Cardiosphere-derived cells (CDCs) reduce scarring after myocardial infarction, increase
viable myocardium, and boost cardiac function in preclinical models. We aimed to assess
safety of such an approach in patients with left ventricular dysfunction after myocardial
infarction.
In the prospective, randomised CArdiosphere-Derived aUtologous stem CElls to reverse
ventricUlar dySfunction (CADUCEUS) trial, we enrolled patients 2-4 weeks after myocardial
infarction (with left ventricular ejection fraction of 25-45%) at two medical centres
in the USA. An independent data coordinating centre randomly allocated patients in
a 2:1 ratio to receive CDCs or standard care. For patients assigned to receive CDCs,
autologous cells grown from endomyocardial biopsy specimens were infused into the
infarct-related artery 1·5-3 months after myocardial infarction. The primary endpoint
was proportion of patients at 6 months who died due to ventricular tachycardia, ventricular
fibrillation, or sudden unexpected death, or had myocardial infarction after cell
infusion, new cardiac tumour formation on MRI, or a major adverse cardiac event (MACE;
composite of death and hospital admission for heart failure or non-fatal recurrent
myocardial infarction). We also assessed preliminary efficacy endpoints on MRI by
6 months. Data analysers were masked to group assignment. This study is registered
with ClinicalTrials.gov, NCT00893360.
Between May 5, 2009, and Dec 16, 2010, we randomly allocated 31 eligible participants
of whom 25 were included in a per-protocol analysis (17 to CDC group and eight to
standard of care). Mean baseline left ventricular ejection fraction (LVEF) was 39%
(SD 12) and scar occupied 24% (10) of left ventricular mass. Biopsy samples yielded
prescribed cell doses within 36 days (SD 6). No complications were reported within
24 h of CDC infusion. By 6 months, no patients had died, developed cardiac tumours,
or MACE in either group. Four patients (24%) in the CDC group had serious adverse
events compared with one control (13%; p=1·00). Compared with controls at 6 months,
MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001),
increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional
systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic
volume, and LVEF did not differ between groups by 6 months.
We show intracoronary infusion of autologous CDCs after myocardial infarction is safe,
warranting the expansion of such therapy to phase 2 study. The unprecedented increases
we noted in viable myocardium, which are consistent with therapeutic regeneration,
merit further assessment of clinical outcomes.
US National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart
Stem Cell Center.
Copyright © 2012 Elsevier Ltd. All rights reserved.