Hypertrophic cardiomyopathy: recognition, family screening, and GP management

Hypertrophic cardiomyopathy in general practice

Hypertrophic cardiomyopathy is the most common inherited heart disease, yet it remains significantly under-diagnosed in Australia. The condition — caused by mutations in sarcomeric protein genes that lead to unexplained thickening of the left ventricular wall — affects an estimated 1 in 200 to 1 in 500 Australians, equating to roughly 50,000–125,000 people across the country. Many have no symptoms at all; others present with exertional breathlessness, chest pain, palpitations, or syncope. For some, the first clinical signal is a sudden cardiac death in a young family member.

In general practice, the GP sits at three critical junctions: recognising HCM in someone with cardiac symptoms or a high-risk family history; coordinating a timely cardiology referral and cascade family screening; and supporting ongoing safe living — including guidance on exercise, medications to avoid, and the implications for relatives. The clinical and genetic complexity of HCM means definitive management is specialist-led, but the GP remains the point of contact through which most families first encounter the diagnosis.

This article focuses on GP-relevant aspects of HCM: recognition, the Australian assessment and referral pathway, family screening, key treatment principles, and special populations. It draws on the ESC 2023 Cardiomyopathy Guideline, AHA/ACC 2020 HCM Guideline, and Australian resources including the CSANZ Genetic Heart Disease Position Statement, eTG Cardiomyopathy, and the Australian Genetic Heart Disease Registry.

A. Core clinical — the AU general practice framework

Defining HCM

HCM is defined as left ventricular hypertrophy (LVH) with maximum wall thickness ≥15 mm — or ≥13 mm in someone with a confirmed family history of HCM — in the absence of any other haemodynamic cause. Causes to exclude include hypertension, aortic stenosis, and athlete’s heart. Importantly, infiltrative conditions such as cardiac amyloidosis are now a leading HCM mimic, and each has its own specific therapies.

Approximately 60% of HCM is caused by sarcomeric mutations, most commonly MYH7 (β-myosin heavy chain, ~30%) and MYBPC3 (myosin-binding protein C, ~30%), with a further set of genes accounting for the remainder. These follow an autosomal dominant inheritance pattern. Non-sarcomeric phenocopies — Fabry disease, Pompe disease, PRKAG2 syndrome, Danon disease, and cardiac amyloidosis — must be excluded in appropriate clinical contexts, as each has targeted treatment.

Two major clinical subtypes exist: obstructive HCM (HOCM) (~70%), where septal hypertrophy and systolic anterior motion (SAM) of the mitral valve produce left ventricular outflow tract (LVOT) obstruction; and non-obstructive HCM (~30%), with concentric, apical, or mid-ventricular hypertrophy without obstruction.

History

The Heart Foundation Australia recommends structured cardiac history-taking in anyone with suspected HCM:

• Symptoms: exertional dyspnoea, chest pain, palpitations, pre-syncope, or syncope — especially exertional (a red flag)
• Family history (3-generation pedigree): sudden cardiac death before age 50 (including “drowning while swimming”), unexplained heart failure, HCM diagnosis, pacemaker, ICD, cardiac transplant in a first-degree relative
• Sports and occupation: competitive athlete, physically demanding work
• Drug history: diuretics, ACE inhibitors and ARBs (vasodilation worsens LVOT gradient), digoxin (avoided in HOCM), beta-agonist inhalers
• Pregnancy plans

Examination

The classic murmur of HOCM is a harsh ejection systolic murmur at the left lower sternal edge that increases with Valsalva or standing (manoeuvres that reduce venous return and worsen obstruction) and decreases with squatting or isometric handgrip. Associated mitral regurgitation may be audible at the apex radiating to the axilla. An S4 gallop reflects a stiff, non-compliant left ventricle.

Features suggesting HCM mimics warrant specific investigation: angiokeratomas and acroparaesthesia (Fabry disease); proximal muscle weakness (Pompe); periorbital purpura and macroglossia (AL amyloid); facial dysmorphic features and pulmonic stenosis (Noonan syndrome).

