Impella Reverse Remodeling in End-Stage Heart Failure

Percutaneous endovascular mechanical circulatory support (MCS) devices have been increasingly utilized in patients on the waitlist for heart transplantation in the new heart allocation system. However, the number of patients recovering from heart failure and delisted from cardiac transplantation has declined in the new heart allocation system. While significant research has been performed on myocardial recovery with durable left ventricular assist device (LVAD) support, natural course and mechanistic basis of reverse remodeling on percutaneous endovascular MCS remains unknown. The primary objective of this prospective, observational, single-center study is to evaluate whether mechanical circulatory support with Impella 5.5 LVAD in decompensated patients on the waitlist for heart transplantation results in left ventricular reverse remodeling and improvement in end-organ function within 14 days of initiating support. Phenotypic data including clinical information, echocardiography, and hemodynamics will be serially obtained in participants before and after Impella 5.5 LVAD placement. Paired serum samples (pre- and post- Impella support) will be obtained for proteomic analysis. Cardiac tissue samples will be collected at the time of cardiac transplantation for histopathological analysis as well as RNA-sequencing. Candidate genes and proteins of reverse remodeling will be validated using quantitative polymerase chain reaction (qPCR) and Western Blotting. This study will definitively establish the natural course of reverse remodeling in patients with chronically failing ventricles on Impella 5.5 support and determine molecular signals and novel biomarkers of myocardial recovery in this growing population. Data obtained from this study will help determine which patients should pursue recovery pathway as opposed to transplant.

Inclusion criteria

• Age 18 years or older
• Dilated cardiomyopathy (LVEDD > 5.5 cm and LVEF <25%)
• Indication for temporary mechanical circulatory support therapy with Impella 5.5 LVAD as a bridge to transplant or bridge to transplant decision based on treating physician's discretion

Exclusion criteria

• Intra-aortic balloon pump (IABP) use for more than 7 days at the time of Impella 5.5 implantation
• Percutaneous mechanical circulatory support device, extracorporeal membrane oxygenation (ECMO) or paracorporeal ventricular assist device (VAD) support prior to Impella 5.5 implantation
• Congenital heart disease
• Restrictive or hypertrophic Cardiomyopathy including hypertrophic obstructive cardiomyopathy (HOCM) Amyloidosis, and Sarcoidosis
• Evidence of acute myocarditis by endomyocardial biopsy
• Prior heart transplantation
• Mechanical aortic / mitral valve
• Patient with known aortic diseases such as Marfan-Syndrome, Morbus Erdheim-Gsell or others
• Left Ventricular thrombus
• Left Ventricular rupture
• Cardiac tamponade
• Presence of an Atrial or Ventricular Septal Defect
• Severe right ventricular (RV) Failure requiring mechanical RV support
• Severe peripheral vascular disease precluding placement of the Impella System
• Recent stroke resulting in significant neurological deficit
• Hypercoagulable disease precluding device implantation
• Severe thrombocytopenia (<50,000)
• Contraindication to anticoagulation
• Suspected or known pregnancy or lactating women
• Subject belongs to a vulnerable population