Dual-organ transplantation in older recipients: outcomes after heart kidney transplant versus isolated heart transplant in patients aged 65 years

Transcription

1 Interactive CardioVascular and Thoracic Surgery 28 (2019) doi: /icvts/ivy202 Advance Access publication 3 July 2018 ORIGINAL ARTICLE Cite this article as: Reich H, Dimbil S, Levine R, Megna D, Mersola S, Patel J et al. Dual-organ transplantation in older recipients: outcomes after heart kidney transplant versus isolated heart transplant in patients aged >_65 years. Interact CardioVasc Thorac Surg 2019;28: Dual-organ transplantation in older recipients: outcomes after heart kidney transplant versus isolated heart transplant in patients aged 65 years a b Heidi Reich a,b, Sadia Dimbil a,ryanlevine a, Dominick Megna a,b, Savannah Mersola a,jigneshpatel a, Michelle Kittleson a,lawrenceczer a, Jon Kobashigawa a and Fardad Esmailian a,b, * Cedars-Sinai Heart Institute, Los Angeles, CA, USA Division of Cardiac Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA * Corresponding author. Cedars-Sinai Heart Institute, 127 S. San Vicente Boulevard, A-3600, Los Angeles, CA 90048, USA. Tel: ; fax: ; fardad.esmailian@cshs.org (F. Esmailian). Received 11 September 2017; received in revised form 22 May 2018; accepted 29 May 2018 Abstract OBJECTIVES: Combined heart kidney transplantation has successful outcomes. With an increasing number of patients with end-stage heart disease, there is a high incidence of significant renal insufficiency that may necessitate combined heart kidney transplant. Outcomes for heart kidney transplant recipients aged >_65 years are not well described. METHODS: Between 2010 and 2015, 163 recipients >_65 years of age were transplanted in a single centre: 12 heart kidney and 151 isolated heart transplants. Outcomes assessed were estimated glomerular filtration rate at 1, 6 and 12 months after transplant, the need for dialysis, 1-year survival, 1-year freedom from rejection, 1-year freedom from cardiac allograft vasculopathy and 1-year freedom from non-fatal major adverse cardiac events. RESULTS: Recipient ages were 67.8 ± 1.6 and 69.0 ± 2.8 years for heart kidney transplant and isolated heart transplant, and pretransplant estimated glomerular filtration rates were 26.6 ± 9.4 vs 55.2 ± 18.9, respectively. At 1 month (66.3 ± 31.4 vs 67.2 ± 28.0, P = 0.92), 6 months (68.1 ± 21.3 vs 60.5 ± 19.6, P = 0.20) and 12 months (58.6 ± 21.5 vs 52.4 ± 18.5, P = 0.27) post-transplant, estimated glomerular filtration rate was similar for heart kidney transplant versus isolated heart transplant. There was a trend towards reduced 1-year freedom from temporary dialysis after heart kidney transplant relative to isolated heart transplant (75.0% vs 90.4%, P = 0.06) without a difference in 1-year freedom from chronic dialysis (100% vs 95.2%, P = 0.46). There were no differences in 1-year survival, 1-year freedom from any treated rejection, acute cellular rejection, antibody-mediated rejection, cardiac allograft vasculopathy and non-fatal major adverse cardiac events. CONCLUSIONS: For patients >_65 years old, heart kidney transplant can achieve outcomes on par with heart transplant alone. Keywords: Dual-organ transplantation Combined heart kidney transplantation Older recipient age INTRODUCTION The first dual heart kidney transplant was reported by Norman et al. [1] in a patient with acute bacterial endocarditis who underwent aortic and mitral valve replacement followed by emergent implantation of left ventricular assist device as a bridge to dual-organ transplantation. The patient died 15 days posttransplantation due to Gram-negative sepsis. Thirty-nine years later, dual heart kidney transplantation is an accepted option for patients with concomitant cardiac and renal failure, but consensus criteria for candidacy are not yet defined. Of particular controversy is whether allocating 2 organs to 1 patient is justifiable for older recipients, who experience a survival benefit from Presented at the 31st Annual Meeting of the European Association for Cardio- Thoracic Surgery, Vienna, Austria, 7 11 October transplant but have inferior post-transplant survival after either isolated heart or kidney transplant relative to younger recipients [2]. In 2016, 3191 heart transplants, kidney transplants and 140 heart kidney transplants were performed in the USA [based on the Organ Procurement and Transplantation Network (OPTN) data as of 26 June 2017]. Dual heart kidney transplant has been shown to have successful outcomes, with post-transplant survival and freedom from rejection on par with isolated heart transplant [3]. The challenge of the potential heart kidney transplant candidate aged 65 years or older may be encountered increasingly as heart kidney transplantation are more frequently performed and as the heart transplant waiting list ages. The 2015 OPTN and Scientific Registry of Transplant Recipients (SRTR) reported that from 2005 to 2015, the number of heart kidney transplants VC The Author(s) Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

