Combined Heart-liver Transplantation Research Articles

Advances in Treatment of ATTRv Amyloidosis: State of the Art and Future Prospects.

Hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy is a progressive disease that is transmitted as an autosomal dominant trait and characterized by multiple organ failure, including axonal sensory-motor neuropathy, cardiac involvement, and autonomic dysfunction. Liver transplantation (LT) and combined heart–liver transplantation, introduced in the 1990s, have been the only therapies for almost two decades. In 2011, tafamidis meglumine became the first specific drug approved by regulatory agencies, since then the attention toward this disease has progressively increased and several drugs with different mechanisms of action are now available. This review describes the drugs already on the market, those that have shown interesting results although not yet approved, and those currently being tested.

Abstract 16533: Heterogeneity of Fibrosis in Patients Undergoing Combined Heart-Liver Transplant

Introduction: Combined heart-liver transplant (CHLT) is indicated for patients with end-stage heart failure and concomitant irreversible liver injury. Given that liver dysfunction from congestive hepatopathy is common in patients with end-stage heart failure, it can be difficult to determine reversible from irreversible liver injury. Transjugular liver biopsy (TJLB) is frequently used to evaluate the severity of parenchymal injury, but is limited by heterogeneity of fibrosis across biopsy specimens. We sought to compare the fibrosis evaluation of the TJLB specimens as compared to the pathology of the liver explant at the time of CHLT. Methods: All CHLT cases at CSMC between 2007 and 2017 were included. Demographic and liver ultrasound (US) or abdominal computed tomography (CT) imaging was retrieved by chart review. TJLB was performed prior to transplant to determine the severity of liver fibrosis and was compared to the pathology of the liver explant. A biopsy was considered to show heterogenous fibrosis if there was at least a 2 stage difference between the predominant and secondary patterns. Results: Thirteen CHLTs were performed at our center during the study period. The median follow-up was 59 months (IQR 48-67). Mean age at transplant was 53 years (SD +/- 14.9) and 77% of patients were male. Indications for CHLT included cardiac cirrhosis (7), amyloidosis (2), HCV cirrhosis (2), and congenital heart disease (2). By imaging, 3/7 patients (43%) had US and CT evidence, 2/7 (29%) had US or CT evidence, and 2/7 (29%) had no evidence of liver nodularity US or CT. All patients diagnosed with cardiac cirrhosis had both TJLB and explant pathology for review. All TJLBs were graded as stage 4 fibrosis. Fibrosis on analysis of the liver explant was variable: stage 4 (2), stage 3-4 (3), stage 2-4 (1), and stage 1-4 (1). Thus, 2/7 patients (29%) showed heterogeneity of fibrosis in their explant as compared to their TJLB. Conclusions: We found heterogeneity of fibrosis in liver explants of patients that had stage 4 fibrosis (cirrhosis) by TJLB and underwent CHLT. Further work is needed to identify which heart transplant candidates will most benefit from CHLT.

Acute kidney injury and chronic kidney disease after combined heart-liver transplant in patients with congenital heart disease: A retrospective case series.

Although it is known that children undergoing heart transplantation are at increased risk for both AKI and CKD, renal function following CHLT remains understudied. All pediatric CHLT patients from 2006 to 2019 were included. The prevalence of AKI in the first 7 post-operative days, renal recovery at 30 post-operative days, and CKD were ascertained. AKI was defined as an increase in creatinine greater than 1.5 times baseline, and CKD, as an eCrCl less than 90mL/min/1.73m2 . The need for RRT was also analyzed. 10 patients were included, with an average age of 20years and an average listing time of 130days. Preoperatively, the median eCrCl was 91.12mL/min/m2 (IQR 70.51, 127.75min/mL/m2 ). 5 (50%) patients had CKD, with 4 at stage 2 and 1 at stage 3. AKI occurred post-operatively in 3 of 9 (33%) patients: 2 at stage 1 and 1 at stage 2. 2 (67%) resolved by 7days. Of the 5 patients who reached their 1-year follow-up, 1 (20%) had stage 3 CKD. Among 2 patients, neither had CKD at 5years. One patient required RRT 2weeks after CHLT. Despite an increased prevalence of preoperative CKD, patients undergoing CHLT have a lower AKI prevalence than those receiving an isolated heart or liver transplant. Of those with AKI, early renal recovery is common, although at 1year CKD remains present in 20%. Among long-term survivors, normal renal function is achievable.

