt-out") phase. Contemporary management has transformed HCM from a disease associated with annual mortality rates of 1–2% (historical data) to a condition with near-normal life expectancy when appropriately managed in specialised centres.

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Australian context: Specialist HCM clinics operate at major tertiary centres including the Royal Melbourne Hospital, Royal Prince Alfred Hospital (Sydney), The Alfred (Melbourne), Princess Alexandra Hospital (Brisbane), and Royal Perth Hospital. Access to cardiac MRI, genetic testing, and multidisciplinary HCM expertise remains concentrated in metropolitan centres, creating barriers for rural and remote populations.

The Australian Institute of Health and Welfare (AIHW) reports that cardiovascular disease remains the leading cause of death in Australia, with cardiomyopathies contributing significantly to premature cardiovascular mortality. The Cardiac Society of Australia and New Zealand (CSANZ) has published position statements on HCM management, and Australian centres contribute actively to international HCM registries including the SHaRe (Sarcomeric Human Cardiomyopathy Registry) and ON-HCM registries.

Pathophysiology

HCM arises from mutations in genes encoding sarcomeric proteins, leading to a complex pathophysiology involving myocyte disarray, myocardial fibrosis, and microvascular dysfunction.

Genetic Basis

Approximately 60% of HCM cases have an identifiable pathogenic or likely pathogenic variant in one of >15 genes encoding sarcomeric proteins. The two most commonly implicated genes account for the majority of genotype-positive cases:

Gene	Protein	Frequency	Clinical Features
MYBPC3	Myosin-binding protein C	~40% of genotype-positive	Later onset, variable penetrance, often frameshift/truncating variants
MYH7	β-myosin heavy chain	~30–40%	Earlier onset, more severe phenotype, higher penetrance
TNNT2	Cardiac troponin T	~5%	May have mild hypertrophy but high SCD risk
TNNI3	Cardiac troponin I	~5%	Variable severity, may cause restrictive physiology
TPM1	α-tropomyosin	~2–3%	Mild-to-moderate hypertrophy
ACTC1	Cardiac actin	<1%	Rare, mid-ventricular pattern

Mechanisms of Disease

The fundamental sarcomeric defect produces hypercontractility and impaired relaxation through several mechanisms:

Myocyte disarray: Disorganised myofibre architecture creates substrate for re-entrant arrhythmias, the primary mechanism of SCD.
Myocardial fibrosis: Replacement fibrosis (detectable as LGE on CMR) and interstitial fibrosis (detected by T1 mapping/native T1 values) increase myocardial stiffness and arrhythmic substrate.
Microvascular dysfunction: Reduced coronary flow reserve leads to subendocardial ischaemia, contributing to fibrosis and symptom burden.
Diastolic dysfunction: Impaired relaxation combined with increased myocardial mass elevates filling pressures, causing exertional dyspnoea and exercise intolerance.
LVOT obstruction (SAM mechanism): Systolic anterior motion (SAM) of the mitral valve leaflets, caused by the Venturi effect in a narrowed LVOT, creates dynamic obstruction and mitral regurgitation.

Phenotypic Spectrum

HCM demonstrates remarkable phenotypic heterogeneity, even within families carrying the same variant. Disease expression is influenced by genetic modifiers, environmental factors, and comorbidities. Approximately 40% of patients have no identifiable sarcomeric variant (genotype-negative HCM), suggesting additional genetic or non-genetic aetiologies including metabolic/infiltrative storage disorders (Fabry disease, amyloidosis, Danon disease, PRKAG2 syndrome) that must be actively excluded.

Diagnosis & Genetic Testing

Diagnostic Criteria

HCM is diagnosed when imaging demonstrates unexplained left ventricular hypertrophy in the absence of loading conditions that could account for the hypertrophy (e.g., hypertension, aortic stenosis, athlete's heart). The ESC 2023 and AHA/ACC 2024 guidelines define the following criteria:

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Diagnostic thresholds: Maximum LV wall thickness ≥15 mm on any imaging modality, OR ≥13 mm in genotype-positive family members or patients with other features suggestive of HCM. Hypertension alone does NOT exclude HCM — diagnostic vigilance is required in hypertensive patients where wall thickness is disproportionate to blood pressure loading.

Echocardiographic Features

Transthoracic echocardiography (TTE) remains the first-line diagnostic investigation. Key features include:

Asymmetric septal hypertrophy: Interventricular septum disproportionately thickened relative to the posterior wall (ratio typically >1.3:1); most common pattern (~70%).
Concentric hypertrophy: Uniform wall thickening (~10–15% of cases).
Apical HCM: Hypertrophy predominantly involving the apex (~10–15%); may be missed on standard parasternal views — requires apical 4-chamber and contrast-enhanced imaging.
Mid-ventricular obstruction: Obstruction at mid-cavitary level with apical aneurysm formation; higher risk of apical thrombus and SCD.
SAM of the mitral valve: Systolic anterior motion of the mitral valve leaflet(s) causing LVOT obstruction and a posteriorly directed mitral regurgitation jet.
LVOT gradient assessment: Resting gradient ≥30 mmHg defines obstruction; provoked gradient ≥50 mmHg with Valsalva manoeuvre, standing, exercise, or post-PVC is clinically significant.
Diastolic dysfunction: Impaired relaxation (grade I) progressing to restrictive filling (grade III) in advanced disease.

