Temporal Properties of Cardiorespiratory Coupling in Patients with Heart Failure During the Circadian Cycle

Heart failure (HF) is accompanied by autonomic dysregulation and disrupted physiological rhythms, yet how cardiorespiratory coupling (CRC) reorganizes across the circadian cycle during everyday life remains incompletely characterized. We studied 24 h ambulatory ECG recordings from 88 healthy controls and 75 patients with HF. Cardiac autonomic dynamics were quantified from RR intervals using standard HRV indices and symbolic/entropy descriptors, and circadian organization was assessed with 24 h cosinor modeling. Respiratory timing was derived from ECG-derived respiration (EDR) to obtain breath-to-breath (BB) intervals and the pulse-respiration quotient (PRQ). System-level coupling was evaluated primarily as event-timing coordination using coordigram-based coordination percentages computed at two timing tolerances (ε = 0.1 s and ε = 0.2 s) over 24 h and hour-by-hour, and complemented by entropy-based timing irregularity for RR, BB, PRQ, and RR-BB cross-entropy. Patients with HF exhibited lower global HRV and reduced information content in RR dynamics, together with circadian chronodisruption characterized mainly by weaker rhythmic expression and increased inter-individual phase dispersion. CRC differences depended on both tolerance and time of day. In entropy-based profiles, RR-BB cross-entropy and RR entropy did not show hour-specific differences; instead, group separation was localized to higher early-night ApEn in BB in HF and to consistently higher daytime/early-evening FuzzEn in PRQ in controls. Together, these findings indicate a time-structured remodeling of cardiac autonomic dynamics and CRC in HF, in which autonomic function is compromised, and coupling alterations become most evident when examined at appropriate timing tolerances and with circadian (hour-resolved) resolution.