Perioperative Characteristics and Outcomes of Fontan Versus Non-Fontan Patients Undergoing Combined Heart-Liver Transplantation: A Retrospective Cohort Study.

OBJECTIVES: Combined heart-liver transplantation (CHLT) is becoming increasingly frequent as a maturing population of patients with Fontan-palliated congenital heart disease develop advanced liver fibrosis or cirrhosis. The authors present their experience with CHLT for congenital and noncongenital indications, and identify characteristics associated with poor outcomes that may guide intervention in high-risk patients. DESIGN: This was a single-center retrospective cohort study. SETTING: This study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee. PARTICIPANTS: The study included 16 consecutive adult recipients of CHLT at the authors' institution between April 2017 and February 2022. INTERVENTIONS: Eleven patients underwent transplantation for Fontan indications, and 5 were transplanted for non-Fontan indications. MEASUREMENTS AND MAIN RESULTS: Compared with non-Fontan patients, Fontan recipients had longer cardiopulmonary bypass duration (199 v 119 minutes, p =m0.002), operative times (786 v 599 minutes, p = 0.01), and larger blood product transfusions (15.4 v 6.3 L, p = 0.18). Six of 16 patients required extracorporeal membrane oxygenation (ECMO), of whom 4 were Fontan patients who subsequently died. Patients who required ECMO had lower 5-hour lactate clearance (0.0 v 3.5 mmol/L, p = 0.001), higher number of vasoactive infusions, lower pulmonary artery pulsatility indices (0.58 v 1.77, p = 0.03), and higher peak inspiratory pressures (28.0 v 18.5 mmHg, p = 0.01) after liver reperfusion. CONCLUSIONS: Combined heart-liver transplantation in patients with Fontan-associated end-organ disease is particularly challenging and associated with higher recipient morbidity compared with non-Fontan-related CHLT. Early hemodynamic intervention for signs of ventricular dysfunction may improve outcomes in this growing high-risk population.

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era.

BACKGROUND: Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre-direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test-positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. METHODS AND RESULTS: We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. CONCLUSIONS: These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

Outcomes of Heart Transplant Donation After Circulatory Death.

BACKGROUND: Heart transplantation using donation after circulatory death (DCD) allografts is increasingly common, expanding the donor pool and reducing transplant wait times. However, data remain limited on clinical outcomes. OBJECTIVES: We sought to compare 6-month and 1-year clinical outcomes between recipients of DCD hearts, most of them recovered with the use of normothermic regional perfusion (NRP), and recipients of donation after brain death (DBD) hearts. METHODS: We conducted a single-center retrospective observational study of all adult heart-only transplants from January 2020 to January 2023. Recipient and donor data were abstracted from medical records and the United Network for Organ Sharing registry, respectively. Survival analysis and Cox regression were used to compare the groups. RESULTS: During the study period, 385 adults (median age 57.4 years [IQR: 48.0-63.7 years]) underwent heart-only transplantation, including 122 (32%) from DCD donors, 83% of which were recovered with the use of NRP. DCD donors were younger and had fewer comorbidities than DBD donors. DCD recipients were less often hospitalized before transplantation and less likely to require pretransplantation temporary mechanical circulatory support compared with DBD recipients. There were no significant differences between groups in 1-year survival, incidence of severe primary graft dysfunction, treated rejection during the first year, or likelihood of cardiac allograft vasculopathy at 1 year after transplantation. CONCLUSIONS: In the largest single-center comparison of DCD and DBD heart transplantations to date, outcomes among DCD recipients are noninferior to those of DBD recipients. This study adds to the published data supporting DCD donors as a safe means to expand the heart donor pool.

Extracorporeal Life Support for Cardiogenic Shock in Adult Congenital Heart Disease-An ELSO Registry Analysis.

