Cell Therapy for Heart Failure With Preserved Ejection Fraction∗

SEE PAGE 14 O ne-half of patients with heart failure (HF) have a preserved ejection fraction (HFpEF), and there is no proven effective treatment (1). The traditional thinking has been that left ventricular (LV) diastolic dysfunction caused by hypertensive ventricular remodeling causes the clinical syndrome of HFpEF. More recent data suggest that it is not so simple, and that other systemic processes such as inflammation, oxidative stress, and fibrosis play important roles in the pathophysiology (2,3). It is therefore hoped that interventions targeting inflammation and fibrosis might be effective to treat HFpEF. Cell-based therapy for HF patients with reduced ejection fraction has been under investigation for nearly 2 decades, with mixed results to date (4). More recently, cardiosphere-derived cells (CDC) have emerged as a novel cell-based approach to treat various cardiac diseases (5). Unlike bone marrow– derived cells, CDCs are harvested directly from the heart via endomyocardial biopsy. These cells are cultured and plated to yield CDCs, which can then be injected by intracoronary infusion. CDCs are believed to exert pleiotropic salutary effects in the heart in addition to their stem cell–like regenerative behaviors (5). Although there is great enthusiasm that cell therapies could help patients where cardiomyocyte loss is the problem (like HF with reduced ejection fraction), it remains unclear whether patients with cardiovascular diseases without marked cardiomyocyte loss (like HFpEF) might also derive benefit.