The PARACHUTE IV trial design and rationale: Percutaneous ventricular restoration using the parachute device in patients with ischemic heart failure and dilated left ventricles Marco A. Costa, MD, PhD, a Michael Pencina, PhD, b Serjan Nikolic, PhD, c Thomas Engels, c Barry Templin, c and William T. Abraham, MD d Cleveland, and Columbus, OH; Boston, MA; and Menlo Park, CA Background Left ventricle (LV) remodeling after anterior wall myocardial infarction leads to increased LV volumes, myocardial stress, and, ultimately, heart failure (HF). Patients have high morbidity and mortality risk, and treatment remains limited. Percutaneous ventricular restoration (PVR) therapy using the Parachute device, a fluoropolymer membrane stretched over a nitinol conical frame, is a novel approach to partition off the damaged myocardium. In the European and United States PARACHUTE feasibility trials, the observed rates of death or rehospitalization for HF were b17% at 12 months. These data compare favorably with historical data and support the need of a randomized trial to determine the clinical efficacy of PVR on outcomes for patients with ischemic HF. Objective To determine the safety and efficacy of PVR utilizing a LV partitioning device, Parachute, in a randomized clinical trial compared with optimal medical therapy. Methods This US pivotal trial is approved by the Food and Drug Administration (ClinicalTrials.gov Identifier: NCT01286116) and will randomly assign (1:1) 478 patients with New York Heart Association class III-IV ischemic HF, akinetic or dyskinetic LV wall abnormality, and ejection fraction between 15% and 35% to optimal medical therapy (control) versus Parachute device implantation in approximately 65 hospitals. The primary endpoint is death or rehospitalization for worsening HF. Sample size calculation assumes constant hazards and follow-up ≥12 months using an event-driven trial design. Conclusions We reported the rational and design of the first multicenter randomized trial to test the efficacy of PVR using the Parachute device to treat patients with ischemic HF and dilated LV. (Am Heart J 2013;165:531-6.) Heart failure (HF) imposes one of the highest burdens of any medical condition with an estimated 23 million patients suffering from this condition worldwide. The process of left ventricle (LV) dilatation and remodeling after acute myocardial infarction (MI) has been well documented in experimental and clinical investigations. 1 Left ventricle remodeling has been associated with development of congestive heart failure, and LV end- systolic and end-diastolic volumes have been shown to be independent predictors of clinical outcomes. Medication remains the cornerstone of conventional treatment for HF. Neurohormonal modulators such as angiotensin converting enzyme inhibitors, beta-blockers, angiotensin receptor blockers, and aldosterone antago- nists have been shown to reduce morbidity and mortality associated with HF. 2 Patients with advanced HF, remote MI and ventricular dyssynchrony also benefit from the simultaneous pacing of both right and left ventricles. 3-5 In addition, surgical interventions to treat concomitant dysfunctional mitral valve and coronary artery disease, implantation of LV assist device (LVAD), and ultimately heart transplantation are integral components of modern strategies to improve outcomes of patients with HF. 6,7 In spite of advances in both pharmacological and mechanical approaches to HF, its overall mortality and hospital readmission rates remain unacceptably high. 8 Therapeutic efficacy depends, albeit not exclusively, on improvements in LV volumes and geometry. 9 Surgical ventricular reconstruction (SVR) showed promising early results, but recently has been the subject of intense debate on appropriate patient selection and tech- niques. 10,11 Parachute is the first device designed for From the a University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, b Harvard Clinical Research Institute, Boston, MA, c CardioKinetix, Inc, Menlo Park, CA, and d The Ohio State University, Columbus, OH. RCT reg #NCT01614652. Submitted June 12, 2012; accepted December 16, 2012. Reprint requests: William T. Abraham, MD, OSU Heart Center, Division of Cardiovascular Medicine, 473 West 12th Avenue, Room 110P DHLRI, Columbus, OH 43210. E-mail: william.abraham@osumc.edu 0002-8703/$ - see front matter © 2013, Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ahj.2012.12.022