A pilot clinical trial of cell therapy in heart failure with preserved ejection fraction

Aims: We investigated the effects of CD34⁺ cell therapy in patients with heart failure with preserved ejection fraction (HFpEF).

Methods and results: In a prospective pilot study, we enrolled 30 patients with HFpEF. In Phase 1, patients were treated with medical therapy for 6 months. Thereafter, all patients underwent CD34⁺ 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: In this non-randomized trial, transendocardial CD34⁺ 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.