Influence of persistent atrial fibrillation on the prognosis of heart failure with preserved, mildly reduced, and reduced ejection fraction in women and men

Abstract Introduction Heart failure (HF) is one of the leading causes of death from cardiovascular disease. Persistent atrial fibrillation (PAF) is associated with a worse prognosis in HF. However, little is known about the influence of AF on mortality in women and men with heart failure with preserved (HFpEF ≥50%), mildly reduced (HFmrEF 41% to 49%), and reduced ejection fraction (HFrEF ≤40%). Purpose to analyze the characteristics and influence of PAF on the prognosis of different HF phenotypes. Methods From February 2017 to September 2020, we analyzed hospitalizations, emergency admissions, and mortality of different HF phenotypes with and without PAF. Baseline data included clinical features and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) and Cox proportional hazards methods to analyze mortality rates. Results We studied 11,543 patients, with a mean of 64.1±14.0 years: 55.1% male, 42% with HFrEF, 12.8% with HFmrEF, and 45.1% with HFpEF. PAF was associated with higher mean age (67.6±14.3 vs. 62.8±13.4 years, p<0.001) and more prevalent in men (21% vs. 19%; p=0.019) and in patients with valvular and Chagas etiologies, chronic kidney disease (CKD), stroke, and anemia. The prevalence of PAF in women and men was, respectively, 12.4% vs. 18.3% (p<0.001) in HFrEF, 18.1% vs. 22.2% (p=0.029) in HFmrEF, and 23.3% vs. 23.9 (p=NS) in HFpEF. The overall mortality was 21.6%, with mortality being 2.4 times higher in patients with PAF (40.9% vs. 16.7%, p<0.001) compared to sinus rhythm but similar in women and men with PAF (39.5% vs. 41.9%; p=NS), respectively. The hospitalization (30.3% vs 19.4%, p<0.001) and emergency admissions (38.4% vs 25.7%, p<0.001) were higher in patients with AF. Cumulative mortality was higher in patients with PAF in all HF phenotypes: HFrEF (36.6%), HFmrEF (16.8%), HFpEF (46.6%; p<0.001). Men had higher cumulative mortality in HFrEF (18.3% vs. 12.4%; p<0.001) and in HFmrEF (22.2% vs. 18.09%; p=0.029), but not for HFpEF (23.9% vs. 23.3%; p=NS). In the multivariate analysis, adjusted for age, sex, previous myocardial infarction and stroke, diabetes, CKD, PAF, Cardiac surgery, and electronic device implantation, PAF was an independent predictor of death in all HF phenotypes: HFrEF [HR=1.78(95%CI:1.57-2.02); p<0.001], HFmrEF [HR=2.14(95%CI:1.74-2.65); p<0.001], HFpEF [HR=2.08(95%CI:1.82-2.37); p<0.001]. Conclusion PAF is a frequent comorbidity in HF and is associated with a worse prognosis in all HF phenotypes. Women with PAF had a better prognosis than men with AF in HFrEF and HFmrEF. Sex-specific strategies to maintain sinus rhythm in HF patients on the overall risk of death are needed.