The Impact of Local Programmatic Decisions on Outcomes in Transplant-Listed Adults With Congenital Heart Disease.

BACKGROUND: We investigated variables impacting waitlist times and negative waitlist outcomes in adults with congenital heart disease (ACHD) who were waiting for orthotopic heart transplant (OHT) after the 2018 allocation change. METHODS: Adult candidates for OHT who were listed between 10/18/2018 and 12/31/2022 in the United Network for Organ Sharing database were categorized as ACHD vs non-ACHD. Waitlist time and time to upgrade for those upgraded into status 1-3 were compared by using rank-sum tests. Death/delisting for deterioration was assessed by using Fine-Gray subdistribution hazard ratios (SHRs). RESULTS: Of 15,424 OHT candidates, 589 (3.8%) were ACHD. ACHD vs non-ACHD candidates had less urgent status at initial listing (4.2% vs 4.7% listed at status 1; 17.2% vs 23.7% listed at status 2; P < 0.001), but not final listing (5.9% vs 7.6% final status 1; 35.6% vs 36.8% final status 2; P < 0.001). ACHD vs non-ACHD candidates upgraded into status 1 (65.0 vs 30.0 days; P = 0.09) and status 2 (113.0 vs 64.0 days; P = 0.003) spent longer times on the waitlist. ACHD vs non-ACHD candidates spent longer times waiting for an upgrade into status 1 (51.4 vs 17.6 days; P = 0.027) and status 2 (76.7 vs 34.7 days; P = 0.003). Once upgraded, there was no difference between groups in waitlist time to status 1 (9.7 vs 5.5 days = 0.66). ACHD vs non-ACHD candidates with a final status of 1 (20.0% vs 8.6%; SHR 2.47 [95%CI = 1.19-5.16]; P = 0.02) and 2 (8.9% vs 2.3%; SHR 3.59 [95%CI = 2.18-5.91]; P < 0.001) experienced higher rates of death and deterioration. CONCLUSIONS: ACHD candidates have longer waitlist times, have lower priority status at initial listing, wait longer for upgrades, and have higher mortality rates at the same final status as non-ACHD candidates, suggesting that they are being upgraded too late.

Achieving Consensus: Severity-Graded Definitions of Fontan-Associated Complications to Characterize Fontan Circulatory Failure.

BACKGROUND: Fontan physiology leads to chronic changes in other organ systems that may affect long-term survival and the success of heart transplantation. Inadequate assessment and treatment of the extra-cardiac effects of Fontan may contribute to poor outcomes. Severity-graded/ordinal consensus definitions of Fontan complications are lacking, which limits understanding of how Fontan-specific morbidity affects patients' outcomes. METHODS AND RESULTS: A panel of Fontan patient and physiology experts, including pediatric, adult congenital, heart failure, and critical-care cardiology as well as pediatric nephrology, hepatology and psychology, convened to develop definitions of Fontan complications. Definitions were created by using a severity-graded ordinal scale: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, disabling or life threatening. Following definition creation, a second panel of 21 experts in Fontan circulatory failure used a modified Delphi methodology to modify and vote on definitions until consensus (> 90% agreement without recommended further modification) was reached on final definitions. After 3 rounds of modifications and voting, consensus agreement was achieved on all Fontan-specific definitions. The defined complications and morbidities of Fontan include: anatomic Fontan pathway obstruction, cyanosis, systemic venous abnormalities resulting from venous insufficiency, atrial arrhythmia, ventricular arrhythmia, bradycardia, chronic pleural effusions, chronic ascites, protein-losing enteropathy, plastic bronchitis, hemoptysis and pulmonary hemorrhage, sleep apnea, Fontan-associated liver disease, portal and hepatic variceal disease, acute kidney injury affecting clinical treatment, polycythemia, thrombotic disease, recurrent or severe bacterial infection, skin atrophy, adrenal insufficiency, physical impact of previous stroke, mood/behavior disorder, and neurodevelopmental disorder. CONCLUSION: Consensus and severity-graded definitions of Fontan-specific cardiac and extra-cardiac complications were achieved and are available for use in research. They will allow future robust analyses of Fontan patient outcomes.

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.

Outcomes after initial heart failure consultation in Fontan patients.