Research priorities in Fontan-associated liver disease.

Fontan-associated liver disease (FALD) is an emerging condition in patients who have undergone surgical correction of univentricular congenital heart disease. There is little known about the epidemiology of FALD, including risk factors for end-organ failure or hepatocellular carcinoma nor a consensus on surveillance guidelines. Furthermore, there is a need to understand the role of heart versus combined heart-liver transplantation in this population. Research is limited by systemic barriers hindering the ability to track longitudinal FALD outcomes. Nearly all patients post-Fontan develop histological features of FALD as a function of time post-Fontan, regardless of Fontan hemodynamics. In cases of end-organ disease, single-center studies have shown promising outcomes of combined heart-liver transplant in this population, with decreased rates of acute rejection. However, despite the burden of disease, it is not currently possible to identify the population of patients with FALD using existing clinical databases and registries due to a lack of diagnostic codes. Strategies proposed to address barriers to understanding FALD include developing appropriate diagnostic and transplant-related codes for existing registries. Efforts should also be targeted at initiating prospective studies to understand recognized comorbidities related to Fontan physiology, guided by a team of multidisciplinary subspecialists.

En Bloc Combined Heart and Liver Transplantation for End-Stage Heart Failure

Combined heart-liver transplant (CHLTx) remains the only option for long-term survival in patients with end-stage heart and hepatic failure. To date, there are a limited number of transplant centers in the United States that have conducted a CHLTx. Between July of 2009 and December 2019, our group has performed the largest series (N = 20) of <i>en bloc</i> CHLTx to date. En block combined heart-liver transplantation offers both grafts the opportunity to minimize dysfunction with shorter ischemic time compared to sequential heart-liver transplant. This technique simplifies the surgery in patients with complex venous anatomy such as heterotaxy patients and can be performed in dextrocardia or levocardia patients, irrespective of the side of inferior vena cava or superior vena cava. We describe our indications and detailed en block technique for combined heart-liver with its midterm outcome.

Considerations and experience driving expansion of combined heart-liver transplantation.

Heart transplantation concomitant with a liver transplant may be warranted when end-stage heart failure results in irreversible liver failure. Previously reported outcomes have been excellent yet the specific immunoprotective role of the liver allograft is not known. We review the current literature about the immunologic benefit for combined heart and liver transplantation (CHLT). The total number of combined heart and liver transplants continues to increase and accounts for approximately 25 cases per year. Familial amyloid polyneuropathy with cardiac cirrhosis is the most common indication for CHLT while adult congenital heart disease (CHD) with associated cirrhosis is increasing in frequency. The majority of recent registry data suggest a statistically equivalent to modestly improved survival advantage for CHLT compared with isolated heart transplantation. Direct mechanisms accounting for this survival advantage are not proven, but combined heart and liver transplants experience lower rates of acute cardiac rejection and cardiac allograft vasculopathy (CAV). Combined heart and liver transplants remain a small percentage of the total heart transplants worldwide, but the majority of recent literature confirms the safety and viability of this option for patients with end-stage heart and liver disease. Equivalent to modestly improved survival outcomes, lower rates of acute cardiac rejection and CAV warrant further investigation into the liver allograft's immunoprotective effect on the transplanted heart. The key mechanisms of tolerogenicity have important implications for surgical technique and immunosuppression requirements. Future directions include development of criteria for heart-liver transplant candidacy and identification of equitable allocation protocols.

