Dual Organ Transplantation Research Articles

Short Term Outcomes in Case Series of 21 Congenital Heart Disease Recipients of Heart or Dual-Solid Organ Transplants

<h3>Purpose</h3> Heart transplantation for patients with end-stage congenital heart disease (CHD) is considered high risk due to increased peri-operative mortality at index hospitalization. However, survivors have comparable conditional 1-year survival and a superior 15-year survival when compared to non-CHD recipients. Outcomes from a multidisciplinary CHD team caring for this complex population are presented. <h3>Methods</h3> We conducted a retrospective review, at a large volume transplant center from 2017-2021 to identify consecutive patients who underwent single or dual-solid organ transplantation for the indication of end-stage CHD. Overall post-transplant survival at 6 and 12 months for this CHD cohort were compared to the other heart, heart-lung, and heart-liver transplants during the same period. <h3>Results</h3> There were 21 consecutive patients with end-stage CHD who were transplanted during the study period. A total of 12 recipients (57%) had single ventricle physiology with the most common defects being tricuspid atresia and hypoplastic left heart syndrome. Most were male (71%) with a mean age of 29 years (Table 1). There was a high proportion of dual-organ transplants (43%) with the most common being heart-liver (Table 1). Post-transplant survival at 6 and 12 months were 95% and 94%, respectively compared to 97% and 96%, respectively for similar transplant recipients for non-CHD indications. The single mortality in the CHD cohort occurred in a dual-organ transplant recipient (listed status 1A) with single ventricle and died 72 hours post-operatively due to severe, nonspecific graft dysfunction requiring extracorporeal membrane oxygenation support. <h3>Conclusion</h3> This study demonstrates an excellent post-transplant survival (94% at 12 months) for CHD patients can be achieved when a collaborative approach between pediatric and adult transplantation teams with congenital disease expert is employed in the pre-, peri- and post-transplantation period.

Value of Renal Histology for Predicting Cardiorenal Outcomes in Patients Listed for Cardiac Transplantation

<h3>Purpose</h3> Cardiorenal syndrome is associated with excess morbidity and mortality, particularly in patients requiring durable mechanical circulatory support or cardiac transplantation. There are minimal data regarding predictors of renal outcomes in these patients and identifying those who may benefit from dual organ-transplantation. <h3>Methods</h3> We identified 18-patients with renal histology supporting the diagnosis of cardiorenal syndrome, from 665 consecutive patients listed for cardiac transplantation between 2010-2019. These were prospectively analysed for glomerular, tubular, interstitial and arteriolar changes as shown in table 1, tallied to give a severity score. The primary outcome, major adverse kidney events (MAKE), was a composite of death, need for renal replacement therapy (RRT), drop in estimated glomerular filtration rate (eGFR) >50% or stage V chronic kidney disease occurring prior to transplantation for the baseline cohort, and following transplantation for the transplanted cohort. The secondary outcomes included the individual components of MAKE at the two different time points. <h3>Results</h3> Mean age 52.3, 22% female. 5 patients did not survive to transplant (2 of these died on ventricular assist device). 1 patient had successful heart-kidney transplant. MAKE occurred in 7/17 of baseline; this was associated with a higher severity score, mean 5 vs. 2.3, p=0.03. There was no difference in age, creatinine or eGFR at biopsy. MAKE following transplantation occurred in 8/13 patients. There were no significant associations with this outcome. MAKE in the baseline cohort was primarily driven by need for RRT (mean 5.2 vs. 2.5, p=0.04). Contrary to limited previous literature, interstitial fibrosis did not predict any outcome, whilst presence of glomerular ischaemic changes, tubular atrophy and arteriosclerosis were associated with pre-transplant MAKE. <h3>Conclusion</h3> More severe renal histology prior cardiac transplantation are associated with adverse renal endpoints.

Outcomes Following Heart Transplant for Patients with Cardiac Amyloidosis

<h3>Purpose</h3> Cardiac amyloidosis (CA) results from myocardial transthyretin (ATTR) or immunoglobulin light chain (AL) deposition and is associated with high mortality. Heart transplant (HT) has emerged as an option for patients (pts) with advanced disease. We present long-term survival data following HT for pts with CA. <h3>Methods</h3> All adult HT pts at our center between 1/1/2012 and 12/31/2020 were included. Heart explant pathology reports were reviewed for evidence of amyloid deposition based on Congo red staining. ATTR subtyping was confirmed with mass spectrometry analysis. Kaplan-Meier survival analysis was computed using a log-rank test for between-group differences. <h3>Results</h3> 63 pts with CA [AL (17), wild type - ATTR (20), variant - ATTR (24), amyloidosis leukocyte chemotactic factor 2 (1), beta 2 microglobulin (1)] underwent HT during the study period. Pts with CA were older (65.4 vs. 54.2), more likely to be male (90% vs. 70%), and less likely to be white (56% vs. 71%) compared to pts without CA. 9 ATTR pts (21%) and 5 AL patients (29%) underwent dual organ transplant. 5 patients with AL amyloidosis underwent subsequent autologous stem cell transplant (ASCT). Post-HT survival at 5 years was similar for pts with AL amyloidosis, ATTR amyloidosis, and other HT patients (n = 911) (p=0.67). AL and variant-ATTR pts had numerically lower survival than wild type - ATTR patients. Cause of death for pts with AL CA included primary graft dysfunction (1), complications related to ASCT (1), and anoxic brain injury (1). For pts with ATTR CA, cause of death included liver graft rejection (1), multi organ failure (1), respiratory failure (1), decompensated heart failure (1), and acute myocardial infarction (1). <h3>Conclusion</h3> Pts with CA that meet criteria for HT experience survival comparable to that for other indications. HT remains a viable option for CA pts with advanced disease, despite older age at the time of HT.

