WASHINGTON, DC — It was with heavier hearts that ischemic heart-failure patients concluded therapy in a recent randomized trial. More precisely, it was with greater end-systolic myocardial mass and perhaps less myocardial scar.
They had been assigned to receive intramyocardial injections of autologous mesenchymal stromal cells (MSC), a kind of stem cell, for their ischemic heart disease. After six months, their proportion of functional heart muscle had gone up along with LV end-systolic volumes, stroke volume, and LVEF, compared with control patients who had received similar intramyocardial injections of saline.
Those gains, however, failed to translate into clinical benefit as measured by NYHA class and six-minute-walk distance. Interestingly, those measures did improve significantly for patients who received the cell therapy, but also for patients in the control group.
The MSC-HF trial, which entered 59 patients with chronic ischemic heart failure despite maximal medications for whom coronary revascularization wasn't an option, was reported here this week by Dr Anders Bruun Mathiasen (Rigshospitalet University Hospital Copenhagen, Denmark) at the American College of Cardiology 2014 Scientific Sessions . Those with LVEF <45% and in NYHA functional class 2 to 3 were eligible; the group's average LVEF was 28%.
At a briefing for media, Dr James B Hermiller (St Vincent Hospital, Indianapolis, IN) said that the trial showed "very dramatic improvements in metrics of heart performance," but that what might have been functional improvements seemed to be lost in a marked placebo effect among controls. Hermiller wasn't part of the MSC trial.
The 59 patients had been randomized 2:1 to cell therapy or placebo; MSCs were obtained from all patients, their numbers amplified in the laboratory, and then injected into ischemic viable myocardial regions guided by the NOGA XP (Cordis) catheter-based navigation system.
Of the randomized patients, 37 of the 39 getting cell therapy and 18 of the 20 controls were available for a six-month follow-up. At that time, mean LV end-systolic volume, LVEF, stroke volume, and end-systolic myocardial mass had improved significantly in the MSC-therapy group, both with respect to baseline levels and vs the control group.
Changes in Cardiac Measures Six Months after Mesenchymal Stromal Cell (MSC) Therapy or Placebo in MSC-FH
|End points at 6 mo||MSC group (p vs baseline)||Placebo||p (MSC vs placebo)|
|LV end-systolic volume* (mL)||-8.2 (0.001)||+6.0||0.001|
|LVEF (percentage points)||+5 (<0.0001)||-1.4||<0.0001|
|Stroke volume (mL)||+17.4 (<0.002)||-3.1||<0.0001|
|End-systolic myocardial mass (g)||+10.1 (<0.0001)||-2.1||<0.0001|
|Scar-tissue mass (g)||-4.4 (<0.017)||-0.5||NS|
*By MRI or CT, primary end point
There were no such differences in LV end-diastolic volume or LV end-diastolic myocardial mass. The MSC group showed significant improvements vs baseline in NYHA class (p<0.0001), six-minute-walk distance (p=0.001), and overall score on the Kansas City Cardiomyopathy Questionnaire (p=0.0001). But then so did the control group (p=0.001, 0.0004, and 0.003, respectively).
There were no significant differences in severe adverse events, including MI, stroke, HF worsening, syncope, need for revascularization, arrhythmias, or need for implantable defibrillators or biventricular pacemakers.
Dr William O'Neill (Henry Ford Hospital, Detroit, MI), speaking from the panel following Mathiasen's presentation of the study, noted that it continues a longtime trend in trials of cell therapy for cardiomyopathy in having a small sample size. "We still aren't even close to having this as an accepted mainstay therapy. And I think the challenge for you is to prove that there's actually clinical benefit by a five-percentage-point increase in ejection fraction when the patients feel equally well in both groups. I wonder how is it that this field is going to progress if we do see some modest benefit in LV function but no other clinical correlates."
Mathiasen replied, "We are going to follow this study up with a phase 3 trial that will run across six centers in Europe and will treat 140 patients also randomized in a 2:1 pattern. These patients will receive injections of either placebo or allogeneic MSAs from adipose tissue." And "it will be powered for the same end points as this trial."
Mathiasen had no disclosures. Hermiller discloses receiving consulting fees or honoraria from St Jude Medical, Abbott Vascular, Boston Scientific, and Medtronic. O'Neill discloses receiving consulting fees or honoraria from Medtronic and Edwards Lifesciences, being an officer or director for Neovasc, and having an ownership stake in or being a partner or other principal with Accumed Systems and Syntheon Cardiology.
Heartwire from Medscape © 2014 Medscape, LLC
Cite this: MSC Trial: Stem-Cell Therapy for Ischemic HF Inches Forward - Medscape - Apr 04, 2014.