High risk and low incidence diseases: Cyanotic critical congenital heart disease.

Generation of three induced pluripotent stem cell clones from a functional single ventricle patient carrying the BRAF c.1897T>C variant.

No reports on atrial leadless pacing have been demonstrated in patients with the Fontan palliation. We present the case of a patient with a Lateral tunnel Fontan palliation with leadless pacing system for symptomatic bradycardia in the setting of sinus node dysfunction. After internal review board approval, a retrospective case review was performed with follow-up of atrial leadless pacing in a patient with a Lateral tunnel Fontan. A 32-year-old male with a medical history of tricuspid atresia status post: Blalock-Taussig Shunt (BT) shunt, Glenn procedure, and Fontan surgery at 5 years of age presented with persistent atrial flutter and a history of symptomatic heart failure in the setting sick sinus syndrome with a dual chamber epicardial pacemaker procedure. After ablation of his intra-atrial re-entrant tachycardia he continued with symptomatic bradycardia in the setting of epicardial lead fracture. Implant values demonstrated an atrial threshold of 1 Volts (V) at 0.4 ms (ms), impedance at 820 ohms and sensing at < 1 mV. He was programmed AAIR (VVIR) 80-130 bpm, rate response of 2/7, and discharged on apixaban 5 mg twice a day. Follow-up at 4 months demonstrated no intracardiac thrombus, 98% atrial pacing, threshold of 0.75 V@0.15 ms, impedance of 590 ohms, and R-wave of 2.5 mV. The estimated device longevity was 17.2 years. Atrial leadless pacing is feasible in the lateral tunnel Fontan. Larger patient population data sets are needed to assess safety of this type of pacing long-term.

Primary pulmonary malignancies in single-ventricle patients are rare. Improved survival following surgical palliation has resulted in a growing Fontan population whose malignancy risk remains undefined. Standard oncologic approaches, especially for adenocarcinoma of the lung, need to be considered within the context of Fontan physiology. We present our management of primary lung adenocarcinoma in an adult with tricuspid atresia status postlateral tunnel Fontan palliation, highlighting considerations for this unique scenario.

Background: Ventricular function assessments in Fontan patients remain challenging. Ejection fraction (EF) lacks sensitivity for early dysfunction, and the roles of strain and advanced imaging in systemic left ventricle (LV) physiology are not fully defined. We aimed to compare (i) LV and atrial strain indices between pediatric Fontan patients with preserved EF (P-LVEF) versus reduced EF (R-LVEF) and (ii) echocardiographic global longitudinal strain, segmental longitudinal strain indices, and conventional 2D and 3D echocardiographic parameters through cardiac morphology. Methods: Pediatric patients with Fontan circulation and systemic LV morphology underwent clinical, hemodynamic, and multimodality echocardiographic evaluation, including 2D/3D parameters, global and segmental LV strain, and left atrial strain. Outcomes were analyzed according to EF status and congenital morphology. Significant results from multiple comparisons were followed by post hoc analysis, where appropriate. Results: Patients with a reduced EF exhibited a worse clinical status, a higher pulmonary vascular resistance index, and greater systemic congestion compared with those with a preserved EF. Conventional 2D indices showed no significant differences between the two studied groups except for LV end-systolic volume (ESV) (p = 0.0315) and LV end-systolic longitudinal diameter (ESL) (p = 0.0024), which showed higher values in the R-LVEF group. Although the relative frequency of impaired deformation was higher in Fontan patients with an unbalanced atrioventricular canal compared with the Fontan patients with a tricuspid atresia + pulmonary stenosis + ventricular septal defect, the difference did not reach statistical significance (p = 0.1365). Most segmental longitudinal strain values were not significantly different across patients with different cardiac morphology, except for the basal anterior segment and apical inferoseptal segment (p < 0.05). Conclusions: In pediatric Fontan patients with systemic LV morphology, a reduced EF was associated with a worse clinical and hemodynamic status. Conventional echocardiographic indices showed a limited ability to differentiate between the compared groups. Although no statistically significant differences were detected between pediatric Fontan patients with preserved EF and reduced EF, LV and atrial strain indices provided complementary information on ventricular–atrial interactions and myocardial deformation. These findings are exploratory and warrant confirmation in larger, prospective studies.

