Actigraphy-Quantified Physical Activity Measurements in Patients With Symptomatic LMNA-Related Dilated Cardiomyopathy in REALM-DCM

Introduction: Actigraphy-quantified physical activity (PA) allows for continuous measurements of physical activity that are reflective of real-world day-to-day functioning and morbidity in persons living with cardiomyopathy. This analysis reports the results of actigraphy monitoring and relates these to other clinical outcome assessments in the Phase 3, multinational REALM-DCM (NCT03439514) clinical trial in LMNA-related dilated cardiomyopathy. Methods: Between 2020 and 2022, REALM-DCM randomized 37 patients with actigraphy worn on the non-dominant wrist continuously to monitor daily physical activity. Of those 35 participants had analyzable data for this analysis. Results: The median duration of actigraphy monitoring for all participants was 293 days across 120 patient visits. Over 85% of the visits met a predefined threshold of wear-time compliance of ten hours of awake wear time for at least four days within the two-week monitoring period prior to and after clinic visits. Kansas City Cardiomyopathy Questionnaire (KCCQ) physical limitation scores was positively associated with several actigraphy-quantified PA metrics, including Moderate to Vigorous Physical Activity (MVPA), moderate activity, non-sedentary behavior, total step counts, total activity counts (all 3 axes and their vector magnitude). 6 minute walk time (6MWT) distance was positively associated with time spent in MVPA and moderate activity, and total step counts. Patient Global Impression (PGI) Symptom Heart Failure Severity were negatively associated with non-sedentary behavior, total activity counts (vector magnitude, X, and Y axes), and light activity. Actigraphy endpoints also distinguished between NYHA class II and class III patients. Actigraphy endpoints did not correlate with the KCCQ total score. Conclusion: This is the largest and most longitudinal dataset of LMNA-DCM patients collected and reported to date using wearable sensors to gain understanding of physical activity patterns in these patients. These data help to understand the potential use of actigraphy monitoring and wearable technologies in genetic cardiomyopathy and heart failure clinical trials.