Effect of Aficamten on Cardiac Structure and Function in Patients With Symptomatic Nonobstructive Hypertrophic Cardiomyopathy.

In 30 seconds

This prespecified exploratory analysis of the phase 3, multicentre, randomised, placebo-controlled ACACIA-HCM trial examined serial echocardiographic changes in symptomatic patients with nonobstructive hypertrophic cardiomyopathy assigned to aficamten or placebo for up to 72 weeks. Among 517 participants, aficamten improved measures of diastolic function versus placebo: at 36 weeks, lateral and septal e′ velocities increased by 0.9 cm/s and 0.7 cm/s, respectively (P<0.001 for both). Aficamten also reduced left ventricular ejection fraction and increased ventricular volumes. The findings suggest cardiac effects beyond left ventricular outflow tract gradient reduction.

Key findings

• At 36 weeks, lateral e′ increased by 0.9 cm/s and septal e′ by 0.7 cm/s versus placebo (P<0.001 for both).
• Aficamten reduced left ventricular ejection fraction versus placebo at 36 weeks (-4.6% [-5.5, -3.6]; P <0.001) and increased left ventricular volumes.
• By end of treatment, septal E/e′ was lower versus placebo (-1.4 [-2.1, -0.6]; P <0.001).
• Peak tricuspid regurgitation velocity improved at 36 weeks (-10.4 cm/s [-19.9, -1.0]; P =0.030), with an effect sustained through end of treatment.

Why it matters

The echocardiographic findings indicate that aficamten’s effects in symptomatic nonobstructive hypertrophic cardiomyopathy may include changes in diastolic function, not only effects related to outflow tract gradients. This helps characterise the cardiac changes accompanying treatment, while the exploratory analysis does not establish that these imaging changes themselves account for clinical benefit.

What to keep in mind

This was a prespecified exploratory analysis of echocardiographic measures; the reported findings concern imaging outcomes and do not establish that these changes cause improvements in symptoms or functional capacity.