Use of durable mechanical circulatory support on outcomes of heart–kidney transplantation

Use of durable mechanical circulatory support on outcomes of heart–kidney transplantation Abstract OBJECTIVES Previous studies have demonstrated that preheart transplant mechanical circulatory support (MCS) can lead to a small but significant increase in mortality. However, data on outcomes of patients with MCS who require simultaneous heart–kidney transplant are limited. METHODS A retrospective review of simultaneous heart–kidney transplantations (HKTxs) performed at a single institution over a 5-year period was performed. Patients were divided based on the preoperative use of durable MCS. Renal graft-related end points were evaluated, including glomerular filtration rate following transplantation, prevalence of delayed renal graft function and freedom from antibody and cellular-mediated graft rejection. Patient-specific outcomes, including survival and frequency of non-fatal major adverse cardiac events at 1 year, were additionally assessed. RESULTS During the study period, 50 HKTxs were performed, 14 of which had preoperative MCS. HKTx patients with and without MCS implantations had a similar prevalence of delayed graft function (57.1% vs 50.0%; P = 0.757). A numerical trend was observed towards a reduced glomerular filtration rate 1-month post-transplant in patients without an MCS device (81.2 ± 32.8 vs 64.4 ± 27.5; P = 0.072), but no significant difference was observed at 6 and 12 months. No significant difference was observed on the need for post-transplant renal replacement therapy, non-fatal major adverse cardiac events, freedom from graft rejection and overall survival at 1 year. CONCLUSIONS The use of preoperative MCS in patients undergoing combined HKTx was not found to affect renal graft function post-transplantation and does not seem to be associated with increase in morbidity or mortality. Heart transplantation, Kidney transplantation, Mechanical circulatory support INTRODUCTION It has been well established that the presence of chronic renal disease prior to heart transplantation is associated with increased morbidity and mortality and was previously considered a contraindication to heart transplant candidacy [1, 2]. The presence of renal insufficiency with heart failure is not an uncommon association; more than 30% of heart transplant recipients have an estimated glomerular filtration rate (GFR) of less than 45 ml/min [3]. With advancements in surgical technique, perioperative management and immunosuppression, it has since been shown that simultaneous heart–kidney transplantation (HKTx) can be performed successfully in patients with end-stage failures of both organs with survival equivalent to isolated heart transplant recipients [4–6]. This technique was first described by Norman et al. [7] in 1978, and the number of HKTxs has steadily grown. Since 2000, the annual frequency of these simultaneous transplants performed in the USA has increased over 2-fold [2, 8]. Concurrently, mechanical circulatory support (MCS) has demonstrated to play a critical role as a bridge to transplantation option in patients with end-stage heart failure [9–11]. The rapid evolution of heart failure management using MCS is additionally reflected by remarkable and frequent innovations in device technologies [12–14]. With newer continuous-flow MCS devices becoming ever more prevalent, and with current increase in the number of HKTxs being performed, the determination of the potential impact of pretransplant MCS implantation on outcomes is essential. Unfortunately, the literature evaluating outcomes in MCS patients receiving HKTx remains limited. In this study, we sought to evaluate outcomes of HKTx recipients using preoperative MCS in the contemporary era performed at a single, high-volume transplant institution. MATERIALS AND METHODS All simultaneous adult orthotopic heart–kidney transplants performed at a single tertiary care institution from 2010 to 2015 were retrospectively evaluated. Patients were divided based on the preoperative use of durable MCS. Durable MCS was defined as the use of a left ventricular assist device, a biventricular assist device or a total artificial heart. Indications for MCS implantation followed standard criteria and included patients with severe and progressively decompensating heart failure without contraindications (e.g. active infection, ongoing bleeding and high risk for non-compliance) to therapy. The institutional electronic medical record was used to query variables. Preoperative demographics, such as medical history, was assessed. The primary outcome assessed included renal function, which was described in terms of GFR up to 12 months (1, 6 and 12 months post-transplantation), the prevalence of delayed graft function (the need for dialysis within 7 days post-transplantation) and the need for chronic (≥1 month) renal replacement therapy. Additionally, 1-year survival and 1-year graft outcomes were evaluated. Graft outcomes were evaluated based on incidence of any treated rejection, acute cellular rejection and antibody-mediated rejection. Secondary patient outcomes were additionally assessed based on freedom from cardiac allograft vasculopathy and freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention or angioplasty, implantable cardioverter-defibrillator or pacemaker implant and stroke) at 1 year. Institutional review board approval was attained, and informed consent was obtained. Continuous variables are expressed as a median with interquartile range (IQR) or mean and standard deviation, whereas categorical variables are expressed as a percentage. Continuous variables were compared using the Student’s t-test, and categorical variables were analysed using the Fisher’s exact test. The Kaplan–Meier curve analysis was used to display patient survival and freedom from chronic renal replacement therapy. Statistical analysis was performed using the SAS Software, Version 9.2 (Statistical Analysis System Institute, Cary, NC, USA). RESULTS During the 5-year study period, 50 simultaneous HKTxs were performed, with 14 (28%) receiving a pretransplant MCS. Demographics between HKTx + MCS and HKTx-only patients, as listed in Table 1, were similar with regard to age, body mass indices and gender. Evaluation of medical comorbidities such as diabetes, hyperlipidaemia and peripheral vascular disease were not statistically different between cohorts. Table 1: Patient demographics   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Recipient age (years)  54.4 ± 6.8  58.2 ± 11.0  0.235  Body mass index (kg/m2)  25.3 ± 6.0  24.7 ± 5.0  0.720  Female  14.3  25.0  0.705   Prior pregnancy  100.0  75.0  1.000  Race   Caucasian  71.4  55.6  0.353   African American  14.3  16.7  1.000   Hispanic  14.3  13.9  1.000   Other  0.0  13.9  0.304  Medical history   Coronary artery disease  50.0  69.4  0.325   Diabetes mellitus  42.9  36.1  1.000   Hypertension  66.7  58.3  1.000   Hyperlipidaemia  28.6  30.5  1.000   Hypothyroidism  28.6  11.1  0.197   Peripheral vascular disease  14.3  16.7  1.000   Stroke  7.1  5.6  1.000   COPD  50.0  27.8  0.187    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Recipient age (years)  54.4 ± 6.8  58.2 ± 11.0  0.235  Body mass index (kg/m2)  25.3 ± 6.0  24.7 ± 5.0  0.720  Female  14.3  25.0  0.705   Prior pregnancy  100.0  75.0  1.000  Race   Caucasian  71.4  55.6  0.353   African American  14.3  16.7  1.000   Hispanic  14.3  13.9  1.000   Other  0.0  13.9  0.304  Medical history   Coronary artery disease  50.0  69.4  0.325   Diabetes mellitus  42.9  36.1  1.000   Hypertension  66.7  58.3  1.000   Hyperlipidaemia  28.6  30.5  1.000   Hypothyroidism  28.6  11.1  0.197   Peripheral vascular disease  14.3  16.7  1.000   Stroke  7.1  5.6  1.000   COPD  50.0  27.8  0.187  Values are presented as a mean ± standard deviation or percentage. COPD: chronic obstructive pulmonary disease; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Table 1: Patient demographics   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Recipient age (years)  54.4 ± 6.8  58.2 ± 11.0  0.235  Body mass index (kg/m2)  25.3 ± 6.0  24.7 ± 5.0  0.720  Female  14.3  25.0  0.705   Prior pregnancy  100.0  75.0  1.000  Race   Caucasian  71.4  55.6  0.353   African American  14.3  16.7  1.000   Hispanic  14.3  13.9  1.000   Other  0.0  13.9  0.304  Medical history   Coronary artery disease  50.0  69.4  0.325   Diabetes mellitus  42.9  36.1  1.000   Hypertension  66.7  58.3  1.000   Hyperlipidaemia  28.6  30.5  1.000   Hypothyroidism  28.6  11.1  0.197   Peripheral vascular disease  14.3  16.7  1.000   Stroke  7.1  5.6  1.000   COPD  50.0  27.8  0.187    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Recipient age (years)  54.4 ± 6.8  58.2 ± 11.0  0.235  Body mass index (kg/m2)  25.3 ± 6.0  24.7 ± 5.0  0.720  Female  14.3  25.0  0.705   Prior pregnancy  100.0  75.0  1.000  Race   Caucasian  71.4  55.6  0.353   African American  14.3  16.7  1.000   Hispanic  14.3  13.9  1.000   Other  0.0  13.9  0.304  Medical history   Coronary artery disease  50.0  69.4  0.325   Diabetes mellitus  42.9  36.1  1.000   Hypertension  66.7  58.3  1.000   Hyperlipidaemia  28.6  30.5  1.000   Hypothyroidism  28.6  11.1  0.197   Peripheral vascular disease  14.3  16.7  1.000   Stroke  7.1  5.6  1.000   COPD  50.0  27.8  0.187  Values are presented as a mean ± standard deviation or percentage. COPD: chronic obstructive pulmonary disease; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Transplant-related factors (Table 2) revealed that a significantly greater proportion of HKTx + MCS were United Network for Organ Sharing (UNOS) status 1 when compared with HKTx-alone patients (100.0% vs 66.7%; P = 0.012). Furthermore, all HKTx + MCS patients were reoperative cardiac surgery patients compared with 55.6% of patients in the HKTx group (P = 0.002). The frequency of ≥2 sternotomies was also significantly increased in HKTx + MCS patients. As noted in the detailed profile of mechanical device support, the majority were in place for >90 days (92.9%): 64.3% comprised total artificial heart devices, 21.4% biventricular assist device and 14.3% left ventricular assist device. Table 3 displays a preoperative medication use. Treatment prevalence with various antihypertensives, aspirin or clopidogrel was not significantly different between cohorts. Table 2: Pretransplant factors   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  UNOS status 1 at transplant  100.0  66.7  0.012  Cytomegalovirus mismatch  21.4  33.3  0.507  Prior blood transfusion  92.9  62.5  0.072  Pretransplant PRA ≥10%  28.6  27.8  1.000  MCS support length   Short-term support (≤90 days)  7.1       Long-term support (>90 days)  92.9      MCS device type         LVAD  14.3       BiVAD  21.4       TAH  64.3      Prior interventions   Previous cardiac surgery  100.0  55.6  0.002   ≥2 sternotomies  64.3  11.1  <0.001   Prior CABG  14.3  12.4  1.000   Prior PCI  42.9  50.0  0.757    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  UNOS status 1 at transplant  100.0  66.7  0.012  Cytomegalovirus mismatch  21.4  33.3  0.507  Prior blood transfusion  92.9  62.5  0.072  Pretransplant PRA ≥10%  28.6  27.8  1.000  MCS support length   Short-term support (≤90 days)  7.1       Long-term support (>90 days)  92.9      MCS device type         LVAD  14.3       BiVAD  21.4       TAH  64.3      Prior interventions   Previous cardiac surgery  100.0  55.6  0.002   ≥2 sternotomies  64.3  11.1  <0.001   Prior CABG  14.3  12.4  1.000   Prior PCI  42.9  50.0  0.757  Values are presented as a percentage. BiVAD: biventricular assist device; CABG: coronary artery bypass grafting; HKTx: heart–kidney transplantation; LVAD: left ventricular assist device; MCS: mechanical circulatory support; PCI: percutaneous coronary intervention; PRA: panel reactive antibody; TAH: total artificial heart; UNOS: United network for organ sharing. Table 2: Pretransplant factors   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  UNOS status 1 at transplant  100.0  66.7  0.012  Cytomegalovirus mismatch  21.4  33.3  0.507  Prior blood transfusion  92.9  62.5  0.072  Pretransplant PRA ≥10%  28.6  27.8  1.000  MCS support length   Short-term support (≤90 days)  7.1       Long-term support (>90 days)  92.9      MCS device type         LVAD  14.3       BiVAD  21.4       TAH  64.3      Prior interventions   Previous cardiac surgery  100.0  55.6  0.002   ≥2 sternotomies  64.3  11.1  <0.001   Prior CABG  14.3  12.4  1.000   Prior PCI  42.9  50.0  0.757    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  UNOS status 1 at transplant  100.0  66.7  0.012  Cytomegalovirus mismatch  21.4  33.3  0.507  Prior blood transfusion  92.9  62.5  0.072  Pretransplant PRA ≥10%  28.6  27.8  1.000  MCS support length   Short-term support (≤90 days)  7.1       Long-term support (>90 days)  92.9      MCS device type         LVAD  14.3       BiVAD  21.4       TAH  64.3      Prior interventions   Previous cardiac surgery  100.0  55.6  0.002   ≥2 sternotomies  64.3  11.1  <0.001   Prior CABG  14.3  12.4  1.000   Prior PCI  42.9  50.0  0.757  Values are presented as a percentage. BiVAD: biventricular assist device; CABG: coronary artery bypass grafting; HKTx: heart–kidney transplantation; LVAD: left ventricular assist device; MCS: mechanical circulatory support; PCI: percutaneous coronary intervention; PRA: panel reactive antibody; TAH: total artificial heart; UNOS: United network for organ sharing. Table 3: Preoperative medication profile   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  β-blockers  53.8  66.7  0.508  Nitrates  57.1  61.1  1.000  ACE inhibitors  44.4  38.9  1.000  Angiotensin II receptor blockers  15.4  30.6  0.293  Calcium channel blockers  35.7  13.9  0.118  Phosphodiesterase inhibitors  21.4  11.1  0.384  Midodrine  57.1  37.1  0.222  Aspirin  92.9  100.0  0.280  Clopidogrel  38.5  29.4  0.728    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  β-blockers  53.8  66.7  0.508  Nitrates  57.1  61.1  1.000  ACE inhibitors  44.4  38.9  1.000  Angiotensin II receptor blockers  15.4  30.6  0.293  Calcium channel blockers  35.7  13.9  0.118  Phosphodiesterase inhibitors  21.4  11.1  0.384  Midodrine  57.1  37.1  0.222  Aspirin  92.9  100.0  0.280  Clopidogrel  38.5  29.4  0.728  Values are presented as a percentage. ACE: angiotensin converting enzyme; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Table 3: Preoperative medication profile   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  β-blockers  53.8  66.7  0.508  Nitrates  57.1  61.1  1.000  ACE inhibitors  44.4  38.9  1.000  Angiotensin II receptor blockers  15.4  30.6  0.293  Calcium channel blockers  35.7  13.9  0.118  Phosphodiesterase inhibitors  21.4  11.1  0.384  Midodrine  57.1  37.1  0.222  Aspirin  92.9  100.0  0.280  Clopidogrel  38.5  29.4  0.728    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  β-blockers  53.8  66.7  0.508  Nitrates  57.1  61.1  1.000  ACE inhibitors  44.4  38.9  1.000  Angiotensin II receptor blockers  15.4  30.6  0.293  Calcium channel blockers  35.7  13.9  0.118  Phosphodiesterase inhibitors  21.4  11.1  0.384  Midodrine  57.1  37.1  0.222  Aspirin  92.9  100.0  0.280  Clopidogrel  38.5  29.4  0.728  Values are presented as a percentage. ACE: angiotensin converting enzyme; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Table 4 presents perioperative characteristics of both groups. Both cardiopulmonary bypass [166.5 (IQR 48.0) min vs 153.0 (IQR 41.0) min; P = 0.007] and total operative time [623.0 (IQR 96.5) min vs 479.0 (IQR 106.0) min; P = 0.029] were greater in HKTx + MCS cases, as were perioperative blood product requirements [30.0 (IQR 10.9) units vs 19.1 (IQR 8.6) units; P < 0.001]. Postoperatively, however, no significant difference was demonstrated in reoperative interventions for bleeding. The need for temporary supplemental MCS (extracorporeal membrane oxygenation or intra-aortic balloon pump), intubation times or overall hospital length-of-stay seemed to be similar. Table 4: Peritransplant characteristics   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  CPB duration (min)  166.5 (48.0)  153.0 (41.0)  0.007  Total operative time (min)  623.0 (96.5)  479.0 (106.0)  0.029  Total blood products (units)  30.0 (10.9)  19.1 (8.6)  <0.001  Reoperation for bleeding  0.0  5.6  1.000  Postoperative circulatory support   IABP  0.0  0.0  1.000   ECMO  7.1  2.8  0.486  Mechanical ventilation time (h)  68.0 (44.7)  58.1 (10.0)  0.464  ICU length of stay (days)  8.0 (2.0)  6.0 (3.0)  0.122  Total hospital length of stay (days)  15.0 (10.0)  15.5 (10.0)  0.916    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  CPB duration (min)  166.5 (48.0)  153.0 (41.0)  0.007  Total operative time (min)  623.0 (96.5)  479.0 (106.0)  0.029  Total blood products (units)  30.0 (10.9)  19.1 (8.6)  <0.001  Reoperation for bleeding  0.0  5.6  1.000  Postoperative circulatory support   IABP  0.0  0.0  1.000   ECMO  7.1  2.8  0.486  Mechanical ventilation time (h)  68.0 (44.7)  58.1 (10.0)  0.464  ICU length of stay (days)  8.0 (2.0)  6.0 (3.0)  0.122  Total hospital length of stay (days)  15.0 (10.0)  15.5 (10.0)  0.916  Values are presented as a median (interquartile range) or percentage. CPB: cardiopulmonary bypass; ECMO: extracorporeal membrane oxygenation; HKTx: heart–kidney transplantation; IABP: intra-aortic balloon pump; ICU: intensive care unit; MCS: mechanical circulatory support. Table 4: Peritransplant characteristics   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  CPB duration (min)  166.5 (48.0)  153.0 (41.0)  0.007  Total operative time (min)  623.0 (96.5)  479.0 (106.0)  0.029  Total blood products (units)  30.0 (10.9)  19.1 (8.6)  <0.001  Reoperation for bleeding  0.0  5.6  1.000  Postoperative circulatory support   IABP  0.0  0.0  1.000   ECMO  7.1  2.8  0.486  Mechanical ventilation time (h)  68.0 (44.7)  58.1 (10.0)  0.464  ICU length of stay (days)  8.0 (2.0)  6.0 (3.0)  0.122  Total hospital length of stay (days)  15.0 (10.0)  15.5 (10.0)  0.916    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  CPB duration (min)  166.5 (48.0)  153.0 (41.0)  0.007  Total operative time (min)  623.0 (96.5)  479.0 (106.0)  0.029  Total blood products (units)  30.0 (10.9)  19.1 (8.6)  <0.001  Reoperation for bleeding  0.0  5.6  1.000  Postoperative circulatory support   IABP  0.0  0.0  1.000   ECMO  7.1  2.8  0.486  Mechanical ventilation time (h)  68.0 (44.7)  58.1 (10.0)  0.464  ICU length of stay (days)  8.0 (2.0)  6.0 (3.0)  0.122  Total hospital length of stay (days)  15.0 (10.0)  15.5 (10.0)  0.916  Values are presented as a median (interquartile range) or percentage. CPB: cardiopulmonary bypass; ECMO: extracorporeal membrane oxygenation; HKTx: heart–kidney transplantation; IABP: intra-aortic balloon pump; ICU: intensive care unit; MCS: mechanical circulatory support. Baseline GFR in both groups (Table 5) was not statistically different (mean 19.2 ± 7.2 ml/min vs 22.5 ± 17.4 ml/min; P = 0.497). A notable trend towards reduced GFR was observed in non-MCS HKTx patients at 1-month post-transplantation (mean 81.2 ± 32.8 ml/min vs 64.4 ± 27.5 ml/min; P = 0.072), although no significant differences were identified at 6 and 12 months. HKTx recipients with and without MCS implantations demonstrated a similar prevalence of delayed graft function (57.1% vs 50.0%; P = 0.757). Although percentage of patients requiring haemodialysis was similar, median duration of haemodialysis support was significantly greater in HKTx without prior MCS [5.0 (IQR 1.0) days vs 9.0 (IQR 12.5) days; P = 0.035]. Table 5: Pretransplant and post-transplant renal function   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  GFR (ml/min)   Pretransplant  19.2 ± 7.2  22.5 ± 17.4  0.497   1-Month post-transplant  81.2 ± 32.8  64.4 ± 27.5  0.072   6-Month post-transplant  66.6 ± 32.2  74.8 ± 29.1  0.447   12-Month post-transplant  72.3 ± 26.3  61.9 ± 21.2  0.235  Delayed graft function  57.1  50.0  0.757  Haemodialysis  42.9  38.9  1.000  Haemodialysis duration (days)  5.0 (1.0)  9.0 (12.5)  0.035    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  GFR (ml/min)   Pretransplant  19.2 ± 7.2  22.5 ± 17.4  0.497   1-Month post-transplant  81.2 ± 32.8  64.4 ± 27.5  0.072   6-Month post-transplant  66.6 ± 32.2  74.8 ± 29.1  0.447   12-Month post-transplant  72.3 ± 26.3  61.9 ± 21.2  0.235  Delayed graft function  57.1  50.0  0.757  Haemodialysis  42.9  38.9  1.000  Haemodialysis duration (days)  5.0 (1.0)  9.0 (12.5)  0.035  Values are presented as mean ± standard deviation, median (interquartile range) or percentage. GFR: glomerular filtration rate; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Table 5: Pretransplant and post-transplant renal function   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  GFR (ml/min)   Pretransplant  19.2 ± 7.2  22.5 ± 17.4  0.497   1-Month post-transplant  81.2 ± 32.8  64.4 ± 27.5  0.072   6-Month post-transplant  66.6 ± 32.2  74.8 ± 29.1  0.447   12-Month post-transplant  72.3 ± 26.3  61.9 ± 21.2  0.235  Delayed graft function  57.1  50.0  0.757  Haemodialysis  42.9  38.9  1.000  Haemodialysis duration (days)  5.0 (1.0)  9.0 (12.5)  0.035    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  GFR (ml/min)   Pretransplant  19.2 ± 7.2  22.5 ± 17.4  0.497   1-Month post-transplant  81.2 ± 32.8  64.4 ± 27.5  0.072   6-Month post-transplant  66.6 ± 32.2  74.8 ± 29.1  0.447   12-Month post-transplant  72.3 ± 26.3  61.9 ± 21.2  0.235  Delayed graft function  57.1  50.0  0.757  Haemodialysis  42.9  38.9  1.000  Haemodialysis duration (days)  5.0 (1.0)  9.0 (12.5)  0.035  Values are presented as mean ± standard deviation, median (interquartile range) or percentage. GFR: glomerular filtration rate; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Table 6 lists outcomes at 1-year post-transplantation. The incidence of any treated rejection, acute cellular rejection and antibody-mediate rejection was not significantly different. Similarly, the rate of cardiac allograft vasculopathy (0% vs 3.7%; P = 0.505) and NF-MACE (7.1% vs 5.6%; P = 0.868) between the 2 groups was similar. The Kaplan–Meier analysis of freedom from chronic dialysis requirement (Fig. 1) was comparable between cohorts at 1 year (85.7% vs 94.4%; P = 0.306). Additionally, evaluation of 1-year survival between groups (Fig. 2) revealed no statistically significant differences in mortality rates between prior MCS and no MCS use after HKTx (100% vs 94%; P = 0.365). Table 6: Survival, allograft rejection and complication rates   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Survival   6 Months  100.0  97.2  0.533   1 Year  100.0  94.0  0.365  1-Year freedom from any treated infection  23.1  22.2  0.747  1-Year freedom from CAV  100.0  96.3  0.505  1-Year freedom from NF-MACE  92.9  94.4  0.868  Heart transplant rejection   1 Year freedom from ATR  92.9  88.4  0.651   1 Year freedom from ACR  100.0  94.1  0.360   1 Year freedom from AMR  100.0  94.3  0.368   1 Year freedom from BNR  92.9  100.0  0.114    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Survival   6 Months  100.0  97.2  0.533   1 Year  100.0  94.0  0.365  1-Year freedom from any treated infection  23.1  22.2  0.747  1-Year freedom from CAV  100.0  96.3  0.505  1-Year freedom from NF-MACE  92.9  94.4  0.868  Heart transplant rejection   1 Year freedom from ATR  92.9  88.4  0.651   1 Year freedom from ACR  100.0  94.1  0.360   1 Year freedom from AMR  100.0  94.3  0.368   1 Year freedom from BNR  92.9  100.0  0.114  Values are presented as a percentage. ACR: acute cellular rejection; AMR: antibody-mediated rejection; ATR: any-treated rejection; BNR: biopsy negative rejection; CAV: cardiac allograft vasculopathy; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support; NF-MACE: non-fatal major adverse cardiac event. Table 6: Survival, allograft rejection and complication rates   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Survival   6 Months  100.0  97.2  0.533   1 Year  100.0  94.0  0.365  1-Year freedom from any treated infection  23.1  22.2  0.747  1-Year freedom from CAV  100.0  96.3  0.505  1-Year freedom from NF-MACE  92.9  94.4  0.868  Heart transplant rejection   1 Year freedom from ATR  92.9  88.4  0.651   1 Year freedom from ACR  100.0  94.1  0.360   1 Year freedom from AMR  100.0  94.3  0.368   1 Year freedom from BNR  92.9  100.0  0.114    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Survival   6 Months  100.0  97.2  0.533   1 Year  100.0  94.0  0.365  1-Year freedom from any treated infection  23.1  22.2  0.747  1-Year freedom from CAV  100.0  96.3  0.505  1-Year freedom from NF-MACE  92.9  94.4  0.868  Heart transplant rejection   1 Year freedom from ATR  92.9  88.4  0.651   1 Year freedom from ACR  100.0  94.1  0.360   1 Year freedom from AMR  100.0  94.3  0.368   1 Year freedom from BNR  92.9  100.0  0.114  Values are presented as a percentage. ACR: acute cellular rejection; AMR: antibody-mediated rejection; ATR: any-treated rejection; BNR: biopsy negative rejection; CAV: cardiac allograft vasculopathy; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support; NF-MACE: non-fatal major adverse cardiac event. Figure 1: View largeDownload slide One-year freedom from chronic dialysis using the Kaplan–Meier analysis. HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Figure 1: View largeDownload slide One-year freedom from chronic dialysis using the Kaplan–Meier analysis. HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Figure 2: View largeDownload slide One-year survival using the Kaplan–Meier analysis. HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Figure 2: View largeDownload slide One-year survival using the Kaplan–Meier analysis. HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. DISCUSSION Cardiac transplantation has long been established using survival metrics as the standard treatment for patients with end-stage heart disease [15]. A growing number of those with heart failure have been identified to have additional multiorgan function. The adverse outcomes of patients with renal insufficiency undergoing isolated cardiac transplantation are well documented [6, 16]. Multiple studies, including analysis of the UNOS registry database, have demonstrated improved survival in those receiving HKTx when compared with isolated heart transplantation OHT in heart failure patients with concurrent non-dialysis and dialysis-dependent