Grapefruit-Mavacamten Interaction Leading to Reduced Ejection Fraction

Figures

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  Visual Summary. Temporal Relationship Between Mavacamten Therapy, Grapefruit Exposure, and Cardiac Function The clinical timeline demonstrates initial therapeutic response to mavacamten with marked reduction in peak LVOT gradient and preserved LVEF. Around month 5, the patient began daily consumption of grapefruit-containing energy drinks. By month 8, LVEF declined to 45% to 50% while LVOT gradient remained suppressed, prompting discontinuation of mavacamten and grapefruit exposure. LVEF normalized after interruption, with rebound LVOT obstruction. Rechallenge with mavacamten in the absence of grapefruit exposure was associated with stable LVEF and recurrent LVOT gradient reduction. CYP = cytochrome P450; LVEF = left ventricular ejection fraction; LVOT = left ventricular outflow tract.

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  Figure 1. Serial Echocardiographic Doppler Assessment of LVOT Obstruction During Mavacamten Therapy TTE images and continuous-wave Doppler tracings demonstrate changes in LVOT obstruction over the course of therapy. (A) At baseline, severe dynamic LVOT obstruction with peak gradient (Max PG) of 157 mm Hg. (B) After 2 months of mavacamten, peak LVOT gradient decreased to 28 mm Hg. (C) At month 8, during grapefruit-containing beverage exposure, the gradient remained suppressed at 21 mm Hg despite new LVEF decline at 45% to 50%. (D) At month 9, after mavacamten and grapefruit exposure were held, LVOT obstruction rebounded to 70 mm Hg. (E) Following mavacamten rechallenge without grapefruit exposure at month 10, the gradient again decreased and remained controlled at 26 mm Hg by month 12. Abbreviations: TTE = transthoracic echocardiography; LVEF = left ventricular ejection fraction; LVOT = left ventricular outflow tract; PG = pressure gradient; Vmax = peak velocity; Vmean = mean velocity; VTI = velocity-time integral.