Tricuspid atresia (TA) is a cyanotic congenital heart defect defined by agenesis of the tricuspid valve and resultant right ventricular hypoplasia, representing 1.4–2.9% of congenital heart disease. Survival depends on interatrial and interventricular shunts that permit systemic and pulmonary blood flow, with staged surgical palliation culminating in the Fontan procedure. While surgical advances have improved long-term outcomes, Fontan circulation remains a delicate physiology characterized by preload dependence, elevated pulmonary vascular resistance, chronic venous hypertension, and a prothrombotic state. These features predispose patients to arrhythmias, lymphatic complications, hepatic congestion, and progressive circulatory failure. For anesthesiologists, perioperative management of TA and Fontan patients is uniquely complex. Anesthetic considerations include meticulous preload optimization, modulation of systemic and pulmonary vascular resistance, and ventilatory strategies that minimize adverse effects on venous return. Additional challenges include the high risk of air embolism, individualized anticoagulation needs, and hemodynamic sensitivity to patient positioning. Preoperative evaluation with echocardiography and electrocardiography provides critical insight into anatomy and physiology, while intraoperative planning must emphasize goal-directed fluid management, careful agent selection, and tailored ventilation. Postoperatively, vigilant monitoring, effective pain control, and prevention of complications are essential. This review synthesizes classification systems, pathophysiology, and the evolution of surgical palliation, while emphasizing anesthetic principles for the perioperative care of patients with TA and Fontan circulation. As survival improves and the population of Fontan patients expands, a nuanced understanding of this physiology is essential for optimizing outcomes across cardiac and non-cardiac surgical settings.

BACKGROUND Fontan repair in complex congenital heart conditions involves creating a total cavopulmonary connection, redirecting systemic venous blood to the pulmonary circulation, and bypassing cardiac systemic blood flow. Anesthetic management for a patient with a Fontan circulation requires ensuring adequate preload and avoiding circulatory complications. This report describes the anesthetic management of a 32-year-old woman undergoing laparoscopic surgery with a history of Fontan repair of a complex congenital heart defect. CASE REPORT A 32-year-old woman with transposition of the great arteries, hypoplastic right ventricle, tricuspid atresia, and non-communicating vena cavae underwent Fontan repair at 12 months of age (total cavopulmonary connection with extracardiac conduit). She presented for laparoscopy for suspected ovarian cancer. Preoperative cardiac magnetic resonance imaging revealed Fontan conduit patency and borderline systemic ventricular function. Anesthetic management included advanced monitoring (FloTrac-derived cardiac index, stroke volume, stroke volume variation), tailored induction with slow titration of propofol, ventilation with low tidal volumes and zero positive end-expiratory pressure, and vigilant fluid management. During pneumoperitoneum (12 mmHg), decreased stroke volume and mean arterial pressure were corrected with fluid boluses. At the end of surgery, the patient was extubated uneventfully and monitored in the postoperative intensive care unit for 36 hours. CONCLUSIONS Laparoscopic surgery in patients with Fontan circulation poses significant anesthetic challenges. This case highlights the importance of ensuring adequate preload, minimizing pulmonary vascular resistance, maintaining low intra-abdominal pressure, and using advanced hemodynamic monitoring to guarantee perioperative safety.

