BOSTON — A study published in the Journal of the American College of Cardiology reports that 21% of patients with phenotypically mild hypertrophic cardiomyopathy experienced major adverse cardiovascular events over a 7-year follow-up period. The overall incidence rate of major adverse cardiovascular events was 3.4 events per 100 patient-years.

The Sarcomeric Human Cardiomyopathy Registry included 2,500 patients with phenotypically mild hypertrophic cardiomyopathy. This condition was defined by a disease duration of less than 10 years since diagnosis or an age of 30 years or younger, no previous major adverse cardiovascular events, New York Heart Association functional class I symptoms, and a left ventricular maximal wall thickness of less than 25 mm. The mean age of participants was 43 years, and 31% were women.

During the study, 23% of individuals subsequently developed symptoms. Atrial fibrillation was the most common major adverse cardiovascular event, with 289 participants developing the condition. Additionally, 193 participants developed heart failure, and 69 experienced malignant ventricular arrhythmia.

Individuals who progressed from New York Heart Association functional class I to class II or higher symptoms had a hazard ratio of 2.79 for experiencing major adverse cardiovascular events. Predictors of adverse events included older age at baseline, a higher body mass index, a larger left atrial diameter, greater left ventricular maximal wall thickness, a higher left ventricular outflow tract gradient, and the presence of left ventricular late gadolinium enhancement on cardiac MRI.

Carolyn Ho, MD, of Brigham and Women's Hospital and Harvard Medical School, reported the findings. Study authors noted limitations such as potential missing data, bias, and the failure to capture undiagnosed individuals in the general population. "Our intent was to study patients with HCM who are not currently eligible for treatments aimed at improving symptoms, but may be a target for disease-modifying therapy in the future," the study authors stated. "These findings highlight dynamic disease progression as an important feature of risk prediction." "We advocate for a paradigm shift in surveillance strategies, focusing on trajectory in addition to cross-sectional measures at individual timepoints."

Mark Russell, MD, and Joshua Meisner, MD, PhD, of the University of Michigan, wrote an accompanying editorial. "Increasing outflow tract obstruction is an important determinant of future MACE, myosin inhibitors may ultimately have a role in altering the course of the disease in patients with mild HCM who are at risk for progression," they wrote. "Future work could develop these data into a risk calculator for clinical progression of disease, similar to the highly beneficial and widely adopted sudden cardiac death-risk calculators in HCM, which will help guide clinical monitoring and treatment."

Why It Matters

Hypertrophic cardiomyopathy is a myocardial disorder characterized by unexplained left ventricular hypertrophy. The study shifts the focus towards the dynamic progression of this disorder, even in patients initially classified as having mild symptoms. The findings suggest a need for changes in surveillance strategies to evaluate disease trajectory rather than relying solely on cross-sectional measurements at single timepoints. While some therapies like valsartan, SGLT2 inhibitors, GLP-1 receptor agonists, and finerenone are approved for other conditions, they may have the potential to modify the course of hypertrophic cardiomyopathy, indicating future research and treatment avenues.