renal insufficiency, leading to an increasing number of HKTx performed in the past decade [2, 6, 8, 17, 18]. In addition to the changing paradigms of multiorgan transplantation, the introduction and rapid growth of MCS devices have led to a transformation in the overall management of heart failure and are being increasingly used in cardiac transplant programmes as bridging therapy [19–21]. This question is particularly relevant in the context of continued concerns over appropriate and optimal resource allocation due to persistent donor allograft shortages [2]. The haemodynamic advantage of ventricular unloading with continuous flow MCS prior to isolated cardiac transplantation has been demonstrated to improve post-transplant survival [19]. Despite this benefit, some authors have raised concerns regarding the use of MCS prior to transplantation. Using the UNOS database, Patolla et al. [22, 23] found a small but significant increase in risk (hazard ratio 1:2) at 6 months post-transplantation for those receiving intracorporeal VADs, although this hazard ratio was reduced to 1.1 at 4-year follow-up. The literature on the impact of preoperative MCS in the context of HKTx remains limited and conflicting. In a small case series, Yanagida et al. [24] reported excellent outcomes supporting the use of MCS as a viable option prior to HKTx. A UNOS registry-based analysis noted that the survival of HKTx patients with prior MCS was equivalent to that of non-MCS HKTx [17]. However, Russo et al. [3] found that ventricular assist device was an independent risk factor and was associated with increased mortality attributed to increased risk of infection. A major notable consideration for these aforementioned studies is that they partly or completely comprised early MCS experiences where the use of pulsatile devices was predominant, prior to the landmark HeartMate II trial in 2009 demonstrating the benefits of continuous-flow VADs [25]. This study makes several unique observations. Over a 5-year contemporary period, patients with prior MCS implementation accounted for over a quarter of all HKTxs performed at our institution and suggests that this clinical association may be even more common as MCS therapy becomes increasingly prevalent. In our experience, HKTx + MCS and HKTx-only patients seemed to have similar preoperative demographics, transplant risk factors and medication use. We did identify an increase in both cardiopulmonary bypass support and total operative duration, which was likely attributed to the requisite time spent on removing the MCS device prior to orthotopic transplantation. Despite the increased procedural time and total number of blood products transfused, no increase was observed in in-hospital morbidity, including reoperative interventions for bleeding, the need for postoperative circulatory support and intubation duration or prolonged length of stay. Of additional interest was that median haemodialysis duration was greater in the HKTx-only cohort, despite having statistically similar rates of haemodialysis requirement frequency and incidence of delayed graft function. A numerical trend was observed in increased GFR in the MCS group immediately post-transplantation. Although this did not reach statistical significance and was not sustained, it potentially supports the concept of device pretransplantation optimization of intravascular haemodynamics. Nevertheless, based on overall GFR and the frequency of chronic dialysis postoperatively, the use of MCS devices did not seem to be deleterious to renal allograft function. Patient outcomes over 12-month post-transplantation, including freedom from NF-MACE, heart transplant rejection and survival, was not statistically different between both groups. These findings potentially demonstrate that combined HKTx in patients with MCS is reasonable as no significant increase is observed in morbidity or mortality. This seems to be in contradistinction to reports of decreased survival in MCS patients following isolated cardiac transplantation. The burden of low cardiac output in end-stage heart failure and the resulting reduction in organ perfusion have been known to precipitate renal dysfunction [4]. There may be a subset of patients undergoing isolated heart transplantation with underlying, undiagnosed renal dysfunction, thereby affecting mortality rates. Furthermore, many of these initial considerations of MCS’s negative impact on isolated cardiac transplantation outcomes were primarily based on pulsatile devices and, therefore, may not correlate to the newest MCS generation [21]. Limitations We acknowledge several limitations of this study. We appreciate the challenges inherent in a single-institution retrospective study. The small sample size also impacted the power of this study; simultaneous HTKxs are a relatively infrequently performed procedure, and, therefore, obtaining larger sample sizes is intrinsically difficult. Pooled assessment of HKTxs performed at multiple centres may provide improved statistical power while adjusting for potential geographical or institutional-specific variables. Follow-up over the past 1-year end point will additionally be of interest for longer-term outcome analyses. Despite these limitations, this study provides a preliminary evaluation of MCS prior to HKTx in the contemporary era. These results encourage further evaluation but seem to suggest that HKTx is a viable treatment option in patients with MCS as a bridge to transplantation with concomitant renal insufficiency. Conflict of interest: none declared. REFERENCES 1 McGiffin DC, Kirklin JK, Naftel DC. Acute renal failure after heart transplantation and cyclosporine therapy. J Heart Transplant  1985; 4: 396– 9. Google Scholar PubMed  2 Lund LH, Khush KK, Cherikh WS, Goldfarb S, Kucheryavaya AY, Levvey BJ et al.   The Registry of the International Society for Heart and Lung Transplantation: thirty-fourth Adult Heart Transplantation Report-2017; Focus Theme: allograft ischemic time. J Heart Lung Transplant  2017; 36: 1037– 46. Google Scholar CrossRef Search ADS PubMed  3 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: 241– 6. Google Scholar CrossRef Search ADS PubMed  4 Narula J, Bennett LE, DiSalvo T, Hosenpud JD, Semigran MJ, Dec GW. Outcomes in recipients of combined heart-kidney transplantation: multiorgan, same-donor transplant study of the International Society of Heart and Lung Transplantation/United Network for Organ Sharing Scientific Registry. Transplantation  1997; 63: 861– 7. Google Scholar CrossRef Search ADS PubMed  5 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: 456– 61.e1. Google Scholar CrossRef Search ADS PubMed  6 Schaffer JM, Chiu P, Singh SK, Oyer PE, Reitz BA, Mallidi HR. Heart and combined heart-kidney transplantation in patients with concomitant renal insufficiency and end-stage heart failure. Am J Transplant  2014; 14: 384– 96. Google Scholar CrossRef Search ADS PubMed  7 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 stone-heart syndrome by a partial artificial heart (ALVAD) for 5 days followed by heart and kidney transplantation. Lancet  1978; 311: 1125– 7. Google Scholar CrossRef Search ADS   8 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: 286– 356. Google Scholar CrossRef Search ADS PubMed  9 Anand J, Singh SK, Antoun DG, Cohn WE, Frazier OH, Mallidi HR. Durable mechanical circulatory support versus organ transplantation: past, present, and future. Biomed Res Int  2015; 2015: 849571. Google Scholar CrossRef Search ADS PubMed  10 Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Stevenson LW, Blume ED et al.   Seventh INTERMACS annual report: 15,000 patients and counting. J Heart Lung Transplant  2015; 34: 1495– 504. Google Scholar CrossRef Search ADS PubMed  11 Holley CT, Harvey L, John R. Left ventricular assist devices as a bridge to cardiac transplantation. J Thorac Dis  2014; 6: 1110– 9. Google Scholar PubMed  12 Marinescu KK, Uriel N, Adatya S. The future of mechanical circulatory support for advanced heart failure. Curr Opin Cardiol  2016; 31: 321– 8. Google Scholar CrossRef Search ADS PubMed  13 Kilic A. The future of left ventricular assist devices. J Thorac Dis  2015; 7: 2188– 93. Google Scholar PubMed  14 Ensminger SM, Gerosa G, Gummert JF, Falk V. Mechanical circulatory support: heart failure therapy “in motion”. Innovations (Phila)  2016; 11: 305– 14. Google Scholar CrossRef Search ADS PubMed  15 Garrity ER, Moore J, Mulligan MS, Shearon TH, Zucker MJ, Murray S. Heart and lung transplantation in the United States, 1996-2005. Am J Transplant  2007; 7: 1390– 403. Google Scholar CrossRef Search ADS PubMed  16 Alam A, Badovinac K, Ivis F, Trpeski L, Cantarovich M. The outcome of heart transplant recipients following the development of end-stage renal disease: analysis of the Canadian Organ Replacement Register (CORR). Am J Transplant  2007; 7: 461– 5. Google Scholar CrossRef Search ADS PubMed  17 Zalawadiya SK, Wigger M, DiSalvo T, Haglund N, Maltais S, Lindenfeld J. Mechanical circulatory support and simultaneous heart-kidney transplantation: an outcome analysis. J Heart Lung Transplant  2016; 35: 203– 12. Google Scholar CrossRef Search ADS PubMed  18 Kilic A, Grimm JC, Whitman GJ, Shah AS, Mandal K, Conte JV et al.   