Intramyocardial Injection of Stem Cells Shows Promise for Severe Ischemic Heart Failure

WASHINGTON, DC—In patients with severe ischemic heart failure, autologous transplantation of bone marrow-derived mesenchymal stromal cells results in improved myocardial function at 6 months, according to results presented March 31, 2014, at the American College of Cardiology/i2 Scientific Session.

For the MSC-HF trial, Anders Bruun Mathiasen, MD, of Rigshospitalet (Copenhagen, Denmark), and colleagues randomized 59 patients with severe ischemic heart failure to intramyocardial injection of mesenchymal stromal cells (n = 39) or placebo (n = 20). The stem cells were isolated, culture expanded, and injected into an ischemically viable region of the myocardium using the NOGA XP cardiac navigation system (Cordis, Miami, FL).

After 6 months, left ventricular end systolic volume (primary endpoint) was reduced in the treatment arm. Patients treated with mesenchymal stem cells also saw improvements in ejection fraction, stroke volume, and end systolic myocardial mass (table 1).

Table 1. Outcomes at 6 Months

 

 
Reduced scar tissue mass was found in the treatment group (-4.4 ± 5.1 g; P = 0.017), but not in the placebo cohort (-0.5 ± 3.8 g; P = 0.755), and no significant difference was observed between the 2 arms.

NYHA class, 6-minute walking test, and Kansas City Cardiomyopathy Questionnaire quality of life results all improved within, but not between groups. “We believe these results are a symbol of the placebo effect of this trial,” Dr. Mathiasen said.

With regard to safety, there were 3 instances of hospitalization for angina in the placebo group and none in the study arm (P = 0.03). There were no instances of MI or revascularization in either cohort.

While only 55 patients were available for follow-up at 6 months, “end systolic volume improved more than expected so post-hoc power is 95.4% and for ejection fraction the post-hoc power was about 99.9%, so this demonstrates that this study was well-powered,” Dr. Mathiasen reported.

Treatment with mesenchymal stem cells in this patient population is “safe and compared to placebo, the treatment improved end systolic volume, ejection fraction and stroke volume,” he concluded.

Unending Potential or Something More?

Session comoderator Cindy L. Grines, MD, of Detroit Medical Center Cardiovascular Institute (Detroit, MI), said the study “offers a lot of hope for our patients with chronic heart disease and heart failure.”

Panelist William W. O’Neill, MD, of Henry Ford Health System (Detroit, MI), said the endpoints were “very crisp and clean.” However, he was “kind of struck by the fact that over the last 10 years we’ve seen a lot of these studies with small sample sizes and we still aren’t close to having this as an accepted mainstay therapy. The challenge for you is to prove that there is actual clinical benefit by a high percentage point increase in ejection fraction when the patients feel equally well in both groups.”

Dr. Mathiasen reported that the study will be followed up by a phase III randomized trial of 140 patients at 6 European centers to be powered for the same endpoints.

Panelist David L. Brown, MD, of The Heart Hospital Baylor (Plano, TX), pointed out that a French research group “presented almost virtually the same data, wowing the crowd” about 20 years ago. “Stem-cell therapy has great potential and always will,” he concluded.

Study Details

Average patient age was 65.5 years and mean ejection fraction was 28.1 ± 8.8%. All patients were classified as NYHA class II-III with no further treatment options. Baseline differences were well balanced between the groups and most patients had a previous MI and revascularization.

 

 

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Source:Mathiasen AB. Autotransplantation of bone marrow derived mesenchymal stromal cells in patients with severe ischemic heart failure: the MSC-HF trial. Presented at: American College of Cardiology/i2 Scientific Session; March 31, 2014; Washington, DC.

 

 

 

 

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