Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial.

Abstract

BACKGROUND:

Most cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.

METHODS:

In this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF <45% and 15% or greater LV scar size were randomised in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6 months was compared between CDCs and placebo groups.

RESULTS:

In total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (-0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of -0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04).

CONCLUSIONS:

In patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI.

TRIAL REGISTRATION NUMBER:

NCT01458405.

• Authors: Mohammad R Ostovaneh, Raj R Makkar, Bharath Ambale-Venkatesh, Deborah Ascheim, Tarun Chakravarty, Timothy D Henry, Glen Kowalchuk, Frank V Aguirre, Dean J Kereiakes, Thomas J Povsic, Richard Schatz, Jay H Traverse, Janice Pogoda, Rachel D Smith, Linda Marbán, Eduardo Marbán, Joao A C Lima
• Journal: Open heart (Open Heart) Vol. 8 Issue 2 (07 2021) ISSN: 2053-3624 [Print] England
• PMID: 34233913 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Topics

• Female
• Follow-Up Studies
• Humans
• Magnetic Resonance Imaging, Cine
• Male
• Middle Aged
• Myocardial Infarction (complications, diagnosis, therapy)
• Myocardium (pathology)
• Myocytes, Cardiac (cytology)
• Retrospective Studies
• Stem Cell Transplantation (methods)
• Stroke Volume (physiology)
• Transplantation, Autologous
• Ventricular Dysfunction, Left (etiology, physiopathology, therapy)
• Ventricular Function, Left (physiology)