There are minimal data on the use of venoarterial extracorporeal membrane life support (VA-ECLS) in adult congenital heart disease (ACHD) patients presenting with cardiogenic shock (CS). This study sought to describe the population of ACHD patients with CS who received VA-ECLS in the Extracorporeal Life Support Organization (ELSO) Registry. This was a retrospective analysis of adult patients with diagnoses of ACHD and CS in ELSO from 2009-2021. Anatomic complexity was categorized using the American College of Cardiology/American Heart Association 2018 guidelines. We described patient characteristics, complications, and outcomes, as well as trends in mortality and VA-ECLS utilization. Of 528 patients who met inclusion criteria, there were 32 patients with high-complexity anatomy, 196 with moderate-complexity anatomy, and 300 with low-complexity anatomy. The median age was 59.6 years (interquartile range, 45.8-68.2). The number of VA-ECLS implants increased from five implants in 2010 to 81 implants in 2021. Overall mortality was 58.3% and decreased year-by-year (ß= -2.03 [95% confidence interval, -3.36 to -0.70], p = 0.007). Six patients (1.1%) were bridged to heart transplantation and 21 (4.0%) to durable ventricular assist device. Complications included cardiac arrhythmia/tamponade (21.6%), surgical site bleeding (17.6%), cannula site bleeding (11.4%), limb ischemia (7.4%), and stroke (8.7%). Utilization of VA-ECLS for CS in ACHD patients has increased over time with a trend toward improvement in survival to discharge.

Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation.

BACKGROUND: The impact of Fontan-associated liver disease (FALD) on post-transplant mortality and indications for combined heart-liver transplant (CHLT) in adult Fontan patients remains unknown. OBJECTIVES: The purpose of this study was to assess the impact of FALD on post-transplant outcomes and compare HT vs CHLT in adult Fontan patients. METHODS: We performed a retrospective-cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers. Inclusion criteria were as follows: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at referral. Pretransplant FALD score was calculated using the following: 1) cirrhosis; 2) varices; 3) splenomegaly; or 4) ≥2 paracenteses. RESULTS: A total of 131 patients (91 HT and 40 CHLT) were included. CHLT recipients were more likely to be older (P = 0.016), have a lower hemoglobin (P = 0.025), require ≥2 diuretic agents pretransplant (P = 0.051), or be transplanted in more recent decades (P = 0.001). Postmatching, CHLT demonstrated a trend toward improved survival at 1 year (93% vs 74%; P = 0.097) and improved survival at 5 years (86% vs 52%; P = 0.041) compared with HT alone. In patients with a FALD score ≥2, CHLT was associated with improved survival (1 year: 85% vs 62%; P = 0.044; 5 years: 77% vs 42%; P = 0.019). In a model with transplant decade and FALD score, CHLT was associated with improved survival (HR: 0.33; P = 0.044) and increasing FALD score was associated with worse survival (FALD score: 2 [HR: 14.6; P = 0.015], 3 [HR: 22.2; P = 0.007], and 4 [HR: 27.8; P = 0.011]). CONCLUSIONS: Higher FALD scores were associated with post-transplant mortality. Although prospective confirmation of our findings is necessary, compared with HT alone, CHLT recipients were older with higher FALD scores, but had similar survival overall and superior survival in patients with a FALD score ≥2.

Morbidity and Mortality in Adult Fontan Patients After Heart or Combined Heart-Liver Transplantation.

BACKGROUND: An increasing number of adult Fontan patients require heart transplantation (HT) or combined heart-liver transplant (CHLT); however, data regarding outcomes and optimal referral time remain limited. OBJECTIVES: The purpose of this study was to define survivorship post-HT/CHLT and predictors of post-transplant mortality, including timing of referral, in the adult Fontan population. METHODS: A retrospective cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers in the United States and Canada was performed. Inclusion criteria included the following: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at the time of referral. Date of "failing" Fontan was defined as the earliest of the following: worsening fluid retention, new ascites, refractory arrhythmia, "failing Fontan" diagnosis by treating cardiologist, or admission for heart failure. RESULTS: A total of 131 patients underwent transplant, including 40 CHLT, from 1995 to 2021 with a median post-transplant follow-up time of 1.6 years (Q1 0.35 years, Q3 4.3 years). Survival was 79% at 1 year and 66% at 5 years. Survival differed by decade of transplantation and was 87% at 1 year and 76% at 5 years after 2010. Time from Fontan failure to evaluation (HR/year: 1.23 [95% CI: 1.11-1.36]; P < 0.001) and markers of failure, including NYHA functional class IV (HR: 2.29 [95% CI: 1.10-5.28]; P = 0.050), lower extremity varicosities (HR: 3.92 [95% CI: 1.68-9.14]; P = 0.002), and venovenous collaterals (HR: 2.70 [95% CI: 1.17-6.20]; P = 0.019), were associated with decreased post-transplant survival at 1 year in a bivariate model that included transplant decade. CONCLUSIONS: In our multicenter cohort, post-transplant survival improved over time. Late referral after Fontan failure and markers of failing Fontan physiology, including worse functional status, lower extremity varicosities, and venovenous collaterals, were associated with post-transplant mortality.