Fontan-Associated Liver Disease: Screening, Management, and Transplant Considerations.

Surgical innovation and multidisciplinary management have allowed children born with univentricular physiology congenital heart disease to survive into adulthood. An estimated global population of 70 000 patients have undergone the Fontan procedure and are alive today, most of whom are <25 years of age. Several unexpected consequences of the Fontan circulation include Fontan-associated liver disease. Surveillance biopsies have demonstrated that virtually 100% of these patients develop clinically silent fibrosis by adolescence. As they mature, there are increasing reports of combined heart-liver transplantation resulting from advanced liver disease, including bridging fibrosis, cirrhosis, and hepatocellular carcinoma, in this population. In the absence of a transplantation option, these young patients face a poor quality of life and overall survival. Acknowledging that there are no consensus guidelines for diagnosing and monitoring Fontan-associated liver disease or when to consider heart transplantation versus combined heart-liver transplantation in these patients, a multidisciplinary working group reviewed the literature surrounding Fontan-associated liver disease, with a specific focus on considerations for transplantation.

Anesthetic considerations for combined heart--liver transplantation in patients with Fontan-associated liver disease.

The success of the Fontan procedure has led to increased survival of patients born with certain congenital heart disease to the point that new sequlae, as a result of Fontan circulation, are being discovered. Included among these is Fontan-associated liver disease (FALD). The purpose of this review is to present available literature on the perioperative management of the combined heart--liver transplantation (CHLT) in patients with FALD. The perioperative management of a combined heart-liver transplant in a patient with Fontan circulation is complex. The patient is at risk for hemodynamic disturbances, significant blood loss, coagulopathies, and metabolic derangements. The maintenance of an appropriate transpulmonary pressure gradient is paramount to success. Postoperative management should be accomplished by a multidisciplinary care team. Limited series have demonstrated good outcomes in patients who have undergone CHLT. The perioperative management of CHLT in patients with FALD is complex and available literature is limited. Future studies are needed to further assess proper perioperative management of patients with FALD who undergo CHLT.

Big Data in Transplantation Practice-the Devil Is in the Detail-Fontan-associated Liver Disease.

As a result of the Fontan procedure, the prognosis of congenital single-ventricle heart disease has improved, with many affected children surviving into adulthood. However, the unanticipated consequences of chronic exposure to Fontan hemodynamics have revealed a new set of secondary noncardiac complications. Fontan-associated liver disease (FALD) is characterized by progressive hepatic fibrosis in nearly all patients post-Fontan, with the potential to develop cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. A lack of data regarding FALD-related prognosis makes consideration of indications for and timing of heart alone versus combined heart-liver transplantation challenging. A multidisciplinary group within the American Society for Transplantation analyzed several administrative datasets to study the epidemiology of FALD. This approach presented several obstacles, and efforts to characterize FALD were limited by a lack of Fontan- and FALD-specific diagnostic codes and an inability to follow individual patients through multiple health systems. Several ongoing Fontan registries were also reviewed but these do not adequately capture FALD-related variables. Such barriers highlight the need for large-scale data collection in patients post-Fontan to better understand and care for this complex population. This study emphasizes the challenges of studying emerging transplant-related diagnoses in existing datasets and the need for mechanisms to adapt registries to appropriately identify patients with rare or emerging conditions.

