Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance

Abstract

Background: SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit(+) cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). In the present study, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results.

Methods and results: A total of 33 patients (20 CSC-treated and 13 control subjects) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5 ± 1.6% to 35.1 ± 2.4% [P=0.004, n=8] and 41.2 ± 4.5% [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: -6.9 ± 1.5 g [-22.7%] at 4 months [P=0.002, n=9] and -9.8 ± 3.5 g [-30.2%] at 12 months [P=0.039, n=6]). LV nonviable mass decreased even more (-11.9 ± 2.5 g [-49.7%] at 4 months [P=0.001] and -14.7 ± 3.9 g [-58.6%] at 12 months [P=0.013]), whereas LV viable mass increased (+11.6 ± 5.1 g at 4 months after CSC infusion [P=0.055] and +31.5 ± 11.0 g at 12 months [P=0.035]).

Conclusions: Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue that persist at least 1 year and are consistent with cardiac regeneration.

Clinical trial registration: This study is registered with clinicaltrials.gov, trial number NCT00474461.

Figure 1

Screening and enrollment as of November 12, 2011. CABG = coronary artery bypass graft surgery, LVEF = left ventricular ejection fraction, CSC = cardiac stem cell. * patient excluded from analysis because baseline cMRI was not performed due to newly placed thoracic staples.† patient excluded from analysis because of refusal to undergo baseline cMRI. ** The majority of those who withdrew refused to follow the rigorous testing regimen schedule set forth for all patients regardless of treatment allocation.

Figure 2

Panel A: LVEF at baseline (27.5±1.6%), 4 months after CSC infusion (35.1± 2.4%), and 12 months after CSC infusion (41.2± 4.5%). Panel B: Change in LVEF at 4 months and 12 months after CSC infusion (absolute EF units). Data are means ± SEMs.

Figure 3

Panel A: Regional EF at baseline and 4 and 12 months after CSC infusion in the infarct-related regions. Panel B: Change in regional EF in the infarct-related regions at 4 and 12 months after CSC infusion (absolute EF units). Panel C: Regional EF in the dyskinetic segments of the infarct-related regions at baseline and 4 and 12 months after CSC infusion. Panel D: Change in regional EF in the dyskinetic segments of the infarct-related regions at 4 and 12 months after CSC infusion (absolute EF units). Panel E: Regional EF in the least functional segment of the infarct-related regions at baseline and 4 and 12 months after CSC infusion. Panel F: Change in regional EF in the least functional segment of the infarct-related regions at 4 and 12 months after CSC infusion (absolute EF units). Data are means ± SEMs.

Figure 4

Example of changes in the size of an infarct from baseline (before CSC infusion) to 4 and 12 months after CSC infusion. The numbers (in white) denote the infarct size (in g) in the slice shown; CSC=cardiac stem cell, FWHM=“full-width half-maximum” method, which uses all areas with >50% of the maximal signal intensity to define the infarcted myocardium. Note the decrease in gadolinium enhancement in the inferolateral wall at 4 months after CSCs, which persisted at 12 months.

Figure 5

Panel A: Infarct size (in g) at 4 and 12 months after CSC infusion measured by manual delineation. Panel B: Reduction in infarct size at 4 and 12 months after CSC infusion measured by manual delineation. Panel C: “Core” infarct size (in g) at 4 and 12 months after CSC infusion measured by the full-width half-maximum (FWHM) method. Panel D: Reduction in core infarct size at 4 and 12 months after CSC infusion measured by the FWHM method. Data are means ± SEMs.

Figure 6

Changes in viable and non-viable LV mass (defined as segments with infarcts involving < or >50% of the LV wall thickness, respectively). Panel A: Non-viable mass (in g) at 4 and 12 months after CSC infusion. Panel B: Reduction in non-viable mass (in g) at 4 and 12 months after CSC infusion. Panel C: Viable mass (in g) at 4 and 12 months after CSC infusion. Panel D: Increase in viable mass (in g) at 4 and 12 months after CSC infusion. Data are means ± SEMs.