Impella 5.5 Support Prior to Heart and Kidney Transplantation

<h3>Introduction</h3> End-stage renal disease (ESRD) is a challenge when evaluating patients for advanced heart failure therapies. We present a patient with end-stage heart failure (HF) and ESRD, who was successfully bridged to heart and kidney transplantation using Impella 5.5 (Abiomed, Danvers, MA, USA) following bilateral nephrectomy. <h3>Case Report</h3> A 37-year-old, obese man with nonischemic cardiomyopathy from remote methamphetamine use presented with symptoms of decompensated HF despite being on a Milrinone infusion. Concomitantly, he had ESRD secondary to xanthogranulomatous pyelonephritis in a setting of chronic staghorn calculi (Figure 1). Given his progression to refractory HF, he was considered for dual organ transplantation. As a prerequisite to kidney transplantation, bilateral nephrectomy was performed for source control of the chronic pyelonephritis. Post-operative course was complicated by hemodynamic deterioration with early end-organ dysfunction despite an intra-aortic balloon pump support. He was brought to the operating room to emergently escalate his support to an Impella 5.5. Upon induction, he went into cardiac arrest. After the return of spontaneous circulation, an Impella 5.5 was placed. The device reached blood flows up to 5.2 liters per minute, which preserved him during his surgical recovery while undergoing continuous renal replacement therapy. There were no complications of malpositioning, thrombosis, or hemolysis. 30 days later, he had a combined heart and kidney transplantation. He continues to have excellent graft function after 5 months. <h3>Summary</h3> To our knowledge, this is the first reported successful use of Impella 5.5 to preserve a patient prior to a heart and kidney transplantation following bilateral nephrectomy. This case highlights how Impella 5.5 can be an invaluable tool to provide left ventricular support and as a bridge to heart transplantation for patients with end-stage HF who have kidney disease and/or recovering from major abdominal operations.

Slow It Down: A Case Report Of Microangiopathic Hemolytic Anemia In A Heartmate III Patient

<h3>Introduction</h3> Incidence of hemolysis in left ventricular assist devices (LVADs) is reported from 13-18%, but with HeartMate 3 (HM3) LVAD has been decreased to <1%. Typically, hemolysis is associated with LVAD thrombosis with subsequent decreased survival rate at 1 year (38.9% vs. 89.3%). We present a case of microangiopathic hemolytic anemia (MAHA), not related to pump thrombosis in a recent implanted HM3 LVAD patient which resolved by decreasing LVAD speed. <h3>Case Report</h3> A 44 year-old man with status post LVAD HM3 4 months prior complicated with right ventricular (RV) failure, pulmonary hypertension and CKD Stage III was admitted for mixed vasodilatory and cardiogenic shock. Patient required dual inotropes, vasopressors and temporary renal replacement therapy in an effort to stabilize him and continue his evaluation for heart and kidney transplant. Meanwhile, patient developed acute, severe thrombocytopenia (platelet count of 26K) and mild anemia. Disseminated intravascular coagulation was unlikely (normal fibrinogen level). Heparin-induced thrombosis (HIT) antibody testing was non-reactive. No active sepsis. There were no power spikes or suspected LVAD thrombosis (Table 1). Intrinsic bone marrow disease was thought to be unlikely. LDH was elevated and haptoglobin level undetectable (Table 2), blood smear showed schistocytes, raising suspicious for MAHA, therefore LVAD speed was decreased to 5100 RPM to diminish red blood cell (RBC) fragmentation and maintained in systemic unfractionated heparin infusion. This resulted in recovery of platelets and hemolysis parameters (Table 2). Ultimately, patient underwent dual organ transplantation without complications. <h3>Conclusions</h3> Per our knowledge, this is the first case reported of MAHA in a LVAD HM3 patient, not related to pump thrombosis that resolves with decrease in LVAD speed. MAHA is caused by mechanical injury of RBCs. The effective treatment in this scenario was to decrease the speed of the LVAD, hypothetically to decrease excessive shear in circulation. Further research should be done to delineate efficacy of reducing LVAD speed in these patients.

Evaluation of Donor Glomerular Filtration Rate on Survival Outcomes among Simultaneous Heart and Kidney Transplant Recipients

