Risk of Atrial Fibrillation in Patients with Sleep-Disordered Breathing and Heart Failure with Preserved or Mildly Reduced Ejection Fraction

Laura Erika Maria Hannen (Hamburg)1, E. Unger (Hamburg)2, D. Engler (Hamburg)3, A. Ghrib (Hamburg)1, K. Rosebrock (Hamburg)1, S. Camen (Hamburg)1, P. Kirchhof (Hamburg)1, S. Blankenberg (Hamburg)1, C. Magnussen (Hamburg)1, R. Schnabel (Hamburg)3

1Universitäres Herz- und Gefäßzentrum Hamburg Klinik für Kardiologie Hamburg, Deutschland; 2Universitätsklinikum Hamburg-Eppendorf Klinik für Kardiologie Hamburg, Deutschland; 3Universitäres Herz- und Gefäßzentrum Hamburg Allgemeine und Interventionelle Kardiologie Hamburg, Deutschland


Background.  Heart failure with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) are linked to multi-organ dysfunction and comorbidities that require individual treatment strategies. Recent studies suggest that comorbidities such as atrial fibrillation (AF) and sleep-disordered breathing (SDB) can each contribute to HFpEF and HFmrEF. To date, the impact of present SDB in patients with HFpEF/HFmrEF at risk for atrial fibrillation remains unclear. Whether these conditions affect outcomes is less well established.

Purpose. This study aimed to investigate the role of SDB in patients with HFpEF or HFmrEF at risk of developing AF and their association with cardiovascular events and all-cause mortality. 

Methods. We enrolled 1,775 patients at our university heart and vascular center in a long-term prospective single-centre clinical cohort study. We analysed three subcohorts: individuals with 1) HFpEF/HFmrEF without SDB [-] but with [+] AF or without AF [-], 2) HFpEF/HFmrEF with SDB [+] but without AF [-] and 3) HFpEF/HFmrEF with SDB [+] as well as AF [+]. Kaplan-Meier estimates were calculated for all-cause mortality after 10 years in each subcohort. A univariate Cox regression model was fitted to assess frequency of common adverse cardiovascular (CV) events. 

Results. A total of 403 patients with HFpEF/HFmrEF were included in the final analysis (HFpEF/HFmrEF [SDB-/AF+-]: N=192 [47.6%]; HFpEF/HFmrEF [SDB+/AF+]: N=117 [29%]; HFpEF/HFmrEF [SDB+/AF-]: N=94 [23.3%]). Overall, the median age was 67 years [interquartile range (IQR) 58-75 years], and 70.2% men. Cardiovascular comorbidities included hypertension (N=325 [80.6%]), coronary artery disease (CAD) (N=254 [63%]) and dyslipidemia (N=240 [59.6%]). Frequent comorbidities in the HFpEF/HFmrEF [SDB+/AF-] subcohort were current smoking (N=26 [27.7%], p=0.004), chest pain (N=63 [67%], p<0.001), coronary artery disease (CAD) (N=79 [84%], p<0.001), prior percutaneous coronary intervention (PCI) (N=91 [96.8%], p<0.001) and prior myocardial infarction (N=63 [67%], p<0.001). Daytime tiredness was highly prevalent in both HFpEF/HFmrEF [SDB+/AF-] (N=41 [43.6%]) and HFpEF/HFmrEF [SDB+/AF+] (N=57 [48.7%], p=0.021). 10-year survival was better in patients with HFpEF/HFmrEF [SDB+/AF-] than in the other groups (r=6.8; p=0.034, Figure 1). In a univariable Cox regression model, adverse CV events were more frequent in HFpEF/HFmrEF [SDB+/AF+] patients (N=107) than in HFpEF/HFmrEF [SDB+/AF-] patients (N=73) (r=2.6; p=0.190).  

Conclusion. Both sleep-disordered breathing and atrial fibrillation are common in patients with heart failure with preserved or mildly reduced ejection fraction. Atrial fibrillation, but not sleep-disordered breathing, is associated with 10-year mortality and more adverse CV. In contrast to atrial fibrillation, sleep-disordered breathing in patients with HFpEF/HFmrEF showed a strong association with current smoking, chest pain, CAD, prior PCI and MI. These findings call for external validation and for intensive therapy of atrial fibrillation in patients with heart failure.

Figure 1: Kaplan Meyer estimates of survival in HFpEF/HFmrEF subgroups
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