Orlando, FL - Three new studies are boosting hopes that cell-transfer therapies may help rejuvenate damaged myocardium in a range of cardiovascular disease settings. During a late-breaking session here at the American College of Cardiology 2005 Scientific Sessions, investigators unveiled new data they say will ensure these strategies are tested in further trials.

Dr Stefan Janssens

In the first of the three—and the only randomized trial of the series—Dr Stefan Janssens (University of Leuven, Belgium) reported four-month outcomes in patients randomized to either intracoronary transplantation of autologous bone-marrow cells (BMCs) or placebo infusion. All patients had been admitted to the hospital with ST-segment-elevation MI >6 mm and had had their MI symptoms for at least two hours before treatment (thereby ruling out patients who may have spontaneously recovered from their MIs). All patients underwent successful reperfusion and BMC aspiration, then were randomized in a blinded fashion to receive either cell or placebo transfer 24 hours later.

At four months, the authors found no differences in improvements from baseline in global LVEF but did observe significantly different changes in reductions in LV mass index and infarct size. The treatment effect attributable to BMC infusion was particularly marked in patients who underwent PCI within six hours and in patients with larger baseline infarct size. Of note, reduced infarct size was associated with significant attenuation of end-diastolic wall thickness, a finding that may carry implications for cardiac remodeling, Janssens speculated. Adverse effects were comparable between the control and BMC groups, with six patients in the BMC group and five in the control group experiencing atrial tachycardia and three in the control group having ventricular tachycardia.

"Intracoronary transplantation of autologous BMCs in timely reperfused myocardium significantly reduces infarct size but does not further augment global left ventricular systolic functional recovery," Janssens concluded. "The confirmed safety profile in our study will facilitate larger clinical trials that are required to investigate whether these changes will translate into improved clinical outcome."

Myoblast transplantation after CABG

In a second study, Dr Nabil Dib (Arizona Heart Institute, Phoenix) presented 11- to 45-month follow-up on 24 patients undergoing CABG who received autologous myoblast cell transplantation by direct injection. All patients had LVEFs below 40%, and half had LVEFs below 30%.

Dr Nabil Dib

As Dib told the late-breaking-session audience here today, adverse events possibly related to cell transplantation included two cases of nonsustained ventricular tachycardias. Overall, patients experienced significant improvement in NYHA class from baseline out to 12 months, but this difference lost statistical significance after two years. LVEF, however, improved significantly from baseline to 12 and 24 months, while LV diastolic volume dropped significantly over this same period. PET scans taken at baseline and six months also indicated increased tissue viability.

Dib and colleagues conclude that isolation and expansion of myoblasts is feasible and safe and may improve myocardial viability. To heartwire, Dib added that the procedure is promising and that he and his colleagues are already moving ahead with further studies, this time employing a catheter-based delivery technique.

Skeletal myoblasts for post-MI chronic HF

In the third and final cell-transfer study of the afternoon's late-breakers, Dr Patrick Serruys (Thoraxcenter, Erasmus Medical Center, the Netherlands) presented results of the BioHEART study, a phase 1/2 study examining autologous skeletal myoblast (ASM) injection for post-MI treatment in patients with chronic heart failure.

In the study, 15 patients received ASM injected into the scarred myocardium by fluoroscopic guidance four to six years after their MI. Out of the first six patients, one died and two others had ventricular tachycardia, prompting the trial's data and safety monitoring board to permit patients with ICDs, who had originally been excluded in the trial design, to be enrolled in the trial and for those already enrolled to receive an ICD.

After 12 months, two patients had died, both within two weeks of the procedure. Two who did not already have ICDs received them for prevention of ventricular arrhythmia, and a total of three patients experienced ventricular events, triggering ICD therapy. In the remaining patients, wall-motion score index at rest improved slightly, with borderline statistical significance from baseline. Other parameters, including end systolic volume and ejection fraction, did not improve over 12 months.

"Skeletal-myoblast injection as a stand-alone clinical procedure is feasible, and this pilot investigation provides preliminary evidence of potential efficacy of the treatment," Serruys concluded. Still, further trials with larger numbers and a randomized design will be mandatory, he said, accompanied by close surveillance of patients long term to detect the types of arrhythmias seen in the study.