Purpose Evaluation of donor co-morbidities is critical in order to risk-stratify and optimize post-transplant survival among simultaneous heart and kidney transplant (HKT) patients. We aimed to characterize the effect of donor glomerular filtration rates (GFR) on HKT recipient survival at 60 months post-transplantation. Methods All patients registered in the UNOS database who received HKT from 1/1/2010 - 6/1/2021 were analyzed. HKT recipients with donors of GFR >30 mL/min/1.73 m2 (n =1934) and donors with GFR <=30 mL/min/1.73 m2 (n = 59) were compared. HKT recipients with donors of GFR >60 mL/min/1.73 m2 (n=1611) and <=60mL/min/1.73 m2 (n=382) were also compared. Baseline characteristics were compared using Mann-Whitney U and Chi-square analyses. Mean age among all recipients was 55.8 years (SE 10.8). Comorbidities including diabetes, smoking, pre transplant dialysis requirements, donor age, use of ventricular assist devices, life support ventilators, intra-aortic balloon pumps, and ischemic time were similar among groups. Kaplan-Meier survival analysis was performed at 60 months post-transplantation. Results At 60 months post-transplant, there were no significant differences in survival among HKT patients with donor GFR <=60mL/min/1.73 m2 and donor GFR>60mL/min/1.73 m2 groups, respectively (p=0.858). At 60 months post transplant, there was no significant survival change among those with donor GFR <=30 mL/min/1.73 m2 and >30 mL/min/1.73 m2 (p=0.400). After adjusting for variables listed above, HKT recipients with donors of GFR <=60 compared to >60 had similar survival rates (adjusted HR 1.016, 95% CI 0.776-1.332, p=0.904). A similar trend was seen for patients with donors of GFR <= 30 mL/min/1.73 m2 compared to those of GFR >30 mL/min/1.73 m2 (adjusted HR 0.650, 95% CI 0.290-1.457, p=0.295). Conclusion Donor GFR in isolation had no significant impact on survival among simultaneous heart kidney transplant recipients at 60 months post transplantation after controlling for comorbidities. Donor kidney function In isolation should also not prohibit consideration for dual organ transplantation. Evaluation of donor co-morbidities is critical in order to risk-stratify and optimize post-transplant survival among simultaneous heart and kidney transplant (HKT) patients. We aimed to characterize the effect of donor glomerular filtration rates (GFR) on HKT recipient survival at 60 months post-transplantation. All patients registered in the UNOS database who received HKT from 1/1/2010 - 6/1/2021 were analyzed. HKT recipients with donors of GFR >30 mL/min/1.73 m2 (n =1934) and donors with GFR <=30 mL/min/1.73 m2 (n = 59) were compared. HKT recipients with donors of GFR >60 mL/min/1.73 m2 (n=1611) and <=60mL/min/1.73 m2 (n=382) were also compared. Baseline characteristics were compared using Mann-Whitney U and Chi-square analyses. Mean age among all recipients was 55.8 years (SE 10.8). Comorbidities including diabetes, smoking, pre transplant dialysis requirements, donor age, use of ventricular assist devices, life support ventilators, intra-aortic balloon pumps, and ischemic time were similar among groups. Kaplan-Meier survival analysis was performed at 60 months post-transplantation. At 60 months post-transplant, there were no significant differences in survival among HKT patients with donor GFR <=60mL/min/1.73 m2 and donor GFR>60mL/min/1.73 m2 groups, respectively (p=0.858). At 60 months post transplant, there was no significant survival change among those with donor GFR <=30 mL/min/1.73 m2 and >30 mL/min/1.73 m2 (p=0.400). After adjusting for variables listed above, HKT recipients with donors of GFR <=60 compared to >60 had similar survival rates (adjusted HR 1.016, 95% CI 0.776-1.332, p=0.904). A similar trend was seen for patients with donors of GFR <= 30 mL/min/1.73 m2 compared to those of GFR >30 mL/min/1.73 m2 (adjusted HR 0.650, 95% CI 0.290-1.457, p=0.295). Donor GFR in isolation had no significant impact on survival among simultaneous heart kidney transplant recipients at 60 months post transplantation after controlling for comorbidities. Donor kidney function In isolation should also not prohibit consideration for dual organ transplantation.

Combined Heart Kidney Transplantation in a Previous Heart Transplant Recipient with Pheochromocytoma and Monoclonal Gammopathy of Uncertain Significance

Introduction Cancer survivors and patients with active malignancies are considered high risk for solid organ transplantation, as there is concern for recurrence and their concurrent co-morbidities. We present a case of combined kidney and repeat heart transplant (HT) for a patient with cardiac allograft vasculopathy (CAV) found to have pheochromocytoma and monoclonal gammopathy of unknown significance (MGUS) on pre-transplant evaluation. Case Report A 47-year-old male with a history of orthotopic HT 20 years prior due to viral myocarditis with post-transplant course complicated by CAV, chronic kidney disease stage 4 (presumed due to tacrolimus), MGUS, and atrial fibrillation presented with acute decompensated heart failure requiring inotropes. Echocardiogram revealed EF of 35%, global hypokinesis; RHC showed RA 19, RV 37/2, PA 38/17/25, PW 27, CI 1.6. LHC showed ISHLT CAV3: 70% mLAD lesion and diffuse 50-80% disease in distal LAD, Cx, and RCA. An IABP was placed and the patient was managed in the cardiac intensive care unit. Imaging revealed a right adrenal mass. He underwent an IR guided adrenal biopsy that demonstrated a pheochromocytoma, with biochemical markers of active tumor. The patient received a laparoscopic adrenalectomy and was listed for dual organ transplant. With worsening hemodynamics, he required peripheral VA-ECMO and received combined heart and renal transplant a month later. His post-operative course was complicated by RV dysfunction requiring central VA-ECMO, transplant pyelonephritis, and delayed renal allograft function requiring transient hemodialysis. Cardiac function recovered in 2 weeks post-transplant. Two and a half months post-transplant, a renal biopsy was performed for worsening acute kidney injury and demonstrated kappa light chain proximal tubulopathy. Given known MGUS, patient was diagnosed with monoclonal gammopathy of renal significance and started on started on Ixazomib-Cytoxan-Dexamethasone. He has shown improvement clinically and is now over one year post-transplant. Summary Combined heart kidney transplantation may be an option for selected patients with active malignancies like localized pheochromocytoma with MGUS. Long term follow up outcomes are unknown in this patient population. Cancer survivors and patients with active malignancies are considered high risk for solid organ transplantation, as there is concern for recurrence and their concurrent co-morbidities. We present a case of combined kidney and repeat heart transplant (HT) for a patient with cardiac allograft vasculopathy (CAV) found to have pheochromocytoma and monoclonal gammopathy of unknown significance (MGUS) on pre-transplant evaluation. A 47-year-old male with a history of orthotopic HT 20 years prior due to viral myocarditis with post-transplant course complicated by CAV, chronic kidney disease stage 4 (presumed due to tacrolimus), MGUS, and atrial fibrillation presented with acute decompensated heart failure requiring inotropes. Echocardiogram revealed EF of 35%, global hypokinesis; RHC showed RA 19, RV 37/2, PA 38/17/25, PW 27, CI 1.6. LHC showed ISHLT CAV3: 70% mLAD lesion and diffuse 50-80% disease in distal LAD, Cx, and RCA. An IABP was placed and the patient was managed in the cardiac intensive care unit. Imaging revealed a right adrenal mass. He underwent an IR guided adrenal biopsy that demonstrated a pheochromocytoma, with biochemical markers of active tumor. The patient received a laparoscopic adrenalectomy and was listed for dual organ transplant. With worsening hemodynamics, he required peripheral VA-ECMO and received combined heart and renal transplant a month later. His post-operative course was complicated by RV dysfunction requiring central VA-ECMO, transplant pyelonephritis, and delayed renal allograft function requiring transient hemodialysis. Cardiac function recovered in 2 weeks post-transplant. Two and a half months post-transplant, a renal biopsy was performed for worsening acute kidney injury and demonstrated kappa light chain proximal tubulopathy. Given known MGUS, patient was diagnosed with monoclonal gammopathy of renal significance and started on started on Ixazomib-Cytoxan-Dexamethasone. He has shown improvement clinically and is now over one year post-transplant. Combined heart kidney transplantation may be an option for selected patients with active malignancies like localized pheochromocytoma with MGUS. Long term follow up outcomes are unknown in this patient population.

