Sudden death in heart failure with preserved ejection fraction and beyond: an elusive target.

Heart failure (HF) with preserved ejection fraction (HFpEF) represents half of HF patients, who are more likely older, women, and hypertensive. Mortality rates in HFpEF are higher compared with age- and comorbidity-matched non-HF controls and lower than in HF with reduced ejection fraction (HFrEF); the majority (50-70%) are cardiovascular (CV) deaths. Among CV deaths, sudden death (SD) (~ 35%) and HF-death (~ 20%) are the leading cardiac modes of death; however, proportionally, CV deaths, SD, and HF-deaths are lower in HFpEF, while non-CV deaths constitute a higher proportion of deaths in HFpEF (30-40%) than in HFrEF (~ 15%). Importantly, the underlying mechanism of SD has not been clearly elucidated and non-arrhythmic SD may be more prominent in HFpEF than in HFrEF. Furthermore, there is no specific strategy for identifying high-risk patients, probably due to wide heterogeneity in presentation and pathophysiology of HFpEF and a plethora of comorbidities in this population. Thus, the management of HFpEF remains problematic due to paucity of data on the clinical benefits of current therapies, which focus on symptom relief and reduction of HF-hospitalization by controlling fluid retention and managing risk-factors and comorbidities. Matching a specific pathophysiology or mode of death with available and novel therapies may improve outcomes in HFpEF. However, this still remains an elusive target, as we need more information on determinants of SD. Implantable cardioverter-defibrillators (ICDs) have changed the landscape of SD prevention in HFrEF; if ICDs are to be applied to HFpEF, there must be a coordinated effort to identify and select high-risk patients.