[TCT2007]MYOHEART: Myoblast Transplantation Shows Promise in CHF Patients

Next phase of myoblast research, the MARVEL trial, will enroll 330 post-MI heart-failure patients.

Six-month results from the MYOHEART study indicate that implantation of autologous myoblasts into the myocardial tissue of patients with CHF and prior MI is feasible and safe.

“Safety, I think, has been established fairly effectively,” said Warren Sherman, MD, of Columbia University Medical Center.

MYOHEART consisted of four cohorts of five patients each, with each cohort receiving increasing doses of myoblasts (MyoCell, BioHeart). One patient in cohort 2 and one in cohort 4 died; one had ventricular tachycardia and the other had progressive heart failure and multiple organ failure. Six of the 20 patients experienced arrhythmias after transplantation, but all six entered the study with a history of arrhythmia.

“The incidence of first-time arrhythmias outside of the two mortalities was very low,” Sherman said. No other significant adverse events related to therapy were noted, he added. Paired analyses of patients’ 6-minute walk test from baseline to 3 months showed an average improvement of 54 meters (n = 18; P = .0074). Minnesota Living With Heart Failure (MLHF) scores also showed a significant improvement in paired analyses at both 3 and 6 months (n = 14 and n = 16, P = .0016 and P = .0004, respectively; Figure 1).

Cell doses

The first study cohort received two injections and a total of 25 x 106 cells using the MyoCath (Bioheart) needle-injection catheter; each subsequent study group had an increased dose, to 75 x 106 cells, 225 x 106 cells, and 675 x 106 cells. Before dose escalation, there was a 30-day safety evaluation for each cohort. All included patients had NYHA class II-III heart failure (8 of 20 were class III), MI more than 12 weeks previously, prior ICD implantation, and an LVEF between 20% and 40%. The patients ranged in age from 31 to 77 years.

When the endpoints were divided by cohorts, there was significant variability. Six-minute walk test improvement reached significance from baseline to 3 months in cohorts 2 and 3, but not in cohorts 1 and 4 (Figure 2). Changes in MLHF reached significance in cohort 3 but no other cohorts. The average LVEF improved significantly from baseline to 3 and 6 months in cohort 3 but no others.

A phase II/III trial called MARVEL has been initiated. MARVEL will be randomized and placebo-controlled and will have two treatment groups receiving injections of 800 x 106 cells and 400 x 106 cells.

Endpoint selection

Emerson C. Perin, MD, PhD, of the Texas Heart Institute in Houston, discussed the need to rethink the way molecular therapy heart failure trials are conducted. “How do the end¬points get chosen? The answer is that people have picked different things to look at,” he said. “There is no rigorous or specific method that has been used. This is a major problem, and it reflects on the results of the trials.”

Perin noted that although many trials have used LVEF as a primary endpoint, the lack of understanding regarding underlying mechanisms makes use of this and other endpoints somewhat meaningless. “We need to learn observationally what we’re doing so we can be a little more intelligent about how we’re gathering the data.” He suggested looking at patients in a tiered manner, beginning with the tis¬sue itself, then stepping back to look at the heart as a whole, and then stepping back again to look at the patient in terms of functional capacity.