Piero Anversa

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

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.

Ventricular Remodeling Following Coronary Artery Constriction and Hypertension

In coronary artery disease in humans, the severity of the atherosclerotic involvement of the coronary circulation frequently does not correlate with the impairment in cardiac pump performance, and therefore anatomic condition is a poor predictor of clinical outcome and mortality of the patient population [1–4]. Based on acute studies in animal models [5], the conclusion has been reached that severe reductions in coronary artery diameter of nearly 80% are required to create an imbalance between oxygen demand and supply, possibly leading to scattered myocardial damage and the initiation of ischemic cardiomyopathy. However, it has recently been shown that coronary artery constriction of moderate degree may induce diffuse myocytolytic necrosis and marked alterations in ventricular hemodynamics [6]. Moreover, the phenomenon of myocyte cell death was documented to persist with time, chronically affecting the functional and anatomical characteristics of the heart [7,8]. Thus, modest decreases in coronary diameter may have clinical implications that have not been previously appreciated, and untreated coronary artery narrowing may progressively affect the structural integrity of the myocardium.