Investigations

Initial GP workup:

• ECG — abnormal in ~90% of HCM: LVH by voltage criteria, deep narrow Q-waves in lateral leads (pseudo-infarct), lateral ST-T changes, giant negative T-waves in V3–V5 (apical HCM), atrial fibrillation
• TTE (transthoracic echocardiogram) — referred to cardiology; central for diagnosis, quantifying LVOT gradient, SAM, and left atrial size
• Cardiac MRI — gold standard for hypertrophy quantification and detection of late gadolinium enhancement (LGE), focal fibrosis that is an independent sudden cardiac death risk marker, especially when LGE exceeds 15% of LV mass
• Holter monitor — detects non-sustained ventricular tachycardia (NSVT, ≥3 consecutive ventricular ectopic beats), an ICD-indicating high-risk feature
• Genetic testing — proband-first; HCM gene panel; once mutation identified, cascade testing of first-degree relatives is Medicare-funded (MBS 73297)
• Phenocopy workup — α-galactosidase activity and GLA sequencing (Fabry); free light chains and urine immunofixation (AL amyloid); nuclear bone scan (ATTR amyloid); Pompe enzyme assay

Risk stratification and ICD

SCD risk is stratified using the ESC HCM Risk-SCD calculator, which generates a 5-year SCD probability from age, maximum wall thickness, left atrial size, LVOT gradient, family history of SCD, NSVT, and unexplained syncope. An ICD is indicated for secondary prevention (prior cardiac arrest or sustained VT) and is considered for primary prevention when 5-year SCD risk is ≥6% or when major risk markers are present — maximum wall thickness ≥30 mm, hypotensive exercise blood pressure response, or LGE >15% LV mass on cardiac MRI.

B. The evidence base — EXPLORER-HCM and the LIVE-HCM registry

Two landmark trials have reshaped HCM management in recent years and altered recommendations that had stood largely unchanged for decades.

Mavacamten — EXPLORER-HCM

Mavacamten is a selective allosteric cardiac myosin inhibitor — the first disease-targeted therapy for HCM. The EXPLORER-HCM RCT (Olivotto et al. Lancet 2020) randomised 251 adults with symptomatic obstructive HCM (NYHA class II/III, LVOT gradient ≥50 mmHg) to mavacamten or placebo over 30 weeks:

• Primary composite endpoint (NYHA class improvement or ≥1.5 mL/kg/min improvement in peak VO₂): 37% mavacamten vs 17% placebo
• LVOT gradient reduction: median resting LVOT gradient fell from 67 to 12 mmHg in the mavacamten group
• Quality of life (KCCQ): significantly improved
• Septal reduction therapy eligibility: eliminated in 82% of mavacamten recipients vs 68% placebo

The follow-up VALOR-HCM trial confirmed that mavacamten significantly reduced the proportion of patients still meeting eligibility criteria for invasive septal reduction therapy after 16 weeks (18% vs 77% placebo).

Mavacamten was listed on the PBS Section 100 (Highly Specialised Drugs) in Australia in 2024 for adults with symptomatic NYHA class II/III obstructive HCM whose symptoms persist despite first-line therapy. It requires specialist initiation, serial echocardiographic monitoring (LV systolic dysfunction is a known adverse effect), and attention to CYP2C19 genotype which influences dosing.

Exercise — LIVE-HCM registry

Historically, competitive sport was broadly discouraged in HCM. The LIVE-HCM registry (Lampert et al. Circulation 2023) challenged this with prospective data from 1,094 people with HCM — 42% competitive athletes — followed for a median of three years:

• Major arrhythmic cardiac events did not differ significantly between competitive athletes and non-vigorous-activity participants
• No exercise-related sudden deaths occurred in the prospective cohort
• Quality of life was better in those who exercised vigorously

Both the ESC 2023 and AHA/ACC guidelines updated their recommendations accordingly: competitive sport is now a shared decision between patient and cardiologist following thorough risk stratification, rather than a blanket prohibition. Moderate-intensity exercise (recreational walking, swimming, cycling) is generally encouraged for all patients. The Heart Foundation Australia and CSANZ support this individualised approach.

C. Family screening and genetic counselling

HCM follows autosomal dominant inheritance — each first-degree relative has a 50% probability of carrying the same mutation. Family screening is one of the highest-yield interventions in HCM management.