Early Outcomes of Donation After Circulatory Death Heart Transplantation with Thoracoabdominal Normothermic Regional Perfusion

<h3>Purpose</h3> To evaluate the early outcomes of donation after circulatory death (DCD) heart transplantation using thoracoabdominal normothermic regional perfusion (TA-NRP). <h3>Methods</h3> The study is designed as a single center prospective study with single arm. Institutional Review Board approved this pilot for a total number of 60 potential DCD heart recipients using grafts recovered with TA-NRP technique (IRB#460-20-FB). The first patient was enrolled on January 3rd 2021. The anticipated study duration is one year for a total of 10 transplant procedures. Recipient inclusion criteria are age ≥ 19 years, signed informed consent, and eligibility for heart transplantation based on standardized institutional criteria. Patients listed for dual organ transplantation and patients with previous cardiac operation including durable LVAD implantation will also be included. All hearts will be recovered with TA-NRP after no more than 30 minutes of warm ischemia (defined as the time period commencing from SBP < 50 mmHg to in-situ reperfusion). TA-NRP protocol is summarized in Figure 1. Acceptance for transplantation will be based upon the functional assessment with TEE and invasive hemodynamic measurements combined with the visual inspection after separation from mechanical support. Grafts will be recovered using 2,000mL of Celsior® for cardio protection, and transported with colds storage. All implantation procedures will be performed at our institution. Recipients will receive standardized immunosuppression and infection prophylaxis and will undergo rejection surveillance with serial endomyocardial biopsies. <h3>Endpoints</h3> Primary outcome is 30-day patient survival. Secondary outcomes are primary graft dysfunction and inotropic score at 72 hours, ICU and hospital length of stay, ventilation duration, and the need for renal replacement therapy.

Feasibility Of Outpatient Hemodialysis For Patients With Total Artificial Heart

<h3>Introduction</h3> Total artificial hearts (TAH) are used in patients with end-stage heart failure as a bridge-to-transplant. AKI is a common post-operative complication associated with TAH implant. Patients requiring temporary dialysis are denied implantation of TAH due to the inability to provide outpatient (OP) dialysis in the long term. In most cases, patients with a TAH with renal dysfunction requiring dialysis remain hospitalized until either a heart-kidney becomes available for transplant or renal function recovers. To our knowledge, there is only one case describing a TAH patient successfully maintained on OP dialysis, and he did not survive to transplant. Here we discuss four cases from a single center who were successfully maintained on OP hemodialysis (HD) after implantation of TAH. <h3>Case Presentation</h3> All four patients were implanted with a 70cc Syncardia TAH for NICM. Two were INTERMACS profile 2 and two were profile 3. The profile 2 patients had preoperative CKD Stage III. The profile 3 patients had normal preoperative renal function<b>.</b> Age at time of implant ranged from 31-61 years; two were female and 2 were male. Average post-op hospital length of stay was 63 days. Three patients required discharge to acute rehab, and one was discharged directly home. All patients were on scheduled OP HD QMWF. The average length of service of OP HD was 185 days (ranging 75-483 days). Outcomes for each patient differed: one remains on OP HD with TAH, one died before transplant due to anoxic brain injury, one underwent orthotopic heart transplantation but did not survive to renal transplant, and one had subsequent improvement in renal function still awaiting heart transplant. <h3>Discussion</h3> Maintaining TAH patients with renal failure on OP HD can increase patient quality of life and decrease inpatient hospital burden and costs. In these four cases, one patient survived to transplant, one did not survive to transplant, one is still awaiting dual-organ transplant, and one was successfully weaned off HD as an OP. A total of 318 days of OP HD was performed among these four patients without complications. These cases confirm that OP HD is a feasible option for TAH patients with post-implant chronic renal dysfunction provided that the dialysis centers are trained and supported by the implanting program.

Ultrashort Duration Prophylaxis for Hepatitis C Donor Positive to Recipient Negative Simultaneous Kidney/Pancreas Transplants.

