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.

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.

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.

Impact of the new UNOS donor heart allocation system on waitlist outcomes and early posttransplant mortality among adults with congenital heart disease.

Adults with congenital heart disease (ACHD) experience worse waitlist outcomes and higher early posttransplant mortality compared to non-ACHD patients. On October 18, 2018; the UNOS donor heart allocation system was redesigned giving unique listing status to ACHD patients. The impact of this change on outcomes in transplant-listed patients is unstudied. Using the Scientific Registry of Transplant Recipients (SRTR) we compared ACHD patients listed for the first-time for heart transplantation from two eras of equal duration. We analyzed waitlist outcomes, posttransplant mortality and length of stay among ACHD patients in both eras and between ACHD and non-ACHD patients in the new era. Of 12 723 listed patients, 535 had ACHD (293 in the new era) and 12 188 did not (6258 in the new era). A total of 163 (56%) ACHD patients in the new era versus 150 (62%) in the prior era were transplanted; 11 (3.8%) versus 15 (6.2%) died on the waitlist; 32 (11%) versus 35 (14%) were delisted and 15 (9.2%) versus 19 (12.7%) died within 30 days of transplant, respectively. The new UNOS donor heart allocation system improved waitlist time and decreased the proportion not transplanted during the first 300 days after listing among ACHD patients without altering early posttransplant outcomes or significantly changing the gap in outcomes compared to non-ACHD patients.

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.

Limited Balloon Atrial Septostomy for Left Ventricular Unloading in Peripheral Extracorporeal Membrane Oxygenation.

BACKGROUND: This study describes the authors' experience with a limited balloon atrial septostomy technique, using a median balloon size of 15 mm, as a left ventricular (LV) unloading strategy in venoarterial extracorporeal membrane oxygenation (VA-ECMO). There has been increasing use of VA-ECMO in cardiogenic shock. Although LV unloading strategies have been suggested to improve outcomes, it is unclear which strategy is optimal. METHODS AND RESULTS: We performed a retrospective study of patients who underwent a limited balloon atrial septostomy for LV unloading in peripheral VA-ECMO at a single center. The goal of this study was to define the procedural outcomes and clinical characteristics of these patients. Of the 12 patients identified, none had complications related to the procedure. There was a significant decrease in the mean left atrial pressure and the majority of patients had radiologic improvement in pulmonary vascular congestion. Of the 12 patients, 58.3% survived to discharge. CONCLUSIONS: Limited BAS is an elegant and safe method for unloading the LV in peripheral VA-ECMO.

No survival benefit associated with waiting for non-lung donor heart transplants for adult recipients with congenital heart disease.

BACKGROUND: Adults with congenital heart disease (CHD) awaiting heart transplant (HT) have higher mortality and waitlist removal due to clinical deterioration than those without CHD. The selective use of non-lung donors (NLD) to recover donor pulmonary vasculature to assist in graft implantation may be a contributing factor and is supported by consensus statements despite the recent use of pericardium or graft material as an alternative in pulmonary vascular reconstruction. The impact of selecting NLD for CHD recipients on wait time and mortality has not been evaluated. METHODS/RESULTS: In the United Network for Organ Sharing (UNOS) Registry, 1271 HT recipients age ≥ 18 with CHD were identified between 1987 and 2016, 68% of which had NLDs. Prior to HT, NLD recipients were significantly less likely to be listed UNOS Status 1A, require mechanical ventilation, or intra-aortic balloon pump support. There was no difference in mean waitlist time (254 vs. 278 days, p = .31), 1-year mortality (82% vs. 80%, p = .81; adjusted odds ratio 1.32, 95% confidence interval [CI] 0.96-1.83, p = .08), or overall mortality (adjusted hazard ratio 1.08, 95% CI 0.86-1.36, p = .48) between recipients from NLD and concomitant lung donors. CONCLUSIONS: Adult CHD patients who are less critically ill or listed at a lower status are more likely to receive HT from NLD. There is no overall mortality benefit associated with this practice. While specific cases may necessitate waiting for NLD, programs need to re-evaluate whether this should remain a more widespread practice among CHD patients.

Adult Combined Heart-Liver Transplantation: The United States Experience.