The impact of donor consent mechanism on organ procurement organization performance in the United States.

BACKGROUND: Lack of donor organ availability represents a major limitation to the success of solid organ transplantation. The Scientific Registry of Transplant Recipients (SRTR) publishes performance reports of organ procurement organizations (OPO) in the United States, but does not stratify by the mechanism of donor consent, namely first-person authorization (organ donor registry) and next-of-kin authorization. This study aimed to report the trends in deceased organ donation in the United States and assess the regional differences in OPO performance after accounting for the different mechanisms of donor consent. METHODS: The SRTR database was queried for all eligible deaths (2008-2019) which were then stratified based on the mechanism of donor authorization. Multivariable logistic regression was performed to assess the probability of organ donation across OPOs based on specific donor consent mechanisms. Eligible deaths were divided into 3 cohorts based on the probability to donate. Consent rates at the OPO level were calculated for each cohort. RESULTS: Organ donor registration among adult eligible deaths in the U.S. increased over time (2008: 10% vs 2019: 39%, p < 0.001), coincident with a decline in next-of-kin authorization rates (2008: 70% vs 2019: 64%, p < 0.001). At the OPO level, the increased organ donor registration was associated with lower next-of-kin authorization rates. Among eligible deaths with medium- and low-probability of donation, recruitment was highly variable across OPO's, ranging from 36% to 75% in the medium-probability group (median 54%, IQR 50%-59%) and 8% and 73% in the low-probability group (median 30%, IQR 17%-38%). CONCLUSION: Significant variability exists across OPOs in the consent of potentially persuadable donors after adjusting for population demographic differences and the mechanism of consent. Current metrics may not truly reflect OPO performance as they do not account for consent mechanism. There is further opportunity for improvement in deceased organ donation through targeted initiatives across OPOs, modeled after regions with the best performance.

Austin Powers' Steamroller: Lessons Learned to Benefit Patients with Congenital Heart Disease.

A structural crisis is brewing in advanced care for patients with congenital heart disease (CHD)-specifically, single-ventricle patients palliated by the Fontan procedure. The largest study evaluating management practices in pediatric cardiac teams found that 93% of providers believe that after the Fontan procedure, patients "will eventually have signs/symptoms of heart failure (HF) and will need a heart transplant (HT) at some point in their lives."1 Despite this, the majority either disagreed about (45%) or were undecided about (24%) "whether routine evaluation by a HF/HT cardiologist is needed." This may be, in part, attributable to the lack of an HF/HT subspecialty in the American College of Pediatrics, but these findings highlight a concerning disconnect in the minds of providers caring for patients undergoing the Fontan procedure, for whom the providers' preparation seems incongruous in terms of the anticipated endpoint. This disconnect would likely be even worse had the survey been conducted in adult providers, given that the providers of care for adults with congenital heart disease (ACHD) have limited required HF/HT training, and adult HF/HT cardiologists have little required training in CHD.

Management of Heart Failure With Arrhythmia in Adults With Congenital Heart Disease: JACC State-of-the-Art Review.

