Association of recipient age and causes of heart transplant mortality: Implications for personalization of post-transplant management-An analysis of the International Society for Heart and Lung Transplantation Registry.
BACKGROUND
Survival beyond 1 year after heart transplantation has remained without significant improvement for the last 2 decades. A more individualized approach to post-transplant care could result in a reduction of long-term mortality. Although recipient age has been associated with an increased incidence of certain post-transplant morbidities, its effect on cause-specific mortality has not been established.


METHODS
We analyzed overall and cause-specific mortality of heart transplant recipients registered in the International Society for Heart and Lung Transplantation Registry between 1995 and 2011. Patients were grouped by recipient age: 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥ 70 years. Multivariable regression models were used to examine the association between recipient age and leading causes of post-transplant mortality. We also compared immunosuppression (IS) use among the different recipient age groups.


RESULTS
There were 52,995 recipients (78% male; median age [5th, 95th percentile]: 54 [27, 66] years). Survival through 10 years after transplant was lower in heart transplant recipients in the 2 more advanced age groups: 49% for 60 to 69 years and 36% for ≥ 70 years (p < 0.01 for pairwise comparisons with remaining groups). The risk of death caused by acute rejection (hazard ratio [HR], 4.11; p < 0.01), cardiac allograft vasculopathy (HR, 2.85; p < 0.01), and graft failure (HR, 2.29; p < 0.01) was highest in the youngest recipients (18-29 years) compared with the reference group (50-59 years). However, the risk of death caused by infection (HR, 2.10; p < 0.01) and malignancy (HR, 2.23; p < 0.01) was highest in older recipients (≥ 70 years). Similarly, the risk of death caused by renal failure was lower in younger recipients than in the reference group (HR, 0.53; p < 0.01 for 18-49 years vs 50-59 years). The use of induction IS was similar among the different recipient age groups, and differences in maintenance IS were not clinically important.


CONCLUSIONS
Causes of death in this large cohort of heart transplant recipients varied significantly with recipient age at the time of transplant, with cause-specific mortality profiles suggesting a possible effect of inadequate IS in younger recipients and over-IS in older recipients. Thus, a more personalized approach, possibly including different IS strategies according to recipient age, might result in improved post-transplant survival.
Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, University of Utah Health Center and Veterans Affairs Medical CentePlease check the following authors groups Abdallah G. Kfoury, Stavros G. Drakos, Craig H. Selzman affilation citation is missing.-->r, Intermountain Medical Center, Salt Lake City, Utah.
Omar
O
Wever-Pinzon
International Society for Heart and Lung Transplantation Registry, Dallas, Texas.
Leah B
LB
Edwards
Heart and Vascular Institute, Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio.
David O
DO
Taylor
Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, University of Utah Health Center and Veterans Affairs Medical CentePlease check the following authors groups Abdallah G. Kfoury, Stavros G. Drakos, Craig H. Selzman affilation citation is missing.-->r, Intermountain Medical Center, Salt Lake City, Utah.
Abdallah G
AG
Kfoury
Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, University of Utah Health Center and Veterans Affairs Medical CentePlease check the following authors groups Abdallah G. Kfoury, Stavros G. Drakos, Craig H. Selzman affilation citation is missing.-->r, Intermountain Medical Center, Salt Lake City, Utah.
Stavros G
SG
Drakos
Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, University of Utah Health Center and Veterans Affairs Medical CentePlease check the following authors groups Abdallah G. Kfoury, Stavros G. Drakos, Craig H. Selzman affilation citation is missing.-->r, Intermountain Medical Center, Salt Lake City, Utah.
Craig H
CH
Selzman
Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, University of Utah Health Center and Veterans Affairs Medical CentePlease check the following authors groups Abdallah G. Kfoury, Stavros G. Drakos, Craig H. Selzman affilation citation is missing.-->r, Intermountain Medical Center, Salt Lake City, Utah.
James C
JC
Fang
Unit of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Lars H
LH
Lund
Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, University of Utah Health Center and Veterans Affairs Medical CentePlease check the following authors groups Abdallah G. Kfoury, Stavros G. Drakos, Craig H. Selzman affilation citation is missing.-->r, Intermountain Medical Center, Salt Lake City, Utah. Electronic address: Josef.stehlik@hsc.utah.edu.
Josef
J
Stehlik
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000401:mortality*; D006333:Heart Failure / Q000150:complications / Q000401:mortality* / Q000601:surgery*; D016027:Heart Transplantation / Q000009:adverse effects / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology / Q000401:mortality*; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
donor age; heart transplantation; immunosuppression; individualized approach; recipient age; survival