Background: We aimed to review the indications and outcomes of adults undergoing combined heart-liver transplantation (CHLT) in the US using national registry data. Methods: Adult (≥18 years) CHLT recipients in the United Network for Organ Sharing database were included (09/1987-09/2020; era 1 = 1989-2000, era 2 = 2001-2010, era 3 = 2011-2020). Survival analysis was conducted by means of Kaplan-Meier method, log-rank test, and Cox regression. Results: We identified 369 adults receiving CHLT between 12/1989-08/2020. The number of adult CHLT recipients (R2 = 0.75, p < 0.001) and centers performing CHLT (R2 = 0.80, p < 0.001) have increased over the study period. The most common cardiac diagnosis in the first two eras was restrictive/infiltrative cardiomyopathy, while the most common in era 3 was congenital heart disease (p = 0.03). The 1-, 3-, and 5-years patient survival was 86.8, 80.1, and 77.9%, respectively. In multivariable analysis, recipient diabetes [adjusted hazard ratio (aHR) = 2.35, 95% CI: 1.23-4.48], CHLT between 1989-2000 compared with 2011-2020 (aHR = 5.00, 95% CI: 1.13-22.26), and sequential-liver first CHLT compared with sequential-heart first CHLT (aHR = 2.44, 95% CI: 1.15-5.18) were associated with increased risk of mortality. Higher left ventricular ejection fraction was associated with decreased risk of mortality (aHR = 0.96, 95% CI: 0.92-0.99). Conclusion: CHLT is being increasingly performed with evolving indications. Excellent outcomes can be achieved with multidisciplinary patient and donor selection and surgical planning.

Sizing Up Fontan Failure: Association with Increasing Weight in Adulthood.

Obesity has become increasingly recognized in adults with Fontan palliation, yet the relationship between weight changes in adulthood and Fontan failure is not clearly defined. We hypothesize that increasing weight in adulthood among Fontan patients is associated with the development of Fontan failure. Single-center data from adults with Fontan palliation who were not in Fontan failure at their first clinic visit in adulthood and who received ongoing care were retrospectively collected. Fontan failure was defined as death, transplant, diagnosis of protein losing enteropathy, predicted peak VO2 less than 50%, or new loop diuretic requirement. Anthropometric data including weight and BMI were collected. Change in weight was compared between those that developed Fontan failure, and those that remained failure-free. To estimate the association between weight change during adulthood and the risk of developing Fontan failure, a survival analysis using multiple Cox's proportional hazards regression model was performed. Overall, 104 patients were included in the analysis. Those that developed Fontan failure had a larger associated median weight gain than those who remained failure-free (7.8 kg vs. 4.9 kg, respectively; p = 0.011). In multivariable Cox regression analysis, increased weight during adulthood was associated with increased likelihood of developing Fontan failure (HR 1.36; CI 1.07-1.73; p = 0.011). Weight gain in adulthood is associated with the development of Fontan failure.

Impact of increased donor distances following adult heart allocation system changes: A single center review of 1-year outcomes.

BACKGROUND: On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes. METHODS: In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006). CONCLUSIONS: Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed.

Prioritizing heart transplantation during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has significantly impacted the healthcare landscape in the United States in a variety of ways including a nation-wide reduction in operative volume. The impact of COVID-19 on the availability of donor organs and the impact on solid organ transplant remains unclear. We examine the impact of COVID-19 on a single, large-volume heart transplant program. METHODS: A retrospective chart review was performed examining all adult heart transplants performed at a single institution between March 2020 and June 2020. This was compared to the same time frame in 2019. We examined incidence of primary graft dysfunction, continuous renal replacement therapy (CRRT) and 30-day survival. RESULTS: From March to June 2020, 43 orthotopic heart transplants were performed compared to 31 performed during 2019. Donor and recipient demographics demonstrated no differences. There was no difference in 30-day survival. There was a statistically significant difference in incidence of postoperative CRRT (9/31 vs. 3/43; p = .01). There was a statistically significant difference in race (23 W/8B/1AA vs. 30 W/13B; p = .029). CONCLUSION: We demonstrate that a single, large-volume transplant program was able to grow volume with little difference in donor variables and clinical outcomes following transplant. While multiple reasons are possible, most likely the reduction of volume at other programs allowed us to utilize organs to which we would not have previously had access. More significantly, our growth in volume was coupled with no instances of COVID-19 infection or transmission amongst patients or staff due to an aggressive testing and surveillance program.

Exercise testing for assessment of heart failure in adults with congenital heart disease.

Congenital heart disease (CHD)-related heart failure is common and associated with significant morbidity, mortality, and resource utilization. In adults with CHD (ACHD), exercise limitation is often underestimated. Quantitative assessment with cardiopulmonary exercise testing (CPET) provides a comprehensive evaluation of exercise capacity and can help risk stratify patients, particularly across serial testing. CPET parameters must be interpreted within the context of the underlying anatomy, specifically for patients with either single ventricle physiology and/or cyanosis. Acknowledging differences in CPET parameters between ACHD and non-ACHD patients with heart failure are also important considerations when evaluating the overall benefit of advanced heart failure therapies. CPET testing can also guide safe exercise recommendation, including those with ACHD-related heart failure.