Background: In patients who have undergone Fontan palliation, suboptimal geometry of the reconstructed aorta may contribute to abnormal aortic blood flow patterns, ventriculo-vascular decoupling, and worse clinical outcomes. 4D Flow magnetic resonance imaging (MRI) enables detailed hemodynamic assessment, but large-scale studies are hindered by labor-intensive image analysis. Deep learning models have successfully automated aortic segmentation in single-center adult cohorts with bicuspid aortic valve or conventional anatomy but perform poorly in patients with complex congenital heart disease. Training on 4D Flow data from Fontan patients may improve performance in this heterogeneous population. Methods: We compiled 215 4D Flow CMR studies (200 unique patients from 17 centers) from the Fontan Outcomes Registry Using Cardiac Magnetic Resonance Examination (FORCE). Manual aortic segmentation was performed on a subset of 78 studies (n=63 training, n=15 testing). Studies with metallic artifact obscuring the aorta, aortic cropping, or non-sagittal image orientation were excluded. A convolutional neural network with 3D U-Net architecture incorporating dense blocks was used to generate 3D aortic segmentations from the 4D Flow data. Segmentation accuracy was evaluated using dice similarity coefficients (DSCs). Results: The mean age at MRI was 17.7 ± 8.8 years. The most common diagnoses were hypoplastic left heart syndrome (33%), double outlet right ventricle (16.6%), and tricuspid atresia (12%). Segmentation performance was variable, with DSCs ranging from 0.001 to 0.47 (mean=0.20). Modeling was likely challenged by the heterogeneity of Fontan anatomy as well as variation in imaging protocols across the 17 contributing centers. Conclusions: Anatomical and imaging variability across centers likely contributed to poor model performance compared to more uniform, single-center adult studies. To mitigate this, we plan to standardize images and segmentations to a uniform voxel size and field of view. We will also apply data augmentation techniques, including spatial transformations and intensity perturbations, to synthetically increase dataset size and expose the model to a wider range of anatomical and imaging variability. This approach may improve generalizability and robustness in the setting of a small, non-uniform training dataset. Future efforts will also include k-fold cross-validation and expansion of the training cohort to further enhance model performance.

Introduction: The prevalence of heart failure (HF) among U.S. patients (pts) with Fontan physiology is poorly defined, with estimates generally derived from single centers. We leveraged a 7-state administrative dataset—the largest single ventricle (SV) cohort to date—to estimate HF prevalence across the lifespan and its associated comorbidities. Methods: This is a study from the CDC-funded STAR1 registry of CHD pts ages 0-45. All ICD diagnostic/procedural codes from 2010-2019 were collected. SV pts ≥5 yrs (presumed post-Fontan) were identified via ICD-9/10 codes associated with SV physiology and Fontan palliation. HF of any type was identified via ICD9/10 query. To depict HF burden over the lifespan (Figure 1), HF prevalence was calculated per 5-year age range via the following: total number of pts with HF coded in an encounter for that age range divided by the total number of pts at risk in that age range. Results: Of the 4,753 Fontan pts identified, 2,836 (60%) were 5-17 years old (yo), 1,358 (28%) were 18-30 yo and 559 (12%) were ≥31 yo at first encounter. Diagnoses included hypoplastic left heart in 1,752 (37%), tricuspid atresia in 1,945 (41%), and SV not otherwise specified in 1,056 (22%), of which 36%, 41% and 46% were adults, respectively; 168 SV patients were &gt;45 yo by end of the surveillance period. Overall, 1,401 (29%) had a diagnosis of HF at any time. HF prevalence increased over the lifespan, ranging from 8.3% in patients 5-9 yo to 58.3% of pts ≥45 yo ( Figure 1 ). HF patients had higher rates of cardiac and non-cardiac comorbidities than their non-HF peers ( Table 1 ). Traditional modifiable cardiovascular risk factors, including hypertension, hyperlipidemia, smoking, and diabetes, were significantly higher among pts with HF across all ages. Heart transplant occurred in 22% of all HF pts (occurring in 30% of 5-17 yo, 16% of ≥ 31 yo, p &lt; 0.05) vs. 0.2% in non-HF pts. 231 (16%) of HF pts died (mortality rate 184 deaths/10,000 person-years) vs. 81 deaths among 3,352 (2%) pts without HF (mortality rate 28 deaths/10,000 person-years, p &lt; 0.05). Conclusions: In the largest Fontan cohort studied to date, ~1/3 were diagnosed with HF at any time, with steady increase to &gt;50% after age 45. The HF cohort had a significantly higher burden of comorbid disease, including potentially targetable risk factors. This emphasizes the need for close surveillance and early diagnosis in this complex patient population.

