Device for Treatment of Cardiac No-Option Patients

ABSTRACT Of the nearlymillion US patients suffering from myocardial infarction each yearare poor candidates for CABG or PCI because of diffuse CADmultiple stentsand failed CABG and are therefore considered andquot nooptionandquotpatientsThese patients suffer daily from severe anginashortness of breathfatigueand the like and are frequently untreatable by CABG or PCI which has been shown to have very poor outcomes under these conditionsWithout a heart transplantthe no option patient typically progresses to CHFThe Company s technology enables a revascularization therapy for the no option patient that is not reliant on repairing the arterial systemThe therapy is a staged approach which uses a novel venous pressure preconditioningVPPdevice to prime the coronary vein for retroperfusion via coronary vein bypass graftCVBGDevelopment of the VPP device has focused on overcoming limitations associated with coronary retroperfusion that have stemmed from abrupt increases in perfusion pressureleading to edema and hemorrhage of the myocardiumOur approach avoids acutely raising the pressure in the coronary veins from venousmmHgto arterial valuesmmHgin a single step and insteadregulates the pressure at an intermediate levelbetween arterial and venous levelsImportantlyresults from our Phase I studies have shown safe and selective pre arterialization of the left anterior descending coronary vein using the percutaneously delivered VPP devicesThis proof of concept was demonstrated by thicker vessel walls and with greater degree of functional smooth muscle cellsi erespond to pharmacological agonist and antagonistin the preconditioned vessels occluded by the VPP device compared to normal veinsOur previous studies have demonstrated that veins with this degree of remodeling safely enable retroperfusion at full arterial pressure without edema or hemorrhageTo advance these outstanding findingsthe chronic retroperfusion therapeutic approach must be challenged under clinically relevant conditions that resemble the multiple comorbidities ofno optionpatientsAccordinglythis Phase II proposal advances this promising technology in two specific aimsTo 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 comorbiditiesandTo collect GLP safety data in a chronic animal study for an IDE submission to the FDAThis Phase II study addresses a highly significant clinical need for providing revascularization forno optionpatients and can reach across various NIH Institutes and Centers NARRATIVE Approximatelyof the patients that suffer heart attack per year in the US are poor candidates for bypass or coronary intervention and are considered andquot no optionandquotpatientsThe purpose of this Phase II proposal is to validate the safety and efficacy of a novel venous pressure preconditioning device that enables heart revascularization in theno optionpatient