Genetic counselling before testing

Genetic counselling is mandatory before genetic testing — a clinically essential step, not a bureaucratic formality. It covers variable penetrance (some mutation carriers never develop HCM), the implications of variants of uncertain significance, reproductive decisions including pre-implantation genetic diagnosis, and the Australian insurance context. Under a Financial Services Council moratorium, genetic test results below specified policy thresholds cannot be used by life insurers — an important consideration to raise before patients decide whether to test.

State genetic services and the Australian Genetic Heart Disease Registry provide coordinated pathways for families navigating referral networks.

Cascade family screening protocol

Once the proband’s mutation is identified:

1. First-degree relatives are offered targeted genetic testing (blood test, Medicare-funded MBS 73297)
2. Relatives who do not carry the mutation require no further cardiac surveillance
3. Relatives who carry the mutation (even with currently normal echocardiogram and ECG) enter a surveillance programme:
   • Adolescents aged 12–21: ECG + TTE every 1–2 years
   • Adults: ECG + TTE every 3–5 years, lifelong
   • Phenotypic expression may emerge at any point in adulthood — penetrance is age-related
4. If the proband’s mutation cannot be identified (~40% of HCM), phenotypic screening (ECG + TTE) is offered to first-degree relatives on the same schedule

GP’s role in family screening

The GP is often the first to receive a cascade screening request. Key actions include obtaining the 3-generation family history at the index consultation, explaining the 50% inheritance risk in plain language, referring first-degree relatives for genetic counselling and cardiac screening (often coordinated through the proband’s HCM specialist clinic), discussing insurance implications proactively before testing is initiated, and flagging adolescents and young adults who may not yet have been informed of their relative’s diagnosis.

D. Australian operations

Specialist pathway

Suspected HCM in general practice → cardiology referral. Standard wait is appropriate unless the patient has exertional syncope, a resuscitated cardiac arrest, or new haemodynamically significant atrial fibrillation — these warrant urgent or emergency pathways.

HCM expert centres in Australia include Royal Prince Alfred Hospital (Sydney), Royal Melbourne Hospital, St Vincent’s Hospital (Sydney), Royal Brisbane and Women’s Hospital, Sir Charles Gairdner Hospital (Perth), and Royal Adelaide Hospital. These centres run multidisciplinary clinics integrating cardiology, genetic counselling, clinical genetics, cardiac electrophysiology, and cardiothoracic surgery. The Australian Genetic Heart Disease Registry coordinates research and clinical pathway integration nationally.

MBS items relevant to general practice

• MBS 11700/11701 — 12-lead ECG
• MBS 23/36/44 — standard GP consultations, including care coordination and family discussion
• MBS 73297 — genetic testing (Medicare-funded for qualifying proband and first-degree relatives once proband mutation is identified)
• Holter monitoring, TTE, cardiac MRI, and exercise stress testing are billed under specialist MBS items and coordinated through the cardiology team

PBS medications

Beta-blockers (atenolol, metoprolol, bisoprolol), verapamil, diltiazem, disopyramide, and DOACs for atrial fibrillation are all PBS-listed for standard indications. In HCM with atrial fibrillation, anticoagulation is recommended regardless of the CHA₂DS₂-VASc score — HCM carries high stroke risk that this scoring system underestimates, and DOACs are preferred over warfarin. Mavacamten is PBS Section 100 since 2024; specialist initiation and ongoing echo monitoring are required.

Medications to avoid in obstructive HCM

The following agents worsen LVOT obstruction or increase arrhythmia risk and should be avoided in obstructive HCM: nitrates, ACE inhibitors, ARBs, dihydropyridine calcium channel blockers (amlodipine, nifedipine), high-dose diuretics (reduce preload and worsen gradient), and digoxin. Stimulants — cocaine, amphetamines, and ephedrine-containing decongestants — are a significant harm risk and should be flagged explicitly.

