This is an application for a K23 award for Dr. Kiran Khush, an instructor in cardiology and heart transplantation at Stanford University, who is establishing herself as a young investigator studying donor evaluation for heart transplantation. This K23 award will provide Dr. Khush with the support necessary to accomplish the following goals: (1) to independently design, implement, and analyze cohort study data;(2) to obtain fluency in biostatistical methodology and genetic epidemiology;and (3) to develop an independent clinical research career. To achieve these goals, Dr. Khush will work closely with her primary mentor Dr. Hannah Valantine, Director of Heart Transplant Research at Stanford, and her co-mentor Dr. Thomas Quertermous, Research Chief of the Division of Cardiovascular Medicine at Stanford. Dr. Valantine has extensive clinical research experience within the realm of heart transplantation and has a proven track record of successfully mentoring junior faculty. Dr. Quertermous is an internationally-recognized expert in cardiovascular genetics and has guided many junior faculty members towards independent careers. Heart transplantation provides the most effective treatment for end-stage heart disease. The critical deficit in suitable donor hearts, however, continues to limit transplant rates in the United States and worldwide. One solution to the donor shortage is to increase the yield of acceptable hearts from available donors through development of systematic, evidence-based criteria for donor selection. Dr. Khush will leverage the resources available at Stanford University to identify clinical and genetic risk factors for graft left ventricular dysfunction (Aim 1), to identify donor clinical and genetic predictors of poor recipient outcomes after transplantation (Aim 2), and to perform a prospective cohort study evaluating whether early post-transplant biomarkers mediate the associations between donor risk factors and recipient outcomes. This research will provide Dr. Khush with the skills and preliminary data necessary to investigate the mechanisms that modulate recipient outcomes after heart transplantation, to be proposed in an R01 grant application before the end of the K award period.

Public Health Relevance

Approximately 60% of potential donor hearts are discarded, primarily due to left ventricular dysfunction. Understanding the mechanisms responsible for graft dysfunction may facilitate the development of prevention or treatment strategies to increase the availability of donor hearts. Moreover, systematic evaluation of donor risk factors for adverse post-transplant outcomes may help to refine current donor selection criteria.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL091143-02
Application #
7876701
Study Section
Special Emphasis Panel (ZHL1-CSR-R (F1))
Program Officer
Scott, Jane
Project Start
2009-08-01
Project End
2014-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
2
Fiscal Year
2010
Total Cost
$134,854
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Goldstein, Benjamin A; Thomas, Laine; Zaroff, Jonathan G et al. (2016) Assessment of Heart Transplant Waitlist Time and Pre- and Post-transplant Failure: A Mixed Methods Approach. Epidemiology 27:469-76
Khush, K K; Zaroff, J G; Nguyen, J et al. (2015) National decline in donor heart utilization with regional variability: 1995-2010. Am J Transplant 15:642-9
Khush, Kiran K; Nguyen, John; Goldstein, Benjamin A et al. (2015) Reliability of transthoracic echocardiogram interpretation in potential adult heart transplant donors. J Heart Lung Transplant 34:266-9
Khush, Kiran K; Pham, Michael X; Teuteberg, Jeffrey J et al. (2015) Gene expression profiling to study racial differences after heart transplantation. J Heart Lung Transplant 34:970-7
Chen, Sharon; Selamet Tierney, Elif Seda; Khush, Kiran K et al. (2015) Reliability of echocardiographic measurements of left ventricular systolic function in potential pediatric heart transplant donors. J Heart Lung Transplant 34:100-6
De Vlaminck, Iwijn; Khush, Kiran K; Strehl, Calvin et al. (2013) Temporal response of the human virome to immunosuppression and antiviral therapy. Cell 155:1178-87
Ginwalla, M; Pando, M J; Khush, K K (2013) Pregnancy-related human leukocyte antigen sensitization leading to cardiac allograft vasculopathy and graft failure in a heart transplant recipient: a case report. Transplant Proc 45:800-2
Khush, Kiran K; Menza, Rebecca; Nguyen, John et al. (2013) Donor predictors of allograft use and recipient outcomes after heart transplantation. Circ Heart Fail 6:300-9
Ho, Jennifer E; Waters, David D; Kean, Allison et al. (2012) Relation of improvement in estimated glomerular filtration rate with atorvastatin to reductions in hospitalizations for heart failure (from the Treating to New Targets [TNT] study). Am J Cardiol 109:1761-6
Khush, K K; Pawlikowska, L; Menza, R L et al. (2012) Beta-adrenergic receptor polymorphisms and cardiac graft function in potential organ donors. Am J Transplant 12:3377-86

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