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

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.

Stem cells for treatment of cardiovascular diseases: An umbrella review of randomized controlled trials

“…After removing the duplicates, we started our selection and evaluated 184 papers, with 52 assessed as full text. As reported in the PRISMA flow-chart (Figure 1), we identified 11 meta-analyses as eligible, with 34 outcomes (Fan et al, 2019;Fernandes et al, 2019;Jayaraj et al, 2019;Jeong et al, 2018;Jiang et al, 2016;Jones et al, 2019;Kuswardhani and Soejitno, 2011;Liu et al, 2015;Marquis-Gravel et al, 2014;Sun et al, 2015;Velagapudi et al, 2019).…”

The National Heart, Lung, and Blood Institute‐funded Production Assistance for Cellular Therapies (PACT) program: Eighteen years of cell therapy

“…Recently, Dr. Hare and colleagues performed a meta‐analysis of arrhythmia end points that showed that non‐skeletal myoblast transendocardial cell therapy was associated with a significantly lower risk of sudden cardiac death or resuscitated sudden cardiac arrest, compared to control, with no proarrhythmic effects. 9 , 10 …”