SCIPIO: Cardiac Stem Cells Reverse Heart Failure

Reed Miller

November 06, 2012

LOS ANGELES — Encouraging two-year follow-up from the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial, a small study of cardiac stem-cell (CSC) injections in patients with ischemic cardiomyopathy, stood out among the mixed results of stem-cell trials presented here at the American Heart Association 2012 Scientific Sessions.

Dr Roberto Bolli (University of Louisville, KY), who presented complete four-month results and initial two-year results from the trial, pointed out that this trial is among the first to look at the benefits of CSCs--instead of cells derived from bone marrow--in heart-failure patients.

"We are just at the beginning of a dramatic revolution in cardiovascular medicine," Bolli said. "It's amazing. We picked an arbitrary dose. We don't understand when the best time to give [the cells] is or if you can give them multiple times to the same patient--which we probably can, but it hasn't been done so far--so we're still learning how to use them, but the very first time with this totally new therapy we found such a dramatic improvement. This is very encouraging."

As previously reported by heartwire , SCIPIO is a phase 1, randomized, open-label trial of c-KIT-positive CSCs in patients with left ventricular dysfunction (LVEF <40%) following an MI. In the trial, the cells were harvested from the patient's right atrial appendage, isolated and expanded, and then infused to repair an infarction during coronary bypass surgery.

Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 29.0% before infusion to 36.0% (p <0.001) four months after the procedure. During that period, LVEF improved only from 29.2% to 29.4% in 13 control patients.

The benefits seen in the treated group grew relative to the control group at the one- and two-year follow-up. The average LVEF grew insignificantly from 30.3% at baseline to 31.7% at one-year postprocedure in the 12 control patients followed that long. In 17 patients in the CSC-treatment group at the one-year follow-up, LVEF increased to 37.8% from a baseline average of 29.7%. At two years, five control patients still showed no significant change in LVEF, while average LVEF rose to 41.7% in the 12 CSC-treated patients who had reached the two-year follow-up. Global wall-motion scores declined slightly in the control group over 24 months while they improved from -2.50 to -3.92 (p=0.006) in the treatment group.

Cardiac MRI showed that the CSC-treated patients had statistically significant improvements in mass of nonviable myocardial tissue and the percentages of viable tissue within the infarcted region. Minnesota Heart Failure Scores improved significantly in the CSC-treated patients while remaining almost flat in the control group.

No adverse effects attributable to CSCs have been reported in the trial out to two years. "The most reassuring consideration with stem cells is that with almost 3000 patients treated with different kinds of stem cells in many trials worldwide, there have been absolutely no serious adverse effects. So it seems fairly reasonable to say that, at least, they don't do harm," Bolli said.

"The implication of this study is that now we need to perform larger multicenter randomized blinded phase 2 and phase 3 studies to confirm these data, but the important point is that we can now apply this therapy to almost every patient with heart failure, because we can obtain the cells with a percutaneous biopsy that can be done as an outpatient procedure," Bolli said. Bolli told heartwire that his group is developing a plan for a multicenter two-year phase 2 study of this CSC therapy that will enroll at least 100 patients.

Commenting on the study, American College of Cardiology president Dr William Zoghbi (Methodist Hospital, Houston, TX) told heartwire , "Really, this is an excellent finding--a small number of patients, certainly preliminary, but a very promising finding to see sustained improvement in ventricular function and in cardiac viability by MRI at two years."

Mixed News for Stem Cells

SCIPIO was one of five stem-cell trials presented as late-breaking clinical trials. As previously reported by heartwire , the small POSEIDON trial showed that myocardial injections of allogeneic mesenchymal stem cells are safe and associated with improvements in some, but not all, measures of benefit. Zogbhi said POSEIDON offers a "glimpse of hope" for the possibility that allogeneic stem cells could someday be an off-the-shelf therapy, but the data are too preliminary to conclude that this approach will be effective.

Also, results of the ALCADIA trial, presented by Dr Naofumi Takehara (Kyoto Prefectural University of Medicine, Japan) showed that administration of autologous human cardiac-derived stem cells to seven patients with ischemic cardiomyopathy is safe and improved the patients' average maximum oxygen consumption by about one-third (p=0.0308).

However, the other stem-cell trials presented at AHA did not offer good news for proponents of stem-cell therapy to repair infarcted myocardium. Four-month results from the 200-patient SWISS-AMI study, presented by Dr Daniel Suerder (Fondazione Cardiocentro Ticino, Lugano, Switzerland) found that intracoronary infusion of bone-marrow mononuclear cells did not improve left ventricular function as assessed by magnetic imaging compared with controls either at one week or four weeks after primary PCI for ST-elevation MI. However, subgroup analysis suggests this approach may offer some benefit in patients reperfused within 4.5 hours of the onset of chest pain.

Results from the TIME randomized trial of intracoronary delivery of autologous bone-marrow mononuclear cells after PCI to treat acute MI were presented by principal investigator Dr Jay Traverse (Minneapolis Heart Institute, MN) and simultaneously published in the Journal of the American Medical Association [1]. The 120-patient trial found that administration of the cells at either three days or seven days after the AMI had no significant effect on recovery of global or regional left ventricular function.

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