In a new analysis, investigators probed multiple exercise response patterns before and after exposure to the drug in patients with hypertrophic obstructive cardiomyopathy.
Summary: A clinical trial led by researchers from Mass General Brigham examined the effects of aficamten, an investigational heart drug, on exercise capacity in patients with hypertrophic obstructive cardiomyopathy. The study assessed the drug’s impact on exercise capacity, using measurements such as peak oxygen uptake and cardiac function improvements. The trial, which included 263 patients over 24 weeks, found significant improvements in exercise tolerance, including enhanced breathing efficiency and cardiac power. The findings have implications for treating hypertrophic obstructive cardiomyopathy and potentially broader populations with similar conditions.
Key Takeaways:
- Improved Exercise Capacity: Aficamten significantly enhanced exercise tolerance in hypertrophic obstructive cardiomyopathy patients, as shown by improvements in peak oxygen uptake and workload achieved during testing.
- Enhanced Cardiac Function: The trial demonstrated that aficamten not only improved exercise performance but also led to positive changes in cardiac structure and function, as measured through echocardiography.
- Broader Clinical Implications: The results suggest that aficamten could benefit patients beyond hypertrophic obstructive cardiomyopathy, possibly offering therapeutic benefits for other forms of hypertrophic cardiomyopathy.
Exercise intolerance is often severe among patients with cardiovascular disease and can impose significant limitations on their physical abilities and quality of life. Medications known as cardiac myosin inhibitors (CMIs) are being developed to help patients with hypertrophic obstructive cardiomyopathy, a disease in which the heart muscle becomes thickened leading to reduced blood flow out of the heart.
In a new analysis led by researchers from Mass General Brigham, investigators probed multiple exercise response patterns before and after exposure to the CMI aficamten in the SEQUIOA-HCM trial. The results are published in JAMA Cardiology.
“My laboratory has had a longstanding focus on understanding mechanisms of exercise intolerance and exploration of therapeutic interventions to improve exercise capacity,” says corresponding author Gregory Lewis, MD, the section head of heart failure and director of cardiopulmonary exercise testing at Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, in a release.
Evaluating Effects of Aficamten on Exercise Capacity
The phase-3, placebo-controlled, randomized clinical trial, SEQUIOA-HCM, sponsored by Cytokinetics, Inc, evaluated effects of aficamten on exercise capacity and cardiac function. The primary endpoint of the study was change in peak oxygen uptake as measured by cardiopulmonary exercise testing under the oversight of the MGH Cardiopulmonary Exercise Testing Core Laboratory directed by Lewis.
The study found marked improvements in both peak oxygen uptake as recently reported in the New England Journal of Medicine. In addition, cardiac structure and function measures improved significantly, as adjudicated by the Echocardiography Core Laboratory directed by Scott Solomon, MD, from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system.
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The team assessed 263 patients who completed exercise testing at the start of the trial and 24 weeks later. They saw significant improvements in several measurements, including workload achieved, breathing efficiency and cardiac power generated during exercise, and submaximum exercise capacity measured at the anaerobic threshold.
In addition, they describe a novel measurement that combined submaximum and maximum exercise capacity as an integrated way to assess exercise capacity improvement. The investigators found that changes in exercise responses related to changes in cardiac structure and function beyond just outflow obstruction.
Their findings have important clinical implications for treating hypertrophic obstructive cardiomyopathy and could also be relevant to broader populations of non-obstructive hypertrophic cardiomyopathy.
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