Long-term outcomes in heart transplantation using donors with a history of past and present cocaine use

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1 European Journal of Cardio-Thoracic Surgery 47 (2015) e146 e150 doi: /ejcts/ezu512 Advance Access publication 9 January 2015 ORIGINAL ARTICLE Cite this article as: Jayarajan S, Taghavi S, Komaroff E, Shiose A, Schwartz D, Hamad E et al. Long-term outcomes in heart transplantation using donors with a history of past and present cocaine use. Eur J Cardiothorac Surg 2015;47:e146 e50. a Long-term outcomes in heart transplantation using donors with a history of past and present cocaine use Senthil Jayarajan a, Sharven Taghavi a, Eugene Komaroff b, Akira Shiose c, Daniel Schwartz d, Eman Hamad d, Rene Alvarez d, Grayson Wheatley c, Thomas Sloane Guy c and Yoshiya Toyoda c, * Department of Surgery, Temple University School of Medicine, Philadelphia, PA, USA b Department of Public Health, Temple University, Philadelphia, PA, USA c Section of Cardiothoracic Surgery, Temple University School of Medicine, Philadelphia, PA, USA d Section of Cardiology, Temple University School of Medicine, Philadelphia, PA, USA * Corresponding author. Temple University Hospital, 3401 N Broad Street, Parkinson Pavilion Third Floor, Philadelphia, PA 19140, USA. Tel: ; fax: ; yoshiya.toyoda@tuhs.temple.edu (Y. Toyoda). Received 25 July 2014; received in revised form 8 October 2014; accepted 23 October 2014 Abstract OBJECTIVES: Organ donors with a history of cocaine use are thought to be less favourable for orthotopic heart transplantation (OHT). This study examined long-term survival in OHT using donors with a history of cocaine use. METHODS: The United Network for Organ Sharing (UNOS) database was examined for primary, adult heart transplants from 2000 to Cox proportional hazards analysis using covariates associated with mortality was used to examine survival. RESULTS: There were total OHTs with 2274 (11.6%) using donors with a history of dependent cocaine use (DCU). Of these, 1008 (44.3%) donors were current cocaine users. Recipients of DCU were more likely to be male (79.0 vs 75.7%, P < 0.001), more likely diabetic (16.5 vs 14.8%, P = 0.003) and were less likely to be sex mismatched (23.0 vs 28.6%, P < 0.001). DCU donors were older (32.5 vs 31.4 years, P < 0.001), more likely male (79.7 vs 69.8%, P < 0.001) and had higher ischaemic times (3.27 vs 3.20 h, P = 0.001). On multivariate analysis, DCU was not associated with mortality [hazard ratio (HR): 0.95, 95% CI: , P = 0.22]. Variables associated with mortality included recipient body mass index, sex mismatch, race mismatch, black race, ischaemic time, recipient creatinine, donor age, donor smoking history and mechanical ventilation or extracorporeal membrane oxygen as a bridge to transplantation. On subset analysis, CCU was not associated with mortality (HR: 0.97, 95% CI: , P = 0.42). On Kaplan Meier analysis, median survival was not different when comparing current ( days), past (3,889.0 days) and non-cocaine using donors ( days); P = CONCLUSIONS: Use of carefully selected donors with a history of past and current cocaine use does not result in worse outcomes. Keywords: Heart failure Heart transplantation Congestive heart failure INTRODUCTION Cardiac transplantation remains the gold standard treatment for patients in end-stage heart failure [1, 2]. However, a shortage of donor organs has led to the use of donor hearts once thought to be unsuitable for transplantation [3 8]. Donors with a history of substance abuse are considered to be higher risk for cardiac transplantation [9], and there has been a reluctance to use donors with a history of cocaine use due to the drug s negative effects on the heart. Cocaine abuse can cause coronary vasospasm, leading to myocardial infarction. Repeated long-term use can lead to dilated cardiomyopathy [10 14]. However, because of the critical shortage of organ donors, the number of transplants using donors with Presented at the International Society of Heart and Lung Transplantation Annual Meeting in San Diego, CA, USA, April a history of cocaine use has been on the rise. Previous studies