Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

SPS commentary:

In the study, patient-reported health status was measured using the disease-specific 23-item KCCQ, which has a recall period of 2 weeks over which patients describe the frequency and severity of their symptoms, their physical and social limitations, and how they perceive their heart failure symptoms to affect their quality of life.

According to a commentary, an area that the researchers have not fully explored is whether there is an association between the improvements in health status and reductions in left ventricular outflow tract obstruction, which is a dynamic measure affected by heart rate and volume status, limiting its use as a biomarker for monitoring treatment efficacy. It notes the treatment duration was limited to 30 weeks, and the dissipation of benefit within 8 weeks of drug cessation suggests that longer-term treatment is required. These issues will be addressed in the ongoing 5-year extension of the EXPLORER-HCM study. It adds future studies will need to establish whether the benefits apply to a broader range of patients who were not enrolled in EXPLORER-HCM, including patients with chronic AF and NYHA class IV symptoms. In addition, it remains to be seen whether the observed improvements in health status can circumvent the need for more invasive strategies such as alcohol septal ablation or septal myectomy in patients with refractory left ventricular outflow tract obstruction. It concludes that the importance of health status measures as endpoints in treatment trials of obstructive hypertrophic cardiomyopathy cannot be overstated. Several studies have shown the adverse impact of hypertrophic cardiomyopathy on physical activity and quality of life, and apart from implantable cardioverter-defibrillators, all other treatments are prescribed primarily to improve symptoms and quality of life.