QUALITY OF LIFE Modeling the Effects of Functional Performance and Post-transplant Comorbidities on Health-related Quality of Life After Heart Transplantation Javed Butler, MD, MPH, a,b,g,h,i Nicole S. McCoin, MD, f Irene D. Feurer, PhD, a,f Theodore Speroff, PhD, d Stacy F. Davis, MD, a,b Don B. Chomsky, MD, a,b John R. Wilson, MD, b Walter H. Merrill, MD, c,e Davis C. Drinkwater, Jr., MD, c,e Richard N. Pierson III, MD, c,e and C. Wright Pinson, MD, MBA a,c,f Background: Health-related quality of life and functional performance are important outcome measures following heart transplantation. This study investigates the impact of pre-transplant functional performance and post-transplant rejection episodes, obesity and osteopenia on post-transplant health-related quality of life and functional performance. Methods: Functional performance and health-related quality of life were measured in 70 adult heart transplant recipients. A composite health-related quality of life outcome measure was computed via principal component analysis. Iterative, multiple regression– based path analysis was used to develop an integrated model of variables that affect post-transplant functional performance and health-related quality of life. Results: Functional performance, as measured by the Karnofsky scale, improved markedly during the first 6 months post-transplant and was then sustained for up to 3 years. Rejection Grade 2 was negatively associated with health-related quality of life, measured by Short Form-36 and reversed Psychosocial Adjustment to Illness Scale scores. Patients with osteopenia had lower Short Form-36 physical scores and obese patients had lower functional performance. Path analysis demonstrated a negative direct effect of obesity ( 0.28, p  0.05) on post-transplant functional performance. Post-transplant functional performance had a positive direct effect on the health-related quality of life composite score ( 0.48, p  0.001), and prior rejection episodes grade 2 had a negative direct effect on this measure (0.29, p  0.05). From the a Transplant Center, b Division of Cardiovascular Dis- eases, c Department of Surgery, d Center for Clinical Improve- ment, e Department of Cardiothoracic Surgery, f Department of Surgery, and g Center for Education and Research in Thera- peutics, Vanderbilt University, Nashville, Tennessee, and h Transplant Center, and i Geriatric, Research, Education, and Clinical Center, Nashville VA Medical Center, Nashville, Tennessee. Submitted June 13, 2002; revised November 12, 2002; accepted November 13, 2002. Supported by a grant from Roche Laboratories, Inc. Reprint requests: Javed Butler, MD, Division of Cardiovascular Diseases, 383 PRB, Vanderbilt University Medical Center, Nashville, Tennessee37232. Telephone: 615-322-2318. Fax: 615-321-6374. E-mail: javed.butler@vanderbilt.edu. Copyright © 2003 by the International Society for Heart and Lung Transplantation. 1053-2498/03/$–see front matter doi:10.1016/S1053-2498(02)01188-9 1149