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Critical differential — Mimics of HCM: All newly diagnosed HCM patients should be screened for infiltrative/storage diseases: serum α-galactosidase A (Fabry disease), serum/urine light chains and technetium-99m pyrophosphate scintigraphy (cardiac amyloidosis), and LAMP-2 immunohistochemistry when clinically suspected (Danon disease). Treatment pathways differ significantly.

Cardiac MRI (CMR)

CMR with late gadolinium enhancement (LGE) has become an essential investigation in HCM management. Indications include:

Inconclusive echocardiographic findings or suboptimal acoustic windows.
Quantification of LV mass, wall thickness (particularly apical segments), and volumes.
LGE assessment for fibrosis: Present in ~60% of HCM patients. LGE quantified as ≥15% of LV mass is an independent predictor of SCD and ventricular arrhythmias.
T1 mapping and extracellular volume (ECV) fraction for detection of diffuse interstitial fibrosis.
Identification of apical aneurysms, mid-ventricular obstruction, and RV involvement.
Differentiation from athlete's heart, hypertensive heart disease, and infiltrative cardiomyopathies.

Essential 12-lead ECG Abnormal in >90% of HCM patients — deep T-wave inversions (particularly lateral leads V4–V6 in apical HCM), pathological Q waves, LVH voltage criteria, left atrial enlargement. Normal ECG does NOT exclude HCM but significantly reduces likelihood.

Essential Transthoracic echocardiography First-line diagnostic imaging. Assess wall thickness, LVOT gradient (rest and provoked), SAM, mitral regurgitation, diastolic function, and LVEF. Available at most Australian hospitals and private echocardiography labs (MBS item 55116).

Available Cardiac MRI with LGE Second-line and risk stratification imaging. Available at all major tertiary centres. Essential for SCD risk assessment (LGE quantification). MBS item 63501 (MRI heart). Bulk-billed at some public hospitals; private gap $200–500.

Available 24-hour Holter monitoring Detect non-sustained VT (≥3 beats at ≥120 bpm), atrial fibrillation, and ventricular ectopy burden. Required for SCD risk stratification. MBS item 11105.

Specialist Genetic testing (comprehensive HCM panel) Offered to all patients with confirmed HCM. Panels typically include MYBPC3, MYH7, TNNT2, TNNI3, TPM1, ACTC1, MYL2, MYL3, and mimicking-disease genes. Available via specialised genetics services (e.g., Victorian Clinical Genetics Services, SA Pathology, NSW Health Pathology). Turnaround 4–12 weeks.

Specialist Cardiopulmonary exercise testing (CPET) Objective assessment of functional capacity (peak VO₂), exercise-induced LVOT gradient changes, and chronotropic competence. Available at major cardiac rehabilitation and HCM centres.

Referral Invasive haemodynamic assessment Simultaneous LV and aortic pressure measurement to confirm LVOT gradient when non-invasive assessment is equivocal. Performed at tertiary centres prior to septal reduction therapy.

Genetic Counselling & Cascade Screening

Genetic counselling is an essential component of HCM evaluation and should be provided both pre- and post-testing:

Pre-test counselling: Discuss implications of positive, negative, and variant of uncertain significance (VUS) results. Address insurance and employment implications (Australian moratorium on genetic discrimination in life insurance expired March 2024; discuss current protections).
Post-test counselling: Interpretation of results, family planning implications, and cascade screening recommendation.
Cascade screening: When a pathogenic or likely pathogenic variant is identified, ALL first-degree relatives should be offered genetic testing. Genotype-positive relatives require longitudinal clinical surveillance (echocardiography and ECG every 1–2 years from age 10–12 years, or earlier if high-risk variant).
Genotype-negative relatives: Can generally be discharged from surveillance, though expert review is recommended before discontinuing follow-up.
Genotype-negative/phenotype-positive patients: ~40% of HCM patients; clinical surveillance continues based on phenotype regardless of genetic results.

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Australian Genetic Testing Access: Medicare-funded genetic testing for HCM is available through state-based clinical genetics services with a referral from a cardiologist. Direct-to-consumer genetic testing is NOT recommended for HCM diagnosis due to incomplete gene panels and lack of clinical interpretation support.