2 46 H. Reich et al. / Interactive CardioVascular and Thoracic Surgery increased from 53 to 140 [2]. Over the same time period, the number of transplant candidates aged 65 years or older increased from 11.4 to 18.9% [2] for heart and from 14.5 to 22.0% for kidney [4]. For listed patients, heart pretransplant mortality has improved to 10.6 per 100 waitlist years [2], and kidney pretransplant mortality was 5 deaths per 100 waitlist years [4]. With the increasing number of patients with end-stage heart disease, there is a high incidence of significant renal insufficiency that may necessitate dual heart kidney transplant. The outcomes for older (>_65 years) heart kidney transplant recipients relative to older isolated heart transplant recipients are not well known. Herein, post-transplantation survival, graft function and rejection are compared for older recipients after heart kidney transplantation versus heart transplantation in a single, high-volume transplant centre. METHODS This study was reviewed and approved by the Cedars-Sinai Medical Center Institutional Review Board. Patient population All heart kidney and heart transplant recipients were identified from a prospectively maintained institutional database at the Cedars-Sinai Medical Center, and the data were retrospectively analysed. All heart kidney and isolated heart transplants performed from 2010 to 2015 in recipients >_65 years of age were included. Patients with additional organs transplanted, such as heart liver kidney or heart lung kidney transplants, were excluded. For all heart kidney transplants, both organs were from the same donor. Donors were matched with recipients by blood ABO group compatibility and prospective crossmatch. Donor heart preservation techniques were standardized for both heart kidney transplantation and heart transplantation: allografts were preserved in University of Wisconsin (UW) solution on ice during transport. No additional cardioplegia was administered during the implantation, which was performed using bicaval technique. Haemofiltration was used during cardiopulmonary bypass to maintain fluid balance in patients with inadequate urine output. Staged transplant procedures, in which the patient went to the intensive care unit after heart transplantation for haemodynamic stabilization before returning to the operating room for kidney transplant within 24 h, and non-staged procedures, where the kidney was transplanted immediately following the heart transplant, were included. Donor and recipient demographic data were retrospectively analysed. Postoperative inotrope and vasopressor support strategies were the same following heart kidney transplant and heart transplant: dobutamine and epinephrine infusions were first- and second-line treatments for inotropic support, respectively, inhaled nitric oxide was used selectively for patients with elevated pulmonary pressure and/or right ventricular dysfunction and vasopressin was reserved for patients with significant, persistent vasoplegia. Immunosuppression and treatment of rejection were performed according to previously reported protocols [5, 6]. In brief, renal-sparing immunosuppression was routinely employed after heart kidney transplant and heart transplant. This approach uses rabbit antithymocyte globulin (1.5 mg/kg) for the first 5 days post-transplant with the avoidance of calcineurin inhibitors in the first few days post-transplant until the serum creatinine is <2.0 mg/dl, in addition to steroids and mycophenolate. The steroid protocol includes administration of 1 g of methylprednisolone at the time of aortic cross-clamp removal. Thereafter, 125 mg of methylprednisolone was administered every 8 h for 3 doses and followed by a prednisone taper (initially 0.5 mg/kg/ day, weaned gradually over 3 12 months). End points Post-transplant outcomes, including estimated glomerular filtration rate (egfr) at 1, 6 and 12 months, the need for temporary (<1 month duration) or chronic (>_1 month) dialysis, 1-year patient survival, 1-year freedom from any treated rejection, 1-year freedom from acute cellular rejection, 1-year freedom from antibody-mediated rejection, 1-year freedom from coronary allograft vasculopathy and 1-year freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention and/or angioplasty, implantable cardioverter-defibrillator and/or pacemaker insertion or stroke) were retrospectively compared. Statistical analysis Continuous