Assessing the Applicability of Cardiac Myosin Inhibitors for Hypertrophic Cardiomyopathy Management in a Large Single Center Cohort.

Background: Cardiac myosin inhibitors (CMIs), including Mavacamten and Aficamten, have emerged as a groundbreaking treatment for hypertrophic cardiomyopathy (HCM). The results from phase 2 and 3 randomized clinical trials for both drugs have showed promising outcomes. However, the highly selective patient recruitment for these trials raises questions about the generalizability of the observed positive effects across broader patient populations suffering from HCM.
Methods: A retrospective cohort study at University Hospital Heidelberg included 404 HCM patients. Baseline assessments included family history, electrocardiograms (ECGs), and advanced cardiac imaging, to ensure the exclusion of secondary causes of left ventricular hypertrophy.
Results: Among the HCM patients evaluated, only a small percentage met the inclusion criteria for recent CMI trials: 10.4% for EXPLORER-HCM and 4.7% for SEQUOIA-HCM. The predominant exclusion factor was the stringent left ventricular outflow tract (LVOT) gradient requirement.
Conclusions: This study highlights a significant discrepancy between patient demographics in clinical trials and those encountered in routine HCM clinical practice. Despite promising results from the initial randomized clinical trials that led to the approval of Mavacamten, the selected patient population only represents a small part of the HCM patient cohort seen in routine clinics. This study advocates for further expanded randomized clinical trials with broader inclusion criteria to represent diverse primary HCM patient populations.
Competing Interests: The members of the study group have participated in clinical trials sponsored by Bristol Myers Squibb and Cytokinetics, focusing on several studies involving Mavacamten and Aficamten. Prof. B. Meder and PD Dr. F. Sedaghat-Hamedani have received funding from Bristol Myers Squibb. Additionally, they serve as scientific advisors for Bristol Myers Squibb and are engaged in the planning and execution of clinical trials for Mavacamten. Furthermore, Prof. B. Meder holds a position as a speaker for the DGK AG 12 Cardiomyopathies. Our study had no sponsors and no influence from any external sources. The studies mentioned in the conflict of interest were not influenced by the sponsors. Farbod Sedaghat-Hamedani is serving as Guest Editor of this journal. We declare that Farbod Sedaghat-Hamedani had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Francesco Pelliccia. The authors declare no conflict of interest.
(Copyright: © 2024 The Author(s). Published by IMR Press.)