Recent clinical trials have successfully used a strategy of hepatitis C virus (HCV) D+ (donor nucleic acid test [NAT] positive)/R– (recipient NAT negative) kidney and/or pancreas transplants followed by 8 to 12 wk of pangenotypic direct-acting antiviral (DAA) therapy.1,2 Translating these trials into real-world practice has revealed limitations. One concern is a delay in timely access to DAAs for these newly transplanted immunosuppressed patients. This early HCV viremia has been associated with abnormal liver function, acute fibrosing cholestatic hepatitis, and development of de novo donor-specific antibodies.3,4 Utilization of abbreviated regimens may obviate the need for insurance approval and delay in therapy. We have previously shown a low transmission rate of 4% with a prophylactic perioperative 7-d DAA regimen ( ±ezetimibe) for “kidney-only” transplants.5 Ezetimibe, a cholesterol-lowering drug, was used, as it has been shown to restrict HCV entry in hepatocytes in a humanized mouse model.6 Here, we present our early experience using the same strategy for simultaneous kidney/pancreas transplants (SKPT), where the risk of transmission is conceivably higher because of a cumulative higher HCV load delivered with dual-organ transplantation. Data were collected via an ethics board-approved prospective registry (REgistry for the study of ORgan transplants froM HEPatitis C infected donors)5 with informed consent for all participants. Of 12 eligible SKPT candidates, 10 (83%) agreed to accept HCV NAT+ SKPT offers. Inclusion criteria included (1) a de novo transplant; (2) a calculated panel reactive antibody ≤50%; (3) an absence of synthetic liver dysfunction; and (4) an absence of HIV, HCV, and hepatitis B. The primary outcome was donor HCV transmission at 90 d posttransplant. Secondary outcomes included posttransplant organ function, development of de novo donor-specific antibodies, and acute rejection. Patients were screened with HCV NAT at day 7, 14, 28, and 90 posttransplant. All subjects received an initial dose of sofosbuvir/velpatasvir (SOF/VEL) with ezetimibe on day 0 ≤6 h before transplant and then daily for a total of 7 d. Proton pump inhibitors were not initiated early posttransplant to avoid a known drug–drug interaction and reduced absorption of SOF/VEL. Immunosuppression included induction with rabbit antithymocyte globulin followed by maintenance tacrolimus, mycophenolate, and steroids. The protocol mandated initiation of full-course DAA therapy in the case of 2 consecutive positive NATs. Of the 10 candidates, 4 received HCV NAT+ SKPT at a median of 4.7 mo post consent. Summary characteristics of these 4 patients are presented in Table 1. All patients had immediate graft functions of both transplanted organs. At a median follow-up of 7 mo posttransplant, all patients maintained excellent graft functions. All subjects remained negative for HCV at all monitored time points, including at 90 d posttransplant, resulting in an HCV transmission rate of 0%. One patient had acute kidney injury because of biopsy-proven thrombotic microangiopathy at 1 mo posttransplant that improved with conversion of tacrolimus to belatacept. No other major adverse events were recorded at the most recent follow-up. TABLE 1. - Selected donor and recipient characteristics of study cohort Recipient characteristics Variable N 4 Age (y, mean ± SD) 41 ± 13 Male sex 3 (75%) African American race 2 (50%) Blood type A 1 (25%) B 1 (25%) O 2 (50%) Median total wait time (mo, range) 5.3 (4–31) Postenrollment wait time (mo, range) 4.7 (3.6–5.8) Cold ischemia time (h, mean ± SD) 9 ± 1 Donor characteristics Donor age (y, mean, mean ± SD) 27 ± 1 Donor KDPI (%, mean ± SD) 28 ± 9 Donor corrected KDPIa (%, mean ± SD) 7 ± 6 Donor terminal creatinine (mg/dL, mean ± SD) 1.0 ± 0.1 Selected outcomes Delayed graft function 0 (0%) Time of follow-up (mo, range) 7.3 (4.4–10.7) ALT at 3 mo posttransplant (IU/L, mean ± SD) 67 ± 22 Lipase at 3 mo posttransplant (U/L, mean ± SD) 15 ± 11 GFR at 3 mo posttransplant (mean ± SD) 77 ± 25 Most recent GFR (mean ± SD) 87 ± 14 Acute rejection 0 (0%) De novo donor-specific antibody at 3 mo posttransplant 0 (0%) aKDPI recalculated after exclusion of hepatitis C as a contributing factor.ALT, alanine aminotransferase; GFR, glomerular filtration rate (mL/min/1.73 m2); KDPI, Kidney Donor Profile Index. This early experience suggests that ultrashort duration 7-d perioperative DAA prophylaxis with SOF/VEL can be successfully used for patients with SKPT. These data are limited by a small sample size, a single-center design, and an absence of donor virological data.

Trends and Outcomes of Hypothermic Machine Perfusion Preservation of Kidney Allografts in Simultaneous Liver and Kidney Transplantation in the United States.

Optimal kidney graft outcomes after simultaneous liver-kidney (SLK) transplant may be threatened by the increased cold ischemia time and hemodynamic perturbations of dual organ transplantation. Hypothermic machine perfusion (MP) of kidney allografts may mitigate these effects. We analyzed U.S. trends and renal outcomes of hypothermic non-oxygenated MP vs. static cold storage (CS) of kidney grafts from 6,689 SLK transplants performed between 2005 and 2020 using the United Network for Organ Sharing database. Outcomes included delayed graft function (DGF), primary non-function (PNF), and kidney graft survival (GS). Overall, 17.2% of kidney allografts were placed on MP. Kidney cold ischemia time was longer in the MP group (median 12.8 vs. 10.0h; p < 0.001). Nationally, MP utilization in SLK increased from <3% in 2005 to >25% by 2019. Center preference was the primary determinant of whether a graft underwent MP vs. CS (intraclass correlation coefficient 65.0%). MP reduced DGF (adjusted OR 0.74; p = 0.008), but not PNF (p = 0.637). Improved GS with MP was only observed with Kidney Donor Profile Index <20% (HR 0.71; p = 0.030). Kidney MP has increased significantly in SLK in the U.S. in a heterogeneous manner and with variable short-term benefits. Additional studies are needed to determine the ideal utilization for MP in SLK.