variables are reported as mean ± standard deviation and categorical variables as a percentage and compared between groups using the unpaired Student s t-tests and Fisher s exact test, respectively. Survival and freedom from event analysis were performed using the Kaplan Meier method and compared between groups using log-rank tests. Standard 95% confidence intervals of the differences were applied based on normal distribution. A general linear model and univariate analysis was used to calculate statistical power. Two-tailed P-values <0.05 were considered significant. All statistical analyses were performed using the SPSS software, Version 22 (IBM Corp, Armonk, NY, USA). RESULTS From 2010 to 2015, 163 transplant recipients >_65 years of age were identified. This cohort was divided by the type of transplant into 2 groups: those receiving dual heart kidney transplant (n = 12) and those receiving isolated heart transplant (n = 151). Donor and recipient preoperative characteristics are summarized in Table 1. The mean recipient age and sex were 67.8 ± 1.5 years and 25% female in heart kidney and 69.0 ± 2.8 years and 18.5% female in heart transplant groups (P = 0.18 and 0.70, respectively). Average pretransplant left ventricular ejection fraction was higher for patients undergoing heart kidney transplant (32.8%) than isolated heart transplant (25.0%, P = 0.04). As expected, patients undergoing heart kidney transplant had significantly worse renal function, with pretransplant egfr 26.6 ± 9.4 ml/min, relative to heart transplant alone (55.2 ± 18.9 ml/min) and greater frequency of pretransplant need for dialysis (25.0% vs 4.6%, P = 0.02). The 8 patients undergoing heart kidney transplant who did not require pretransplant dialysis underwent intensive medical management of their renal insufficiency. The 7 isolated heart transplant recipients who received pretransplant dialysis primarily had acute kidney injury that was judged to be reversible.

3 H. Reich et al. / Interactive CardioVascular and Thoracic Surgery 47 Table 1: Donor and recipient characteristics prior to HKTx or HTx in older adults Variables HKTx in patients aged >_65 years (n = 12) HTx in patients aged >_65 years (n = 151) P-value Donor Age (years), mean ± SD 42.8 ± ± Female gender (%) BMI (kg/m 2 ), mean ± SD 27.1 ± ± Causes of death (%) Cerebrovascular accident Head trauma Anoxia Other Recipient Age (years), mean ± SD 67.8 ± ± Female gender (%) BMI (kg/m 2 ), mean ± SD 24.7 ± ± Ischaemic cardiomyopathy (%) LV ejection fraction (%), mean ± SD 32.8 ± ± UNOS Status 1A a (%) Intra-aortic balloon pump (%) Mechanical circulatory support device (%) (19/151) LV assist device 78.9 (15/19) Biventricular assist device 10.5 (2/19) Total artificial heart 10.5 (2/19) Dialysis (%) Duration of dialysis (days), mean ± SD 19.3 ± ± Inotropic support (%) Creatinine (mg/dl), mean ± SD 2.6 ± ± 0.4 <0.001 egfr (ml/min), mean ± SD 26.6 ± ± 18.9 <0.001 Coronary artery disease (%) Hypertension (%) Diabetes (%) Tobacco smoking (%) Alcohol use (%) Peripheral vascular disease (%) a Assigned for candidates on the heart transplant waiting list who have the highest priority on the basis of medical urgency. Status 1A requirements are available online at the Organ Procurement and Transplantation Network (OPTN) Policies: pdf#nameddest=policy_06. BMI: body mass index; egfr: estimated glomerular filtration rate; HKTx: heart kidney transplant; HTx: heart transplant; LV: left ventricular; SD: standard deviation; UNOS: united network for organ sharing. The aetiologies of renal failure in patients undergoing heart kidney transplant included cardiorenal syndrome (n = 4), diabetic nephropathy (n = 3), hypertensive nephrosclerosis (n = 2), renal amyloidosis (n = 2) and ischaemic nephropathy (n = 1). A higher proportion of heart kidney transplant recipients had underlying peripheral vascular disease (47.7%) than isolated heart transplant recipients (8.0%, P = 0.003). Of note, no patients in the heart kidney transplant group had preoperative mechanical circulatory support, whereas 19 (12.6%) patients in the heart transplant group required mechanical circulatory support as a bridge to transplantation. Older patients undergoing heart kidney transplant and isolated heart transplant had cold ischaemic times of ± 67.3 vs ± 60.9 min (P = 0.48), cardiopulmonary bypass times of ± 38.5 vs ± 47.5 min (P = 0.65) and cross-clamp times of 96.2 ± 32.7 vs 91.0 ± 29.9 min, respectively (P = 0.57, Table 2). Post-transplant outcomes were comparable for older patients undergoing heart kidney transplant and isolated heart transplant (1-year freedom from composite outcome 50.0% vs 68.3%, P = 0.11, Table 3). No difference was seen in 1-year patient survival (91.7% and 93.5%, P = 0.78, Fig. 