Obstruction Management

Approximately 70% of HCM patients demonstrate LVOT obstruction at rest or with provocation. Symptom management is centred on reducing the LVOT gradient, improving diastolic filling, and controlling heart rate. Treatment is indicated for patients with an LVOT gradient ≥30 mmHg at rest or ≥50 mmHg with provocation who have symptoms attributable to obstruction (dyspnoea, chest pain, presyncope, syncope).

Medical Therapy

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Metoprolol (Betaloc®, Lopresor®)

Beta-1 selective blocker · First-line

Adult dose 25–50 mg PO BD, titrate to 100–200 mg daily (controlled release) or 50 mg PO TDS. Target resting HR 50–60 bpm if tolerated.

Paediatric dose 0.5–2 mg/kg/day PO divided BD–TDS

Route Oral (IV for acute decompensation)

Renal adjustment None required — hepatically metabolised

Hepatic adjustment Reduce dose in severe hepatic impairment

PBS status ✔ PBS General Benefit

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Atenolol (Tenormin®)

Beta-1 selective blocker · First-line alternative

Adult dose 50 mg PO daily, titrate to 100 mg PO daily. Once-daily dosing advantageous for adherence.

Paediatric dose 1–2 mg/kg/day PO (max 100 mg/day)

Renal adjustment eGFR 15–35: max 50 mg daily; eGFR <15: 25 mg daily or 50 mg every 48 hours

PBS status ✔ PBS General Benefit

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Verapamil (Isoptin®, Veracaps®)

Non-dihydropyridine calcium channel blocker · Second-line (when beta-blockers contraindicated)

Adult dose 240–480 mg PO daily (SR formulation). Start 120–240 mg daily, titrate slowly.

Key caution AVOID in patients with severe LVOT obstruction (resting gradient >50 mmHg) or significant resting symptoms — can cause haemodynamic deterioration due to vasodilatory effect.

Renal adjustment No specific adjustment; use with caution in renal impairment

PBS status ✔ PBS General Benefit

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Disopyramide (Rythmodan®)

Class IA antiarrhythmic · Adjunctive therapy for obstructive HCM

Adult dose 150 mg PO BD (controlled release), titrate to 300 mg PO BD. Used in combination with a beta-blocker for refractory LVOT obstruction.

Mechanism Negative inotropic effect (reduces SAM and LVOT gradient) + Class IA antiarrhythmic properties

Key cautions Anticholinergic effects (dry mouth, urinary retention, constipation); QTc prolongation — monitor ECG; avoid in patients with prolonged QTc or concurrent QT-prolonging drugs. Must be combined with AV nodal blocking agent (beta-blocker or verapamil) due to risk of 1:1 atrial flutter conduction.

Renal adjustment eGFR 30–60: 100 mg BD; eGFR 15–30: 100 mg daily; eGFR <15: avoid

Hepatic adjustment Reduce dose; monitor levels

PBS status ⚕ PBS Authority Required

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Mavacamten (Kardiozine®)

Cardiac myosin inhibitor · Targeted therapy for obstructive HCM

Adult dose Starting dose based on echocardiographic LVEF: 2.5 mg PO daily (LVEF 55–69%), 5 mg PO daily (LVEF ≥70%). Titrate at ≥8-week intervals based on Valsalva LVOT gradient and LVEF. Maximum dose 15 mg daily. LVEF must be ≥50% before each dose increase.

Mechanism Selective allosteric inhibitor of cardiac myosin ATPase — reduces excessive actin–myosin cross-bridge formation, directly addressing the sarcomeric hypercontractility underlying HCM.

Key cautions LVEF reduction: 5–7% of patients develop LVEF <50% — echocardiographic monitoring required at baseline, 4 weeks, 8 weeks, 12 weeks, then every 3 months. WITHHOLD if LVEF <50%. CYP2C19 poor metabolisers (~15% of Caucasians) have higher exposure — consider genotyping. Avoid strong CYP2C19 inhibitors (fluconazole, fluvoxamine).

Renal adjustment No dose adjustment for mild–moderate impairment; not studied in severe CKD (eGFR <30)

Hepatic adjustment Not recommended in moderate–severe hepatic impairment (Child-Pugh B or C)

PBS status ⚕ PBS Authority Required — Symptomatic obstructive HCM, NYHA Class II–III, refractory to or intolerant of beta-blockers/verapamil. Must be prescribed through a specialised HCM centre.

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Mavacamten monitoring requirement: Echocardiographic LVEF assessment is mandatory before initiation, at 4 weeks, 8 weeks, 12 weeks, and then every 3 months during dose titration and maintenance. If LVEF <50% at any assessment, withhold mavacamten and reassess within 2 weeks. This is a REMS-equivalent requirement in Australia — prescribers must be enrolled in the Kardiozine® Risk Management Programme.

Septal Reduction Therapies

Indicated for patients with severe, drug-refractory LVOT obstruction (gradient ≥50 mmHg at rest or provocation) with persistent NYHA Class III–IV symptoms despite maximal tolerated medical therapy. Referral to a specialist HCM centre is mandatory.