Introduction/Background - Research Questions/Hypothesis: There is a notable lack of robust evidence regarding imaging follow-up in Fontan patients from resource-limited settings, where access to advanced imaging modalities remains scarce. This study aims to describe the prevalence of cardiac magnetic resonance (CMR) use, key findings, and associated clinical outcomes in a Latin American cohort of Fontan patients. Methods/Approach: A retrospective, observational, single-center study included patients who underwent Fontan procedure completion and had an available postoperative cardiac magnetic resonance scan performed between 2006 and 2024. Data were analyzed descriptively using means ± SD, and frequencies (%). Results: Of 174 Fontan surgeries performed in our center, we included 27 (12.7%) with a follow-up CMR, spanning all age groups. The cohort comprised 15 males (55.6%), with a mean age at the time of CMR of 23.4 years. The most prevalent congenital defect was tricuspid atresia (55.6%), and in 88.8% of patients, the left ventricle was the systemic ventricle. For the Fontan pathway the extracardiac conduit was the preferred surgical technique (92.5%) and fenestration was present in 48.1% of patients. CMR was performed 19 ± 7.4 years after Fontan completion, revealing a mean indexed systemic ventricular end-diastolic volume of 101.7 ± 44.9 mL/m2 and a mean indexed end-systolic volume of 52.8 ± 30.8 mL/m2. The mean ventricular ejection fraction was 49.7% ± 7.2%, and the mean cardiac index was 4.25 ± 1.78 L/min/m2. Among those with a documented fenestration, 7.4% remained patent at time of CMR. Venovenous collaterals were present in 55.5% of the cohort. With 29.6% having more than moderate atrioventricular valve regurgitation. Venovenous collaterals were identified in 55.5% of patients, and 29.6% had more than moderate atrioventricular valve regurgitation. Findings consistent with Fontan-associated liver disease were present in 55.6% of patients, and 7.4% were diagnosed with hepatocellular carcinoma all of whom died, yielding an overall mortality rate of 7.4%. Conclusion(s): Despite limitations, our findings highlight that few Fontan patients undergo routine CMR follow-up. The high prevalence of complications suggests that CMR surveillance may be occurring too late to enable timely interventions. These results underscore the need for guideline-adherent imaging protocols to improve outcomes in this high-risk population.

The Fontan operation and its modifications have transformed the management of children with functional single ventricle physiology. While outcomes have improved, peri-operative complications remain common. This study aimed to assess early outcomes and complications following Fontan completion in a large international European cohort. The EuroFontan registry is a multicentre retrospective study involving 21 congenital heart disease and transplant centres across Europe. Data were collected on patients who underwent Fontan surgery from January 1990 to January 2023. Analyses focused on the most recent 15-year period. A composite early adverse outcome (death within 30 days or in-hospital, low cardiac output syndrome, stroke, or Fontan takedown) was used. Predictors were assessed using multivariable mixed-effects logistic regression, with centre included as a random effect. Missing data were handled using multiple imputation with Rubin's rules, and sensitivity analyses were performed to assess robustness. Of 3510 patients, this analysis focused on 2075 individuals from the past 15 years, with a median age of 4.2 [interquartile range 3.2-6.2] years at Fontan completion. Early mortality was 1.0% (95% confidence interval .66%-1.54%). The composite adverse outcome occurred in 5.1% (95% confidence interval 4.2%-6.1%). On multivariable analysis, morphology other than tricuspid atresia was the only significant predictor of the composite outcome (odds ratio 2.2, 95% confidence interval 1.21-3.99, P = .01). Fontan surgery has evolved and, in contemporary practice, has low peri-operative morbidity and mortality. Morphology other than tricuspid atresia was associated with increased risk of early adverse outcomes, highlighting the importance of pre-operative risk stratification.