Role of Veno-arterial Extracorporeal Membrane Oxygenation in Left Ventricular Conditioning after Lung Transplantation

End-stage pulmonary hypertension alters intracardiac pressures, leading to distention and failure of the right ventricle, leftward shifting of the intraventricular septum, and, thus, underfilling of the left ventricle (LV). Following the resolution of severely elevated pulmonary vascular resistance with bilateral lung transplantation, the LV is exposed to relatively high filling pressures from a potentially hypertrophic right ventricle pushing blood through normalized pulmonary vascular resistance. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) may be a valuable tool to provide a more gradual exposure of the LV to the newly available preload in the immediate postoperative phase of transplantation, thereby reducing the likelihood of primary graft dysfunction developing from the LV diastolic dysfunction. This paper presents a case in which V-A ECMO was initiated during cardiac arrest in a patient with advanced pulmonary hypertension and right ventricular failure and maintained for two days for postoperative patient stability and cardiac conditioning. The discussion includes data from transplant programs using this method to reduce the need for dual organ transplantation and postoperative primary graft dysfunction in the allograft.

Estimating Glomerular Filtration Rate in Cirrhosis Using Creatinine-Based and Cystatin C-Based Equations: Systematic Review and Meta-Analysis.

Accurate estimation of kidney function in cirrhosis is crucial for prognosis and decisions regarding dual-organ transplantation. We performed a systematic review/meta-analysis to assess the performance of creatinine-based and cystatin C (CysC)-based eGFR equations compared with measured GFR (mGFR) in patients with cirrhosis. A total of 25 studies (n = 4565, 52.0 years, 37.0% women) comprising 18 equations met the inclusion criteria. In all GFR equations, the creatinine-based equations overestimated GFR (standardized mean difference, SMD, 0.51; 95% confidence interval [CI], 0.31-0.71) and CysC-based equations underestimated GFR (SMD, -0.3; 95% CI, -0.60 to -0.02). Equations based on both creatinine and CysC were the least biased (SMD, -0.14; 95% CI, -0.46 to 0.18). Chronic kidney disease-Epi-serum creatinine-CysC (CESC) was the least biased but had low precision and underestimated GFR by -3.6 mL/minute/1.73 m2 (95% CI, -17.4 to 10.3). All equations significantly overestimated GFR (+21.7 mL/minute/1.73 m2 ; 95% CI, 17.7-25.7) at GFR <60 mL/minute/1.73 m2 ; of these, chronic kidney disease-Epi-CysC (10.3 mL/minute/1.73 m2 ; 95% CI, 2.1-18.4) and GFR Assessment in Liver Disease (12.6 mL/minute/1.73 m2 ; 95% CI, 7.2-18.0) were the least biased followed by Royal Free Hospital (15 mL/minute/1.73 m2 ; 95% CI, 5.5-24.6) and Modification of Diet in Renal Disease 6 (15.7 mL/minute/1.73 m2 ; 95% CI, 10.6-20.8); however, there was an overlap in the precision of estimates, and the studies were limited. In ascites, overestimation of GFR was common (+8.3 mL/minute/1.73 m2 ; 95% CI, -3.1 to 19.7). However, overestimation of GFR by 10 to 20 mL/minute/1.73m2 is common in patients with cirrhosis with most equations in ascites and/or kidney dysfunction. A tailored approach is required especially for decisions regarding dual-organ transplantation.

Use of Extended Criteria Donor Hearts in Simultaneous Heart-Kidney Transplantation

PurposeInsufficiency of donor organ supply has led to the utilization of extended criteria donor (ECD) hearts. Several groups have demonstrated that careful use of ECD hearts has acceptable outcomes in select patients. However, the use of ECD hearts has yet to be studied in patients undergoing simultaneous heart-kidney transplantation (SKHT). This study evaluates the outcomes of patients receiving standard criteria donor (SCD) vs. ECD hearts in the setting of SHKT.MethodsRetrospective review of the Organ Procurement and Transplantation Network database was performed for adults undergoing SHKT since 1/1/2010. Patients were stratified by receipt of an ECD heart. SCD hearts were defined by the 2020 International Society for Heart and Lung Transplantation Consensus Statement on Donor Heart and Lung Procurement. ECD hearts were defined as those that failed to meet any of these criteria. The primary outcome was patient survival. Secondary outcomes included several post-operative complications.ResultsOverall 1,389 SHKTs were performed during the study period, of which 345 (24.8%) utilized ECD hearts. Recipients of ECD hearts were more likely to have a higher body mass index (25.6 vs. 29.5, p<0.001) and were more likely to have diabetes (39.5% vs. 48.5%, p=0.005). Postoperatively, the SCD and ECD cohorts experienced similar rates of pacemaker implantation (2.1% vs. 0.9%, p=0.16), hemodialysis (29.9% vs. 32.2%, p=0.42), and stroke (3.3% vs. 3.5%, p=0.86). However, the ECD cohort experienced greater incidence of cardiac graft failure due to primary nonfunction (0.7% vs. 2.9%). ECD patients experienced decreased survival at 30 days (96.6% vs. 91.2%, p=0.001) and at 5 years (80.2% vs. 72.5%, p=0.002) as shown in Figure 1.ConclusionUse of ECD hearts in the setting of SHKT is associated with increased mortality. Careful consideration should be given before accepting an ECD heart for SHKT given the increased consequences of recipient death on responsible organ allocation in dual organ transplantation. Insufficiency of donor organ supply has led to the utilization of extended criteria donor (ECD) hearts. Several groups have demonstrated that careful use of ECD hearts has acceptable outcomes in select patients. However, the use of ECD hearts has yet to be studied in patients undergoing simultaneous heart-kidney transplantation (SKHT). This study evaluates the outcomes of patients receiving standard criteria donor (SCD) vs. ECD hearts in the setting of SHKT. Retrospective review of the Organ Procurement and Transplantation Network database was performed for adults undergoing SHKT since 1/1/2010. Patients were stratified by receipt of an ECD heart. SCD hearts were defined by the 2020 International Society for Heart and Lung Transplantation Consensus Statement on Donor Heart and Lung Procurement. ECD hearts were defined as those that failed to meet any of these criteria. The primary outcome was patient survival. Secondary outcomes included several post-operative complications. Overall 1,389 SHKTs were performed during the study period, of which 345 (24.8%) utilized ECD hearts. Recipients of ECD hearts were more likely to have a higher body mass index (25.6 vs. 29.5, p<0.001) and were more likely to have diabetes (39.5% vs. 48.5%, p=0.005). Postoperatively, the SCD and ECD cohorts experienced similar rates of pacemaker implantation (2.1% vs. 0.9%, p=0.16), hemodialysis (29.9% vs. 32.2%, p=0.42), and stroke (3.3% vs. 3.5%, p=0.86). However, the ECD cohort experienced greater incidence of cardiac graft failure due to primary nonfunction (0.7% vs. 2.9%). ECD patients experienced decreased survival at 30 days (96.6% vs. 91.2%, p=0.001) and at 5 years (80.2% vs. 72.5%, p=0.002) as shown in Figure 1. Use of ECD hearts in the setting of SHKT is associated with increased mortality. Careful consideration should be given before accepting an ECD heart for SHKT given the increased consequences of recipient death on responsible organ allocation in dual organ transplantation.