Together, heart failure and arrhythmia represent the most important cardiovascular sources of morbidity and mortality among adults with congenital heart disease (ACHDs). Although traditionally conceptualized as operating within 2 distinct clinical silos, these scenarios frequently coexist within the same individual; consequently the mechanistic, therapeutic, and prognostic overlap between them demands increased recognition. In fact, given the near ubiquity of heart failure and arrhythmia among ACHDs, there is perhaps no other arena within cardiology where this critical intersection is more frequently observed. Optimal care for ACHDs therefore requires a heightened awareness of the relevant interactions as well as the pharmacologic and interventional resources that are increasingly available to the treating cardiologist. This review explores and highlights the overlap between these 2 fields to recommend a parallel, yet interactive, multidisciplinary approach to clinical management. Congenital heart disease categories are broken down into their archetypal subtypes to highlight subtleties of the pathophysiology, evaluation, and therapeutic approach.

Association of Donors With US Public Health Service Risk Criteria and Outcomes After Adult vs Pediatric Cardiac Transplant.

Importance: The United Network for Organ Sharing (UNOS) evaluates donor risk for acute transmission of HIV, hepatitis B, or hepatitis C based on US Public Health Services (PHS)-specific criteria. However, recent data regarding use and outcomes of those donors with PHS risk criteria among pediatric and adult heart transplant recipients are lacking. Objective: To compare use and outcomes of graft from donors with PHS risk criteria vs those with a standard-risk donor (SRD) in children vs adults in a contemporary cohort. Design, Setting, and Participants: This cohort was a nationwide analysis of heart transplants in the US that used data from the UNOS database. Participants were children (<18 years old) and adults (≥18 years old) who received a heart transplant from January 1, 2010, to December 31, 2021. Exposures: UNOS-defined donor risk status. Main Outcomes and Measures: Trend analysis compared changes in PHS risk criteria use among children and adults. Patient survival was analyzed using Kaplan-Meier curves with log rank and Cox proportional hazards to compare PHS risk-criteria outcomes vs SRD-criteria outcomes in children and adult heart transplant recipients. Additional analysis was performed among adults who received a PHS-risk criteria graft that was previously declined for pediatric recipients. Results: Of 5115 pediatric transplant recipients (donor without PHS risk median [IQR] age, 5 [0-13] years and donor with PHS risk median [IQR] age, 8 [0-14] years) and 30 289 adult heart transplant recipients (donor without PHS risk median [IQR] age, 56 [46-63] years and donor with PHS risk median [IQR] age, 57 [47-63] years), PHS risk criteria comprised 8% in children vs 25% in adults. PHS criteria are being increasingly used over the past decade with the proportion of recipients transplanted with PHS risk-criteria donors being approximately 3 times greater among adult recipients than children recipients. Pediatric recipients of a PHS risk-criteria donor had greater pretransplant ventilatory support, whereas adult recipients of a PHS risk-criteria donor had greater pretransplant extracorporeal membrane oxygenation use. Patient survival was similar between pediatric recipients of PHS risk-criteria grafts vs SRD-criteria grafts and slightly higher among adult recipients of PHS risk-criteria grafts vs SRD-criteria grafts. The 1778 adult recipients who received a PHS criteria-risk donor that was previously declined for pediatric recipients had similar patient survival recipients compared with SRD-criteria donors (HR, 0.92; 95% CI, 0.81-1.03; P = .18). Conclusions and Relevance: In the current era, a 3-fold greater proportion of adult recipients receive a PHS risk-criteria graft compared with children despite similar posttransplant patient survival. The ongoing organ donor shortage underscores the need for consideration of PHS risk criteria where these donors remain underused.

Early Blood Pressure Variables Associated With Improved Outcomes in VA-ECLS: The ELSO Registry Analysis.