Heart transplantation and in-hospital outcomes in adult congenital heart disease patients with Fontan: A decade nationwide analysis from 2004 to 2014.

INTRODUCTION: Treatment of adult congenital heart disease patients who require advanced therapies remains challenging due to high perioperative and wait-list mortality and limited donors. Patients palliated with Fontan are at the highest risk of early mortality due to multiorgan involvement and few centers able to safely transplant them. We sought to evaluate the early outcomes of heart transplants in these adult Fontan patients. METHODS: Using the Nationwide Inpatient Sample database, we identified all adults aged at least 18 years old who underwent heart transplantation across U.S. hospitals from 2004 to 2014. We then identified those with specific ICD-9 codes to include tricuspid atresia, hypoplastic left heart syndrome and common ventricle. Multivariate regression models were created to adjust for potential confounders. RESULTS: A total of 93 Fontan patients underwent heart transplant during the study time (0.5% of all heart transplants). Compared to non-Fontan heart transplantations, Fontan patients were younger, with a higher incidence of liver disease and coagulopathy. Fontan patients receiving heart transplant had higher mortality during transplant hospitalization compared to non-Fontan patients (26.3% vs 5.3% OR, 18.10, CI, 5.06-65.0 P < .001). Extracorporeal membrane oxygenator (ECMO) usage and bleeding were also higher in the Fontan cohort with an OR of 5.30 (P = .016) and 5.32 (P = .015) for ECMO and bleeding, respectively. The remaining outcomes were similar for both cohorts. CONCLUSION: Adults with Fontan palliation undergoing heart transplantation have exceptionally high inpatient mortality, which is nearly five times that of non-Fontan heart transplant recipients, perhaps related to a delayed referral, surgical complexity, and coexistent, underrecognized liver failure.

Pulmonary arterial hypertension in adults with systemic right ventricles referred for cardiac transplantation.

BACKGROUND: Systemic right ventricular (RV) failure may progress necessitating referral for orthotropic heart transplantation (OHT). Pulmonary hypertension (PH) frequently coexists in adult congenital heart disease and can complicate the assessment for OHT. METHODS: Single-center case series of six patients (median age 34.9 years [IQR, 31.9-42.4]) with systemic RV physiology with PH referred for OHT evaluation from 2008 to 2017. RESULTS: One-third (n = 6) of 18 patients with systemic RV physiology referred for OHT evaluation had pulmonary arterial hypertension (PAH) defined as mean pulmonary artery pressure (mPAP) > 25 mm Hg and pulmonary vascular resistance (PVR) > 3 Wood Units. Two of the six patients were considered OHT-ineligible due to PH and comorbidities. Of the remaining four, two had pre-capillary PH and underwent heart-lung transplant (HLTx). The other two demonstrated reversibility of PVR with vasodilator testing and underwent OHT alone, one of whom died post-transplant from PH crisis. CONCLUSIONS: Pulmonary arterial hypertension is common in systemic RV patients referred for OHT. Systemic RV dysfunction places these patients at risk for post-capillary PH but pre-capillary PH can exist. Despite management with selective pulmonary vasodilators and afterload reduction, criteria for listing patients for HLTx vs OHT are not known and need further elucidation.

Pulmonary Hypertension in Advanced Heart Failure: Assessment and Management of the Failing RV and LV.

PURPOSE OF REVIEW: In patients with heart failure with reduced ejection fraction, the presence of pulmonary hypertension (PH-LHD) has a significant impact on their prognosis. The purpose of this review is to explain the methods of diagnosing PH-LHD and then discuss the available therapeutic options. RECENT FINDINGS: We begin by examining the methods of assessment of PH-LHD-echocardiography, cardiopulmonary exercise testing, and right heart catheterization-with a particular focus on the importance of accurate measurement to ensure the proper determination of PH-LHD. We then focus primarily on management of PH-LHD, with an examination of trials of therapeutic options, use of mechanical circulatory support, and transplantation. This review highlights the complexities in diagnosis and management of PH-LHD. We outline a number of useful ways to maximize the yield of diagnostic testing, as well as give suggestions on the use of medical therapies, the role of both temporary mechanical support and left ventricular assist device, and finally the ways to best bridge these patients to transplantation.

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.

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.