PRA is Not Associated with Rejection in Combined Heart and Liver Transplantation

Combined heart liver transplantation (CHLT) is relatively rare with approximately 250 cases from 1988-2018 nationally, but with rising numbers each year due to excellent survival. CHLT outcomes have potential immunological benefits compared to heart transplant alone. Liver allografts have long been observed to be more tolerant to HLA mismatch while showing some degree of immune protection in combined organ transplantation. A retrospective analysis from our center's experience of CHLT was performed. Outcomes of patients who had pre-transplant elevated panel reactive antibodies (PRA) >50-99% were compared to those with 0% and those with a low to moderate PRA (1-50%). The hypothesis was tested with the Fisher's exact test. Between 1997 and 2019, 37 patients underwent CHLT. The average age was 42.4 years +/- 10 with 8 deaths (21.6%) ranging from day 2 to 4.5 years post-transplant (5, 13.5% within the first year). None of the deaths were due to rejection or primary graft dysfunction. There were no episodes of humoral rejection and there were 2 episodes (5.4%) of cellular rejection in hearts and 4 (10.8%) in livers (of these, one episode was dual organ rejection). There was no statistical significance at baseline between PRA and history of Fontan physiology, protein losing enteropathy, prior sternotomy, diabetes, hypertension or renal disease. Furthermore, there was no correlation between PRA and death, rejection of either organ, presence of donor specific antibodies, ejection fraction below 50% (1 month and 1 year), length of stay over 30 days, post-transplant hypertension, diabetes or renal disease (table 1). The degree of allosensitization was not associated with worse outcomes in the CHLT population. While the sample is small, it is a reassuring finding that may change the perception of risk when planning a CHLT in a highly sensitized patient.

Outcomes of Induction Immunosuppressive Therapy in Combined Heart-Liver Transplantation

Combined heart-liver transplantation is increasingly performed in the United States. The utility and outcomes of induction immunosuppression in this patient population is not well studied. Recipients of combined heart-liver transplants between January 1st, 2000 and June 30th, 2018 were identified in the United Network of Organ Sharing database. Survival and rejection episodes were reviewed among these patients with or without induction therapy and by various induction agents: ATGAM (horse-derived polyclonal antibody), Thymoglobulin (rabbit-derived polyclonal antibody), Campath (Alemtuzumab), OKT3 (Muromonab) and Interleukin-2 receptor antagonists (IL-2 RA). A total of 260 patients received combined heart-liver transplantation in the United States between January 1ST, 2000 and June 30th, 2018. The mean age was 46.4 years, mean donor age was 30.1 years, 30% of recipients were females, 64.6% were White, 19.6% were Black, 11.9% were Hispanic, 14.7% were diabetic, 7.1% were on dialysis, 61.5% were on life support and 20% were listed as status 1A at the time of transplantation. These findings were similar between the induction and the non-induction groups. Of the 260 patients, 134 (52%) patients received induction therapy. Of these, 36% received IL-2 receptor antagonists, 28% received Thymoglobulin, 23% received ATGAM, 6% received Campath and 6% received OKT3. Survival in combined heart-liver transplant recipients was comparable to that of recipients of heart transplant only (P=0.63). Across 15 years of follow up, survival was similar among patients who received induction therapy versus no induction therapy (P=0.62). Subgroup analysis showed no survival difference among the studied induction agents across 15 years of follow up as well (P=0.80). Approximately 6.7% of the non-induction group patients had at least 1 episode of acute rejection versus 2.4% of the induction group patients (P=0.13), which indicates a favorable trend in the induction group. In this retrospective analysis of the UNOS database, recipients of combined heart-liver transplantation have comparable survival to recipients of heart transplantation only. Induction immunosuppressive therapy was not associated with improved survival in patients undergoing combined heart-liver transplantation however showed a favorable trend towards less acute rejection.

Outcomes of Heart and Combined Heart-Liver Transplant in Pediatric Fontan Patients