The survival benefit of simultaneous heart-kidney transplantation extends beyond dialysis-dependent patients. Ann Thorac Surg  2015; 99: 1321– 7. Google Scholar CrossRef Search ADS PubMed  19 Kamdar F, John R, Eckman P, Colvin-Adams M, Shumway SJ, Liao K. Postcardiac transplant survival in the current era in patients receiving continuous-flow left ventricular assist devices. J Thorac Cardiovasc Surg  2013; 145: 575– 81. Google Scholar CrossRef Search ADS PubMed  20 Pagani FD, Miller LW, Russell SD, Aaronson KD, John R, Boyle AJ et al.   Extended mechanical circulatory support with a continuous-flow rotary left ventricular assist device. J Am Coll Cardiol  2009; 54: 312– 21. Google Scholar CrossRef Search ADS PubMed  21 Miller LW, Pagani FD, Russell SD, John R, Boyle AJ, Aaronson KD et al.   Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med  2007; 357: 885– 96. Google Scholar CrossRef Search ADS PubMed  22 Miller L. The impact of mechanical circulatory support on post-transplant survival a different view. J Am Coll Cardiol  2009; 53: 272– 4. Google Scholar CrossRef Search ADS PubMed  23 Patlolla V, Patten RD, Denofrio D, Konstam MA, Krishnamani R. The effect of ventricular assist devices on post-transplant mortality an analysis of the United network for organ sharing thoracic registry. J Am Coll Cardiol  2009; 53: 264– 71. Google Scholar CrossRef Search ADS PubMed  24 Yanagida R, Czer LS, Ruzza A, Schwarz ER, Simsir SA, Jordan SC et al.   Use of ventricular assist device as bridge to simultaneous heart and kidney transplantation in patients with cardiac and renal failure. Transplant Proc  2013; 45: 2378– 83. Google Scholar CrossRef Search ADS PubMed  25 Slaughter MS, Rogers JG, Milano CA, Russell SD, Conte JV, Feldman D et al.   Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med  2009; 361: 2241– 51. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Interactive CardioVascular and Thoracic Surgery Oxford University Press

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© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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Abstract

Abstract OBJECTIVES Previous studies have demonstrated that preheart transplant mechanical circulatory support (MCS) can lead to a small but significant increase in mortality. However, data on outcomes of patients with MCS who require simultaneous heart–kidney transplant are limited. METHODS A retrospective review of simultaneous heart–kidney transplantations (HKTxs) performed at a single institution over a 5-year period was performed. Patients were divided based on the preoperative use of durable MCS. Renal graft-related end points were evaluated, including glomerular filtration rate following transplantation, prevalence of delayed renal graft function and freedom from antibody and cellular-mediated graft rejection. Patient-specific outcomes, including survival and frequency of non-fatal major adverse cardiac events at 1 year, were additionally assessed. RESULTS During the study period, 50 HKTxs were performed, 14 of which had preoperative MCS. HKTx patients with and without MCS implantations had a similar prevalence of delayed graft function (57.1% vs 50.0%; P = 0.757). A numerical trend was observed towards a reduced glomerular filtration rate 1-month post-transplant in patients without an MCS device (81.2 ± 32.8 vs 64.4 ± 27.5; P = 0.072), but no significant difference was observed at 6 and 12 months. No significant difference was observed on the need for post-transplant renal replacement therapy, non-fatal major adverse cardiac events, freedom from graft rejection and overall survival at 1 year. CONCLUSIONS The use of preoperative MCS in patients undergoing combined HKTx was not found to affect renal graft function post-transplantation and does not seem to be associated with increase in morbidity or mortality. Heart transplantation, Kidney transplantation, Mechanical circulatory support INTRODUCTION It has been well established that the presence of chronic renal disease prior to heart transplantation is associated with increased morbidity and mortality and was previously considered a contraindication to heart transplant candidacy [1, 2]. The presence of renal insufficiency with heart failure is not an uncommon association; more than 30% of heart transplant recipients have an estimated glomerular filtration rate (GFR) of less than 45 ml/min [3]. With advancements in surgical technique, perioperative management and immunosuppression, it has since been shown that simultaneous heart–kidney transplantation (HKTx) can be performed successfully in patients with end-stage failures of both organs with survival equivalent to isolated heart transplant recipients [4–6]. This technique was first described by Norman et al. [7] in 1978, and the number of HKTxs has steadily grown. Since 2000, the annual frequency of these simultaneous transplants performed in the USA has increased over 2-fold [2, 8]. Concurrently, mechanical circulatory support (MCS) has demonstrated to play a critical role as a bridge to transplantation option in patients with end-stage heart failure [9–11]. The rapid evolution of heart failure management using MCS is additionally reflected by remarkable and frequent innovations in device technologies [12–14]. With newer continuous-flow MCS devices becoming ever more prevalent, and with current increase in the number of HKTxs being performed, the determination of the potential impact of pretransplant MCS implantation on outcomes is essential. Unfortunately, the literature evaluating outcomes in MCS patients receiving HKTx remains limited. In this study, we sought to evaluate outcomes of HKTx recipients using preoperative MCS in the contemporary era performed at a single, high-volume transplant institution. MATERIALS AND METHODS All simultaneous adult orthotopic heart–kidney transplants performed at a single tertiary care institution from 2010 to 2015 were retrospectively evaluated. Patients were divided based on the preoperative use of durable MCS. Durable MCS was defined as the use of a left ventricular assist device, a biventricular assist device or a total artificial heart. Indications for MCS implantation followed standard criteria and included patients with severe and progressively decompensating heart failure without contraindications (e.g. active infection, ongoing bleeding and high risk for non-compliance) to therapy. The institutional electronic medical record was used to query variables. Preoperative demographics, such as medical history, was assessed. The primary outcome assessed included renal function, which was described in terms of GFR up to 12 months (1, 6 and 12 months post-transplantation), the prevalence of delayed graft function (the need for dialysis within 7 days post-transplantation) and the need for chronic (≥1 month) renal replacement therapy. Additionally, 1-year survival and 1-year graft outcomes were evaluated. Graft outcomes were evaluated based on incidence of any treated rejection, acute cellular rejection and antibody-mediated rejection. Secondary patient outcomes were additionally assessed based on freedom from cardiac allograft vasculopathy and freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention or angioplasty, implantable cardioverter-defibrillator or pacemaker implant and stroke) at 1 year. Institutional review board approval was attained, and informed consent was obtained. Continuous variables are expressed as a median with interquartile range (IQR) or mean and standard deviation, whereas categorical variables are expressed as a percentage. Continuous variables were compared using the Student’s t-test, and categorical variables were analysed using the Fisher’s exact test. The Kaplan–Meier curve analysis was used to display patient survival and freedom from chronic renal replacement therapy. Statistical analysis was performed using the SAS Software, Version 9.2 (Statistical Analysis System Institute, Cary, NC, USA). RESULTS During the 5-year study period, 50 simultaneous HKTxs were performed, with 14 (28%) receiving a pretransplant MCS. Demographics between HKTx + MCS and HKTx-only patients, as listed in Table 1, were similar with regard to age, body mass indices and gender. Evaluation of medical comorbidities such as diabetes, hyperlipidaemia and peripheral vascular disease were not statistically