Are arrhythmias the drivers of sudden cardiac death in heart failure with preserved ejection fraction? A review.

In patients with heart failure with preserved ejection fraction (HFpEF), sudden cardiac death (SCD) accounts for approximately 25-30% of all-cause mortality and 40% of cardiovascular mortality in properly adjudicated large clinical trials. The mechanism of SCD in HFpEF remains unknown but thought to be driven by arrhythmic events. Apart from atrial fibrillation, which is prevalent in approximately 45% of HFpEF patients, the true burden of other cardiac arrhythmias in HFpEF remains undetermined. The incidence and risk of clinically significant advanced cardiac conduction disease with bradyarrhythmias and ventricular arrhythmias remain less known. Recommendations have been made for long-term cardiac rhythm monitoring to determine the incidence of arrhythmias and clarify mechanisms and mode of death in HFpEF patients. In animal studies, spontaneous ventricular arrhythmias and SCD are significantly elevated in HFpEF animals compared with controls without heart failure. In humans, these studies are scant, with a few published small-size studies suggesting an increased incidence of ventricular arrhythmias in HFpEF. Higher rates of clinically significant conduction disease and cardiac pacing are seen in HFpEF compared with the general population. Excepting atrial fibrillation, the predictive effect of other arrhythmias on heart failure hospitalization, all-cause mortality, and precisely SCD remains unknown. Given the high occurrence of SCD in the HFpEF population, it could potentially become a target for therapeutic interventions if driven by arrhythmias. Studies to address these knowledge gaps are urgently warranted. In this review, we have summarized data on arrhythmias and SCD in HFpEF while highlighting avenues for future research in this area.