While combined heart-liver transplant (HLT) is being performed for Fontan patients, outcomes and indications remain poorly defined. We compared listing characteristics and post-transplant outcomes of Fontan patients with HLT to those with heart-only transplant (HT). We retrospectively reviewed all Fontan patients undergoing HT or HLT at our institution between 2006-2019. Pre-transplant liver disease at the time of listing, as determined by laboratory and radiology data, and MELD-XI, Child Pugh, and VAST scores, were compared between groups. The Kaplan Meier survival method was used to compare post-transplant survival and freedom from rejection (ISHLT Grade 2R+ or pAMR2+). Forty-two patients (33 HT, 9 HLT) were included. HLT patients were older, more likely to be on dual-inotrope therapy, had worse Child Pugh and VAST scores, and were more likely to have varices, ascites, splenomegaly, and cirrhosis on imaging (Table 1). While not significant, HLT patients tended to be more sensitized, had higher total bilirubin and creatinine, and lower platelet count. Over a median post-transplant follow-up of 22 (5, 62) months, overall mortality for the entire cohort was 19%; only one HLT patient died (11%) versus 7 (21%) HT patients (p=0.58, Figure 1). None of the HLT patients experienced rejection, whereas 11 (33%) HT patients had rejection (p=0.06). Despite a greater inotrope need and more severe liver disease at time of listing, patients undergoing HLT have post-transplant outcomes that are comparable, if not better, than Fontan patients with HT. There appears to be a protective effect from rejection with HLT.

MORBIDITY AND MORTALITY IN ADULT FONTAN PATIENTS AFTER HEART OR COMBINED HEART LIVER TRANSPLANT: A REPORT FROM THE FOSTER STUDY

We examined a retrospective, multicenter cohort of adult Fontan patients referred for heart transplant (HT) to assess the impact of comorbidities and combined heart-liver transplant (CHLT) on mortality. All patients at participating institutions with a history of a Fontan-type palliation referred

En-Bloc Simultaneous Heart-Liver Transplantation in Adult Patients.

Complexity of combined heart-liver transplantation has resulted in low adoption rates. We report a case series of adult patients receiving en-bloc heart-liver transplantation (HLTx), describe technical aspects, and discuss benefits of the technique. Retrospective review of patients receiving en-bloc HLTx over 18 months, with clinical follow up to 1 year. Primary outcomes included postoperative mortality and major complications. Secondary outcomes included 1-year survival, cardiac or hepatic allograft rejection, and infection. Five patients received en-bloc HLTx. Mean recipient age was 43 years (26-63), and 3 patients were male. Total operative time was 430 minutes (393-480), cold and warm ischemic times of 85 (32-136) and 37.5 (31-47) minutes. Hospital survival was 80%. One patient died on postoperative day 55 due to fungal sepsis. Major postoperative complications included prolonged mechanical ventilation in 2 of 5 patients (40%), and renal insufficiency requiring hemodialysis in 2 of 5 patients (40%). Among patients discharged from hospital 1-year survival was 100%, with no evidence of rejection or infectious complications. En-bloc HLTx technique is a safe and effective strategy, decreasing operative times, and allograft ischemic times, whereas offering protection of implanted allografts during early stages of reperfusion while patient is hemodynamically supported on cardiopulmonary bypass.

Indications and outcomes of combined heart-liver transplant: A systematic review and met-analysis.

Combined heart-liver transplantation (CHLT) has become a viable option for treating concomitant heart and liver failure. However, data are lacking with respect to long-term outcomes. An electronic search was performed to identify all studies on CHLT. Following application of inclusion and exclusion criteria, a total of seven studies consisting of 99 CHLT patients were included from the original 1864 articles. CHLT recipient mean age was 53.0 years (95% CI 48.0-58.0), 67.5% of which (95% CI 56.5-76.9) were male. 65.5% (95% CI 39.0-85.0) of patients developed heart failure due to amyloidosis whereas 21.6% (95% CI 12.3-35.2) developed heart failure due to congenital causes. The most common indication for liver transplant was amyloidosis [65.5% (95% CI 39.0-85.0)] followed by liver failure due to hepatitis C [13.8% (95% CI 2.1-54.4)]. The mean intensive care unit length of stay was 8 days (95% CI 5-11) with a mean length of stay of 24 days (95% CI 17-31). Cardiac allograft rejection within the first year was 24.7% (95% CI 9.5-50.7), including antibody mediated [5% (95% CI 1.7-15.2)] and T-cell mediated rejection [22.7% (95% CI 8.8-47.1)]. Overall survival was 87.5% (95% CI 78.6-93.0) at 1 year and 84.3% (95% CI 75.4-90.5) at 5 years. CHLT in select patients with coexisting end-stage heart and liver failure appears to offer high survival and low rejection rates.

