Abstract 15652: Cell Therapy in Heart Failure With Preserved Ejection Fraction (CELLpEF)

Abstract

Introduction: Previous studies have demonstrated that cell therapy may improve diastolic parameters in heart failure. Hypothesis: We sought to investigate the effects of transendocardial CD34 + cell therapy in patients with heart failure with preserved ejection fraction (HFpEF). Methods: In a prospective crossover study, we enrolled 30 patients with HFpEF (LVEF>50%, E/e'>15, NT-proBNP >300 pg/ml). In Phase 1, patients were treated with stable medical therapy for 6 months. Thereafter, all patients underwent transendocardial CD34 + cell transplantation. They received bone marrow stimulation with filgrastim (10 mcg/kg, 5 days); CD34 + cells were collected by apheresis. We performed electroanatomical mapping of the left ventricle, and injected the cells transendocardialy in the areas of local diastolic dysfunction (80 million CD34 + cells divided into 20 injections). Patients were followed for 6 months after the procedure (Phase 2). Results: Our cohort included 23 male and 7 female patients aged 62±10 years, with LVEF of 58.7±7.3%, creatinine of 93±35 μmol/L, and bilirubin of 14.3±6.8 μmol/L. In Phase 1 (medical therapy), we found no change in E/e' (from 18.0±3.5 to 17.4±3.0, P=0.97), global systolic strain (from -12.5±2.4% to -12.8±2.6%, P=0.77), NT-proBNP levels (from 1463±1247 pg/mL to 1298±931 pg/mL, P=0.31), or 6-minute walk test distance (from 391±75 m to 402±93 m, P=0.42). In contrast, in Phase 2 (cell therapy), we found a significant improvement in E/e' (from 17.4±3.0 to 11.9±2.6, P=<0.0001), a decrease in NT-proBNP levels (from 1298±931 pg/ml to 887±809 pg/ml, P=0.02), and an improvement in 6-minute walk test distance (from 402±93 m to 438±72 m, P=0.02). Although global systolic strain did not change significantly in Phase 2 (from -12.8±2.6% to -13.8±2.7%, P=0.36), we found a significant improvement of local systolic strain in myocardial segments that were injected with stem cells (-3.4±6.8%, P=0.005). Conclusion: In patients with HFpEF, transendocardial CD34 + cell therapy appears to be associated with improved left ventricular diastolic parameters, better exercise capacity, a decrease in NT-proBNP levels, and improved local systolic strain at cell injection sites.