Biology of Long-Term Mechanical Circulatory Support

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DESCRIPTION (provided by applicant): Congestive heart failure (CHF) is a highly prevalent and morbid condition. Randomized trials have shown that the one-year mortality in the subset of heart failure patients with refractory endstage disease ranges from 50 to 75%. Outcomes are worse than those for breast, colon and even lung cancer. Pharmacological treatment offers limited benefit to these patients while heart transplantation is severely limited by the shortage of human donors. Implantable left ventricular assist devices (LVADs) have been developed and clinically investigated in order to fill the obvious gap in our clinical armamentarium. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) Trial recently demonstrated significant survival and quality of life benefit in LVAD recipients compared to medically managed patients. However, the trial also documented the remaining serious adverse events associated with LVAD therapy, which, if overcome, would add substantially to its effectiveness while reducing costs. The proposed SCCOR seeks to elucidate and modulate the biology of the interface between implanted long-term mechanical circulatory support devices and patients with end-stage heart failure. A combination of closely linked animal model and human clinical trials is planned. Studies will evaluate novel interventions directed at the adverse impact of infection and coagulopathy that result from this interface. Furthermore, the feasibility of improving native myocardial function through cellular transplantation in order to facilitate device removal will be explored. While observations and interventions will focus on end-stage heart failure, the exploration of coagulation in this setting could enhance interventions to prevent and manage bleeding and thrombo-embolism while exploration of cellular transplantation has the potential to improve therapeutic approaches to less severe forms of heart failure. The planned research on infection has broader implications for prosthetic implants in general.