Assessing hepatic impairment in Fontan-associated liver disease using the HepQuant SHUNT test.

Fontan surgery for single ventricle congenital heart disease leads to Fontan-associated liver disease (FALD). Typical laboratory tests, imaging, and histopathology cannot predict clinical severity in FALD. HepQuant SHUNT is a proprietary serum test of hepatic function and physiology that has not yet been evaluated in FALD. Fourteen adult FALD patients at a single urban tertiary care center who underwent a Fontan procedure in childhood received HepQuant SHUNT testing between September 2015 and April 2018. The HepQuant SHUNT disease severity index (DSI) assesses global liver function and physiology from systemic and portal hepatic filtration rates (HFRs, clearances adjusted for body mass) of orally and intravenously administered cholates labeled with deuterium or 13C. The SHUNT parameter of the test measures portal systemic shunting from the ratio of Systemic HFR to Portal HFR. Chart review included laboratory tests, imaging, and clinical findings. Data from FALD patients were compared with data from healthy controls. The average DSI and SHUNT values for the FALD patients were 17.5% and 36.1%, respectively, compared to 9.2% and 24.1%, respectively, for controls. Twelve (85.7%) FALD patients had a DSI >15 (upper limit of normal). Seven (50.0%) FALD patients had SHUNT values >30% (upper limit of normal), while three FALD patients (21.4%) had SHUNT values >49%. One FALD patient with preoperative SHUNT of 69%, who underwent a combined heart-liver transplant, had confirmed cirrhotic morphology within the liver explant. This pilot study demonstrated that most FALD patients had hepatic impairment detected by abnormal DSI, with a smaller number having markedly elevated SHUNT values >49% suggesting intrinsic liver disease. The HepQuant SHUNT test may be useful in detecting and quantifying liver disease severity in FALD patients.

Outcomes of Combined Heart-Liver Transplant: A Systematic Review

Purpose In patients with liver failure who have coexisting heart failure, combined heart-liver transplantation (CHLT) can be performed. Outcomes in terms of survival and freedom from rejection remain largely unknown due to lack of sufficient data. The goal of this study was to pool the existing literature for evaluating outcomes after CHLT. Methods An electronic search was performed to identify all studies on CHLT in the English literature. All identified articles were systematically assessed for inclusion and exclusion criteria. Of 1864 articles identified, a total of seven studies were pooled for final analysis. Results A total of 99 patients who underwent CHLT between 1997 to 2014 were included in the analysis. The mean age of CHLT recipients was 52 years (95% CI 40.8 - 57.96) and 67.5% (95% CI 56.5 - 76.9) of patients were male. Amyloidosis was the most common indication for both the heart [65.5% (95% CI 39.0 - 85.0)] and the liver transplant [65.5% (95% CI 39.0 - 85.0)]. Mean follow up period was 31.4 months (95% CI 14.66 - 48.14). Total cardiac allograft rejection within the first year was 24.7% (95% CI 9.5 - 50.7), including antibody mediated [5% (95% CI 1.7 - 15.2)] and T-cell mediated rejection [22.7% (95% CI 8.8 - 47.1)]. Freedom from rejection at five years was 81.8% (95% CI 69.2 - 89.9). Survival after CHLT was 93.3% (95% CI 84.2 - 97.3) at 6 months, 87.5% (95% CI 78.6 - 93.0) at 1 year and 84.3% (95% CI 75.4 - 90.5) at 5 years (Figure). Conclusion CHLT in selected patients with coexisting end-stage heart and liver disease can be a viable treatment option and with acceptable survival and freedom from rejection.

