Comparison of mesenchymal stem cell efficacy in ischemic versus nonischemic dilated cardiomyopathy

Bryon A. Tompkins, Angela C. Rieger, Victoria Florea, Monisha N. Banerjee, Makoto Natsumeda, Evan D. Nigh, Ana Marie Landin, Gianna M. Rodriguez, Konstantinos E. Hatzistergos, Ivonne Hernandez Schulman, Joshua M. Hare

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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; d 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.

Original languageEnglish (US)
Article numbere008460
JournalJournal of the American Heart Association
Volume7
Issue number14
DOIs
StatePublished - Jul 1 2018

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Keywords

  • Functional capacity impairment
  • Mesenchymal stem cell
  • Remodeling heart failure
  • Stem cell

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Tompkins, B. A., Rieger, A. C., Florea, V., Banerjee, M. N., Natsumeda, M., Nigh, E. D., Landin, A. M., Rodriguez, G. M., Hatzistergos, K. E., Schulman, I. H., & Hare, J. M. (2018). Comparison of mesenchymal stem cell efficacy in ischemic versus nonischemic dilated cardiomyopathy. Journal of the American Heart Association, 7(14), [e008460]. https://doi.org/10.1161/JAHA.117.008460