BACKGROUND: As utilization of veno-arterial extracorporeal life support (VA-ECLS) in treatment of cardiogenic shock (CS) continues to expand, clinical variables that guide clinicians in early recognition of myocardial recovery and therefore, improved survival, after VA-ECLS are critical. There remains a paucity of literature on early postinitiation blood pressure measurements that predict improved outcomes. OBJECTIVES: The objective of this study is to help identify early blood pressure variables associated with improved outcomes in VA-ECLS. METHODS: The authors queried the ELSO (Extracorporeal Life Support Organization) registry for cardiogenic shock patients treated with VA-ECLS or venovenous arterial ECLS between 2009 and 2020. Their inclusion criteria included treatment with VA-ECLS or venovenous arterial ECLS; absence of pre-existing durable right, left, or biventricular assist devices; no pre-ECLS cardiac arrest; and no surgical or percutaneously placed left ventricular venting devices during their ECLS runs. Their primary outcome of interest was the survival to discharge during index hospitalization. RESULTS: A total of 2,400 CS patients met the authors' inclusion criteria and had complete documentation of blood pressures. Actual mortality during index hospitalization in their cohort was 49.5% and survivors were younger and more likely to be Caucasian, intubated for >30 hours pre-ECLS initiation, and had a favorable baseline SAVE (Survival After Veno-arterial ECMO) score (P < 0.05 for all). Multivariable regression analyses adjusting for SAVE score, age, ECLS flow at 4 hours, and race showed that every 10-mm Hg increase in baseline systolic blood pressure (HR: 0.92 [95% CI: 0.89-0.95]; P < 0.001), and baseline pulse pressure (HR: 0.88 [95% CI: 0.84-0.91]; P < 0.001) at 24 hours was associated with a statistically significant reduction in mortality. CONCLUSIONS: Early (within 24 hours) improvements in pulse pressure and systolic blood pressure from baseline are associated with improved survival to discharge among CS patients treated with VA-ECLS.

UNOS listing status-related changes in mechanical circulatory support utilization and outcomes in adult congenital heart disease patients.

BACKGROUND: The aim of this study was to investigate the impact of the new United Network for Organ Sharing (UNOS) listing criteria on mechanical circulatory support (MCS) utilization and outcomes in adult congenital heart disease (ACHD) patients. METHODS: We identified all ACHD and non-ACHD heart transplant candidates in the Scientific Registry of Transplant Recipients database listed during the 590 days prior to (historical cohort) or following (recent cohort) the UNOS allocation revision on October 18, 2018. Patients were grouped based on whether they received central temporary MCS (tMCS), peripheral tMCS, durable MCS, or no MCS. RESULTS: A total of 535 ACHD (242 historical, 293 recent) and 12,188 non-ACHD (6,258 historical, 5,930 recent) patients were included in our study. For ACHD patients, we found no differences in the historical versus recent cohort in utilization of central tMCS (3.31% vs 3.07%, p = .88) or durable MCS (3.31% vs 3.41%, p = .95), whereas the rate of peripheral tMCS increased (2.07% historical vs 6.83% recent, p = .009). Across both cohorts, ACHD patients supported with peripheral tMCS had shorter time-to-transplant than non-supported patients (25.7 vs 121.7 days, p = .002). ACHD patients supported with central tMCS had greater rates of post-transplant mortality relative to other ACHD patients (40.0% vs 12.6%, p = .006), while those supported with durable or peripheral temporary MCS had no differences in waitlist or post-transplant mortality compared to non-supported ACHD patients. CONCLUSIONS: The 2018 UNOS allocation changes increased utilization of peripheral temporary MCS in ACHD patients, decreasing waitlist time without impact on post-transplant outcomes.

Exception-Status Listing: A Critical Pathway to Heart Transplantation for Adults With Congenital Heart Diseases.

Adults with congenital heart diseases may not be candidates for conventional therapies to control ventricular systolic dysfunction, including mechanical circulatory support, which moves potential heart-transplantation recipients to a listing status of higher priority. This results in longer waitlist times and greater mortality rates. Exception-status listing allows a pathway for this complex and anatomically heterogenous group of patients to be listed for heart transplantation at appropriately high listing status. Our study queried the United Network for Organ Sharing registry to evaluate trends in the use of exception-status listing among adults with congenital heart diseases awaiting heart transplantation. Uptrend in the use of exception-status listing precedes the new allocation system, but it has been greatest since changes were made in the allocation system. It continues to remain a vital pathway for adults with congenital heart disease (whose waitlist mortality rates are often not characterized adequately by using the waitlist-status criteria) timely access to heart transplantation.