1A). Early mortality and stroke were infrequent: 1 mortality occurred in the heart kidney cohort vs 2 were seen in the heart transplant cohort within 30 days, corresponding to 91.7% and 98.7% survival at 30 days, respectively (P = 0.080, Table 3). There was 1 stroke after heart kidney transplant vs 2 strokes after heart transplant (91.7% and 98.7% 30-day freedom from stroke, P = 0.059, Table 3). Rates of rejection did not differ significantly, with freedom from rejection at 1 year (any treated 81.8% vs 87.1%, acute cellular rejection 81.8% vs 92.1% and antibody mediated 100% vs 96.5%) for heart kidney and heart transplant recipients (P = ). Likewise, freedom from coronary allograft vasculopathy and NF- MACE were not significantly different for older patients undergoing heart kidney (82.5% and 84.6%) or heart (89.1% and 88.3%) transplant (P = 0.58 and 0.58). No significant differences in posttransplant egfrs were seen after heart kidney and heart transplants at 1, 6 or 12 months. However, the heart kidney transplant group had a trend towards reduced freedom from temporary dialysis (75.0%) compared to the heart transplant group (90.4%, P = 0.06, Fig. 1B). Indications for temporary dialysis after heart kidney transplant included hypervolaemia (n = 1), hypervolaemia with azotaemia (n = 1) and hyperkalaemia (n = 1) and after heart transplant included hypervolaemia (n = 5), hypervolaemia with azotaemia (n = 3), hypervolaemia with acidosis (n = 3), acidosis

4 48 H. Reich et al. / Interactive CardioVascular and Thoracic Surgery Table 2: Operative data for HKTx relative to isolated HTx in older patients Operative time (min) HKTx in patients aged >_65 years (n = 12) HTx in patients aged >_65 years (n = 151) 95% confidence interval of the difference Point estimate of the difference P-value Heart cold ischaemic time ± ± to Cardiopulmonary bypass time ± ± to Aortic cross-clamp time 96.2 ± ± to HKTx: heart kidney transplant; HTx: heart transplant. (n = 1), azotaemia (n = 2) and not specified (n = 2). This increase in the need for dialysis in the first month did not lead to differences in chronic dialysis: freedom from dialysis 1 12 months posttransplant was 100.0% with heart kidney transplant and 95.2% with heart transplant (P = 0.46, Fig. 1C). DISCUSSION This study is the first investigation, to our knowledge, of outcomes after dual heart kidney transplant for older recipients. Our results suggest that, even in older adults >_65 years of age, acceptable early post-transplant outcomes are achievable with dual heart kidney transplant with acceptable outcomes relative to isolated heart transplant. Concurrent rises in the number of heart kidney transplants performed and the number of adults >_65 years listed for heart transplant suggest that the question of whether dual heart kidney transplant in older adults is a viable option is timely and may arise increasingly in clinical practice. The positive early outcomes we report for older patients undergoing heart kidney transplant suggest that this option may be viable. Our findings suggest that outcomes of dual transplant may be, at best, equal to those for isolated heart transplant, and, as such, dual transplant could be viewed as successful in addressing the challenge of additional serious kidney disease that is more frequent in these older patients. The 2016 International Society for Heart and Lung Transplantation (ISHLT) listing criteria for heart transplantation comment on the comorbidities of age and renal dysfunction, advising that carefully selected patients >70 years of age may be considered for cardiac transplantation and it is reasonable to consider the presence of irreversible renal dysfunction (egfr <30 ml/min/1.73 m 2 ) as a relative contraindication for heart transplantation alone [7]. Consensus criteria for listing for dual heart kidney transplantation have not been established and vary by centre. In our institution, heart kidney transplant is considered for select patients who otherwise fulfilled the criteria for listing for heart transplant and are thought to have irreversible renal dysfunction with egfr <30 ml/min/1.73 m 2. Candidates for heart kidney transplant are reviewed by independent multidisciplinary heart and kidney transplant selection committees prior to listing for dual-organ transplantation. An individualized approach to estimate whether the patient will tolerate and benefit from heart kidney transplant is employed, and when both committees agree, the patient is considered a suitable candidate, listing is pursued. It is our institutional practice not to deny dual-organ transplant solely on the basis of numerical age, and we do not have an absolute cut-off for the upper age limit. In general, the older the patient, the