Autonomic effects of simulated periodic breathing in patients with chronic heart failure on contemporary guideline-directed therapy

PURPOSE: The aim of this study was to evaluate sympathetic responses to experimentally induced periodic breathing/Cheyne-Stokes respiration (PB/CSR)-like patterns in optimally treated patients with chronic heart failure (CHF) compared with matched healthy controls. METHODS: Muscle sympathetic nerve activity (MSNA) was recorded in 22 patients with systolic CHF (63 ± 9 years; left ventricular ejection fraction 31 ± 8%) and 10 age- and sex-matched healthy controls during spontaneous breathing and during two experimental protocols designed to reproduce PB/CSR-like oscillations: a short-cycle protocol (five cycles of 30-s apnea/30-s recovery breathing) and a long-cycle protocol (five cycles of 30-s apnea/60-s recovery breathing). RESULTS: At baseline, MSNA was comparable between patients with CHF and controls, whereas heart rate variability indices were reduced in CHF. Compared with spontaneous breathing, simulated PB/CSR-averaging apnea and recovery phases-was associated with modest reductions in MSNA, with no significant differences between protocols or groups (p > 0.05). Both maneuvers elicited reproducible oscillatory patterns in MSNA, characterized by increases during apnea and decreases during recovery breathing, consistent with PB/CSR-like entrainment. However, patients with CHF exhibited weaker and more temporally dispersed coupling between MSNA and cardiorespiratory variables compared with controls. CONCLUSIONS: In optimally treated CHF, baseline sympathetic activity is comparable to that of healthy controls, and PB/CSR-like breathing primarily induces phase-locked oscillatory modulation of MSNA rather than sustained sympathetic activation. Impaired autonomic-hemodynamic coupling may represent a key mechanism underlying the clinical relevance of abnormal breathing patterns in CHF.