Citation: Circulation Research. 120(2):332-340, 2017 Jan 20.Journal: Circulation research.Published: 2017ISSN: 0009-7330.Full author list: Butler J; Epstein SE; Greene SJ; Quyyumi AA; Sikora S; Kim RJ; Anderson AS; Wilcox JE; Tankovich NI; Lipinski MJ; Ko YA; Margulies KB; Cole RT; Skopicki HA; Gheorghiade M.UI/PMID: 27856497.Subject(s): Adult | Cardiomyopathies/bl [Blood] | *Cardiomyopathies/di [Diagnosis] | *Cardiomyopathies/th [Therapy] | Cross-Over Studies | Female | *Health Status | Humans | Infusions, Intravenous | Male | *Mesenchymal Stem Cell Transplantation/mt [Methods] | Middle Aged | Pilot Projects | Recovery of Function/ph [Physiology] | Single-Blind Method | Transplantation, Homologous/mt [Methods] | Treatment OutcomeInstitution(s): MedStar Health Research Institute | MedStar Heart & Vascular InstituteActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: https://dx.doi.org/10.1161/CIRCRESAHA.116.309717 (Click here)Abbreviated citation: Circ Res. 120(2):332-340, 2017 Jan 20.Local Holdings: Available online from MWHC library: 1953 - present.Abstract: RATIONALE: Potential benefits of mesenchymal stem cell (MSC) therapy in heart failure may be related to paracrine properties and systemic effects, including anti-inflammatory activities. If this hypothesis is valid, intravenous administration of MSCs should improve outcomes in heart failure, an entity in which excessive chronic inflammation may play a pivotal role.Abstract: OBJECTIVE: To assess the safety and preliminary efficacy of intravenously administered ischemia-tolerant MSCs (itMSCs) in patients with nonischemic cardiomyopathy.Abstract: METHODS AND RESULTS: This was a single-blind, placebo-controlled, crossover, randomized phase II-a trial of nonischemic cardiomyopathy patients with left ventricular ejection fraction <40% and absent hyperenhancement on cardiac magnetic resonance imaging. Patients were randomized to intravenously administered itMSCs (1.5x10<sup>6</sup> cells/kg) or placebo; at 90 days, each group received the alternative treatment. Overall, 22 patients were randomized to itMSC (n=10) and placebo (n=12) at baseline. After crossover, data were available for 22 itMSC patients. No major differences in death, hospitalization, or serious adverse events were noted between the 2 treatments. Change from baseline in left ventricular ejection fraction and ventricular volumes was not significantly different between therapies. Compared with placebo, itMSC therapy increased 6-minute walk distance (+36.47 m, 95% confidence interval 5.98-66.97; P=0.02) and improved Kansas City Cardiomyopathy clinical summary (+5.22, 95% confidence interval 0.70-9.74; P=0.02) and functional status scores (+5.65, 95% confidence interval -0.11 to 11.41; P=0.06). The data demonstrated MSC-induced immunomodulatory effects, the magnitude of which correlated with improvement in left ventricular ejection fraction.Abstract: CONCLUSIONS: In this pilot study of patients with nonischemic cardiomyopathy, itMSC therapy was safe, caused immunomodulatory effects, and was associated with improvements in health status and functional capacity.Abstract: CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02467387.Abstract: Copyright � 2016 American Heart Association, Inc.