Central Apneas Are More Detrimental in Female Than in Male Patients With Heart Failure

Abstract

Background Central apneas (CA) are a frequent comorbidity in patients with heart failure (HF) and are associated with worse prognosis. The clinical and prognostic relevance of CA in each sex is unknown. Methods and Results Consecutive outpatients with HF with either reduced or mildly reduced left ventricular ejection fraction (n=550, age 65±12 years, left ventricular ejection fraction 32%±9%, 21% women) underwent a 24‐hour ambulatory polygraphy to evaluate CA burden and were followed up for the composite end point of cardiac death, appropriate implantable cardioverter‐defibrillator shock, or first HF hospitalization. Compared with men, women were younger, had higher left ventricular ejection fraction, had lower prevalence of ischemic etiology and of atrial fibrillation, and showed lower apnea‐hypopnea index (expressed as median [interquartile range]) at daytime (3 [0–9] versus 10 [3–20] events/hour) and nighttime (10 [3–21] versus 23 [11–36] events/hour) (all P <0.001), despite similar neurohormonal activation and HF therapy. Increased chemoreflex sensitivity to either hypoxia or hypercapnia (evaluated in 356 patients, 65%, by a rebreathing test) was less frequent in women ( P <0.001), but chemoreflex sensitivity to hypercapnia was a predictor of apnea‐hypopnea index in both sexes. At adjusted survival analysis, daytime apnea‐hypopnea index ≥15 events/hour (hazard ratio [HR], 2.70; 95% CI, 1.06–7.34; P =0.037), nighttime apnea‐hypopnea index ≥15 events/hour (HR, 2.84; 95% CI, 1.28–6.32; P =0.010), and nighttime CA index ≥10 events/hour (HR, 5.01; 95% CI, 1.88–13.4; P =0.001) were independent predictors of the primary end point in women but not in men (all P >0.05), also after matching women and men for possible confounders. Conclusions In chronic HF, CA are associated with a greater risk of adverse events in women than in men.

Association of Sleep Duration, Napping, and Sleep Patterns With Risk of Cardiovascular Diseases: A Nationwide Twin Study

“…Snoring could indicate sleep‐disordered breathing, which might cause acute or long‐term adverse effects on heart health. 39 , 40 Therefore, it is plausible that different sleep characteristics may influence each other and jointly affect cardiovascular health. By applying a comprehensive assessment of sleep incorporating these characteristics, 17 in line with 2 previous studies, 17 , 18 we found that the poor sleep pattern was associated with a higher risk of CVDs.…”

Sex‐related difference in sympathetic chemoreflex response: does it matter in clinical disease?

“…In a recent study (Gentile et al., 2022) enrolling 550 HF patients (mean left ventricular ejection fraction 32 ± 9%), women, compared with men, showed lower HVR and HCVR, and a lower burden of PB/CA/CSR across the 24‐hour period. HCVR was an independent predictor of the apnoea–hypopnea index in both sexes.…”

“…HCVR was an independent predictor of the apnoea–hypopnea index in both sexes. At adjusted survival analysis, PB/CA/CSR were independent predictors of the primary endpoint (a composite of cardiac death, appropriate implantable cardioverter–defibrillator shock or first HF hospitalization) only in women, but not in men (Gentile et al., 2022).…”

Effects of hyperventilation length on muscle sympathetic nerve activity in healthy humans simulating periodic breathing

“…In patients with HFrEF and Cheyne-Stokes respiration apnea duration is usually less heterogenous, while HP length may vary, and this has been mainly attributed to differences in cardiac output and circulation time ( Hall et al, 1996 ; Giannoni et al, 2019b ; Gentile et al, 2022 ). Regarding the impact of CA on sympathetic outflow in the context of CSR the current evidence is contradictory ( Lorenzi-Filho et al, 1999 ; Fatouleh et al, 2014 ; Oldenburg et al, 2015 ; Giannoni et al, 2019b ).…”

“…Thus, the overall impact of PB on sympathetic outflow, a major driver of HFrEF progression, may depend on the net effect of CA and HP and particularly by the relative duration of HP within the PB cycle. This is of major clinical interest as two large multicentric studies using either continuous positive airway pressure or assisted servo-ventilation to treat CA in HFrEF showed neutral or even detrimental impact on survival (Bradley et al, 2005;Cowie et al, 2015;Eulenburg et al, 2016) In patients with HFrEF and Hunter-Cheyne-Stokes respiration apnea duration is usually less heterogenous, while HP length may vary, and this has been mainly attributed to differences in cardiac output and circulation time (Hall et al, 1996;Giannoni et al, 2019b;Gentile et al, 2022). Therefore, to investigate whether the duration of HP may specifically impact on sympathetic outflow, we instructed a group of healthy subjects to simulate two different oscillatory patterns of PB while measuring sympathetic outflow directly by means of intraneural MSNA recordings (Velez-Roa et al, 2004;Macefield, 2012;Macefield and Wallin, 2018;Macefield and Henderson, 2019) and indirectly via noninvasive assessment of heart rate variability (Oldenburg et al, 2015).…”