BACKGROUND: Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care. METHODS: This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as "too late" (death or declined for transplant due to being too sick) and/or "care escalation" (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. "Late referral" was defined as those referred too late and/or had care escalation. RESULTS: Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8-21.5, p=0.004). CONCLUSIONS: Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.

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.

Fetal Echocardiographic Predictors of Postnatal Surgical Strategies in Critical Pulmonary Stenosis or Atresia with Intact Ventricular Septum: A Meta-Analysis.

BACKGROUND: Critical pulmonary stenosis or atresia with intact ventricular septum (PSAIVS) may be managed either by biventricular repair or univentricular palliation. This systematic review and meta-analysis aimed to synthesize the evidence for the role of fetal echocardiography in predicting the postnatal treatment pathway. METHODS: PubMed/MEDLINE, CINHAL, Cochrane Library, Academic Search Complete, Web of Science, and Trip Pro were searched for observational studies published before July 2021. Random-effects meta-analysis was performed to identify factors associated with biventricular repair. RESULTS: Eleven individual studies published between 2006 and 2021, including a total of 285 participants (159 biventricular repair; 126 univentricular palliation), met our eligibility criteria. The pooled estimated prevalence of biventricular repair among patients with PSAIVS was 55.6% (95% confidence interval 48.5-62.5%). Those who underwent biventricular repair had greater right to left ventricle and tricuspid to mitral valve dimension ratios, greater TV z score, and longer TV inflow duration/cardiac cycle length by fetal echocardiography. They were also more likely to have significant tricuspid regurgitation and less likely to have ventriculo-coronary connections (VCCs). CONCLUSIONS: Commonly obtained fetal echocardiographic measurements have strong associations with treatment pathway choice for patients with PSAIVS. Greater RV growth appears to favor biventricular repair, whereas patients with VCC almost invariably undergo univentricular palliation. Future studies should aim to establish how these fetal echocardiographic parameters might predict outcomes for the two treatment pathways.

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.

Factors associated with a lower chance of having gaps in care in adult congenital heart disease.

BACKGROUND: To promote good health in patients with congenital heart disease (CHD), prevention of gaps in care is essential, as adverse prognosis is associated with care gaps. A well-organised, formal transition programme may help prevent loss to follow up after leaving paediatric care. To inform the development of a transition programme, we investigated factors associated with care gaps in adults with CHD. METHODS: Between 15 October 2018 and 15 November 2019 data on patient characteristics and patient experiences with transition-related education, difficulties, and gaps in care were collected and assessed in 87 adults with CHD. Two groups (with gaps in care versus without gaps) were compared to identify informative differences using chi-squared, Fisher's exact tests, or Wilcoxon rank-sum tests. To assess the relationship between care gaps and identified variables, factors with significant difference (p < 0.05) in bivariate analyses were employed as covariates in multivariable logistic regression analysis. RESULTS: About half of the study cohort reported having gaps in care. In a multivariate model, patients having thorough discussion about the importance of receiving adult care in paediatric care were 70% less likely to experience gaps (odds ratio 0.303, 95% CI 0.14, 0.66). Forty-seven percent of patient-perceived barriers to transitioning originated from negative feelings associated with transfer. CONCLUSION: Gaps in care are highly prevalent in adults with CHD. For a transition programme to be most effective, curriculum development may need to consider the differential impact of various factors and target areas to mitigate the psychological stress associated with transfer.

Heart failure-induced activation of phospholipase iPLA2γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore.

