Red Flags
- Sudden cardiac death survivor with HCM — secondary prevention ICD; cascade family screening[1]
- Syncope on exertion in HCM — high SCD risk; primary prevention ICD discussion[1]
- Symptomatic LVOT obstruction (gradient ≥50 mmHg) refractory to optimal medical therapy — septal reduction or cardiac myosin inhibitor[1]
- Family history of premature SCD with HCM phenotype — clinical and genetic cascade screening of first-degree relatives[1]
First-line treatment
Interventions
- Septal reduction therapy[1]Myectomy or alcohol septal ablation for symptomatic obstructive HCM with LVOT gradient ≥50 mmHg and persistent NYHA III–IV despite optimal medical therapy
- Implantable cardioverter-defibrillator[1]Secondary prevention after cardiac arrest or sustained VT. Primary prevention guided by HCM Risk-SCD calculator integrated with LGE burden, apical aneurysm, and family history
- Genetic counselling and cascade screening[1]All probands with HCM; first-degree relatives offered clinical screening every 1–2 years and cascade genetic testing
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Mavacamten[1] | Cardiac myosin inhibitor | 5 mg PO once daily, titrate per LVOT gradient and LVEF (range 2.5–15 mg) | — | Symptomatic obstructive HCM with insufficient response to beta-blocker; monitor LVEF every 4 weeks during titration; reduces need for septal reduction in EXPLORER-HCM and VALOR-HCM |
| Aficamten[1] | Cardiac myosin inhibitor (next-generation) | 5–20 mg PO once daily per dose-titration protocol | — | SEQUOIA-HCM data: improved exercise capacity in symptomatic obstructive HCM; emerging alternative to mavacamten |
| Bisoprolol or metoprolol succinate[1] | Beta-blocker (first-line) | Bisoprolol 1.25–10 mg daily; metoprolol succ 25–200 mg daily | — | First-line in obstructive and symptomatic non-obstructive HCM |
| Disopyramide[1] | Class IA antiarrhythmic (negative inotrope) | 100–250 mg PO QID (or sustained-release equivalent) | — | Alternative for symptomatic obstructive HCM intolerant or refractory to beta-blocker; useful before mavacamten or septal reduction |
| Verapamil[1] | Non-DHP calcium channel blocker | 120–480 mg PO daily (sustained release) | — | Alternative when beta-blocker contraindicated; AVOID in severe LVOT obstruction with elevated PCWP |
Mavacamten[1]
Cardiac myosin inhibitor
- Adult
- 5 mg PO once daily, titrate per LVOT gradient and LVEF (range 2.5–15 mg)
- Paediatric
- —
Symptomatic obstructive HCM with insufficient response to beta-blocker; monitor LVEF every 4 weeks during titration; reduces need for septal reduction in EXPLORER-HCM and VALOR-HCM
Aficamten[1]
Cardiac myosin inhibitor (next-generation)
- Adult
- 5–20 mg PO once daily per dose-titration protocol
- Paediatric
- —
SEQUOIA-HCM data: improved exercise capacity in symptomatic obstructive HCM; emerging alternative to mavacamten
Bisoprolol or metoprolol succinate[1]
Beta-blocker (first-line)
- Adult
- Bisoprolol 1.25–10 mg daily; metoprolol succ 25–200 mg daily
- Paediatric
- —
First-line in obstructive and symptomatic non-obstructive HCM
Disopyramide[1]
Class IA antiarrhythmic (negative inotrope)
- Adult
- 100–250 mg PO QID (or sustained-release equivalent)
- Paediatric
- —
Alternative for symptomatic obstructive HCM intolerant or refractory to beta-blocker; useful before mavacamten or septal reduction
Verapamil[1]
Non-DHP calcium channel blocker
- Adult
- 120–480 mg PO daily (sustained release)
- Paediatric
- —
Alternative when beta-blocker contraindicated; AVOID in severe LVOT obstruction with elevated PCWP
Safety-net
Referral criteria
- Confirmed HCM or strong clinical suspicion (LV wall thickness ≥15 mm or ≥13 mm with family history)Inherited cardiac conditions clinic with HCM expertise[1]
- Symptomatic obstructive HCM despite optimal medical therapyHCM centre for mavacamten/aficamten or septal reduction evaluation[1]
- Family history of premature SCD or sudden unexplained deathInherited cardiac conditions clinic for cascade screening[1]
Clinical summary
HCM-focused diagnosis, sudden death risk stratification, and pharmacological + interventional management with cardiac myosin inhibitors and septal reduction.