Surgical Myectomy (Morrow Procedure)

Gold standard septal reduction therapy
Open-heart surgery: resection of hypertrophied basal septal muscle (10–15 g) to widen the LVOT
Relief of obstruction in >95% of patients
Operative mortality <1% in experienced centres
Concomitant mitral valve repair/replacement if significant structural MR
Available at major Australian cardiac surgical centres (Royal Melbourne, Royal Prince Alfred, The Alfred, Monash Health, Flinders Medical Centre)
Consider extended myectomy (mid-ventricular obstruction) or apical myectomy for non-classic anatomy

Alcohol Septal Ablation (ASA)

Catheter-based alternative — injection of 1–3 mL absolute ethanol into the septal perforator artery
Creates a localised myocardial infarction to thin the basal septum
Gradient reduction comparable to myectomy at experienced centres
Less invasive but higher rate of permanent pacemaker implantation (10–20% vs 3–5% for surgery)
Preferred in patients with significant surgical comorbidities or advanced age
Requires suitable septal perforator anatomy (assessed on coronary angiography)
Available at interventional cardiology centres in Australian capital cities

Therapy Escalation Pathway

1

Beta-blocker monotherapy

Metoprolol or atenolol, titrated to maximum tolerated dose with resting HR target 50–60 bpm

2

Add disopyramide

150–300 mg SR BD with AV nodal blocker. Monitor QTc and anticholinergic effects.

3

Consider mavacamten

Cardiac myosin inhibitor for refractory obstructive HCM. Requires HCM specialist prescribing and REMS-equivalent monitoring.

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Septal reduction therapy

Surgical myectomy (preferred) or alcohol septal ablation for drug-refractory NYHA III–IV obstruction. Referral to specialised HCM centre.

Sudden Death Risk Stratification

Sudden cardiac death (SCD) in HCM is predominantly caused by ventricular tachyarrhythmias arising from myocardial disarray and fibrosis. Risk stratification is a critical component of HCM management, particularly in younger patients, and guides ICD decision-making.

Major Risk Factors

Risk Factor	Definition	SCD Risk Impact
Family history of SCD	≥1 first-degree relative with HCM-related SCD, survived cardiac arrest, or appropriate ICD discharge <40 years	Major risk factor — strongest predictor in young patients
Unexplained syncope	≥1 episode of unexplained syncope within the preceding 6 months (or recurrent, unexplained)	Significant risk factor, particularly if recent or exertional
Maximal LV wall thickness ≥30 mm	Greatest wall thickness on any imaging modality	Independent predictor — rare but high-risk finding
LVOT obstruction	Resting gradient ≥30 mmHg	Modestly elevated SCD risk; also associated with heart failure progression
Non-sustained VT on Holter	≥3 consecutive ventricular beats at ≥120 bpm on 24–48 hour Holter	Moderate risk factor; sensitivity low but specificity meaningful
LGE on CMR	Late gadolinium enhancement ≥15% of LV mass (quantitative)	Independent predictor of SCD and ventricular arrhythmias; increasingly considered a major risk factor
Apical aneurysm	Discrete thin-walled dyskinetic/akinetic apical segment	Associated with mid-ventricular obstruction, scar, and VT/VF — high-risk feature
Systolic dysfunction (LVEF <50%)	End-stage "burnt-out" phase	Elevated SCD and heart failure mortality risk

ESC HCM Risk-SCD Calculator

The ESC 2023 guidelines endorse the HCM Risk-SCD calculator (developed by the ESC HCM Outcome Investigators) to estimate 5-year SCD probability. The calculator integrates age, maximal LV wall thickness, LA diameter, LVOT gradient, family history of SCD, unexplained syncope, and NSVT.

Low Risk

5-year SCD risk <4%

ICD generally not recommended. Routine clinical surveillance every 12–24 months with reassessment of risk factors. Exercise counselling and genetic follow-up.

Setting: Outpatient cardiology/HCM clinic

Intermediate Risk

5-year SCD risk 4–6%

ICD may be considered after thorough shared decision-making. Discuss benefits, risks (inappropriate shocks, device complications), and patient preferences. Additional risk modifiers (LGE burden, apical aneurysm, genotype) may guide decision.

Setting: HCM specialist centre with multidisciplinary team discussion

High Risk

5-year SCD risk ≥6% OR ≥1 major risk factor

ICD recommended. Discuss device type (single-chamber vs dual-chamber, S-ICD options), programming strategies to minimise inappropriate shocks, and lifestyle implications. Survivor of cardiac arrest or sustained VT = Class I indication regardless of calculator score.

Setting: Tertiary HCM centre with EP/cardiology expertise

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Limitations of the ESC Risk-SCD Calculator: The calculator was derived from European cohorts and may underestimate risk in certain populations. It does NOT include LGE burden, apical aneurysm, or genetic information — these modifiers should be integrated into clinical decision-making. Risk assessment should be repeated at 1–2 year intervals, as risk factor profiles change over time (e.g., new syncope, progressive hypertrophy, development of AF).