BackgroundPolycythemia is a physiologic adaptive response to hypoxia seen in children with cyanotic congenital heart disease (Cyanotic CHD). Globally, due to timely cyanotic CHD interventions, polycythemia is underreported or understudied. Timely identification and treatment of polycythemia among unoperated cyanotic CHDs avoids serious hematologic and related complications. This study aimed to determine the burden and factors associated with polycythemia among patients with cyanotic CHD enrolled in chronic care.MethodsThis observational cross-sectional study used a semi-structured questionnaire to collect relevant sociodemographic and clinical data. Children with cyanotic CHD aged 1 month to 18 years were included. Polycythemia was considered when the hemoglobin was ≥ 17 g/dl on the complete blood count report of an automated hematology analyzer. Bivariate and multivariable binary logistic regression models were used to identify associated variables.ResultsIn this study, 384 patients with cyanotic CHD were included, 55.2% males. The median age of study participants was 42 months (Interquartile range/IQR: 20.3–91.5). The median altitude of residence and age at cyanotic CHD diagnosis were 2355 m (IQR: 1826–2470) and 4 months (IQR: 1–12), respectively. Polycythemia was documented in 38% (146) [95% CI: 33.1–43.1] of participants. Males had almost doubled odds of polycythemia, aOR = 1.66 (95% CI: 1.01–2.70). Children with oxygen saturation < 70 and 70–90 had almost tripled odds of polycythemia, aOR 2.71 (95% CI: 1.25–5.88) and aOR 2.79 (1.46–5.33), respectively. Moreover, children with tricuspid atresia had tripled odds of polycythemia, aOR 3.20 (95% CI: 1.19–8.55). Additionally, children who had no phlebotomies in the last six months had reduced odds of polycythemia, aOR 0.07(0.02–0.22).ConclusionThe burden of polycythemia among patients with cyanotic CHD is huge. Male sex, saturation level, diagnosis of tricuspid atresia and phlebotomy frequency were associated with polycythemia among patients with cyanotic CHD. Males with cyanotic heart disease, children with tricuspid atresia, and cyanotic CHDs with saturation of oxygen below ninety should receive targeted screening for polycythemia during chronic follow-up.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12887-025-06072-y.

Contemporary outcomes and health care costs associated with single-ventricle heart failure admissions in adults in the United States.

A 5-day-old newborn, born at 36 weeks of gestation to a mother with preeclampsia, presented with poor initial adaptation, including no movement, no cry, and a heart rate below 100 bpm. Echocardiography revealed a major defect in the atrioventricular valve with torrential regurgitation, tricuspid atresia with absence of flow through the right ventricular outflow tract, and a well-developed pulmonary artery. The newborn was started on prostaglandin therapy, which allowed for pulmonary perfusion with oxygen saturation between 85-90%. A multidisciplinary team discussed three possible management options: dilation of the right ventricular outflow tract, Starnes procedure with Blalock shunt, or discontinuation of prostaglandin therapy.

Outcomes of single ventricle heart defects may be influenced by the morphological type of the hypoplastic ventricle. Recent multi-centre studies have targeted on outcomes of hypoplastic left heart syndrome with limited focus on outcomes of hypoplastic right heart syndrome. We aimed at studying the clinical outcomes of hypoplastic right heart syndrome in the recent era. We performed a retrospective analysis of all hypoplastic right heart syndrome patients (n = 153) born between January 2010 and January 2023. Five-year transplant-free survival was compared with hypoplastic left heart syndrome patients without heterotaxy (n = 144) born during the same time. Double-inlet left ventricle was the most common anatomic hypoplastic right heart syndrome subtype (n = 39, 25%). Twenty-six (17%) patients with hypoplastic right heart had associated heterotaxy. Five-year transplant-free survival was high for most groups (double inlet left ventricle: 100%, pulmonary atresia: 94%, Ebstein's anomaly: 92%, tricuspid atresia: 90% respectively). The heterotaxy group had worse early outcomes with 3 deaths and 3 heart transplants, before Fontan completion. Heterotaxy was a significant risk factor for death/transplant prior to Fontan completion in hypoplastic right heart syndrome patients (p = 0.03). Patients with hypoplastic right heart syndrome with heterotaxy had significantly worse 5-year transplant-free survival (71%) when compared to hypoplastic right heart syndrome without heterotaxy (95%) and hypoplastic left heart syndrome without heterotaxy (75%), p < 0.001. Hypoplastic right heart syndrome patients have excellent clinical outcomes and better early childhood survival than hypoplastic left heart syndrome in the current era, except when associated with heterotaxy. The survival advantage conferred by a single left ventricle appears to be negated by heterotaxy syndrome and should be strongly considered during caregiver counselling and medical decision-making.