Congestive heart failure typically arises from cardiac myocyte necrosis/apoptosis, associated with the pathological opening of the mitochondrial permeability transition pore (mPTP). mPTP opening decreases the mitochondrial membrane potential leading to the activation of Ca2+-independent phospholipase A2γ (iPLA2γ) and the production of downstream toxic metabolites. However, the array of enzymatic mediators and the exact chemical mechanisms responsible for modulating myocardial mPTP opening remain unclear. Herein, we demonstrate that human heart failure activates specific myocardial mitochondrial phospholipases that increase Ca2+-dependent production of toxic hydroxyeicosatetraenoic acids (HETEs) and attenuate the activity of phospholipases that promote the synthesis of protective epoxyeicosatrienoic acids (EETs). Mechanistically, HETEs activated the Ca2+-induced opening of the mPTP in failing human myocardium, and the highly selective pharmacological blockade of either iPLA2γ or lipoxygenases attenuated mPTP opening in failing hearts. In contrast, pharmacological inhibition of cytochrome P450 epoxygenases opened the myocardial mPTP in human heart mitochondria. Remarkably, the major mitochondrial phospholipase responsible for Ca2+-activated release of arachidonic acid (AA) in mitochondria from non-failing hearts was calcium-dependent phospholipase A2ζ (cPLA2ζ) identified by sequential column chromatographies and activity-based protein profiling. In contrast, iPLA2γ predominated in failing human myocardium. Stable isotope kinetics revealed that in non-failing human hearts, cPLA2ζ metabolically channels arachidonic acid into EETs, whereas in failing hearts, increased iPLA2γ activity channels AA into toxic HETEs. These results mechanistically identify the sequelae of pathological remodeling of human mitochondrial phospholipases in failing myocardium. This remodeling metabolically channels AA into toxic HETEs promoting mPTP opening, which induces necrosis/apoptosis leading to further progression of heart failure.

Utilization and Outcomes of Expanded Criteria Donors in Adults with Congenital Heart Disease.

BACKGROUND: Use of donation after circulatory death(DCD) and hepatitis C virus(HCV) positive donors in heart transplantation have increased the donor pool. Given poor waitlist outcomes in the adult congenital heart disease(ACHD) population, we investigated waitlist outcomes associated with willingness to consider DCD and HCV+ offers and post-transplant outcomes following HCV+ and DCD transplantation for these candidates. METHODS: Using the United Network for Organ Sharing database, we identified adult ACHD candidates and recipients listed or transplanted, respectively, between 01/01/2016-09/30/2023 for the HCV analysis and between 12/01/2019-09/30/2023 for the DCD analysis. Among candidates, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider HCV+ and DCD offers. Among recipients of HCV+ (vs. HCV-) and DCD (vs. brain death[DBD]) transplants, we compared perioperative outcomes and post-transplant survival. RESULTS: Of 1,436 ACHD candidates from 01/01/2016-09/30/2023, 37.0% were willing to consider HCV+ heart offers. Of 886 ACHD candidates from 12/01/2019-09/30/2023, 15.5% were willing to consider DCD offers. On adjusted analysis, willingness to consider HCV+ offers was associated with 84% increased likelihood of transplant, and willingness to consider DCD offers was associated with 56% increased likelihood of transplant. Of 904 transplants between 01/01/2016-09/30/2023, 6.4% utilized HCV+ donors, and of 540 transplants between 12/01/2019-09/30/2023, 6.9% utilized DCD donors. Recipients of HCV+ (vs. HCV-) and DCD (vs. DBD) heart transplants had similar likelihood of perioperative outcomes and 1-year survival. CONCLUSIONS: ACHD candidates who were willing to consider HCV+ and DCD offers were more likely to be transplanted and had similar post-transplant outcomes compared to recipients of HCV- and DBD organs.

Management of Prosthetic Mitral Valve Infective Endocarditis in a Patient With Congenital Heart Disease.

We present the case of an adult patient with Kartagener's syndrome, multiple prior sternotomies, and recurrent prosthetic valve endocarditis, a scenario without clear guidelines to direct management. Ultimately, the team elected for medical management given the high mortality risk associated with surgery; the patient responded to antibiotic therapy.

Reoperations in Adolescents and Adults after Prior Arterial Switch Operation: STS Congenital Database Analysis.

BACKGROUND: Arterial switch operation (ASO) has supplanted physiologic repairs for transposition of the great arteries and related anomalies. As survival rates have increased, so has the potential need for cardiac reoperations to address ASO-related complications arising later in life. METHODS: The STS-CHSD (2010-2021) was reviewed to assess prevalence and types of cardiac reoperations among patients aged ≥10 years with prior ASO for TGA or DORV/TGA-type. A hierarchical stratification designating 13 Procedure Categories was established a priori by investigators. Each eligible surgical hospitalization was assigned to the single highest applicable hierarchical category. Outcomes were compared across Procedure Categories, excluding hospitalizations limited to pacemaker-only and/or mechanical circulatory support-only procedures. Variation over the study period in relative proportions of Left Heart vs Non-Left Heart Procedure Category encounters was assessed. RESULTS: There were 698 cardiac surgical hospitalizations among patients aged 10-35 years at 100 centers. The most common Left Heart Procedure Categories were Aortic Valve procedures (n=146), Aortic Root procedures (n=117), and Coronary Artery procedures (n=40). Of 619 hospitalizations eligible for outcomes analysis, Major Complications occurred in 11% (67/619). Discharge mortality was 2.3% (14/619). Year-by-year analysis of surgical hospitalizations reveals substantial growth in numbers for the aggregate of all Procedure Categories. Growth in relative proportions of Left Heart vs Non-Left Heart Procedures was significant, p=0.0029 (Cochran-Armitage trend test). CONCLUSIONS: This largest multicenter study of post-ASO reoperations beyond early childhood documents year-over-year growth in total reoperations. Recently, left heart procedures had the highest rate of rise. These observations have implications for counseling, surveillance, and management.

