Reduced Irregularity of Ventricular Response During Atrial Fibrillation and Long-term Outcome in Patients With Heart Failure

Reduced heart rate variability (HRV) is associated with poor outcome in patients with heart failure (HF). However, the data on predictive value of RR variability during atrial fibrillation (AF) are limited. Therefore, the aim of this study was to evaluate the association between ventricular response characteristics and long-term clinical outcome in the population of ambulatory patients with mild-to-moderate HF and AF at baseline. The study included 155 patients (mean age 69 ± 10 years) with AF at 20-minute Holter electrocardiographic (ECG) recordings at enrollment. HRV analysis included SDNN, rMSSD, and pNN50, whereas irregularity indexes included 2 nonlinear parameters: approximate entropy (ApEn) and Shannon entropy. After median 41 months of follow-up, 54 patients died, including 21 HF related and 16 sudden deaths. Patients with ApEn ≤1.68 (lower tertile) had 40% mortality versus 12% in others (p <0.001) at 2 years of follow-up. Only nonlinear HRV parameters (irregularity but not variability indexes) identified patients at higher risk during follow-up. Decreased ApEn ≤1.68 was an independent predictor of total mortality (hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.61 to 4.89, p <0.001), sudden cardiac death (HR 3.83, 95% CI 1.31 to 11.25, p = 0.014), and HF death (HR 3.45, 95% CI 1.42 to 8.38, p = 0.006) in a multivariate Cox analysis. In conclusion, in a post hoc analysis of Muerte Subita en Insufficiencia Cardiaca study AF cohort, reduced irregularity of RR intervals during AF, likely caused by autonomic dysfunction, was an independent predictor of all-cause mortality and sudden death and HF progression in patients with mild-to-moderate HF, whereas traditional HRV indexes did not predict outcome.