Fighting the pandemic of heart failure: better utilization of current treatments, new drugs, and new therapeutic targets

This Focus Issue on heart failure and cardiomyopathies contains the State of the Art Review article entitled ‘Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy’.1 Eugene Braunwald from the Brigham and Women’s Hospital in Boston, MA, USA, and colleagues remind us that mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association Classes II and III obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten was developed to target the hypercontractile phenotype, which plays a critical role in the pathophysiology of this complex disease.2–6In Phase II and III clinical trials, mavacamten was well tolerated, reduced left ventricular outflow tract gradients, improved exercise capacity and symptoms, and was associated with improvements in other clinically relevant parameters, such as patient-reported outcomes and circulating biomarkers. In addition, treatment with mavacamten was associated with evidence of favourable cardiac remodelling in multi- modality imaging studies. Mavacamten substantially reduced guideline eligibility for septal reduction therapy candidates with oHCM and drug-refractory symptoms. In this article, the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM are reviewed. Longer term extension studies may help address questions related to the positioning of mavacamten in current oHCM management algorithms, interactions with background therapy, as well as the potential for disease modification beyond symptomatic relief of left ventricular outflow tract obstruction .

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