fewer potential contraindications will be acceptable. The potential contraindications to heart kidney transplant in patients aged >65 years include body mass index (BMI) >35 kg/m 2, diabetes with end-organ damage or poor glycaemic control (haemoglobin A1c >7.5%), severe symptomatic cerebral or peripheral vascular disease (particularly if the iliac vessels are involved at the site for potential renal vascular anastomoses), frailty, insufficient social support and severe cognitivebehavioural disabilities or dementia. A review of the United Network for Organ Sharing database found that, among 5330 elderly (>60 years) heart transplant recipients, lower preoperative serum creatinine was predictive of improved 5-year survival [8]. The encouraging results reported in our study suggest that dual heart kidney transplant may mitigate the increased risk of adverse outcomes, including earlier death, after transplant in elderly patients with impaired renal function. Future studies with larger sample sizes and longer-term followup will be important to validate our findings. In our experience, a trend towards increased incidence of temporary (<1 month) dialysis was identified for older heart kidney recipients compared to heart transplant alone without a difference in incidence of chronic (>_1 month) dialysis. Patients in the heart kidney transplant group were dialyzed because of delayed renal graft function, which improved with time and was not predictive of renal graft loss or the need for chronic dialysis. The need for temporary dialysis is unsurprising in light of the incidence of delayed graft function after deceased donor kidney transplant, with over 40% of kidney transplants in the USA having an egfr <30% at the time of discharge [4]. The most frequent indications for post-transplant dialysis in our series were hypervolemia, metabolic acidosis and azotaemia. Whether the need for temporary dialysis correlates with adverse outcomes will be investigated further in our patient cohort with longer duration of follow-up. Prior studies that do not delineate between temporary and chronic dialysis suggest that the need for post-transplant dialysis is not benign in heart only transplant recipients who would not be at risk for delayed renal graft function. Adults older and younger than 65 years experienced similar improvements in functional performance and independence following heart transplant, but postoperative renal dysfunction requiring dialysis is associated with a decline in functional status that is more pronounced for recipients aged >_65 years [9]. This highlights the importance of preserved renal function after transplant, particularly for older recipients. Multiple single-institution experiences with dual heart kidney transplant have been reported previously [3, 5, 10, 11]. The first heart kidney transplant at the Cedars-Sinai Medical Center was performed in Previously, our institution reported the outcome of 10 patients who underwent heart kidney transplant from 1992 to 1999 with survival rates of 100%, 88% and 55% at

5 H. Reich et al. / Interactive CardioVascular and Thoracic Surgery 49 Figure 1: Early outcomes for older patients undergoing HKTx. All patients >_65 years of age undergoing HKTx (blue) or HTx (green) at the Cedars-Sinai Medical Center from 2010 to 2015 were included for analysis. One-year survival (A), freedom from temporary (<1 month) dialysis (B) and freedom from chronic dialysis (C) are shown. Hatch marks denote censoring, and the number at risk is shown for each time point below. HKTx: heart kidney transplant; HTx: heart transplant. 1, 2 and 5 years, respectively, and comparable to heart transplant alone [12]. Later, outcomes for 30 heart kidney transplants (mean age 57.4 ± 12.1 years) relative to 440 heart transplants (57.3 ± 11.9 years) from 1992 to 2009 were compared; survival rates were similar up to 10 years after transplant, and renal function was similar between groups, with 8.5% of heart transplant recipients requiring dialysis [5]. Similar proportions required permanent dialysis: 1 (3.3%) heart kidney transplant vs 17 (3.9%) heart transplant patients required permanent dialysis [5]. Recently, outcomes for patients undergoing heart kidney transplant from 1992 to 2009 (n = 30) were compared to a modern cohort transplanted from 2009 to 2015 (n = 53) and noted a temporal trend towards superior survival for the modern cohort at 5 years (93% vs 70%, P = 0.054) [13]. Other institutional experiences report similar results: in a series of 12 heart kidney transplants, survival of heart and renal allografts was 100% at 6 years

