title: Effects of Transendocardial Stem Cell Injection on Ventricular Proarrhythmia in Patients with Ischemic Cardiomyopathy: Results from the POSEIDON and TAC-HFT Trials.
abstract: Transendocardial stem cell injection in patients with ischemic cardiomyopathy (ICM) improves left ventricular function and structure but has ill-defined effects on ventricular arrhythmias. We hypothesized that mesenchymal stem cell (MSC) implantation is not proarrhythmic. Post hoc analyses were performed on ambulatory ECGs collected from the POSEIDON and TAC-HFT trials. Eighty-eight subjects (mean age 61 ± 10 years) with ICM (mean EF 32.2% ± 9.8%) received treatment with MSC (n = 48), Placebo (n = 21), or bone marrow mononuclear cells (BMC) (n = 19). Heart rate variability (HRV) and ventricular ectopy (VE) were evaluated over 12 months. VE did not change in any group following MSC implantation. However, in patients with ≥ 1 VE run (defined as ≥ 3 consecutive premature ventricular complexes in 24 hours) at baseline, there was a decrease in VE runs at 12 months in the MSC group (p = .01), but not in the placebo group (p = .07; intergroup comparison: p = .18). In a subset of the MSC group, HRV measures of standard deviation of normal intervals was 75 ± 30 msec at baseline and increased to 87 ± 32 msec (p =.02) at 12 months, and root mean square of intervals between successive complexes was 36 ± 30 msec and increased to 58.2 ± 50 msec (p = .01) at 12 months. In patients receiving MSCs, there was no evidence for ventricular proarrhythmia, manifested by sustained or nonsustained ventricular ectopy or worsened HRV. Signals of improvement in ventricular arrhythmias and HRV in the MSC group suggest a need for further studies of the antiarrhythmic potential of MSCs. Stem Cells Translational Medicine 2017;6:1366-1372.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Ramireddy
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Chad R
authors.initials: CR
authors.lastname: Brodt
authors.affiliation: EMMES Corporation, Rockland, MD, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Mendizabal
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Darcy L
authors.initials: DL
authors.lastname: DiFede
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Healy
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Goyal
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Alansari
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: James O
authors.initials: JO
authors.lastname: Coffey
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Viles-Gonzalez
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Heldman
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Goldberger
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Myerburg
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Mitrani
mesh_terms: D000368:Aged; D001145:Arrhythmias, Cardiac / Q000628:therapy*; D009202:Cardiomyopathies / Q000628:therapy*; D005260:Female; D006333:Heart Failure / Q000628:therapy*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000628:therapy*
keywords: Cardiac arrhythmias; Cardiomyopathy; Heart failure; Stem cells; Ventricular tachycardia