Introduction: Single ventricle heart disease (SVHD) includes tricuspid atresia (TA), mitral atresia (MA), hypoplastic left heart syndrome (HLHS), and hypoplastic right heart syndrome (HRHS), managed through staged surgical palliation, culminating in the Fontan procedure. While this procedure has significantly improved survival rates, it is associated with long-term complications, particularly Fontan-associated liver disease (FALD). Despite growing awareness, data on FALD’s prevalence and progression remain limited, highlighting the need for better surveillance and management. Methods: We conducted a retrospective analysis of the National Inpatient Sample (NIS) database (2018–2020) to identify adult (&gt;18 years) hospitalizations with a history of surgically corrected TA, HLHS, and HRHS. Hospitalizations with concurrent diagnoses of of liver fibrosis (LF) and liver cirrhosis (LC) were identified using appropriate ICD-10 codes. Multivariable logistic regression analysis was performed to evaluate the association between SVHD hospitalizations and hepatic complications while adjusting for potential confounders. Results: Between 2018 and 2020, there were 399 TA, 94 HRHS, and 380 HLHS adult hospitalizations following surgical correction. The mean age of these hospitalizations was significantly lower (HRHS: 28, HLHS: 23, TA: 33 years) compared to the general adult hospitalizations. Multivaribale logistic regression analysis revealed surgically corrected adult SVHD hospitalizations had significantly increased odds of liver cirrhosis (TA: OR 17, HLHS: OR 11, HRHS: OR 14) and liver fibrosis (HLHS: OR 498, TA: OR 55, HRHS: OR 619) when compared to other adult hospitalizations. Conclusion: Our study supports existing evidence that patients with Fontan circulation have a significantly increased risk of liver disease. Further research is needed to develop optimal strategies for surveillance, screening of FALD, and determining the appropriate timing for liver transplantation. Additionally, emerging innovations like the cavopulmonary pump aim to address Fontan-related hemodynamic challenges.

Outcomes of Fontan patients undergoing combined heart-liver transplantation in pediatric hospitals across the United States.

Tricuspid atresia (TA) with transposition of the great arteries (TGA) without pulmonary obstruction is a rare type of TA that delays diagnosis due to late onset of cyanosis, which delays surgery, as timely surgical interventions have contributed to converting the high mortality rate into a high survival rate. Clinicians should take into consideration the importance of early diagnosis to avoid irreversible changes that negatively affect the surgical outcome.

The anesthetic management of pediatric patients with congenital heart disease (CHD) requires a thorough understanding of the patient's unique anatomical variations, the planned surgical intervention, and associated physiological changes. CHD is broadly categorized as either cyanotic or a cyanotic. Cyanotic CHD results from the admixture of oxygenated and deoxygenated blood within the systemic circulation. Examples of cyanotic CHD include Tetralogy of Fallot, Double Outlet Right Ventricle (DORV), Total Anomalous Pulmonary Venous Return (TAPVR), Tricuspid Atresia, Critical Pulmonary Stenosis, Pulmonary Atresia, and Hypoplastic Left Heart Syndrome. A cyanotic CHD encompasses conditions such as Atrial Septal Defect, Ventricular Septal Defect, and Patent Ductus Arteriosus. Pre-anesthetic evaluation is essential for determining the patient's pre-operative physical status, assessing the specific congenital anomaly, and evaluating the severity of the cardiac defect. This information allows for meticulous perioperative planning. Intraoperative management must consider the dynamics of shunt flow in CHD, which depends upon the shunt's anatomical characteristics, specifically its size and configuration. While inhalational agents are frequently employed for induction and maintenance of anesthesia in pediatric cardiac cases, patients exhibiting compromised ventricular function or dependence on systemic vascular resistance (SVR) and/or pulmonary vascular resistance (PVR) necessitate pre-induction intravenous access. In these patients, anesthetic agents that could further impair hemodynamic stability should be avoided or used judiciously. Post-induction anesthetic choices are guided by ventricular function (including the presence or absence of congestive heart failure), the anticipated need for cardiopulmonary bypass, and the probability of requiring mechanical ventilation or tracheal extubating post-operatively.

The complex and hazardous course for heterotaxy-associated congenital heart disease