6 50 H. Reich et al. / Interactive CardioVascular and Thoracic Surgery Table 3: Outcomes for older recipients after HKTx and HTx Variables HKTx in patients aged >_65 years (n = 12) HTx in patients aged >_65 years (n = 151) 95% confidence interval of the difference Point estimate of the difference P-value 1-Year composite outcome a (%) to ICU stay (days), mean ± SD 5.6 ± ± to Hospital stay (days), mean ± SD 11.8 ± ± to Day survival (%) Day freedom from CAV (%) Year survival (%) to Year freedom from any-treated rejection (%) Year freedom from acute cellular rejection (%) Year freedom from antibody-mediated rejection (%) Year freedom from CAV (%) Year freedom from NF-MACE (%) Month egfr (ml/min), mean ± SD 66.3 ± ± to Month egfr (ml/min), mean ± SD 68.1 ± ± to Month egfr (ml/min), mean ± SD 58.6 ± ± to Year freedom from temporary (<1 month) dialysis (%) to Year freedom from chronic (>_1 month) dialysis (%) to a One-year composite outcome: 1-year survival, 1-year freedom from any-treated rejection, 1-year freedom from NF-MACE, 1-year freedom from temporary dialysis or 1-year freedom from chronic dialysis. CAV: coronary allograft vasculopathy; egfr: estimated glomerular filtration rate; HKTx: heart kidney transplant; HTx: heart transplant; ICU: intensive care unit; NF-MACE: non-fatal major adverse cardiac events; SD: standard deviation. with a mean egfr of 61 ± 25 [10]. Elsewhere, similar renal graft outcomes were described for heart kidney (n = 13) relative to isolated kidney (n = 13) transplants, with 92% and 93% 3-year renal allograft survival, respectively [11]. Previous reports suggested a correlation between poor outcomes after dual heart kidney transplant and older recipient age. In a review of the UNOS/OPTN database, 264 heart kidney transplants in patients with the mean age of 50.6 ± 11.8 years were identified from 1995 to 2005 [14]. On multivariable analysis, recipients older than 65 years, peripheral vascular disease, non-ischaemic aetiology of heart failure, dialysis dependence at the time of transplantation and ventricular assist device as a bridge to transplantation were risk factors for reduced survival [14]. They recommended that only patients with heart failure, egfr <33 ml/min and low-risk score seem to achieve a survival benefit from heart kidney transplant over heart transplant alone. A subsequent review of the UNOS/OPTN database identified 593 heart kidney transplants from 2000 to 2010 in patients with a mean age of 51.1 ± 13.4 years [15]. In this study, heart transplant recipients with a pretransplant egfr <37 ml/min had inferior survival compared to heart kidney transplant recipients, suggesting a survival benefit for this cohort of dual transplant. Risk factors for increased mortality among HTx recipients included older age, lower egfr, higher recent panel reactive antibody score, African American race, diabetes, longer ischaemic time and certain diagnoses by multivariable modelling. In the multivariable analysis, heart kidney transplant was an independent predictor of survival without comment on any interaction between recipient age and heart kidney transplant. kidney transplants were performed in patients >_65 years of age, which increases the potential for a Type II error. Statistical power estimates show that the risk of Type II error in this study was substantial (Supplementary Material, Table S1), and future larger studies are needed to confirm that our findings are necessary. A sample size of approximately 175 heart kidney transplants would be needed to obtain a statistical power at the recommended 0.80 level. Additionally, both comparison groups were a well-selected, average-risk group of transplant recipients with a relatively good EF, low frequency of left ventricular assist devices (LVADs) as a bridge to transplantation and low BMI, which may limit the generalizability of our findings. Finally, long-term follow-up data will be required for survival analyses at 5 and 10 years. CONCLUSIONS Selected older patients >_65 years of age undergoing dual heart kidney transplant appear to have acceptable outcomes relative to older patients undergoing isolated heart transplant, with similar rates of survival and freedom from major morbidity, including the need for chronic dialysis. These encouraging findings suggest that dual-organ transplant may be a viable option for carefully selected patients >_65 years of age. SUPPLEMENTARY MATERIAL Supplementary material is available at ICVTS online. Limitations The results of this study should be interpreted with appropriate caution as they are subject to the limitations of any small, retrospective study, including the potential for selection bias and other confounding variables. Of note, in our institution, only 12 heart ACKNOWLEDGEMENTS The authors acknowledge the Cedars-Sinai Heart Institute for continued support. Conflict of interest: none declared.