ICD Indications in HCM

Indication	Class	Details
Survived cardiac arrest or sustained VT	Class I	Secondary prevention — ICD recommended regardless of risk factors
≥1 major SCD risk factor	Class I	Family SCD, unexplained syncope, max wall ≥30 mm, LGE ≥15%, apical aneurysm, LVEF <50%
ESC Risk-SCD ≥6%	Class I	Calculator-based high risk
ESC Risk-SCD 4–6%	Class IIa	ICD should be considered with shared decision-making
ESC Risk-SCD <4% without major risk factors	Class III	ICD generally not recommended — risks may outweigh benefits

Family Screening Protocols

Systematic family screening is a cornerstone of HCM management and SCD prevention:

Genotype-positive families: Cascade genetic testing for all first-degree relatives. Genotype-positive/phenotype-negative individuals: clinical surveillance with ECG and echocardiography every 1–2 years from age 10–12 years (or 5 years before the earliest diagnosis in the family), with transition to adult HCM services at age 16–18 years.
Genotype-negative families: If the proband is genotype-negative (no pathogenic variant identified), first-degree relatives should have a single clinical screening (ECG + echocardiography). If normal, they can be discharged from surveillance, though repeat screening at 3–5 year intervals may be considered if clinical suspicion exists.
Athletes: Pre-participation screening in Australia (Australian Institute of Sport protocols) includes ECG. Further investigation with echocardiography is triggered by abnormal ECG findings.
Post-mortem genetic testing: When SCD occurs in a suspected HCM case, post-mortem genetic testing (molecular autopsy) should be offered to inform family screening. Available through the Australian National Coronial Information System and specialist forensic pathology services.

Exercise & Lifestyle

Exercise Recommendations

Exercise counselling in HCM is complex and must be individualised. Historically, all competitive sport was contraindicated. The 2024 AHA/ACC guidelines introduced a more nuanced approach acknowledging that moderate-intensity recreational exercise is safe and beneficial for most HCM patients.

Activity Level	Recommendation	Rationale
Competitive sport (high-intensity)	Generally contraindicated (Class III / Class IIb in selected low-risk patients per AHA 2024)	Exercise-related SCD risk; haemodynamic stress of intense exertion. Individualised shared decision-making permissible for low-risk patients per AHA 2024 update.
Moderate-intensity recreational exercise	Encouraged for most patients (Class I)	Improves functional capacity, quality of life, and cardiovascular fitness. Activities: brisk walking, cycling, swimming at comfortable pace. Target 150 min/week.
Low-intensity activity	No restrictions	Walking, gentle yoga, daily activities. Encourage as baseline.
Isometric/heavy resistance training	Avoid or limit to light weights with proper breathing technique	Valsalva manoeuvre acutely increases LVOT gradient; risk of syncope and arrhythmia.

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Swimming safety: Patients with HCM should swim with a companion and avoid unsupervised open-water swimming. AEDs should be accessible at swimming facilities. Competitive swimming is considered high-intensity sport.

Lifestyle Counselling

Hydration and heat: Avoid dehydration and excessive heat exposure — both reduce preload and can worsen LVOT obstruction and cause hypotension.
Alcohol: Moderate or avoid alcohol. Acute alcohol consumption has negative inotropic effects but may cause vasodilation and worsen obstruction. Chronic heavy alcohol use may contribute to additive cardiomyopathy.
Driving: Australian driving restrictions apply: patients with HCM and ICD implantation must notify their state/territory licensing authority. Austroads guidelines recommend cessation of private vehicle driving for 4 weeks post-ICD implantation and 6 months following appropriate ICD therapy. Commercial driving restrictions are more stringent.
Diving: Scuba diving is generally contraindicated in symptomatic HCM or those with significant obstruction due to risk of syncope underwater and haemodynamic stress.
Medications to avoid: Vasodilators (nitrates, PDE-5 inhibitors, ACE inhibitors/ARBs) may worsen obstruction. Decongestants containing pseudoephedrine may trigger arrhythmias. Discuss with cardiologist before starting any new medication.
Endocarditis prophylaxis: NOT routinely recommended for HCM alone (per ESC/AHA guidelines). Only indicated if concurrent valvular disease or prosthetic material.

Pregnancy Management in HCM

Most women with HCM tolerate pregnancy well, particularly those without significant obstruction and preserved LV function. However, pregnancy-related haemodynamic changes (increased blood volume, decreased SVR, increased HR) can exacerbate LVOT obstruction and heart failure symptoms.

Low Risk

Non-obstructive HCM, no prior SCD, NYHA I, LVEF ≥55%

Pregnancy generally safe. Standard obstetric care with cardiology co-management. Vaginal delivery preferred (avoid prolonged Valsalva; assisted second stage). Echocardiography each trimester.