Outcomes in Combined Heart-Liver Transplantation: A Single-Center Experience

Purpose Combined heart and liver transplantation is an uncommon operation. Given the rarity of this procedure, outcomes data have been limited to case reports and several single-institution series. To better define this patient population and augment the existing data, we report our combined heart and liver transplant experience. Methods An institutional database was queried to identify all patients undergoing combined heart-liver transplantation between 1998 and 2018. A retrospective review of baseline patient characteristics and outcomes was performed. Results Sixteen patients (age 51.4 ± 16, male 69%) underwent combined heart-liver transplantation between 1998 and 2018. The majority (81.3%) of patients were afflicted with non-ischemic cardiomyopathies (idiopathic: 25.0%, congenital: 18.8%, infectious: 12.5%, restrictive: 12.5%, autoimmune: 6.5%), while only 18.8% of patients presented with ischemic cardiomyopathy. Median ejection fraction was 20% [18.3-37.3], and mechanical assist devices or intra-aortic balloon pumps were employed in 25.0% and 18.8%, respectively. Concurrent with cardiac pathology, patients presented with cardiac cirrhosis (43.8%), hepatitis C cirrhosis (25%), primary biliary cirrhosis (6.3%), NASH (6.3%), autoimmune (6.3%) and amyloid (6.3%) liver disease. The median MELD score was 17.5 [12.0-21.3], and 62.5% of patients exhibited ascites. Patients underwent simultaneous transplantation, with median cardiac and hepatic graft ischemia times of 189.0 min and 486.5 min, respectively. Mild cardiac rejection (ACR 1R, AMR 1, DSA:DQ8) occurred in 18.8%, while hepatic rejection occurred in 12.5% of patients. Median intensive care unit and total hospital length of stay were 7.0 [5.0-9.0] and 65.5 [40.8-97.8] days, respectively. In hospital mortality occurred in one patient, with 30-day and 1-year survival rates of 93.8% and 92.8%, respectively. Conclusion This single institution experience with combined heart-liver transplantation augments the available data for this rare procedure, and demonstrates that it can be performed with excellent outcomes.

Heart Transplantation in Cardiac Amyloidosis: A Ten Year Experience

Purpose Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy associated with poor prognosis. We sought to summarize the outcomes for patients with light chain (AL) or transthyretin (ATTR) CA receiving heart transplantation at our institution and a collaborating institution. Methods This is a retrospective examination of patients with end-stage CA who underwent orthotopic heart transplantation (OHT) at the Cleveland Clinic in Cleveland, Ohio, and with collaboration at Baylor Scott & White Advanced Heart Failure Clinic in Dallas, Texas, from May 2008 to September 2018. Results OHT was performed in 14 cases of CA, twelve at Cleveland Clinic and two at Baylor Scott & White Advanced Heart Failure Clinic. Twelve patients had ATTR (3 wild type, 9 hereditary) and 2 patients AL. Twelve patients have completed one-year follow-up and 100% of patients are alive with a median post-transplant survival of 3 years (range 0.1-10.5 years). Median time from amyloidosis diagnosis to OHT was 16 months (IQR, 9-29 months). Median time awaiting transplant was 5 months (IQR, 1-8 months). Four patients received a heart-multiorgan transplantation: one patient with AL received a kidney and three patients with hereditary ATTR (hATTR) due to the T60A mutation received a liver. One patient with AL underwent autologous stem cell transplantation 6 months after OHT and is stable at 4.2 years follow-up. Six patients with hereditary ATTR due to the V122I mutation underwent isolated OHT; two with long-term follow-up of 7.2 and 10.3 years respectively. Three patients displayed presumed signs of extra-cardiac amyloid involvement post-transplantation: an hATTR V122I patient required spinal stenosis surgery 2 years after transplant, a wild-type ATTR patient required spinal stenosis surgery 10 years after transplant, and an hATTR T60A patient developed chronic diarrhea 9 years after combined heart-liver transplant. No patient had evidence of recurrent amyloid deposition in the cardiac allograft. Conclusion Our experience confirmed that heart transplantation is a viable long-term treatment option for select patients with CA. Post OHT, presumed extra-cardiac involvement of amyloidosis occurred in 3 ATTR patients, but no patients showed re-emergence of CA in their recipient organ.

