What are the criteria for initiating mevacamptan (Mevacamptan) in patients with Hypertrophic Obstructive Cardiomyopathy (HOCM)?

Criteria for Initiating Mavacamten in HOCM

Mavacamten should be initiated in adult patients with symptomatic NYHA class II-III obstructive hypertrophic cardiomyopathy who remain symptomatic despite maximally tolerated first-line therapy with beta-blockers or nondihydropyridine calcium channel blockers. 1, 2

Patient Selection Criteria

Required Clinical Features

• Age: Adult patients only (not approved for pediatric use) 2
• Symptom severity: NYHA class II or III heart failure symptoms (dyspnea, angina, or exertional fatigue) 1, 2
• Obstruction: Documented left ventricular outflow tract (LVOT) gradient ≥30 mmHg at rest or with provocation 1
• Preserved systolic function: Left ventricular ejection fraction (LVEF) ≥50% at baseline 1, 2

Mandatory Prior Treatment Requirements

• First-line therapy failure: Persistent symptoms despite adequate trial of beta-blockers (titrated to resting heart rate <60-65 bpm) OR nondihydropyridine calcium channel blockers (verapamil up to 480 mg/day or diltiazem) 3, 1, 2
• Treatment hierarchy: Beta-blockers or calcium channel blockers must be attempted first, with mavacamten positioned as second-line therapy alongside disopyramide or septal reduction therapy 3, 2

Absolute Contraindications

Must Exclude Before Initiation

• Pregnancy: Mavacamten is absolutely contraindicated due to teratogenic effects 3, 2
• Systolic dysfunction: LVEF <50% at baseline precludes initiation 1, 2
• Non-obstructive HCM: Patients without documented LVOT obstruction are not candidates 1

Pre-Treatment Assessment Checklist

Required Baseline Evaluations

• Echocardiography: Document resting and post-Valsalva LVOT gradients, measure baseline LVEF, assess septal thickness 1, 4
• Functional capacity: Confirm NYHA class II-III symptoms with objective exercise limitation 1, 2
• Pregnancy screening: Mandatory negative pregnancy test in women of childbearing potential 3
• Medication review: Ensure no drug interactions that could affect mavacamten metabolism 4

Risk Evaluation and Mitigation Strategy (REMS) Requirements

Mandatory Enrollment and Monitoring

• REMS program enrollment: Both prescriber and patient must be enrolled before first prescription 1, 4
• Certified pharmacy: Medication can only be dispensed through REMS-certified pharmacies 4
• Baseline documentation: Submit Patient Status Form with baseline echocardiogram results 4

Expected Clinical Outcomes After Initiation

Efficacy Benchmarks

• Gradient reduction: 30-60% of patients achieve significant improvement in LVOT gradients 1
• Symptom improvement: At 16 weeks, expect reduction in NYHA class and NT-proBNP levels 5
• Obstruction elimination: 79.1% of patients eliminate hemodynamically significant LVOT obstruction after ≥6 months 6

Critical Safety Monitoring Post-Initiation

Mandatory Follow-Up Schedule

• Echocardiography frequency: Required before each dose adjustment and at regular intervals per REMS protocol 1, 4
• LVEF monitoring: Must interrupt treatment immediately if LVEF drops <50% at any visit 1, 2
• Risk of LVEF reduction: 5.7% attributable to drug alone, up to 7-10% when considering other clinical conditions 1, 2

Dose Titration Protocol

• Starting dose: 5 mg daily for most patients 5, 4
• Titration decisions: Based on echocardiographic LVOT gradient and LVEF measurements 7, 4
• Maintenance dosing: 74.1% of patients remain on 5-10 mg daily after 6 months 4

Special Populations and Considerations

Patients Requiring Caution

• Obesity: Patients with BMI ≥35 kg/m² may experience attenuated symptomatic relief 6
• Racial diversity: Effectiveness and safety appear similar across racial groups 6
• Mid-ventricular obstruction: Mavacamten may be effective even in isolated mid-ventricular obstruction, though this is off-label 5

Common Pitfalls to Avoid

Critical Errors in Patient Selection

• Premature initiation: Do not start mavacamten before adequate trial of first-line beta-blockers or calcium channel blockers 3, 1
• Ignoring LVEF threshold: Never initiate if baseline LVEF <50% 1, 2
• Inadequate contraception counseling: Failure to ensure effective contraception in women of childbearing potential 3
• Bypassing REMS enrollment: Cannot prescribe without proper REMS certification and patient enrollment 4