Setting: Shared care — obstetrician + cardiologist

Moderate Risk

Obstructive HCM (gradient ≥30 mmHg), NYHA II, prior ICD, or intermediate SCD risk

Requires pre-conception planning and multidisciplinary team (obstetric medicine, cardiology, anaesthesia, neonatology). Medication review essential. Beta-blockers continued throughout pregnancy (labetalol or metoprolol preferred). Increased monitoring frequency. Delivery planning with epidural anaesthesia.

Setting: Tertiary centre with MDT pregnancy heart team

High Risk

Prior SCD/appropriate ICD shock, severe obstruction, NYHA III–IV, LVEF <50%

Pregnancy associated with significantly elevated maternal and fetal risk. Pre-pregnancy counselling strongly recommended. Consider whether pregnancy is advisable. Intensive monitoring throughout pregnancy and peripartum. Delivery at tertiary centre with ECMO/cardiac surgery capability.

Setting: Quaternary centre with cardiac surgery, ECMO, and high-risk obstetrics

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Medication safety in pregnancy: Disopyramide and mavacamten are contraindicated in pregnancy. Beta-blockers (metoprolol, labetalol) are generally considered safe. Verapamil has limited safety data but may be used if necessary. ALL women of childbearing age with HCM should receive pre-conception counselling regarding medication teratogenicity and pregnancy risk.

Special Populations

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Paediatric HCM

Prevalence: ~0.3–0.5% in paediatric echocardiographic studies; often more aggressive phenotype than adult-onset disease.

Diagnosis: Age-adjusted z-scores for wall thickness (≥2 SD above mean for body surface area). Echocardiography is primary modality; CMR for risk stratification from age ~8–10 years.

Genetic testing: Particularly important — higher likelihood of identifying genetic aetiology. Consider metabolic/infiltrative causes (Pompe disease, Noonan syndrome, Friedreich ataxia) in all paediatric HCM.

Medical therapy: Beta-blockers first-line (propranolol 1–4 mg/kg/day or atenolol 1–2 mg/kg/day). Verapamil used cautiously (avoid in infants <1 year). Mavacamten NOT approved for paediatric use.

ICD: Higher complication rates in children (lead fracture, inappropriate shocks). Subcutaneous ICD (S-ICD) may be preferred in older children/adolescents. Weight threshold typically ≥30 kg for transvenous ICD.

Sport: Restriction from competitive sport is particularly impactful in paediatric populations — balanced counselling with psychological support. Moderate activity encouraged.

Paediatric HCM should be managed at centres with expertise in inherited cardiomyopathies (e.g., Royal Children's Hospital Melbourne, Children's Hospital Westmead, Queensland Children's Hospital).

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Pregnancy

Prevalence: ~1:500 women of childbearing age; many diagnosed during pregnancy due to new symptoms or incidental echo findings.

Haemodynamic changes: Increased blood volume (30–50%), increased cardiac output, decreased SVR, increased HR — can unmask or worsen LVOT obstruction.

Safe medications: Metoprolol, labetalol (also antihypertensive utility), atenolol (less preferred due to IUGR data at high doses).

Contraindicated: Mavacamten (teratogenicity concerns — Category D equivalent), disopyramide (can stimulate uterine contractions).

Delivery planning: Vaginal delivery preferred. Epidural anaesthesia reduces pain-related catecholamine surges. Avoid prolonged second stage (assisted delivery). Phenylephrine and norepinephrine preferred vasopressors for spinal hypotension (avoid nitroglycerin/nitroprusside).

Management via a dedicated pregnancy heart team (obstetric medicine, cardiology, anaesthetics, neonatology). See Exercise & Lifestyle section for risk stratification by severity.

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Elderly Patients

Phenotype: Older patients (≥65 years) more likely to have hypertensive HCM or hypertrophic phenotype with concurrent hypertension/AS. Differentiation from hypertensive heart disease is critical.

Diagnosis challenge: LVH from hypertension is common — HCM should be suspected when wall thickness is disproportionate to blood pressure burden, when SAM is present, or when there is a family history of HCM/SCD.

Higher AF prevalence: Atrial fibrillation occurs in up to 25% of HCM patients >65 years. Rate control with beta-blockers preferred. Anticoagulation per CHA₂DS₂-VASc score (recognising HCM itself increases thromboembolic risk).

SCD risk: SCD risk decreases with age but ICD implantation still indicated for high-risk features. Device complication rates higher in elderly.

Medication caution: Beta-blockers — falls risk, bradycardia; disopyramide — anticholinergic burden, urinary retention; mavacamten — limited data in patients >75 years.

Alcohol septal ablation preferred over surgical myectomy in elderly patients with significant comorbidities.

