R01HL153516

Development of a Universal Bi-Ventricular Replacement System for the Failing Heart - Project Summary/Abstract

The objective of this project is to develop an implantable blood pump system as a total heart replacement. The use of left ventricular assist devices (LVADs) for destination therapy for end-stage heart failure is expanding. However, right ventricular failure occurs in 10-40% of LVAD patients.

We are developing a system using separate centrifugal left and right pumps with a common controller. The right pump is based on a right heart replacement pump developed for failing Fontan patients. It has unique double inlet ports to connect to the superior and inferior vena cavae, allowing the pump to be placed in the position of the right atrium. The left pump is a single inlet pump of similar design.

Compared to currently available bi-ventricular assist systems and total artificial hearts, our approach will:

1) Allow unobstructed fit in the anatomy of smaller patients,
2) Achieve reliable operation for at least 10 years,
3) Automatically adjust left and right pump output to respond to the varied physiologic needs of the patient,
4) Balance left and right pump outputs to safely control left atrial pressure over a wide range of systemic and pulmonary vascular resistances and central venous pressures,
5) Provide pulsatile flow,
6) Reduce the incidence of thromboembolism and pump thrombosis,
7) Preserve high molecular weight von Willebrand factor to reduce the incidence of bleeding, and
8) Provide a development path to a completely implantable, wireless system.

Specific Aim 1 - Build a bi-ventricular replacement device to replace the failing heart, with the right heart placed in the bicaval position and a left pump anastomosed to the left atrium remnant. Integration of pressure sensors in both pumps will measure inlet pressures (equivalent to right atrial and left atrial pressures), which will be used as inputs to the automatic control system.

Specific Aim 2 - Develop an automatic control system capable of physiologic control of both pumps. The controller will increase right pump output in response to increased venous return, which mimics the normal Frank-Starling cardiac output response, and control left pump output to maintain left atrial pressure within a physiologic range. The controller will also modulate pump speeds to produce pulsatile flow.

Specific Aim 3 - Test and optimize the total artificial heart (TAH) in chronic animal studies to:
A) Demonstrate automatic Starling-like cardiac output control and automatic balance control of the pumps over a wide range of physiologic conditions including exercise, and
B) Examine the biocompatibility of the device by assessing thrombus formation, thromboembolism, von Willebrand factor degradation, and intestinal angiodysplasia. We will study both pulsatile and non-pulsatile modes.

Pennsylvania State University

NOT APPLICABLE

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Hershey, Pennsylvania 170332360 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 337% from $705,738 to $3,085,748.