Pre-Transplant Immune Cell Function Assay as a Predictor of Early Cardiac Allograft Rejection

Purpose ImmuKnow, an immune cell function assay that quantifies overall immune system activity can assist in post-transplant immunosuppression adjustment. The utility of pretransplant ImmuKnow results representing a patient's baseline immune system activity is unknown. We sought to assess if pretransplant ImmuKnow results are predictive of rejection at the time of first biopsy in a cardiac transplant population.. Methods 81 cardiac transplant patients with pre-transplant ImmuKnow results (out of 110 total transplant patients) were identified. ImmuKnow results were analyzed according to the clinical interpretation ranges (low, medium, high activity). Pre-transplant clinical characteristics, induction immunosuppression use, early postoperative tacrolimus levels (Day 7 post transplant), and first endomyocardial biopsy results were collected for all patients. Logistic regression was used to estimate the association of the pre-transplant ImmunKnow group with clinically significant early rejection (≥ 1R/2), and to determine if the association was modified by the use of induction therapy and early tacrolimus levels. Results Significant early rejection was found in 15 patients (18.5%). Early rejection occurred in 0/15 patients with low pretransplant ImmuKnow levels vs. 15/64 patients with moderate or high pre-transplant ImmunoKnow levels (p=0.04). Induction immunosuppression was used for 26 patients (32.1%). The most common reason for induction was dual organ transplantation. Of the 55 patients without induction immunosuppression, 13 had rejection (23.6%). The mean ImmuKnow level in the non-rejection group was 391 ng/ml of ATP compared to 516 ng/ml of ATP for those with rejection (p=0.06). Lower pretransplant ImmuKnow levels among non-rejection patients was not diminished when controlling for tacrolimus level. Conclusion Patients with low pre-transplant ImmunoKnow levels had a lower risk of early rejection when compared with patients with medium or high levels. After adjusting for tacrolimus level, this relationship was maintained. Our study suggests a possible utility in performing pretransplant ImmunoKnow to identify patients at-risk for early rejection who may benefit from intensified upfront immunosuppression.

Role of Cardiac Transplant in Systemic Lupus Erythematosus Complicated by Severe Heart Failure

Purpose Systemic lupus erythematosus (SLE) is a systemic disease and is commonly considered a contraindication for cardiac transplantation. Meanwhile, lupus myocarditis can present with severe left ventricular dysfunction which my progress to cardiogenic shock with a fatal outcome. Heart transplantation is rarely considered a treatment option, due to 1) multi-organ involvement, and 2) possibility of recurrence of lupus in the transplanted heart. We summarized published cases of cardiac transplantation in SLE. Methods Two investigators independently searched PubMed, Ovid/Medline, and Google Scholar using terms “heart transplantation”, “cardiac transplantation” AND “lupus”, “systemic lupus erythematosus”, and “lupus myocarditis” for papers published in English in 1988-2020. We then manually searched the references in relevant articles. We included all cases of adult patients where individual patient data were present. Results We identified 11 cases, six males, and five females, mean age 28 +/- 5.47 years. Six of the patients were male and five were female. While all patients had SLE, the most common indication for transplant was pulmonary hypertension (6), followed by lupus myocarditis (2), dilated cardiomyopathy (2), and infective endocarditis (1). In 6 patients there was a dual organ (heart/lung) transplantation, while in five the heart was the only transplanted organ. Two patients died within 2 months post transplant from bowel infarction, and one died in one year from rejection. Remaining eight patients were alive and well after a follow-up ranging nine months to four years, mean 26 +/- 9.9 months. Recurrence of lupus was not reported in any patient, including six cases where it was specifically indicated that there was no recurrence. Conclusion Based on reported cases, heart transplantation in SLE is a viable option, with good survival and no recurrence of lupus in the transplanted heart. In cases of intractable heart failure in patients with SLE, cardiac transplantation should be considered.

Consensus conference on heart-kidney transplantation.

Simultaneous heart-kidney transplant (sHK) has enabled the successful transplantation of patients with end-stage heart disease and concomitant kidney disease, with non-inferior outcomes to heart transplant (HT) alone. The decision for sHK is challenged by difficulties in differentiating those patients with a significant component of reversible kidney injury due to cardiorenal syndrome who may recover kidney function after HT, from those with intrinsic advanced kidney disease who would benefit most from sHK. A consensus conference on sHK took place on June 1, 2019 in Boston, Massachusetts. The conference represented a collaborative effort by experts in cardiothoracic and kidney transplantation from centers across the United States to explore the development of guidelines for the interdisciplinary criteria for kidney transplantation in the sHK candidate, to evaluate the current allocation of kidneys to follow the heart for sHK, and to recommend standardized care for the management of sHK recipients. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical problems related to multi-organ transplantation were also debated. The findings and consensus statements are presented.

