Circadian Activity Disruption in Cardiac Remodeling Patients Underlies Autonomic Dysfunction in Heart Failure

Background: Heart failure (HF) is a complex clinical syndrome that presents significant challenges in diagnosis and treatment. Exploring innovative pathways to better understand the physiopathological mechanisms has led to the concept of cardiac remodeling (CR), which helps elucidate the diversity in clinical manifestations and treatment responses. However, the extent to which CR influences autonomic cardiac dynamics across the circadian cycle remains unclear. Methods: Recordings of 24 h ECG recordings from 86 Control subjects and 86 patients meeting the criteria for cardiac remodeling were analyzed. Heart rate variability (HRV) parameters were estimated using 5 min Blackman-Harris windows per hour. Autonomic influences on cardiac electrical activity were assessed using time-domain, frequency-domain, and nonlinear methods. Circadian parameters (MESOR, amplitude, and acrophase) were derived via Cosinor modeling, and group differences were evaluated while controlling for age, sex, and medication effects. Results: Patients with CR exhibited reduced oscillatory activity in HRV measures compared with Control. MESOR and amplitude were significantly lower in CR patients, who also displayed an advanced-phase phenotype across multiple HRV domains over 24 h. Additionally, CR patients showed decreased complexity and entropy in nonlinear dynamics. Conclusions: Altered circadian rhythmicity of cardiac electrical activity is evidenced in cardiac remodeling by changes in circadian HRV parameters and nonlinear dynamics.