Assessment of Endothelial Function in Patients With Advanced Heart Failure Requiring Mechanical Circulatory Support

Detailed Summary

The pathophysiology of HF is highly variable, with overlapping pathogenic mechanisms that complicates any attempt to create a simple and unified conceptual model. Left ventricular (LV) ejection fraction (EF), assessed as the fraction of the end-diastolic volume that is ejected upon contraction, has been the cornerstone metric for characterization of LV systolic function in patients with HF. LVEF demonstrates a strong inverse relationship with clinical outcomes in HF in patients with reduced EF (HFrEF). Current management options for the treatment of HFrEF include medical management, mechanical circulatory support, and cardiac transplantation. In the setting of refractory end stage HFrEF, the standard of care is heart transplantation. Since limited organ procurement is a significant constraint to the treatment of patients with advanced disease, durable mechanical circulatory support (MCS) with left ventricular assist devices (LVAD) were developed as a safe and efficacious treatment strategy for patients with advanced HF that is refractory to medical therapy. The advances in LVAD engineering and design, tailored towards defined physiological goals, have resulted in the creation of much smaller continuous-flow (CF) pumps that possess technical superiority, pump durability, and ease of implantation compared to the older and larger pulsatile-flow pumps. The addition of speed modulation algorithms to the next generation centrifugal CF LVADs, has decreased the incidence of device related adverse events. Our interest lies in the impact of continuous flow hemodynamics on endothelial function and the cardiac and end-organ responses to this novel therapy. Current knowledge of the impact of these specific advances in LVAD therapy is however limited by the relative youth of the field. Thus, the goal of this research project is to study human LVAD patients and to determine the impact of speed modulation algorithms in CF physiology on microvascular and endothelial function and its association with cardiac and peripheral organ function. The investigators hypothesize that restoration of cardiac output using an LVAD with modern speed modulation algorithm improves vascular endothelial function. In addition, these changes would have a positive correlation with functional outcomes.

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