E. Special populations

Older adults. HCM in people over 65 often presents with exertional dyspnoea attributed to hypertension or coronary disease. A key pitfall is failing to distinguish HCM from hypertensive heart disease or cardiac amyloidosis — all can coexist. The availability of targeted ATTR amyloid therapies (tafamidis) makes misclassification clinically costly. Cardiac MRI and nuclear bone scan imaging are central to distinguishing these conditions.

Adolescents and young people. Young people with HCM face significant psychosocial challenges: evolving restrictions on sporting participation, driver licensing considerations (driver fitness is governed by Austroads cardiac criteria), and the psychological burden of a genetic cardiac diagnosis. Peer support through HCMA Australia and mental health integration in HCM clinics is important. Following the LIVE-HCM data, conversations about sport are now more nuanced and require direct cardiologist involvement rather than a GP-level prohibition.

Pregnancy. Most women with HCM tolerate pregnancy without major complication. Pre-conception review with a cardiologist identifies high-risk features — severe obstructive HCM (resting LVOT gradient >50 mmHg), prior cardiac arrest, NYHA class III/IV symptoms — that warrant multidisciplinary planning across cardiology, maternal–foetal medicine, and obstetric anaesthesia. Metoprolol is the preferred beta-blocker in pregnancy; ACE inhibitors and ARBs are teratogenic and must be stopped before conception. Vaginal delivery is generally well-tolerated; epidural anaesthesia is used cautiously, as vasodilation can worsen obstruction.

Competitive athletes. Pre-participation screening to detect HCM in athletes is recommended for elite and family-history-positive populations in Australia. CSANZ guidelines do not mandate population-wide ECG screening (unlike Italy or Israel), but cardiac evaluation is recommended for athletes with cardiac symptoms or relevant family history. Post-LIVE-HCM, return-to-sport discussions require shared decision-making with a cardiologist rather than blanket restriction.

When to escalate

Refer urgently or via emergency services when:

• Exertional syncope or sustained pre-syncope — possible malignant arrhythmia or severe obstruction
• Resuscitated sudden cardiac death or sustained ventricular tachycardia
• New-onset rapid atrial fibrillation with haemodynamic compromise
• NYHA class III/IV symptoms not responding to initial GP management
• Suspected HCM in pregnancy with high-risk features (severe obstruction, prior cardiac arrest)

Refer routinely when:

• New diagnosis of HCM or suspected HCM on ECG or echocardiogram
• First-degree relative of a confirmed HCM case requiring evaluation and genetic counselling
• Exertional cardiac symptoms (dyspnoea, chest pain, palpitations) in the context of ECG abnormality or family history of cardiac disease
• Athlete seeking return-to-sport guidance with known HCM

What this article is and is not

This is general health information drawn from current Australian sources — eTG Cardiomyopathy, CSANZ Genetic Heart Disease Position Statement, Heart Foundation Australia — and major international guidelines (ESC 2023, AHA/ACC 2020). It reflects GP-relevant principles for recognition, referral, and family screening and does not replace specialist assessment, genetic counselling, or cardiology-directed management.

HCM requires lifelong specialist partnership. When a GP raises the possibility of HCM — whether for a new patient or a first-degree relative of someone diagnosed — the starting point is a cardiology referral.

For patient-facing resources: HCMA Australia, Heart Foundation Australia, Australian Genetic Heart Disease Registry, HealthDirect.

For cardiac emergencies: call 000.

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Sources cited

1. CSANZ Genetic Heart Disease Position Statement
2. Therapeutic Guidelines (eTG) — Cardiomyopathy
3. Heart Foundation Australia — Cardiomyopathy
4. Australian Genetic Heart Disease Registry
5. HCMA Australia
6. HealthDirect — Heart conditions
7. Arbelo E et al. ESC 2023 Cardiomyopathy Guideline. Eur Heart J 2023;44:3503–3626
8. Ommen SR et al. AHA/ACC 2020 HCM Guideline. Circulation 2020;142:e558–e631
9. Olivotto I et al. EXPLORER-HCM Trial. Lancet 2020;396:759–769
10. Lampert R et al. LIVE-HCM Registry. Circulation 2023;147:1582–1593
11. PBS — Mavacamten Section 100 Highly Specialised Drugs
12. Financial Services Council — Genetic Test Result Moratorium