7 H. Reich et al. / Interactive CardioVascular and Thoracic Surgery 51 REFERENCES [1] Norman JC, Brook MI, Cooley DA, Klima T, Kahan BD, Frazier OH et al. Total support of the circulation of a patient with post-cardiotomy stoneheart syndrome by a partial artificial heart (ALVAD) for 5 days followed by heart and kidney transplantation. Lancet 1978;311:1: [2] Colvin M, Smith JM, Skeans MA, Edwards LB, Uccellini K, Snyder JJ et al. OPTN/SRTR 2015 annual data report: heart. Am J Transplant 2017;17: [3] Ruzza A, Czer LS, Trento A, Esmailian F. Combined heart and kidney transplantation: what is the appropriate surgical sequence? Interact CardioVasc Thorac Surg 2013;17: [4] Hart A, Smith JM, Skeans MA, Gustafson SK, Stewart DE, Cherikh WS et al. OPTN/SRTR 2015 annual data report: kidney. Am J Transplant 2017;17: [5] Czer LS, Ruzza A, Vespignani R, Jordan S, De Robertis MA, Mirocha J et al. Survival and allograft rejection rates after combined heart and kidney transplantation in comparison with heart transplantation alone. Transplant Proc 2011;43: [6] Daneshvar D, Czer LS, Phan A, Schwarz ER, De Robertis M, Mirocha J et al. Heart transplantation in patients aged 70 years and older: a twodecade experience. Transplant Proc 2011;43: [7] Mehra MR, Canter CE, Hannan MM, Semigran MJ, Uber PA, Baran DA et al. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: a 10-year update. J Heart Lung Transplant 2016;35:1 23. [8] Kilic A, Weiss ES, Yuh DD, Shah AS, Conte JV. Factors associated with 5-year survival in older heart transplant recipients. J Thorac Cardiovasc Surg 2012;143: [9] Kilic A, Conte JV, Baumgartner WA, Russell SD, Merlo CA, Shah AS. Does recipient age impact functional outcomes of orthotopic heart transplantation? Ann Thorac Surg 2014;97: [10] Raichlin E, Kushwaha SS, Daly RC, Kremers WK, Frantz RP, Clavell AL et al. Combined heart and kidney transplantation provides an excellent survival and decreases risk of cardiac cellular rejection and coronary allograft vasculopathy. Transplant Proc 2011;43: [11] Kebschull L, Schleicher C, Palmes D, Sindermann J, Suwelack B, Senninger N et al. Renal graft outcome in combined heart-kidney transplantation compared to kidney transplantation alone: a single-centre, matched-control study. Thorac Cardiovasc Surg 2012;60: [12] Blanche C, Kamlot A, Blanche DA, Kearney B, Wong AV, Czer LS et al. Combined heart-kidney transplantation with single-donor allografts. J Thorac Cardiovasc Surg 2001;122: [13] Awad M, Czer LS, Esmailian F, Jordan S, De Robertis MA, Mirocha J et al. Combined heart and kidney transplantation: a 23-year experience. Transplant Proc 2017;49: [14] Russo MJ, Rana A, Chen JM, Hong KN, Gelijns A, Moskowitz A et al. Pretransplantation patient characteristics and survival following combined heart and kidney transplantation: an analysis of the United Network for Organ Sharing Database. Arch Surg 2009;144: [15] Karamlou T, Welke KF, McMullan DM, Cohen GA, Gelow J, Tibayan FA et al. Combined heart-kidney transplant improves post-transplant survival compared with isolated heart transplant in recipients with reduced glomerular filtration rate: analysis of 593 combined heart-kidney transplants from the United Network Organ Sharing Database. J Thorac Cardiovasc Surg 2014;147: e1.