different between cohorts. Table 1: Patient demographics   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Recipient age (years)  54.4 ± 6.8  58.2 ± 11.0  0.235  Body mass index (kg/m2)  25.3 ± 6.0  24.7 ± 5.0  0.720  Female  14.3  25.0  0.705   Prior pregnancy  100.0  75.0  1.000  Race   Caucasian  71.4  55.6  0.353   African American  14.3  16.7  1.000   Hispanic  14.3  13.9  1.000   Other  0.0  13.9  0.304  Medical history   Coronary artery disease  50.0  69.4  0.325   Diabetes mellitus  42.9  36.1  1.000   Hypertension  66.7  58.3  1.000   Hyperlipidaemia  28.6  30.5  1.000   Hypothyroidism  28.6  11.1  0.197   Peripheral vascular disease  14.3  16.7  1.000   Stroke  7.1  5.6  1.000   COPD  50.0  27.8  0.187    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Recipient age (years)  54.4 ± 6.8  58.2 ± 11.0  0.235  Body mass index (kg/m2)  25.3 ± 6.0  24.7 ± 5.0  0.720  Female  14.3  25.0  0.705   Prior pregnancy  100.0  75.0  1.000  Race   Caucasian  71.4  55.6  0.353   African American  14.3  16.7  1.000   Hispanic  14.3  13.9  1.000   Other  0.0  13.9  0.304  Medical history   Coronary artery disease  50.0  69.4  0.325   Diabetes mellitus  42.9  36.1  1.000   Hypertension  66.7  58.3  1.000   Hyperlipidaemia  28.6  30.5  1.000   Hypothyroidism  28.6  11.1  0.197   Peripheral vascular disease  14.3  16.7  1.000   Stroke  7.1  5.6  1.000   COPD  50.0  27.8  0.187  Values are presented as a mean ± standard deviation or percentage. COPD: chronic obstructive pulmonary disease; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Table 1: Patient demographics   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Recipient age (years)  54.4 ± 6.8  58.2 ± 11.0  0.235  Body mass index (kg/m2)  25.3 ± 6.0  24.7 ± 5.0  0.720  Female  14.3  25.0  0.705   Prior pregnancy  100.0  75.0  1.000  Race   Caucasian  71.4  55.6  0.353   African American  14.3  16.7  1.000   Hispanic  14.3  13.9  1.000   Other  0.0  13.9  0.304  Medical history   Coronary artery disease  50.0  69.4  0.325   Diabetes mellitus  42.9  36.1  1.000   Hypertension  66.7  58.3  1.000   Hyperlipidaemia  28.6  30.5  1.000   Hypothyroidism  28.6  11.1  0.197   Peripheral vascular disease  14.3  16.7  1.000   Stroke  7.1  5.6  1.000   COPD  50.0  27.8  0.187    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Recipient age (years)  54.4 ± 6.8  58.2 ± 11.0  0.235  Body mass index (kg/m2)  25.3 ± 6.0  24.7 ± 5.0  0.720  Female  14.3  25.0  0.705   Prior pregnancy  100.0  75.0  1.000  Race   Caucasian  71.4  55.6  0.353   African American  14.3  16.7  1.000   Hispanic  14.3  13.9  1.000   Other  0.0  13.9  0.304  Medical history   Coronary artery disease  50.0  69.4  0.325   Diabetes mellitus  42.9  36.1  1.000   Hypertension  66.7  58.3  1.000   Hyperlipidaemia  28.6  30.5  1.000   Hypothyroidism  28.6  11.1  0.197   Peripheral vascular disease  14.3  16.7  1.000   Stroke  7.1  5.6  1.000   COPD  50.0  27.8  0.187  Values are presented as a mean ± standard deviation or percentage. COPD: chronic obstructive pulmonary disease; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Transplant-related factors (Table 2) revealed that a significantly greater proportion of HKTx + MCS were United Network for Organ Sharing (UNOS) status 1 when compared with HKTx-alone patients (100.0% vs 66.7%; P = 0.012). Furthermore, all HKTx + MCS patients were reoperative cardiac surgery patients compared with 55.6% of patients in the HKTx group (P = 0.002). The frequency of ≥2 sternotomies was also significantly increased in HKTx + MCS patients. As noted in the detailed profile of mechanical device support, the majority were in place for >90 days (92.9%): 64.3% comprised total artificial heart devices, 21.4% biventricular assist device and 14.3% left ventricular assist device. Table 3 displays a preoperative medication use. Treatment prevalence with various antihypertensives, aspirin or clopidogrel was not significantly different between cohorts. Table 2: Pretransplant factors   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  UNOS status 1 at transplant  100.0  66.7  0.012  Cytomegalovirus mismatch  21.4  33.3  0.507  Prior blood transfusion  92.9  62.5  0.072  Pretransplant PRA ≥10%  28.6  27.8  1.000  MCS support length   Short-term support (≤90 days)  7.1       Long-term support (>90 days)  92.9      MCS device type         LVAD  14.3       BiVAD  21.4       TAH  64.3      Prior interventions   Previous cardiac surgery  100.0  55.6  0.002   ≥2 sternotomies  64.3  11.1  <0.001   Prior CABG  14.3  12.4  1.000   Prior PCI  42.9  50.0  0.757    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  UNOS status 1 at transplant  100.0  66.7  0.012  Cytomegalovirus mismatch  21.4  33.3  0.507  Prior blood transfusion  92.9  62.5  0.072  Pretransplant PRA ≥10%  28.6  27.8  1.000  MCS support length   Short-term support (≤90 days)  7.1       Long-term support (>90 days)  92.9      MCS device type         LVAD  14.3       BiVAD  21.4       TAH  64.3      Prior interventions   Previous cardiac surgery  100.0  55.6  0.002   ≥2 sternotomies  64.3  11.1  <0.001   Prior CABG  14.3  12.4  1.000   Prior PCI  42.9  50.0  0.757  Values are presented as a percentage. BiVAD: biventricular assist device; CABG: coronary artery bypass grafting; HKTx: heart–kidney transplantation; LVAD: left ventricular assist device; MCS: mechanical circulatory support; PCI: percutaneous coronary intervention; PRA: panel reactive antibody; TAH: total artificial heart; UNOS: United network for organ sharing. Table 2: Pretransplant factors   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  UNOS status 1 at transplant  100.0  66.7  0.012  Cytomegalovirus mismatch  21.4  33.3  0.507  Prior blood transfusion  92.9  62.5  0.072  Pretransplant PRA ≥10%  28.6  27.8  1.000  MCS support length   Short-term support (≤90 days)  7.1       Long-term support (>90 days)  92.9      MCS device type         LVAD  14.3       BiVAD  21.4       TAH  64.3      Prior interventions   Previous cardiac surgery  100.0  55.6  0.002   ≥2 sternotomies  64.3  11.1  <0.001   Prior CABG  14.3  12.4  1.000   Prior PCI  42.9  50.0  0.757    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  UNOS status 1 at transplant  100.0  66.7  0.012  Cytomegalovirus mismatch  21.4  33.3  0.507  Prior blood transfusion  92.9  62.5  0.072  Pretransplant PRA ≥10%  28.6  27.8  1.000  MCS support length   Short-term support (≤90 days)  7.1       Long-term support (>90 days)  92.9      MCS device type         LVAD  14.3       BiVAD  21.4       TAH  64.3      Prior interventions   Previous cardiac surgery  100.0  55.6  0.002   ≥2 sternotomies  64.3  11.1  <0.001   Prior CABG  14.3  12.4  1.000   Prior PCI  42.9  50.0  0.757  Values are presented as a percentage. BiVAD: biventricular assist device; CABG: coronary artery bypass grafting; HKTx: heart–kidney transplantation; LVAD: left ventricular assist device; MCS: mechanical circulatory support; PCI: percutaneous coronary intervention; PRA: panel reactive antibody; TAH: total artificial heart; UNOS: United network for organ sharing. Table 3: Preoperative medication profile   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  β-blockers  53.8  66.7  0.508  Nitrates  57.1  61.1  1.000  ACE inhibitors  44.4  38.9  1.000  Angiotensin II receptor blockers  15.4  30.6  0.293  Calcium channel blockers  35.7  13.9  0.118  Phosphodiesterase inhibitors  21.4  11.1  0.384  Midodrine  57.1  37.1  0.222  Aspirin  92.9  100.0  0.280  Clopidogrel  38.5  29.4  0.728    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  β-blockers  53.8  66.7  0.508  Nitrates  57.1  61.1  1.000  ACE inhibitors  44.4  38.9  1.000  Angiotensin II receptor blockers  15.4  30.6  0.293  Calcium channel blockers  35.7  13.9  0.118  Phosphodiesterase inhibitors  21.4  11.1  0.384  Midodrine  57.1  37.1  0.222  Aspirin  92.9  100.0  0.280  Clopidogrel  38.5  29.4  0.728  Values are presented as a percentage. ACE: angiotensin converting enzyme; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Table 3: Preoperative medication profile   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  β-blockers  53.8  66.7  0.508  Nitrates  57.1  61.1  1.000  ACE inhibitors  44.4  38.9  1.000  Angiotensin II receptor blockers  15.4  30.6  0.293  Calcium channel blockers  35.7  13.9  0.118  Phosphodiesterase inhibitors  21.4  11.1  0.384  Midodrine  57.1  37.1  0.222  Aspirin  92.9  100.0  0.280  Clopidogrel  38.5  29.4  0.728    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  β-blockers  53.8  66.7  0.508  Nitrates  57.1  61.1  1.000  ACE inhibitors  44.4  38.9  1.000  Angiotensin II receptor blockers  15.4  30.6  0.293  Calcium channel blockers  35.7  13.9  0.118  Phosphodiesterase inhibitors  21.4  11.1  0.384  Midodrine  57.1  37.1  0.222  Aspirin  92.9  100.0  0.280  Clopidogrel  38.5  29.4  0.728  