Combined Sequential Heart-Liver Transplantation

Many single ventricle patients palliated with the Fontan operation suffer from Fontan failure and progressive liver disease. Combined heart-liver transplantation is a rarely utilized and complex transplant strategy available for select Fontan patients. At the Hospital of the University of Pennsylvania, all Fontan patients deemed eligible for a heart transplantation undergo a combined sequential dual organ transplantation with same-donor organs. This article describes the techniques utilized as well as current results.

Use of Rabbit Anti-thymocyte Globulin as a Renal Sparing Strategy: Outcomes from a Single Center

Introduction Acute kidney injury (AKI) complicates up to 25% of patients undergoing orthotopic heart transplant (OHT) and can be exacerbated by the introduction of calcineurin inhibition (CNI). Induction with rabbit anti-thymocyte globulin (ATG) can provide immunosuppression to prevent early rejection until CNI therapy is introduced. However, current data regarding ATG use to allow delayed CNI initiation is limited. Hypothesis ATG induction with delayed initiation of tacrolimus as a renal sparing strategy will result in less renal failure without a significant increase in infection and rejection. Methods From January 2014 to December 2019, 143 patients underwent OHT. Dual organ transplantation, those requiring ATG for non-renal sparing reasons, and patients without 1 -year follow-up were excluded. Using standard statistical analysis, we compared in-hospital and post discharge outcomes at 1, 6, and 12 months between patients with and without ATG administration. Results ATG was given to 26/71 (36.6%) patients as a renal sparing strategy. Compared to the no ATG group, the ATG group had higher pre-transplant creatinine (1.5 vs 1.2 mg/dL, p=0.001) and lower glomerular filtration rate (GFR) (58.6 vs 76.4 ml/min, p=0.002), but no other significant differences in baseline characteristics. Tacrolimus was started later in the ATG group (3.6 vs 0.9 days, p=0.0001). The ATG group had lower GFR at 1 month (64.1 vs 82.5 ml/min, p = 0.009) and 6 months (44.2 vs 58.1 ml/min, p= 0.028) with a non-significant difference at 1 year (50.1 vs 62.4 ml/min, p=0.08). The ATG group was more likely to require renal replacement therapy (RRT) during the index admission (34.6 vs 4.4%, p=0.01). This difference persisted at discharge (19.2% vs 2.2%, p= 0.022) and 1 year (15.4% vs 0%, p= 0.015). No significant difference between the two groups in the rate of worsening chronic kidney disease at 1, 6 and 12 months. Freedom from readmission for infection was lower in the ATG group (53.8 % vs 80%, p= 0.03). There were no significant differences in in-hospital (p=1.00), 1 year mortality (p=0.19), and 1 year freedom from rejection (p=0.80) between groups. Conclusions ATG use as a renal sparing strategy in OHT recipients with renal dysfunction at baseline was associated with a high rate of early RRT but overall change in renal function over one year was similar. Freedom from readmission for infection was lower in the ATG group and freedom from rejection was equal in both groups. Thus, it appears in this retrospective analysis, that a strategy of induction therapy for renal sparing was not beneficial and increased the risk of infection.

Positively Double Jeopardy - Dual Organ Transplantation in an HIV+ Patient

Intro : Solid organ transplantation (SOT) is uncommon in persons living with HIV infection (PLWHIV), as historically, HIV infection was a contraindication to transplantation. However, advancements in antiretroviral therapy (ART) and immunosuppression has led to successful organ transplantation, including heart, in PLWHIV. Here, we present a case of dual-organ transplant in a PLWHIV. Case Report : A 46 yo African American man with Stage D heart failure due to dilated cardiomyopathy, end-stage renal disease (ESRD) on peritoneal dialysis (PD), and longstanding HIV infection (CD4 726 cells/µl, HIV RNA less than 20 copies/mL) presented in cardiogenic shock. On hospital day 5, an axillary intra-aortic balloon pump (IABP) was placed, and the patient was upgraded to a status 2 on the UNOS waitlist for heart-kidney transplantation. On hospital day 33, he received a heart transplant, followed the next day with a deceased donor renal transplant from the same donor. He underwent induction with basiliximab 20 mg, on POD#0 and #4, followed by immunosuppression with mycophenolate mofetil 1g BID, tacrolimus 3mg BID, and prednisone 10mg BID. The pre-transplant ART with dolutegravir/rilpivirine was resumed and he was initiated on standard anti-infective prophylaxis with valganciclovir, atovaquone, and clotrimazole. Hospital course was complicated by hospital-acquired pneumonia and delayed kidney graft function with acute tubular necrosis, initially requiring hemodialysis. There was no evidence of antibody mediated or acute cellular rejection on endomyocardial biopsies. Two months after transplant, the patient was found to have BK viremia, initiated on cidofovir. Four months post-transplant, he was no longer requiring dialysis, had preserved graft function on echocardiogram, and transitioned from atovaquone to sulfamethoxazole-trimethoprim for a lifelong course. Most recent labs notable for sCr 1.66 mg/dL, eGFR 54 mL/min/1.73m2, CD4 890 cells/µl, HIV RNA less than 20 copies/mL, BK virus quantitative PCR 23,875 copies/mL. His current immunosuppressive regimen includes mycophenolate mofetil 250mg BID and tacrolimus 2mg BID. Summary Patients with advanced heart failure who are concomitantly HIV+ are a unique and growing population. Multi-organ transplantation involving heart and kidney in this patient population has not been reported in the literature. As demonstrated in this case, with special considerations to patient selection, immunosuppression, and anti-infective regimens, and collaboration of a multidisciplinary team of heart and kidney transplant physicians and surgeons, along with infectious disease specialists, a successful multi-organ heart-kidney transplant in PLWHIV is feasible with excellent outcomes early after transplant.