A meta-analysis of arrhythmia endpoints in randomized controlled trials of transendocardial stem cell injections for chronic ischemic heart disease

Gilson C. Fernandes, Amanda D.F. Fernandes, Manuel Rivera, Aisha Khan, Ivonne H. Schulman, Litsa K. Lambrakos, Robert J. Myerburg, Jeffrey J. Goldberger, Joshua M. Hare, Raul D. Mitrani

Research output: Contribution to journalArticle

Abstract

Introduction: The electrophysiologic impact of cell-based therapy on the injured myocardium remains highly controversial. We aimed to perform a meta-analysis of studies comparing arrhythmia burden following transendocardial stem cell therapy vs placebo in patients with chronic ischemic heart disease (CIHD). Methods and Results: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. No restriction of stem cell type was specified. The outcomes included sustained supraventricular or ventricular arrhythmias (VAs), sudden cardiac death (SCD), and resuscitated sudden cardiac arrest (SCA). Effect sizes were reported as odds ratio (OR) and 95% CI. Poisson regression was used to account for zero-events data. Twelve randomized trials that included 736 patients (384 in the cell therapy group and 352 in the placebo group) were analyzed. Six different cell types were used. Follow-up ranged from 6 to 12 months. There was a significant decrease in risk of SCD in the cell therapy group, (FE OR, 0.19 [0.04, 0.93]; P =.04). In subgroup analysis, there was a significantly lower risk of SCD or resuscitated SCA in the cell therapy group limited to studies that did not use skeletal myoblasts, (FE OR, 0.23 [0.06, 0.83]; P =.03). There was no significant difference in the incidence of sustained VA between groups (FE OR, 0.91 [0.47, 1.77]; P =.8), even after stratifying by cell type. There was no difference in supraventricular arrhythmias between groups. Conclusion: Nonskeletal myoblast transendocardial cell therapy was associated with a significantly lower risk of SCD or resuscitated SCA compared to control, with no proarrhythmic effects.

Original languageEnglish (US)
Pages (from-to)2492-2500
Number of pages9
JournalJournal of Cardiovascular Electrophysiology
Volume30
Issue number11
DOIs
StatePublished - Nov 1 2019

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Sudden Cardiac Death
Myocardial Ischemia
Cell- and Tissue-Based Therapy
Meta-Analysis
Cardiac Arrhythmias
Stem Cells
Randomized Controlled Trials
Injections
Odds Ratio
Placebos
Skeletal Myoblasts
Myoblasts
PubMed
Myocardium
Incidence

Keywords

  • arrhythmias
  • cell therapy
  • ischemic heart disease
  • stem cell transplantation
  • sudden cardiac death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

A meta-analysis of arrhythmia endpoints in randomized controlled trials of transendocardial stem cell injections for chronic ischemic heart disease. / Fernandes, Gilson C.; Fernandes, Amanda D.F.; Rivera, Manuel; Khan, Aisha; Schulman, Ivonne H.; Lambrakos, Litsa K.; Myerburg, Robert J.; Goldberger, Jeffrey J.; Hare, Joshua M.; Mitrani, Raul D.

In: Journal of Cardiovascular Electrophysiology, Vol. 30, No. 11, 01.11.2019, p. 2492-2500.

Research output: Contribution to journalArticle

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abstract = "Introduction: The electrophysiologic impact of cell-based therapy on the injured myocardium remains highly controversial. We aimed to perform a meta-analysis of studies comparing arrhythmia burden following transendocardial stem cell therapy vs placebo in patients with chronic ischemic heart disease (CIHD). Methods and Results: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. No restriction of stem cell type was specified. The outcomes included sustained supraventricular or ventricular arrhythmias (VAs), sudden cardiac death (SCD), and resuscitated sudden cardiac arrest (SCA). Effect sizes were reported as odds ratio (OR) and 95{\%} CI. Poisson regression was used to account for zero-events data. Twelve randomized trials that included 736 patients (384 in the cell therapy group and 352 in the placebo group) were analyzed. Six different cell types were used. Follow-up ranged from 6 to 12 months. There was a significant decrease in risk of SCD in the cell therapy group, (FE OR, 0.19 [0.04, 0.93]; P =.04). In subgroup analysis, there was a significantly lower risk of SCD or resuscitated SCA in the cell therapy group limited to studies that did not use skeletal myoblasts, (FE OR, 0.23 [0.06, 0.83]; P =.03). There was no significant difference in the incidence of sustained VA between groups (FE OR, 0.91 [0.47, 1.77]; P =.8), even after stratifying by cell type. There was no difference in supraventricular arrhythmias between groups. Conclusion: Nonskeletal myoblast transendocardial cell therapy was associated with a significantly lower risk of SCD or resuscitated SCA compared to control, with no proarrhythmic effects.",
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AU - Lambrakos, Litsa K.

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