Device for Treatment of Cardiac No-Option Patients

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ABSTRACT Of the nearly 1 million US patients suffering from myocardial infarction each year, 15-20% are poor candidates for CABG or PCI because of diffuse CAD, multiple stents, and failed CABG and are therefore considered "no- option" patients. These patients suffer daily from severe angina, shortness of breath, fatigue, and the like and are frequently untreatable by CABG or PCI which has been shown to have very poor outcomes under these conditions. Without a heart transplant, the no-option patient typically progresses to CHF. The Company’s technology enables a revascularization therapy for the no-option patient that is not reliant on repairing the arterial system. The therapy is a staged approach which uses a novel venous pressure preconditioning (VPP) device to prime the coronary vein for retroperfusion via coronary vein bypass graft (CVBG). Development of the VPP device has focused on overcoming limitations associated with coronary retroperfusion that have stemmed from abrupt increases in perfusion pressure, leading to edema and hemorrhage of the myocardium. Our approach avoids acutely raising the pressure in the coronary veins from venous (10-20 mmHg) to arterial values (100-120 mmHg) in a single step and instead, regulates the pressure at an intermediate level (between arterial and venous levels). Importantly, results from our Phase I studies have shown safe and selective pre-arterialization of the left anterior descending coronary vein using the percutaneously delivered VPP devices. This proof-of-concept was demonstrated by thicker vessel walls and with greater degree of functional smooth muscle cells (i.e., respond to pharmacological agonist and antagonist) in the preconditioned vessels occluded by the VPP device compared to normal veins. Our previous studies have demonstrated that veins with this degree of remodeling safely enable retroperfusion at full arterial pressure without edema or hemorrhage. To advance these outstanding findings, the chronic retroperfusion therapeutic approach must be challenged under clinically relevant conditions that resemble the multiple comorbidities of “no-option” patients. Accordingly, this Phase II proposal advances this promising technology in two specific aims: 1) To demonstrate efficacy of chronic retroperfusion enabled by the VPP device in a chronic animal study of a translational animal model of DCAD and focal ischemia comorbidities; and 2) To collect GLP safety data in a chronic animal study for an IDE submission to the FDA. This Phase II study addresses a highly significant clinical need for providing revascularization for “no-option” patients and can reach across various NIH Institutes and Centers.