Values are presented as a percentage. ACE: angiotensin converting enzyme; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Table 4 presents perioperative characteristics of both groups. Both cardiopulmonary bypass [166.5 (IQR 48.0) min vs 153.0 (IQR 41.0) min; P = 0.007] and total operative time [623.0 (IQR 96.5) min vs 479.0 (IQR 106.0) min; P = 0.029] were greater in HKTx + MCS cases, as were perioperative blood product requirements [30.0 (IQR 10.9) units vs 19.1 (IQR 8.6) units; P < 0.001]. Postoperatively, however, no significant difference was demonstrated in reoperative interventions for bleeding. The need for temporary supplemental MCS (extracorporeal membrane oxygenation or intra-aortic balloon pump), intubation times or overall hospital length-of-stay seemed to be similar. Table 4: Peritransplant characteristics   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  CPB duration (min)  166.5 (48.0)  153.0 (41.0)  0.007  Total operative time (min)  623.0 (96.5)  479.0 (106.0)  0.029  Total blood products (units)  30.0 (10.9)  19.1 (8.6)  <0.001  Reoperation for bleeding  0.0  5.6  1.000  Postoperative circulatory support   IABP  0.0  0.0  1.000   ECMO  7.1  2.8  0.486  Mechanical ventilation time (h)  68.0 (44.7)  58.1 (10.0)  0.464  ICU length of stay (days)  8.0 (2.0)  6.0 (3.0)  0.122  Total hospital length of stay (days)  15.0 (10.0)  15.5 (10.0)  0.916    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  CPB duration (min)  166.5 (48.0)  153.0 (41.0)  0.007  Total operative time (min)  623.0 (96.5)  479.0 (106.0)  0.029  Total blood products (units)  30.0 (10.9)  19.1 (8.6)  <0.001  Reoperation for bleeding  0.0  5.6  1.000  Postoperative circulatory support   IABP  0.0  0.0  1.000   ECMO  7.1  2.8  0.486  Mechanical ventilation time (h)  68.0 (44.7)  58.1 (10.0)  0.464  ICU length of stay (days)  8.0 (2.0)  6.0 (3.0)  0.122  Total hospital length of stay (days)  15.0 (10.0)  15.5 (10.0)  0.916  Values are presented as a median (interquartile range) or percentage. CPB: cardiopulmonary bypass; ECMO: extracorporeal membrane oxygenation; HKTx: heart–kidney transplantation; IABP: intra-aortic balloon pump; ICU: intensive care unit; MCS: mechanical circulatory support. Table 4: Peritransplant characteristics   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  CPB duration (min)  166.5 (48.0)  153.0 (41.0)  0.007  Total operative time (min)  623.0 (96.5)  479.0 (106.0)  0.029  Total blood products (units)  30.0 (10.9)  19.1 (8.6)  <0.001  Reoperation for bleeding  0.0  5.6  1.000  Postoperative circulatory support   IABP  0.0  0.0  1.000   ECMO  7.1  2.8  0.486  Mechanical ventilation time (h)  68.0 (44.7)  58.1 (10.0)  0.464  ICU length of stay (days)  8.0 (2.0)  6.0 (3.0)  0.122  Total hospital length of stay (days)  15.0 (10.0)  15.5 (10.0)  0.916    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  CPB duration (min)  166.5 (48.0)  153.0 (41.0)  0.007  Total operative time (min)  623.0 (96.5)  479.0 (106.0)  0.029  Total blood products (units)  30.0 (10.9)  19.1 (8.6)  <0.001  Reoperation for bleeding  0.0  5.6  1.000  Postoperative circulatory support   IABP  0.0  0.0  1.000   ECMO  7.1  2.8  0.486  Mechanical ventilation time (h)  68.0 (44.7)  58.1 (10.0)  0.464  ICU length of stay (days)  8.0 (2.0)  6.0 (3.0)  0.122  Total hospital length of stay (days)  15.0 (10.0)  15.5 (10.0)  0.916  Values are presented as a median (interquartile range) or percentage. CPB: cardiopulmonary bypass; ECMO: extracorporeal membrane oxygenation; HKTx: heart–kidney transplantation; IABP: intra-aortic balloon pump; ICU: intensive care unit; MCS: mechanical circulatory support. Baseline GFR in both groups (Table 5) was not statistically different (mean 19.2 ± 7.2 ml/min vs 22.5 ± 17.4 ml/min; P = 0.497). A notable trend towards reduced GFR was observed in non-MCS HKTx patients at 1-month post-transplantation (mean 81.2 ± 32.8 ml/min vs 64.4 ± 27.5 ml/min; P = 0.072), although no significant differences were identified at 6 and 12 months. HKTx recipients with and without MCS implantations demonstrated a similar prevalence of delayed graft function (57.1% vs 50.0%; P = 0.757). Although percentage of patients requiring haemodialysis was similar, median duration of haemodialysis support was significantly greater in HKTx without prior MCS [5.0 (IQR 1.0) days vs 9.0 (IQR 12.5) days; P = 0.035]. Table 5: Pretransplant and post-transplant renal function   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  GFR (ml/min)   Pretransplant  19.2 ± 7.2  22.5 ± 17.4  0.497   1-Month post-transplant  81.2 ± 32.8  64.4 ± 27.5  0.072   6-Month post-transplant  66.6 ± 32.2  74.8 ± 29.1  0.447   12-Month post-transplant  72.3 ± 26.3  61.9 ± 21.2  0.235  Delayed graft function  57.1  50.0  0.757  Haemodialysis  42.9  38.9  1.000  Haemodialysis duration (days)  5.0 (1.0)  9.0 (12.5)  0.035    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  GFR (ml/min)   Pretransplant  19.2 ± 7.2  22.5 ± 17.4  0.497   1-Month post-transplant  81.2 ± 32.8  64.4 ± 27.5  0.072   6-Month post-transplant  66.6 ± 32.2  74.8 ± 29.1  0.447   12-Month post-transplant  72.3 ± 26.3  61.9 ± 21.2  0.235  Delayed graft function  57.1  50.0  0.757  Haemodialysis  42.9  38.9  1.000  Haemodialysis duration (days)  5.0 (1.0)  9.0 (12.5)  0.035  Values are presented as mean ± standard deviation, median (interquartile range) or percentage. GFR: glomerular filtration rate; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Table 5: Pretransplant and post-transplant renal function   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  GFR (ml/min)   Pretransplant  19.2 ± 7.2  22.5 ± 17.4  0.497   1-Month post-transplant  81.2 ± 32.8  64.4 ± 27.5  0.072   6-Month post-transplant  66.6 ± 32.2  74.8 ± 29.1  0.447   12-Month post-transplant  72.3 ± 26.3  61.9 ± 21.2  0.235  Delayed graft function  57.1  50.0  0.757  Haemodialysis  42.9  38.9  1.000  Haemodialysis duration (days)  5.0 (1.0)  9.0 (12.5)  0.035    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  GFR (ml/min)   Pretransplant  19.2 ± 7.2  22.5 ± 17.4  0.497   1-Month post-transplant  81.2 ± 32.8  64.4 ± 27.5  0.072   6-Month post-transplant  66.6 ± 32.2  74.8 ± 29.1  0.447   12-Month post-transplant  72.3 ± 26.3  61.9 ± 21.2  0.235  Delayed graft function  57.1  50.0  0.757  Haemodialysis  42.9  38.9  1.000  Haemodialysis duration (days)  5.0 (1.0)  9.0 (12.5)  0.035  Values are presented as mean ± standard deviation, median (interquartile range) or percentage. GFR: glomerular filtration rate; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Table 6 lists outcomes at 1-year post-transplantation. The incidence of any treated rejection, acute cellular rejection and antibody-mediate rejection was not significantly different. Similarly, the rate of cardiac allograft vasculopathy (0% vs 3.7%; P = 0.505) and NF-MACE (7.1% vs 5.6%; P = 0.868) between the 2 groups was similar. The Kaplan–Meier analysis of freedom from chronic dialysis requirement (Fig. 1) was comparable between cohorts at 1 year (85.7% vs 94.4%; P = 0.306). Additionally, evaluation of 1-year survival between groups (Fig. 2) revealed no statistically significant differences in mortality rates between prior MCS and no MCS use after HKTx (100% vs 94%; P = 0.365). Table 6: Survival, allograft rejection and complication rates   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Survival   6 Months  100.0  97.2  0.533   1 Year  100.0  94.0  0.365  1-Year freedom from any treated infection  23.1  22.2  0.747  1-Year freedom from CAV  100.0  96.3  0.505  1-Year freedom from NF-MACE  92.9  94.4  0.868  Heart transplant rejection   1 Year freedom from ATR  92.9  88.4  0.651   1 Year freedom from ACR  100.0  94.1  0.360   1 Year freedom from AMR  100.0  94.3  0.368   1 Year freedom from BNR  92.9  100.0  0.114    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Survival   6 Months  100.0  97.2  0.533   1 Year  100.0  94.0  0.365  1-Year freedom from any treated infection  23.1  22.2  0.747  1-Year freedom from CAV  100.0  96.3  0.505  1-Year freedom from NF-MACE  92.9  94.4  0.868  Heart transplant rejection   1 Year freedom from ATR  92.9  88.4  0.651   1 Year freedom from ACR  100.0  94.1  0.360   1 Year freedom from AMR  100.0  94.3  0.368   1 Year freedom from BNR  92.9  100.0  0.114  Values are presented as a percentage. ACR: acute cellular rejection; AMR: antibody-mediated rejection; ATR: any-treated rejection; BNR: biopsy negative rejection; CAV: cardiac allograft vasculopathy; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support; NF-MACE: non-fatal major adverse cardiac event. Table 6: Survival, allograft rejection and complication rates   HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Survival   6 Months  100.0  97.2  0.533   1 Year  100.0  94.0  0.365  1-Year freedom from any