have shown that donors with a history of cocaine use can be used with good short-term survival [15 17]. The goal of this study was to examine long-term survival and the development of acute rejection episodes in cardiac transplantation when using donors with past and present cocaine use. MATERIALS AND METHODS Patient population The Organ Procurement and Transplantation Network Standard Transplantation Analysis and Research data files were acquired and retrospectively reviewed. Inclusion criteria included all adults receiving heart transplantation between January 2000 and December The Author Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

2 S. Jayarajan et al. / European Journal of Cardio-Thoracic Surgery e Exclusion criteria from multivariate analysis included retransplantation and those with missing data. The dataset provides a field encoding for donors with any history of cocaine use. Recipients of donors with a history of cocaine use were compared with those without a history of cocaine use. In addition, the United Network for Organ Sharing (UNOS) database provides another field for donors with a history of current cocaine use (defined as use in the past 6 months prior to transplantation). Subset analysis was carried out in this group of patients that received a donor with a current history of cocaine use. Statistical analysis All continuous variables were reported as mean ± standard deviation and were analysed using t-test or ANOVA as appropriate. All categorical variables were reported as number ( percent) and were analysed using chi-square test. Univariate survival was determined using Kaplan Meier procedure and compared using log-rank test. Cox proportional hazards multivariate regression was used to determine the factors associated with mortality. The covariates were those that were found to have a of at most 0.1 on univariate Cox regression. All covariates missing greater than 15% of data in the registry were excluded from the analysis. Actuarial survival techniques were used to determine time to rejection. All analyses were completed using SAS 9.3 (Cary, NC, USA). RESULTS There were total heart transplants performed during the study period. Of these, 2274 (11.6%) were carried out using donors with a history of cocaine use. Recipient characteristics A comparison of baseline recipient characteristics is given in Table 1. The two recipient groups were similar with respect to age, ethnicity, body mass index (BMI), cardiac output, pulmonary vascular resistance, race mismatch, total HLA mismatches, serum creatinine, and the use of mechanical ventilation, inhaled nitric oxide or extracorporeal membrane oxygenation (ECMO) as a bridge to transplantation. Recipients that received a donor with a history of cocaine use were more likely to be male (79.0 vs 75.7%, P < 0.001), had longer ischaemic time (3.27 vs 3.20 h, P = 0.001) and less likely to be sex-mismatched (23.0 vs 28.6%, P < 0.001). Donor characteristics A comparison of donor characteristics is given in Table 2. Donors with a history of cocaine use were older (32.5 vs 31.4, P < 0.001), more likely to be male (79.7 vs 69.8%, P < 0.001), had lower BMI (26.1 vs 26.5, P < 0.001), were more likely to have a history of heavy cigarette use (41.4 vs 21.8%, P < 0.001) and more likely to show clinical signs of infection (40.5 vs 37.0, P = 0.001). The two donor groups were similar with respect to history of diabetes, history of myocardial infarction, ABO compatibility and history of cancer. Postoperative outcomes A comparison of postoperative outcomes is given in Table 3. Number of acute rejection episodes on index hospitalization was less in recipients of cocaine-using donors (15.5 vs 12.8%, P = 0.004). Acute rejection episodes at 1 year, rate of retransplantation and length of stay were not significantly different. Survival As seen in Fig. 1, median survival was not significantly different on Kaplan Meier analysis (3843 vs 4165 days, P = 0.87). Cox proportional hazards analysis performed at 10 years is given in Table 4. Use of donors with a history of cocaine use was not significantly associated with mortality [hazard ratio (HR): 0.95, 95% CI: , P = 0.22]. Variables associated with mortality included increasing donor age (HR: 1.01, 95% CI: , P < 0.001), donor heavy cigarette use (HR: 0.95, 95% CI: , P = 0.001), worsening recipient creatinine (HR: 1.09, 95% CI: , P < 0.001), increasing recipient BMI (HR: 1.01, 95% CI: , P = 0.04), recipient Black race (HR: 1.35, 95% CI: , P < 0.001), sex mismatch (HR: 1.04, 95% CI: , P = 0.02), race mismatch (HR: 1.07, 95% CI: , P = 0.04) and the use of ECMO (HR: 2.21, 95% CI: , P < 0.001) or mechanical ventilation (HR: 2.05, 95% CI: , P < 0.001) as a bridge to transplantation. There were no significant interactions between donors with a history of cocaine use and donor age (P = 0.62), donor gender (P =0.57),recipient age (P = 0.73), recipient gender (P = 0.97) or ischaemic time (P =0.74). On subset analysis (Fig. 2), median survival in donors with current cocaine use ( days) was not significantly different from that of donors with past cocaine use ( days) or no history of cocaine use ( days); P = In addition, on multivariate analysis, donors with a history of active cocaine use were not associated with mortality (HR: 0.97, 95% CI: , P = 0.42). DISCUSSION The toxic effects of cocaine on the heart are well established. In addition, cocaine can have negative effects on other organs, leading to renal and hepatic failure [12, 13, 15 17]. However, the critical shortage of organ donors [2] obligates us to examine donors that were once thought to be unacceptable for transplantation [14]. In this study, we used the UNOS database to examine the use of donors with a history of cocaine use in cardiac transplantation. Prior studies have shown that cardiac transplantation can be carried out using donors with a history of cocaine use with good short-term survival [15, 16]. Similar to the present study, Breike et al. used the UNOS database to examine heart transplant donors with a history of cocaine use. This study examined both current and past users of cocaine and found that survival was not affected by using such donors [15]. This analysis was carried out to 5 years post-transplantation, however, with median survival in heart transplant recipients currently exceeding 10 years [2, 18] and with numerous changes in immunosuppression medications; an analysis examining long-term survival is warranted. Prior research has shown that variables associated with survival at 10 years differ from those that are associated with survival in the short term [19]. TX & MCS

3 e148 S. Jayarajan et al. / European Journal of Cardio-Thoracic Surgery Table 1: Baseline recipient characteristics Age (years) ± ± Male gender (75.7) (79.0) <0.001 Recipient race 0.71 White (72.8) (72.9) Black (16.5) (16.9) Hispanic (7.1) (7.3) Asian (2.5) (2.0) American Indian/Alaskan (0.3) (0.3) Hawaiian/PI (0.3) (0.2) Multiracial (0.5) (0.5) Recipient BMI ± ± Recipient diabetes (14.8) (16.5) 0.03 Mean ischaemic time (h) ± ± Cardiac output (l/min) ± ± Mean PVR (Woods units) ± ± Sex mismatch (28.6) (23.0) <0.001 Race mismatch (43.0) (41.2) 0.08 Number of HLA mismatches ± ± Creatinine prior to transplant (mg/dl) ± ± Mechanical ventilation prior to transplant (2.9) (2.7) 0.66 Inhaled nitric oxide prior to transplant (0.3) (0.1) 0.12 ECMO prior to transplant (0.5) (0.6) 0.57 BMI: body mass index; ECMO: extracorporeal membrane oxygenation. Table 2: Donor characteristics Donor age (years) ± ± 10.1 <0.001 Donor male (69.8) (79.7) <0.001 Donor BMI ± ± 4.9 <0.001 Diabetic donor (2.4) (2.7) 0.41 ABO compatible donor (14.9) (15.1) 0.81 Donor history of myocardial infarction (1.0) (1.1) 0.72 Donor heavy cigarette use (21.8) (41.4) <0.001 Donor history of cancer (1.8) (1.3) 0.08 Donor history of infection (37.0) (40.5) BMI: body mass index. Table 3: Postoperative outcomes Acute rejection episode prior to discharge (15.5) (12.8) Acute rejection episodes at 1 year (9.1) (8.6) 0.95 Retransplant (1.3) (1.7) 0.14 Length of stay (days) ± ± We found that even at 10 years post-transplantation, use of donors with a history of cocaine use was not independently associated with mortality. Subset analysis demonstrated that this holds true even when the donor has active cocaine use. Finally, we found no significant interaction between donors with a history of cocaine use and ischaemic time, donor age and recipient age. This

