Meta-Analysis of Percutaneous Endomyocardial Cell Therapy in Patients with Ischemic Heart Failure by Combination of Individual Patient Data (IPD) of ACCRUE and Publication-Based Aggregate Data

Abstract

Individual patient data (IPD)-based meta-analysis (ACCRUE, meta-analysis of cell-based cardiac studies, NCT01098591) revealed an insufficient effect of intracoronary cell-based therapy in acute myocardial infarction. Patients with ischemic heart failure (iHF) have been treated with reparative cells using percutaneous endocardial, surgical, transvenous or intracoronary cell delivery methods, with variable effects in small randomized or cohort studies. The objective of this meta-analysis was to investigate the safety and efficacy of percutaneous transendocardial cell therapy in patients with iHF. Two investigators extracted the data. Individual patient data (IPD) (n = 8 studies) and publication-based (n = 10 studies) aggregate data were combined for the meta-analysis, including patients (n = 1715) with chronic iHF. The data are reported in accordance with PRISMA guidelines. The primary safety and efficacy endpoints were all-cause mortality and changes in global ejection fraction. The secondary safety and efficacy endpoints were major adverse events, hospitalization and changes in end-diastolic and end-systolic volumes. Post hoc analyses were performed using the IPD of eight studies to find predictive factors for treatment safety and efficacy. Cell therapy was significantly (p < 0.001) in favor of survival, major adverse events and hospitalization during follow-up. A forest plot analysis showed that cell therapy presents a significant benefit of increasing ejection fraction with a mean change of 2.51% (95% CI: 0.48; 4.54) between groups and of significantly decreasing end-systolic volume. The analysis of IPD data showed an improvement in the NYHA and CCS classes. Cell therapy significantly decreased the end-systolic volume in male patients; in patients with diabetes mellitus, hypertension or hyperlipidemia; and in those with previous myocardial infarction and baseline ejection fraction ≤ 45%. The catheter-based transendocardial delivery of regenerative cells proved to be safe and effective for improving mortality and cardiac performance. The greatest benefit was observed in male patients with significant atherosclerotic co-morbidities.

Keywords: ACCRUE; cell-based regeneration therapy; human clinical trials; meta-analysis; percutaneous transendocardial cell delivery; stem cells.

Figure 1

Search strategies: excluded and included studies.

Figure 2

(a–c). Primary and secondary safety endpoints: clinical outcomes of the studies including patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls. (a) Primary safety endpoint: all-cause mortality in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls. (b) Secondary safety endpoint MACEs (major adverse cardiac events) in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls. (c) Secondary safety endpoint: hospitalization in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls.

Figure 2

(a–c). Primary and secondary safety endpoints: clinical outcomes of the studies including patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls. (a) Primary safety endpoint: all-cause mortality in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls. (b) Secondary safety endpoint MACEs (major adverse cardiac events) in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls. (c) Secondary safety endpoint: hospitalization in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls.

Figure 3

(a) Primary efficacy endpoint: changes in EF in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls. (b) Secondary efficacy endpoint: changes in EDV in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls. (c) Secondary efficacy endpoint: changes in ESV in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls.

Figure 3

(a) Primary efficacy endpoint: changes in EF in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls. (b) Secondary efficacy endpoint: changes in EDV in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls. (c) Secondary efficacy endpoint: changes in ESV in patients randomized to receive percutaneous endocardial delivery of regenerative cells or controls.

Figure 4

Association between baseline EF and changes in EF including only the IPD of the ACCRUE studies (n = 8).

Figure 5

No correlation between number of injected cells and changes in left ventricular ejection fraction (LVEF) at follow-up only IPD of the ACCRUE studies included.