Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy

Abstract

Background: Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) differ in histopathology and prognosis. Although transendocardial delivery of mesenchymal stem cells is safe and provides cardiovascular benefits in both, a comparison of mesenchymal stem cell efficacy in ICM versus DCM has not been done.

Methods and results: We conducted a subanalysis of 3 single-center, randomized, and blinded clinical trials: (1) TAC-HFT (Transendocardial Autologous Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells in Ischemic Heart Failure Trial); (2) POSEIDON (A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction); and (3) POSEIDON-DCM (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy). Baseline and 1-year cardiac structure and function and quality-of-life data were compared in a post hoc pooled analysis including ICM (n=46) and DCM (n=33) patients who received autologous or allogeneic mesenchymal stem cells. Ejection fraction improved in DCM by 7% (within-group, P=0.002) compared to ICM (1.5%; within-group, P=0.14; between-group, P=0.003). Similarly, stroke volume increased in DCM by 10.59 mL (P=0.046) versus ICM (-0.2 mL; P=0.73; between-group, P=0.02). End-diastolic volume improved only in ICM (10.6 mL; P=0.04) and end-systolic volume improved only in DCM (17.8 mL; P=0.049). The sphericity index decreased only in ICM (-0.04; P=0.0002). End-diastolic mass increased in ICM (23.1 g; P<0.0001) versus DCM (-4.1 g; P=0.34; between-group, P=0.007). The 6-minute walk test improved in DCM (31.1 m; P=0.009) and ICM (36.3 m; P=0.006) with no between-group difference (P=0.79). The New York Heart Association class improved in DCM (P=0.005) and ICM (P=0.02; between-group P=0.20). The Minnesota Living with Heart Failure Questionnaire improved in DCM (-19.5; P=0.002) and ICM (-6.4; P=0.03; δ between-group difference P=0.042) patients.

Conclusions: Mesenchymal stem cell therapy is beneficial in DCM and ICM patients, despite variable effects on cardiac phenotypic outcomes. Whereas cardiac function improved preferentially in DCM patients, ICM patients experienced reverse remodeling. Mesenchymal stem cell therapy enhanced quality of life and functional capacity in both etiologies.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifiers: TAC-HFT: NCT00768066, POSEIDON: NCT01087996, POSEIDON-DCM: NCT01392625.

Keywords: functional capacity impairment; mesenchymal stem cell; remodeling heart failure; stem cell.

Figure 1

Changes in cardiac function in DCM (blue) and ICM (red) patients. A, EF increased from baseline in DCM (blue circles) by 7 EF units (2.9, 11.0; P=0.002), but not in ICM (red squares). DCM group showed a significant improvement over time in (B) stroke volume by 10.6 mL (95% CI, 0.2, 21.0; P=0.046) and (C) end‐systolic volume by −17.8 mL (interquartile range, −54.5, 17.0; P=0.049). However, the ICM group improved in (D) end‐diastolic volume by −8.32 mL (95% CI: −21.0, −0.3; P=0.05) from baseline, whereas DCM did not. E, Sphericity index improved in ICM by −0.04% (95% CI, −0.06, −0.02; P=0.0002). F, End‐diastolic mass increased in ICM by 23.1 g (95% 13.9, 32.2; P<0.0001) at follow‐up, with a significant difference between both groups (P=0.0003). DCM indicates dilated cardiomyopathy; ED, end diastolic; EDV, end‐diastolic volume; EF, ejection fraction; ESV, end‐systolic volume; ICM, ischemic cardiomyopathy; SV, stroke volume.

Figure 2

Functional capacity and quality of life in DCM (blue) and ICM (red) patients. A, 6MWT increased at follow‐up from baseline in both groups: DCM group by 31.1 m (95% CI, 3.8, 6.4; P=0.009) and ICM group by 36.3 m (95% CI, 10.9, 61.6; P=0.00062). B, New York Heart Association (NYHA) class improved in both, DCM (P=0.005) and ICM (P=0.02) groups, with no between group differences. C, Minnesota Living with Heart Failure Questionnaire (MLHFQ) total score improved from baseline to 12 months postinjection in both groups, with a difference between means of 11.05 (95% CI, 0.44, 21.67; P=0.042). DCM indicates dilated cardiomyopathy; ICM, ischemic cardiomyopathy.