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Renal Impairment

Disopyramide: Renally cleared — significant dose reduction required. eGFR 30–60: 100 mg BD; eGFR 15–30: 100 mg daily; eGFR <15: avoid.

Metoprolol/Atenolol: Metoprolol hepatically metabolised (minimal renal adjustment). Atenolol requires dose reduction in CKD (see obstruction management section).

Mavacamten: No specific dose adjustment for mild–moderate CKD. Not studied in severe CKD (eGFR <30) — use with caution, specialist oversight.

Contrast precautions: Gadolinium-based contrast for CMR — use gadovist (macrocyclic) in CKD; avoid linear agents. Risk of NSF in eGFR <30. Iodinated contrast for CT/angio — standard pre-hydration protocols.

Patients on dialysis may develop dialysis-related hypotension that exacerbates LVOT obstruction. Coordinate dialysis and HCM management.

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Hepatic Impairment

Metoprolol: Hepatically metabolised — reduce dose in severe hepatic impairment (Child-Pugh C). Use with caution; monitor HR/BP.

Mavacamten: Not recommended in moderate-to-severe hepatic impairment (Child-Pugh B or C). Hepatic metabolism via CYP2C19, CYP3A4.

Disopyramide: Hepatic metabolism — reduce dose; monitor for toxicity.

Amiodarone: (If used for AF management) — contraindicated in severe hepatic disease; hepatotoxicity risk.

Cirrhotic cardiomyopathy may coexist with HCM — diagnostic and management complexity requires specialist hepatology and cardiology input.

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Immunocompromised

No specific HCM drug interactions with standard immunosuppressants (tacrolimus, cyclosporine, mycophenolate). However, calcineurin inhibitors can cause hypertension and LVH — may confound HCM diagnosis in transplant patients.

ICD implantation: Standard perioperative infection precautions. Immunosuppressed patients have higher device infection rates — consider S-ICD if transvenous infection risk is elevated.

HIV-related cardiomyopathy: Should be differentiated from HCM in HIV-positive patients. LVH in the context of HIV may represent antiretroviral cardiotoxicity, hypertension, or infiltrative disease.

Cancer survivors with anthracycline exposure who develop LVH should be investigated for HCM if family history is suggestive — differentiation from chemotherapy-related cardiomyopathy is important.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Prevalence & burden

Cardiovascular disease accounts for a disproportionate burden of morbidity and mortality among Aboriginal and Torres Strait Islander peoples. While HCM-specific prevalence data for ATSI populations are limited, the broader cardiovascular disease burden (2–3 times higher than non-Indigenous Australians) likely includes under-recognised cardiomyopathies. SCD rates are significantly higher in remote Indigenous communities, and autopsy studies suggest HCM as an under-diagnosed contributor.

Diagnostic barriers

Access to echocardiography, cardiac MRI, and genetic testing is significantly limited in remote and very remote communities. Royal Flying Doctor Service (RFDS) and visiting specialist cardiac services (e.g., Heart of Australia, Indigenous Heart Health programmes) provide intermittent echocardiography but cannot deliver the longitudinal surveillance required for HCM monitoring. Cultural and language barriers may impede effective communication about genetic testing implications and family screening.

Geographic access

Specialist HCM clinics are concentrated in metropolitan centres (Sydney, Melbourne, Brisbane, Perth). Patients from remote NT, WA, and QLD communities face significant travel barriers (distance, cost, family disruption). Telehealth consultations can partially bridge this gap for follow-up, but initial diagnosis and advanced investigations require face-to-face assessment. ICD implantation and follow-up requires ongoing access to device clinics — remotely located patients may require temporary relocation for device management.

Genetic considerations

The genetic architecture of HCM in ATSI populations is poorly characterised — current HCM gene panels are derived predominantly from European and North American cohorts. Pathogenic variants specific to ATSI populations may exist but are under-represented in genetic databases. Culturally appropriate genetic counselling is essential, with consideration of kinship systems, community consent models, and the potential for genetic information to cause community-level distress. Genetic health practitioners with Indigenous cultural competence should be involved.

Rheumatic heart disease differential

In remote ATSI communities, rheumatic heart disease (RHD) remains prevalent and may coexist with or mask HCM presentation. Valvular disease from RHD can cause LVH secondary to pressure/volume loading — differentiation from primary HCM requires careful echocardiographic assessment. RHD registers (e.g., RHDAustralia) should prompt consideration of HCM in patients where LVH is disproportionate to the degree of valvular disease.

Culturally safe care

HCM management should incorporate culturally safe practices: gender-concordant health practitioners where preferred, yarning-based education approaches, visual communication aids, involvement of Aboriginal Health Workers/Practitioners (AHWPs) in care coordination, acknowledgement of social determinants of health (housing, food security, transport), and integration with existing chronic disease management programmes (e.g., Indigenous Chronic Disease Package, GP Management Plans under MBS items 721/723). Family screening conversations require sensitivity to the emotional burden of SCD disclosures.

