Risk factors for fatal ventricular arrhythmias in heart failure with preserved ejection fraction: a report from the CHART-2 Study

Abstract Background Fatal ventricular arrhythmia events (FAE), such as sustained ventricular tachycardia (VT) and ventricular fibrillation (VF), along with sudden cardiac death (SCD), represent serious complications in patients with heart failure (HF). While individuals with severely reduced left ventricular ejection fraction (LVEF), particularly below 35%, are deemed at high risk for lethal arrhythmic events and are considered for implantable cardioverter-defibrillator (ICD) therapy, recent studies have highlighted the occurrence of FAE or SCD in heart failure with preserved ejection fraction (HFpEF) as well. However, the specific risk factors for FAE or SCD in patients with HFpEF remain inadequately elucidated. Purpose This study aimed to investigate the incidence of FAE or SCD and identify their associated risk factors in patients with HFpEF. Methods We retrospectively analyzed the data from our multicenter observational study, the CHART-2 Study, where a total of 10,219 patients were enrolled between 2006 and 2010. Among them, we included patients with HF and LVEF≥50% (n=2,423) with available LVEF data at one year (Figure 1A). They were categorized into two groups based on LVEF status; 198 with decreased LVEF (35-50%; D-group) and 2,225 with preserved LVEF (≥50%; P-group). The primary endpoint was the composite event of FAE or SCD, and all statistical analyses were adjusted for competing risks due to all-cause mortality. Results Among the 2,423 patients with HFpEF (mean age: 69±12 years, 35% female), 120 patients (5.0%) experienced the composite event of FAE or SCD during a median follow-up of 9.1 years (interquartile range: 4.5-11.2 years), with a cumulative incidence of 5.1% at 10 years. Gray’s test revealed a significantly higher incidence of the primary endpoint in the D-group compared with the P-group (10.6% vs. 4.5% at 10 years, p<0.001, Figure 2A). Multivariable analysis identified mild decline of LVEF (Hazard Ratio [HR] 2.20, 95% confidence interval [CI] 1.34-1.60; p=0.002) and non-sustained VT (HR 2.33, 95% CI 1.37-3.97; p=0.002) as independent risk factors for composite event. Landmark analysis demonstrated a consistent trend in the composite event of FAE or SCD in both groups (Figure 2B). Conclusion In patients with HFpEF, even a mild decline in LVEF, which typically does not prompt ICD consideration, was significantly associated with a heightened risk of FAE or SCD. Therefore, a chronological clinical assessment, encompassing changes in LVEF, is essential for patients with HFpEF.