Roberto Bolli, Atul R Chugh, Domenico D’Amario, John H Loughran, Marcus F Stoddard, Sohail Ikram, Garth M Beache, Stephen G Wagner,
Annarosa Leri, Toru Hosoda, Fumihiro Sanada, Julius B Elmore, Polina Goichberg, Donato Cappetta, Naresh K Solankhi, Ibrahim Fahsah,
D Gregg Rokosh, Mark S Slaughter, Jan Kajstura, Piero Anversa
Summary
Background c-kit-positive, lineage-negative cardiac stem cells (CSCs) improve post-infarction left ventricular (LV) dysfunction when administered to animals. We under took a phase 1 trial (Stem Cell Infusion in Patients with Ischemic cardiomyopathy [SCIPIO]) of autologous CSCs for the treatment of heart failure resulting from ischaemic heart disease.
Methods In stage A of the SCIPIO trial, patients with post-infarction LV dysfunction (ejection fraction [EF] ≤40%)before coronary artery bypass grafting were consecutively enrolled in the treatment and control groups. In stage B,patients were randomly assigned to the treatment or control group in a 2:3 ratio by use of a computer-generated block randomisation scheme. 1 million autologous CSCs were administered by intracoronary infusion at a mean of 113 days (SE 4) after surgery; controls were not given any treatment. Although the study was open label, the
echocardiographic analyses were masked to group assignment. The primary endpoint was short-term safety of CSCs and the secondary endpoint was effi cacy. A per-protocol analysis was used. This study is registered with ClinicalTrials.
gov, number NCT00474461.
Findings This study is still in progress. 16 patients were assigned to the treatment group and seven to the control group; no CSC-related adverse eff ects were reported. In 14 CSC-treated patients who were analysed, LVEF increased from 30·3% (SE 1·9) before CSC infusion to 38·5% (2·8) at 4 months after infusion (p=0·001). By contrast, in seven control patients, during the corresponding time interval, LVEF did not change (30·1% [2·4] at 4 months after CABG
vs 30·2% [2·5] at 8 months after CABG). Importantly, the salubrious eff ects of CSCs were even more pronounced at 1 year in eight patients (eg, LVEF increased by 12·3 ejection fraction units [2·1] vs baseline, p=0·0007). In the seven treated patients in whom cardiac MRI could be done, infarct size decreased from 32·6 g (6·3) by 7·8 g (1·7; 24%) at
4 months (p=0·004) and 9·8 g (3·5; 30%) at 1 year (p=0·04).
Interpretation These initial results in patients are very encouraging. They suggest that intracoronary infusion of autologous CSCs is eff ective in improving LV systolic function and reducing infarct size in patients with heart failure after myocardial infarction, and warrant further, larger, phase 2 studies.
Funding University of Louisville Research Foundation and National Institutes of Health.
Lancet 2011; 378: 1847–57