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Useful resources: RHDAustralia (rhdaustralia.org.au), Heart Foundation Aboriginal and Torres Strait Islander heart health programmes, AIHW Indigenous cardiovascular disease data, National Aboriginal Community Controlled Health Organisation (NACCHO), and the CSANZ Indigenous Cardiovascular Health Council.

Emerging Therapies

The therapeutic landscape for HCM is rapidly evolving, driven by improved understanding of the molecular pathophysiology. The advent of cardiac myosin inhibitors represents the first disease-modifying therapy for HCM, and multiple pipeline agents are in development.

Cardiac Myosin Inhibitors

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Aficamten (CK-274)

Next-generation cardiac myosin inhibitor · Phase III (SEQUOIA-HCM)

Mechanism Selective allosteric cardiac myosin inhibitor with shorter half-life (~2.5 days vs mavacamten ~7–9 days) — may allow more rapid dose adjustment and potentially faster recovery from LVEF reduction.

Clinical trial data SEQUOIA-HCM Phase III trial demonstrated significant improvement in exercise capacity (pVO₂) and LVOT gradient. REDWOOD-HCM Phase II showed dose-dependent gradient reduction with favourable safety profile.

Potential advantages over mavacamten Shorter half-life (faster reversibility if LVEF drops), potentially less CYP2C19 interaction, and may not require REMS-equivalent monitoring intensity.

Australian availability Not yet TGA-approved. Clinical trial sites active in Australia. Expected TGA submission 2025–2026.

Gene Therapy Research

Gene therapy for HCM is in early-phase investigation, targeting the fundamental genetic defect rather than downstream pathophysiology:

Gene silencing (ASO/siRNA): Antisense oligonucleotides (ASOs) targeting mutant MYBPC3 mRNA are being developed to reduce expression of the dominant-negative protein. Preclinical studies in HCM mouse models show reversal of hypertrophy and fibrosis. Clinical trials are in planning stages.
Gene replacement therapy: AAV-based delivery of functional MYBPC3 to cardiomyocytes. Significant challenges remain: immune response to AAV vectors, achieving sufficient cardiac tropism, and ensuring sustained expression.
CRISPR-based approaches: Preclinical research into allele-specific editing of pathogenic MYH7 or MYBPC3 variants. Ethical and delivery challenges are substantial, but long-term potential for curative therapy exists.
mRNA therapy: Lipid nanoparticle-delivered mRNA encoding functional cardiac proteins — an emerging platform building on COVID-19 vaccine technology. Early preclinical work showing promise.

Other Pipeline Therapies

Agent	Mechanism	Phase	Target Population
Aficamten (CK-274)	Cardiac myosin inhibitor	Phase III	Obstructive and non-obstructive HCM
Bimekizumab-related research	Anti-fibrotic (targeting cardiac fibrosis)	Preclinical	HCM with significant fibrosis
N-acetylcysteine (NAC)	Antioxidant/anti-fibrotic	Phase II (small studies)	Non-obstructive HCM with LV fibrosis
Eleclazine (GS-6615)	Late sodium current inhibitor	Phase II (discontinued — mixed results)	HCM with arrhythmia burden
Ranolazine	Late sodium current inhibitor	Phase II (RHYTHM-HCM)	HCM with ventricular arrhythmias and diastolic dysfunction
Perhexiline	Metabolic modulator (CPT-1 inhibitor)	Phase II (Australian-led trials)	Non-obstructive HCM — improves diastolic function by shifting myocardial metabolism from fatty acid to glucose oxidation

Clinical Trial Opportunities in Australia

Australia is an active contributor to international HCM research, with clinical trial sites at major centres:

ANZCTR (Australian New Zealand Clinical Trials Registry): Search for current HCM trials at anzctr.org.au.
Active Australian HCM research centres: Baker Heart and Diabetes Institute (Melbourne), Victor Chang Cardiac Research Institute (Sydney), Royal Melbourne Hospital HCM Programme, Centenary Institute (Sydney), and multiple university-affiliated hospitals.
Patient registries: The SHaRe Registry (Sarcomeric Human Cardiomyopathy Registry) includes Australian sites and enables genotype–phenotype correlation research. Encourage patients to enrol in registries for research and surveillance.
Clinical trial access: Patients with refractory symptoms, genotype-positive status, or interest in contributing to research should be referred to their nearest HCM specialist centre for discussion of available trials. Trial eligibility typically requires confirmed HCM diagnosis and may have genotype-specific enrolment criteria.

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Paradigm shift in HCM treatment: The approval of mavacamten marks the transition from purely symptom management to disease-modifying therapy in HCM. Cardiac myosin inhibitors directly address the underlying sarcomeric hypercontractility — a first for any inherited cardiomyopathy. Ongoing research into gene therapy offers the prospect of curative treatment in future decades.

📚 References

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