Yacoub, Magdi Habib

Abstract Heart failure (HF) is a major cause of hospitalization and mortality worldwide. Ventricular assist devices (VADs) represent an alternative to cardiac transplantation for advanced HF. The main FDA-approved VAD (HeartMate III, Abbott), while effective, requires major cardiac surgery to insert the inflow cannula into the cardiac apex, and is associated with numerous co-morbidities and re-hospitalizations related to continuous flow and an external drive line and power supply. Mi-VAD, Inc. aspires to improve outcomes and quality of life with a miniature, minimally invasive, pulsatile, transcutaneously-powered VAD that is implanted above the aortic valve and/or the pulmonary valve and offering a wide range of hemodynamic support suitable for both advanced-stage and less advanced HF. Through its unique placement, there is the potential for right ventricular and biventricular cardiac assist for patients with restrictive cardiomyopathy and HFpEF for whom current VAD therapy is ineffective. Mi-VAD, Inc. has achieved proof of concept with its prototype, providing pulsatile ECG gated cardiac assist up to 10L/minute. Following initial bench top performance testing and in vivo efficacy and safety studies future work will focus on the development of wireless charging capability and conducting GLP builds for verification, regulatory clearance and commercialization. Additional technical development will focus on AI-driven hemodynamic optimization using multimodal physiologic sensing towards patient-specific digital twin of the Mi-VAD platform.

Abstract Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.