Meta-analysis: Incidence of cirrhosis and hepatocellular carcinoma in patients with Fontan palliation.

BACKGROUND AND AIMS: The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery. METHODS: A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy. RESULTS: A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis. CONCLUSION: The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.

Atrial Fibrillation Ablation in a Patient With SV ASD and PAPVR Preceding Transcatheter Septal Closure.

Atrial fibrillation (AF) is common in adults with unrepaired atrial septal defects (ASDs). Sinus venosus (SV) ASDs associated with partial anomalous pulmonary venous return (PAPVR) are traditionally managed surgically. We report the first AF catheter ablation in a patient with SV ASD and PAPVR preceding transcatheter ASD repair with a covered stent. (Level of Difficulty: Advanced.).

Mode of delivery among women with maternal cardiac disease.

OBJECTIVE: To determine if maternal cardiac disease affects delivery mode and to investigate maternal morbidity. STUDY DESIGN: Retrospective cohort study performed using electronic medical record data. Primary outcome was mode of delivery; secondary outcomes included indication for cesarean delivery, and rates of severe maternal morbidity. RESULTS: Among 14,160 deliveries meeting inclusion criteria, 218 (1.5%) had maternal cardiac disease. Cesarean delivery was more common in women with maternal cardiac disease (adjusted odds ratio 1.63 [95% confidence interval 1.18-2.25]). Patients delivered by cesarean delivery in the setting of maternal cardiac disease had significantly higher rates of severe maternal morbidity, with a 24.38-fold higher adjusted odds of severe maternal morbidity (95% confidence interval: 10.56-54.3). CONCLUSION: While maternal cardiac disease was associated with increased risk of cesarean delivery, most were for obstetric indications. Additionally, cesarean delivery in the setting of maternal cardiac disease is associated with high rates of severe maternal morbidity.

Data Quality Degradation on Prediction Models Generated From Continuous Activity and Heart Rate Monitoring: Exploratory Analysis Using Simulation.

BACKGROUND: Limited data accuracy is often cited as a reason for caution in the integration of physiological data obtained from consumer-oriented wearable devices in care management pathways. The effect of decreasing accuracy on predictive models generated from these data has not been previously investigated. OBJECTIVE: The aim of this study is to simulate the effect of data degradation on the reliability of prediction models generated from those data and thus determine the extent to which lower device accuracy might or might not limit their use in clinical settings. METHODS: Using the Multilevel Monitoring of Activity and Sleep in Healthy People data set, which includes continuous free-living step count and heart rate data from 21 healthy volunteers, we trained a random forest model to predict cardiac competence. Model performance in 75 perturbed data sets with increasing missingness, noisiness, bias, and a combination of all 3 perturbations was compared to model performance for the unperturbed data set. RESULTS: The unperturbed data set achieved a mean root mean square error (RMSE) of 0.079 (SD 0.001) in predicting cardiac competence index. For all types of perturbations, RMSE remained stable up to 20%-30% perturbation. Above this level, RMSE started increasing and reached the point at which the model was no longer predictive at 80% for noise, 50% for missingness, and 35% for the combination of all perturbations. Introducing systematic bias in the underlying data had no effect on RMSE. CONCLUSIONS: In this proof-of-concept study, the performance of predictive models for cardiac competence generated from continuously acquired physiological data was relatively stable with declining quality of the source data. As such, lower accuracy of consumer-oriented wearable devices might not be an absolute contraindication for their use in clinical prediction models.