The demand for donor hearts for transplantation far outstrips the supply; however, only one in three available cardiac grafts are used for transplantation. There are many reasons for graft non-use, but previous studies have failed to demonstrate consistent associations between donor characteristics, donor cardiac function, and adverse recipient outcomes. Thus, there is a critical need to standardize how cardiac allografts are evaluated and accepted for transplantation. Our long-term goal is to safely expand the use of available cardiac allografts without adversely affecting transplant recipient outcomes. We propose to carefully characterize the current population of cardiac organ donors, particularly with regards to allograft function; to examine how decisions are made regarding graft acceptance for transplantation; and to systematically evaluate associations between donor characteristics and recipient outcomes. Our central hypothesis is that acceptable allografts for heart transplantation are being unnecessarily discarded, and the establishment of an evidence-based process for cardiac donor evaluation and acceptance will increase graft utilization rates while maintaining excellent clinical outcomes. In response to this need, we propose a collaborative study with seven organ procurement organizations representing geographically diverse regions of the United States, to address the following specific aims: (1) To identify clinical correlates of graft function in potential donors being evaluated for heart transplantation An existing online donor research database will be expanded for standardized collection of data on detailed donor characteristics, especially as pertains to cardiac allograft function. We will perform expert core review of donor echocardiograms, including serial echocardiograms in donors with cardiac allograft dysfunction. Serial electrocardiograms and cardiac biomarkers (Troponin I and B-type natriuretic peptide) will also be studied; (2) To prospectively study reasons for cardiac allograft non-utilization for heart transplantation. Real-time data will be collected on specific reasons for allograft non-acceptance for transplantation in order to study graft acceptance practices and variation in graft utilization nationwide; and (3) To prospectively study associations between donor characteristics and recipient outcomes after heart transplantation. Data will be collected on recipient post-transplant length of hospitalization and survival to identify associations between donor predictors and recipient outcomes. This proposal is innovative because it focuses on an entirely different approach to donor-based research, thereby surmounting the limitations of prior investigations. Completion of the proposed study will have a positive impact by defining how to optimize the evaluation and use of available grafts for heart transplantation, thereby safely expanding the donor pool and increasing the number of heart transplants performed nationwide.

Public Health Relevance

The proposed research will provide evidence-based strategies for the evaluation and acceptance of donor hearts for transplantation. This is relevant to public health because judicious expansion of donor hearts used for transplantation will make this life-saving procedure available to a larger number of patients living with end- stage heart disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL125303-05
Application #
9607618
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Desvigne-Nickens, Patrice
Project Start
2014-11-15
Project End
2019-10-31
Budget Start
2018-11-01
Budget End
2019-10-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Khush, Kiran K (2017) Personalized treatment in heart transplantation. Curr Opin Organ Transplant 22:215-220
Pasupneti, Shravani; Khush, Kiran (2016) Elevated Troponin? Take Heart and Reconsider! Circ Heart Fail 9: