Clinical Trials

Heart Failure in Patients With Left Ventricular Assist Devices

Patients with implanted left ventricular assist devices:

Innovative stem cell therapeutic strategy that may be transformative for heart failure treatment 

There are nearly six million Americans with heart failure, and about 650,000 new cases occur each year. Each year 200,000 to 250,000 heart failure patients need heart transplantation, but with the very low supply of donor hearts, left ventricular assist devices (LVADs) are being used with increasing frequency. An LVAD is a small pump that helps circulate the patients’ blood when their heart becomes too weak to pump effectively on its own. Although highly effective in alleviating symptoms and improving longevity, patients with LVAD support still have a high incidence of death and of other serious complications.

Most importantly, the FDA approved a clinical trial that will start shortly at MedStar Heart & Vascular Institute (MHVI).  The trial (the STEMVAD trial), sponsored by MHVI in partnership with CardioCell, will determine whether stem cell therapy improves myocardial function in patients with severe heart failure—severe enough to require the implantation of an LVAD.  The trial will pioneer the use of a novel delivery strategy deriving from a new understanding of the causes of progressive heart failure and the mechanisms by which stem cells exert their beneficial cardiac effects.

Virtually all previous attempts to use stem cells to treat cardiac disease relied on the concept that the cells had to be delivered directly to the target tissue—the heart—and this, in turn, required catheter-based invasive delivery strategies.  This posed to the MHVI investigators a potential major practical issue, as it was their belief that a single injection of stem cells would not lead to a “cure”, but that repeated injections—every few months—would be required for adequate and sustained treatment effect.

The unique aspects of this trial derived from preclinical studies in the laboratory of Stephen Epstein, MD, MHVI director of Translational and Vascular Biology Research.  The investigators developed compelling evidence, using mouse models of heart attack and of heart failure, that one of the major mechanisms leading to progressive myocardial dysfunction in patients with heart failure is the presence of persistent and inappropriate inflammation.  They also demonstrated not only that MSCs have marked anti-inflammatory effects, but that they exert these effects when injected intravenously. Most importantly, these anti-inflammatory effects caused a marked improvement of heart function.

These results led to the design of the clinical trial about to be initiated—which involves the first stem cell trial using repeated intravenous administration of MSCs (every month) to control the inflammation and to sustain any improvements in heart function.  This study is a pilot safety/feasibility trial.  If successful, however, pivotal trials will follow, which will definitively determine whether this strategy—monthly intravenous injections of MSCs–will alter strategies for treating LVAD patients that could markedly improve their symptoms and outcomes.

If the present and future study results show intravenously delivered stem cells improve outcomes in LVAD patients, the results would likely extend to the general population of heart failure patients, and in the process, fundamentally transform current paradigms for treating heart failure.