4 S. Jayarajan et al. / European Journal of Cardio-Thoracic Surgery e149 Figure 1: A comparison of median survival by Kaplan Meier analysis. Figure 2: A comparison of median survival by Kaplan Meier analysis using donors with current and past cocaine use. Table 4: Multiple variable model examining risk of mortality at 10 years Hazard ratio 95% Confidence interval Donor history cocaine use Donor age (per year) <0.001 Donor male gender Donor diabetes Donor heavy cigarette use Ischaemic time <0.001 (per hour) Recipient creatinine <0.001 (per mg/dl) Recipient male gender Recipient age (per year) Recipient history of diabetes Recipient BMI White race Ref. Ref. Ref. Asian race Black race <0.001 Hispanic race HLA mismatch > Sex mismatch Race mismatch ECMO as bridge to <0.001 transplant Mechanical ventilator at transplant <0.001 BMI: body mass index; ECMO: extracorporeal membrane oxygenation. suggests that donors with a history of cocaine use can be safely used even with older recipients and older donors, or when there is prolonged ischaemic time. Numerous donor and recipient variables were found to be associated with mortality including increasing donor age, donor s heavy cigarette use, worsening recipient creatinine, increasing recipient BMI, recipient Black race, sex mismatch, race mismatch and the use of ECMO or mechanical ventilation as a bridge to transplantation. These findings are consistent with previous studies [7, 8, 19 23]. While Breike et al. showed no difference in the development of coronary artery disease when using donors with a history of cocaine use [15], there are little data on the development of acute rejection episodes when using these donors. The present study found that acute rejection episodes on index hospitalization were actually lower in cohort that received donors with a history of cocaine use; however, there was no difference in the number of patients with acute rejection episodes at 1-year post-transplantation. The UNOS database does not provide information on institution surveillance protocols for rejection, nor does it provide discrete criteria for what constitutes a rejection episode or if they were biopsy confirmed. Further studies are needed to determine how donors with a history of cocaine use affect the development of acute rejection episodes in the long term. We found no difference in length of stay between the two cohorts, and this has been corroborated in prior studies [16]. Previous studies have shown no difference in intensive care length of stay [24]; however, these data are not available in the UNOS registry. Number of patients requiring eventual retransplantation was also similar when comparing the two groups. Further studies are needed to determine how using donors with a history of cocaine use may affect the incidence of graft failure leading to eventual retransplantation. This study was not without limitations, including those inherent to retrospective reviews. Not all confounding variables are available in the UNOS database, such as detailed immunosuppression data and socioeconomic status. In addition, detailed information on donor history of cocaine use is not available. Therefore, we were unable to determine how frequently donors used cocaine or the method in which it was used (inhalational, intravenous, smoked) and how this affected outcomes in the recipient. Similarly, information on the consumption of other recreational drugs or other high-risk behaviour was not available, and could not be analysed in the study. In conclusion, use of donors with a history of cocaine use does not appear to affect long-term survival in cardiac transplantation. This holds true even when using donors with active cocaine use. Number of acute rejection episodes at 1 year is also similar; however, further studies are needed to determine how this is affected long term. Donors with a history of cocaine use should be considered as potential donors for cardiac transplantation. TX & MCS

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