Tale of three services: early UK experience with mavacamten treatment for hypertrophic cardiomyopathy with left ventricular outflow tract obstruction

Figures

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  Figure 1. Flow chart for treatment of obstructive HCM (Adapted from ESC, AHA and NICE guidance). Non-DHP calcium, Non-dihydropyridine calcium channel blockers (eg, diltiazem or verapamil); HCM, hypertrophic cardiomyopathy; NICE, National Institute for Health and Care Excellence; NYHA, New York Heart Association functional classification; SRT, septal reduction therapy; ESC, European Society of Cardiology; AHA, American Heart Association.

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  Figure 2. Summary of treatment Schedules. Initiation: Starting dose 5 mg or 2.5 mg (poor or unknown CYP2C19 metaboliser status). The initiation covers the first 12 weeks with clinical review and echocardiography required on a 4 weekly basis. *At weeks 4 and 8, if LVEF <50% or provokable LVOT gradient <20 mm Hg, dose reduction or treatment interruption occurs, with reassessment after 4 weeks. Dose titration: At week 12, if LVEF is >55% and the provokable LVOT gradient remains >30 mm Hg, mavacamten dose can be increased in a stepwise fashion to a maximum of 15 mg daily (5 mg in poor metabolisers). Maintenance: Patient enters maintenance with 12 weekly assessment once max LVOT gradient <30 mm Hg and/or at maximum dose for CYP2C19 status, providing LV ejection fraction remains >50%. Interruption or treatment cessation: If LVEF <50% at any stage, treatment should be interrupted, and reassessment at 4-week intervals is reinitiated. **Treatment cessation may be necessary if there are multiple interruptions for LV systolic dysfunction. LVEF, left ventricular ejection function; LVOT, left ventricular outflow tract.

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  Figure 3. Example multidisciplinary clinical service for treatment with Mavacamten. Patient eligibility for treatment: symptomatic NYHA II or III, left ventricular ejection fraction >55%, left ventricular outflow tract gradient >30 mm Hg. Symptom assessment with both physician-assessed outcome (NYHA classification) and patient-reported outcome measures (PROMs). LVOTO, left ventricular outflow tract obstruction; MDT, multidisciplinary team; NYHA, New York Heart Association; SRT, septal reduction therapy; ICC CNS, Inherited cardiac conditions clinical curse specialist.

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  Figure 4. Change in echocardiographic and biomarker parameters from baseline. (A) Change in resting LVOT gradient. (B) Change in provoked LVOT gradient. (C) Change in LV systolic function. (D) Change in median NT-proBNP level. Intersection line on graphs A and B at 30 mm Hg (threshold for LVOT obstruction). Error bars 95% CI limits. LVEF, left ventricular ejection function; LVOT, left ventricular outflow tract.

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  Figure 5. Change in patient New York Heart Association (NYHA) class from baseline to treatment optimisation. Numerical data on the chart represent patient numbers in each class.