Ischemic vs. Non-Ischemic Dilated Cardiomyopathy: a Comparative Study in Stem Cell Therapy Efficacy

Abstract

Background: Ischemic (ICM) versus dilated cardiomyopathy (DCM) have different pathogenesis and outcomes with standard medical therapy. Mesenchymal stem cell (MSC) therapy has produced improvements in both diseases. However, whether the efficacy of MSCs between ICM and DCM subjects is comparable, remains undetermined. Hypothesis: Subjects with DCM respond better than those with ICM. Methods: We analysed the effects of transendocardial MSC injections in patients with ICM vs. DCM from three single-institution, randomized, double-blinded, clinical trials: TAC-HFT, POSEIDON and POSEIDON-DCM. Cardiac structure, function and subject quality of life data were compared between ICM and DCM groups at baseline and one year follow-up. Results: Ejection fraction improved in DCM 7% (2.9, 11.0, p=0.002) vs. ICM 1.5% (-0.2, 3.2, p=0.08) subjects with a significant difference between groups (p=0.005). Similarly, stroke-volume increased in DCM 10.59mL (0.2, 21, p=0.046) vs. ICM -0.16mL (-4.6, 4.3, p=0.94) subjects with a significant difference between groups (p=0.02). End-diastolic volume improved only in ICM subjects, -10.68mL (-21, -0.1, p=0.047), and end-systolic volume improved only in DCM subjects, -17.8mL (-54.5, 17.0, p=0.049). Sphericity index only decreased in ICM, -0.04 (-0.06, -0.02, p=0.0002), subjects. End-diastolic mass increased in ICM, 3.57g (-3.1, 28, p=0.004), vs. DCM subjects, -4.1g (-15, 7, p=0.45), with a significant difference between groups (p=0.007). Six-minute walk test improved in DCM, 34m (18, 53, p=0.009), and ICM, 30m (-16, 89, p=0.0007), subjects with a difference between groups (p=0.03) favoring ICM subjects. NYHA class improved in both DCM (p=0.005) and ICM (p=0.02) subjects (between group p=0.20). Similarly, the Minnesota Heart Failure Questionnaire improved in DCM, -19 (-31, -7.1, p=0.003), and ICM, -9.3 (-16, -2.7, p=0.007), subjects (between group difference p=0.12). Conclusion: MSC therapy exerts distinct effects in ICM vs DCM. It improves functionality in DCM, cardiac remodelling in ICM, and enhances quality of life parameters in both disease processes.