Predictors for high ventricular arrhythmia burden in patients with heart failure with reduced ejection fraction and central sleep apnea: an analysis of the SERVE-HF major substudy

Aim: Central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) are associated with increased mortality rates in patients with heart failure and reduced ejection fraction (HFrEF) and may trigger ventricular arrhythmias. Therefore, we investigated predictors of ventricular arrhythmias in HFrEF patients with CSA. Methods: 239 patients with HFrEF and CSA (apnea-hypopnea index g15/h with ≥50% central events) of the SERVE-HF major substudy with available polysomnography including nocturnal ECG were analyzed. CSR was quantified in ≥20% and l20% of total recording time. High ventricular arrhythmia burden was defined as g30 premature ventricular contractions (PVCs) per hour of sleep. A subanalysis was performed to evaluate the temporal association of CSR with ventricular arrhythmias in sleep stage N2 (55 hours). Results: High ventricular arrhythmia burden was observed in 44% of the sample. In multivariate regression analysis, male sex, lower systolic blood pressure, antiarrhythmics and CSR≥20% were associated with PVCg30/hour (odds ratio [95%CI]: 5.49 [1.51;19.91], p=0.010; 0.98 [0.97;1.00], p=0.017; 0.20 [0.08;0.52], p=0.001; 2.22 [1.22;4.05]; p=0.009; respectively). PVCs were more frequent in sleep phases with CSR than without CSR (median [IQR]: 64.6 [24.8; 145.7] vs. 34.6 [4.8; 75.2] per hour N2 sleep; p=0.006). Conclusion: High burden of ventricular arrhythmias occurred in 44% of patients with HFrEF and CSA. Risk factors for PVCsg30/hour were male sex, lower systolic blood pressure, antiarrhythmic medication and CSR≥20%. Ventricular arrhythmia burden was higher during sleep with CSR than without CSR.