Combined Pediatric Heart-Liver Transplant Outcomes in the US: A 25 Year National Cohort Study

Purpose Pediatric combined heart-liver transplantation (cHLTx) remains uncommon in the United States and criteria for cHLTx are unclear. The objective of this study was to review the indications, and outcomes of pediatric cHLTx. Methods Data from the Scientific Registry for Transplant Recipients heart and liver databases were used to identify 9245 pediatric heart transplants (PHTx) alone, 14134 pediatric liver transplant alone, and 20 pediatric cHLTx (16 simultaneous HLTx [same organ donor], + 4 previous heart transplants followed by liver transplant [different organ donors]) (age ≤ 21 years) between 1992 and 2017. Outcomes included patient survival, and 1-year rates of acute heart and liver rejection. Results The median age for pediatric cHLTx was 15.6 (IQR: 10.5, 17.9) years, and included 12 males (12/20=60%). In the cHLTx group, the most common indication for heart transplant was congenital heart disease (11/20=55%), and the most common indication for liver transplant was cirrhosis (9/20=45%) due to granulomatous diseases including sarcoidosis, histiocytosis or cryptogenic. Recipients of pediatric cHLTx had a similar 5-year adjusted risk of death compared to PHTx alone (p=0.9; Figure 1). The 1, 3, and 5 year actuarial survival rates in pediatric cHLTx recipients was 80%, 80%, and 80% respectively, and was similar to isolated PHTx alone (88%, 82%, and 78% respectively. There was no heart or liver rejection reported in the cHLTx group versus 9.9% in heart only and 10.6% in liver transplant only group, respectively. Conclusion Pediatric combined heart-liver transplant is an acceptable option for recipients with combined end-organ failure, with intermediate survival outcomes comparable to those of single-organ recipients with no treated heart or liver rejection reported in the first year. Pediatric combined heart-liver transplantation (cHLTx) remains uncommon in the United States and criteria for cHLTx are unclear. The objective of this study was to review the indications, and outcomes of pediatric cHLTx. Data from the Scientific Registry for Transplant Recipients heart and liver databases were used to identify 9245 pediatric heart transplants (PHTx) alone, 14134 pediatric liver transplant alone, and 20 pediatric cHLTx (16 simultaneous HLTx [same organ donor], + 4 previous heart transplants followed by liver transplant [different organ donors]) (age ≤ 21 years) between 1992 and 2017. Outcomes included patient survival, and 1-year rates of acute heart and liver rejection. The median age for pediatric cHLTx was 15.6 (IQR: 10.5, 17.9) years, and included 12 males (12/20=60%). In the cHLTx group, the most common indication for heart transplant was congenital heart disease (11/20=55%), and the most common indication for liver transplant was cirrhosis (9/20=45%) due to granulomatous diseases including sarcoidosis, histiocytosis or cryptogenic. Recipients of pediatric cHLTx had a similar 5-year adjusted risk of death compared to PHTx alone (p=0.9; Figure 1). The 1, 3, and 5 year actuarial survival rates in pediatric cHLTx recipients was 80%, 80%, and 80% respectively, and was similar to isolated PHTx alone (88%, 82%, and 78% respectively. There was no heart or liver rejection reported in the cHLTx group versus 9.9% in heart only and 10.6% in liver transplant only group, respectively. Pediatric combined heart-liver transplant is an acceptable option for recipients with combined end-organ failure, with intermediate survival outcomes comparable to those of single-organ recipients with no treated heart or liver rejection reported in the first year.