A pilot clinical trial of cell therapy in heart failure with preserved ejection fraction
Bojan Vrtovec, Sabina Frljak, Gregor Poglajen, Gregor Zemljič, A. Cerar, Matjaž Sever, François Haddad, Joseph C. Wu
Abstract
AIMS: cell therapy in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: cell transplantation. Using electroanatomical mapping, we measured local mechanical diastolic delay and myocardial viability to guide the targeting of cell injections. Patients were followed for 6 months after cell transplantation (Phase 2), and the primary endpoint was the difference in change in E/e' between Phase 1 and Phase 2. In Phase 1, the decrease in E/e' was significantly less pronounced than in Phase 2 (-0.33 ± 1.72 vs. -3.77 ± 2.66, p = 0.001). During Phase 1, there was no significant change in global systolic strain (GLS; from -12.5 ± 2.4% to -12.8 ± 2.6%, p = 0.77), N-terminal pro-B-type natriuretic peptide (NT-proBNP; from 1463 ± 1247 pg/ml to 1298 ± 931 pg/ml, p = 0.31), or 6-min walk test (6MWT; from 391 ± 75 m to 402 ± 93 m, p = 0.42). In Phase 2, an improvement was noted in NT-proBNP (from 1298 ± 931 pg/ml to 887 ± 809 pg/ml, p = 0.02) and 6MWT (from 402 ± 93 m to 438 ± 72 m, p = 0.02). Although GLS did not change significantly in Phase 2 (from -12.8 ± 2.6% to -13.8 ± 2.7%, p = 0.36), we found improved local systolic strain at cell injection sites (-3.4 ± 6.8%, p = 0.005). CONCLUSIONS: cell therapy in HFpEF was associated with an improvement in E/e', NT-proBNP, exercise capacity, and local myocardial strain at the cell injection sites. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02923609.