treated infection  23.1  22.2  0.747  1-Year freedom from CAV  100.0  96.3  0.505  1-Year freedom from NF-MACE  92.9  94.4  0.868  Heart transplant rejection   1 Year freedom from ATR  92.9  88.4  0.651   1 Year freedom from ACR  100.0  94.1  0.360   1 Year freedom from AMR  100.0  94.3  0.368   1 Year freedom from BNR  92.9  100.0  0.114    HKTx + MCS (n = 14)  HKTx (n = 36)  P-value  Survival   6 Months  100.0  97.2  0.533   1 Year  100.0  94.0  0.365  1-Year freedom from any treated infection  23.1  22.2  0.747  1-Year freedom from CAV  100.0  96.3  0.505  1-Year freedom from NF-MACE  92.9  94.4  0.868  Heart transplant rejection   1 Year freedom from ATR  92.9  88.4  0.651   1 Year freedom from ACR  100.0  94.1  0.360   1 Year freedom from AMR  100.0  94.3  0.368   1 Year freedom from BNR  92.9  100.0  0.114  Values are presented as a percentage. ACR: acute cellular rejection; AMR: antibody-mediated rejection; ATR: any-treated rejection; BNR: biopsy negative rejection; CAV: cardiac allograft vasculopathy; HKTx: heart–kidney transplantation; MCS: mechanical circulatory support; NF-MACE: non-fatal major adverse cardiac event. Figure 1: View largeDownload slide One-year freedom from chronic dialysis using the Kaplan–Meier analysis. HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Figure 1: View largeDownload slide One-year freedom from chronic dialysis using the Kaplan–Meier analysis. HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Figure 2: View largeDownload slide One-year survival using the Kaplan–Meier analysis. HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. Figure 2: View largeDownload slide One-year survival using the Kaplan–Meier analysis. HKTx: heart–kidney transplantation; MCS: mechanical circulatory support. DISCUSSION Cardiac transplantation has long been established using survival metrics as the standard treatment for patients with end-stage heart disease [15]. A growing number of those with heart failure have been identified to have additional multiorgan function. The adverse outcomes of patients with renal insufficiency undergoing isolated cardiac transplantation are well documented [6, 16]. Multiple studies, including analysis of the UNOS registry database, have demonstrated improved survival in those receiving HKTx when compared with isolated heart transplantation OHT in heart failure patients with concurrent non-dialysis and dialysis-dependent renal insufficiency, leading to an increasing number of HKTx performed in the past decade [2, 6, 8, 17, 18]. In addition to the changing paradigms of multiorgan transplantation, the introduction and rapid growth of MCS devices have led to a transformation in the overall management of heart failure and are being increasingly used in cardiac transplant programmes as bridging therapy [19–21]. This question is particularly relevant in the context of continued concerns over appropriate and optimal resource allocation due to persistent donor allograft shortages [2]. The haemodynamic advantage of ventricular unloading with continuous flow MCS prior to isolated cardiac transplantation has been demonstrated to improve post-transplant survival [19]. Despite this benefit, some authors have raised concerns regarding the use of MCS prior to transplantation. Using the UNOS database, Patolla et al. [22, 23] found a small but significant increase in risk (hazard ratio 1:2) at 6 months post-transplantation for those receiving intracorporeal VADs, although this hazard ratio was reduced to 1.1 at 4-year follow-up. The literature on the impact of preoperative MCS in the context of HKTx remains limited and conflicting. In a small case series, Yanagida et al. [24] reported excellent outcomes supporting the use of MCS as a viable option prior to HKTx. A UNOS registry-based analysis noted that the survival of HKTx patients with prior MCS was equivalent to that of non-MCS HKTx [17]. However, Russo et al. [3] found that ventricular assist device was an independent risk factor and was associated with increased mortality attributed to increased risk of infection. A major notable consideration for these aforementioned studies is that they partly or completely comprised early MCS experiences where the use of pulsatile devices was predominant, prior to the landmark HeartMate II trial in 2009 demonstrating the benefits of continuous-flow VADs [25]. This study makes several unique observations. Over a 5-year contemporary period, patients with prior MCS implementation accounted for over a quarter of all HKTxs performed at our institution and suggests that this clinical association may be even more common as MCS therapy becomes increasingly prevalent. In our experience, HKTx + MCS and HKTx-only patients seemed to have similar preoperative demographics, transplant risk factors and medication use. We did identify an increase in both cardiopulmonary bypass support and total operative duration, which was likely attributed to the requisite time spent on removing the MCS device prior to orthotopic transplantation. Despite the increased procedural time and total number of blood products transfused, no increase was observed in in-hospital morbidity, including reoperative interventions for bleeding, the need for postoperative circulatory support and intubation duration or prolonged length of stay. Of additional interest was that median haemodialysis duration was greater in the HKTx-only cohort, despite having statistically similar rates of haemodialysis requirement frequency and incidence of delayed graft function. A numerical trend was observed in increased GFR in the MCS group immediately post-transplantation. Although this did not reach statistical significance and was not sustained, it potentially supports the concept of device pretransplantation optimization of intravascular haemodynamics. Nevertheless, based on overall GFR and the frequency of chronic dialysis postoperatively, the use of MCS devices did not seem to be deleterious to renal allograft function. Patient outcomes over 12-month post-transplantation, including freedom from NF-MACE, heart transplant rejection and survival, was not statistically different between both groups. These findings potentially demonstrate that combined HKTx in patients with MCS is reasonable as no significant increase is observed in morbidity or mortality. This seems to be in contradistinction to reports of decreased survival in MCS patients following isolated cardiac transplantation. The burden of low cardiac output in end-stage heart failure and the resulting reduction in organ perfusion have been known to precipitate renal dysfunction [4]. There may be a subset of patients undergoing isolated heart transplantation with underlying, undiagnosed renal dysfunction, thereby affecting mortality rates. Furthermore, many of these initial considerations of MCS’s negative impact on isolated cardiac transplantation outcomes were primarily based on pulsatile devices and, therefore, may not correlate to the newest MCS generation [21]. Limitations We acknowledge several limitations of this study. We appreciate the challenges inherent in a single-institution retrospective study. The small sample size also impacted the power of this study; simultaneous HTKxs are a relatively infrequently performed procedure, and, therefore, obtaining larger sample sizes is intrinsically difficult. Pooled assessment of HKTxs performed at multiple centres may provide improved statistical power while adjusting for potential geographical or institutional-specific variables. Follow-up over the past 1-year end point will additionally be of interest for longer-term outcome analyses. Despite these limitations, this study provides a preliminary evaluation of MCS prior to HKTx in the contemporary era. These results encourage further evaluation but seem to suggest that HKTx is a viable treatment option in patients with MCS as a bridge to transplantation with concomitant renal insufficiency. Conflict of interest: none declared. REFERENCES 1 McGiffin DC, Kirklin JK, Naftel DC. Acute renal failure after heart transplantation and cyclosporine therapy. J Heart Transplant  1985; 4: 396– 9. Google Scholar PubMed  2 Lund LH, Khush KK, Cherikh WS, Goldfarb S, Kucheryavaya AY, Levvey BJ et al.   The Registry of the International Society for Heart and Lung Transplantation: thirty-fourth Adult Heart Transplantation Report-2017; Focus Theme: allograft ischemic time. J Heart Lung Transplant  2017; 36: 1037– 46. Google Scholar CrossRef Search ADS PubMed  3 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. 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All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Interactive CardioVascular and Thoracic SurgeryOxford University Press

Published: May 24, 2018

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