In a porcine model of implantable pacemakers for pediatric unilateral diaphragm paralysis, the phrenic nerve is the best target.

BACKGROUND: A frequent complication of Fontan operations is unilateral diaphragmatic paresis, which leads to hemodynamic deterioration of the Fontan circulation. A potential new therapeutic option is the unilateral diaphragmatic pacemaker. In this study, we investigated the most effective stimulation location for a potential fully implantable system in a porcine model. METHODS: Five pigs (20.8 ± 0.95 kg) underwent implantation of a customized cuff electrode placed around the right phrenic nerve. A bipolar myocardial pacing electrode was sutured adjacent to the motor point and peripherally at the costophrenic angle (peripheral diaphragmatic muscle). The electrodes were stimulated 30 times per minute with a pulse duration of 200 µs and a stimulation time of 300 ms. Current intensity was the only variable changed during the experiment. RESULTS: Effective stimulation occurred at 0.26 ± 0.024 mA at the phrenic nerve and 7 ± 1.22 mA at the motor point, a significant difference in amperage (p = 0.005). Even with a maximum stimulation of 10 mA at the peripheral diaphragm muscle, however, no effective stimulation was observed. CONCLUSION: The phrenic nerve seems to be the best location for direct stimulation by a unilateral thoracic diaphragm pacemaker in terms of the required amperage level in a porcine model.

Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study.

INTRODUCTION: As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation. METHODS: We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022. RESULTS: The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time > 283 min (4.7 h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis. CONCLUSION: Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

Anesthetic management in pregnant women with Fontan circulation: a case series.

BACKGROUND: Given the advances in medicine, women with Fontan circulation are now reaching childbearing age. However, data on the mode of delivery and anesthetic management of these patients are limited. We report the cases of five pregnant women with Fontan circulation. CASE PRESENTATION: The mean age at delivery was 28 ± 3 years, and the mean gestational period was 34 weeks and 3 days. Anticoagulation therapy was switched from warfarin and aspirin to continuous intravenous heparin. The modes of delivery were scheduled cesarean section (C/S) in one, emergency C/S in three, and vaginal delivery with epidural labor analgesia in one patient. Three patients underwent C/S under regional anesthesia; one received general anesthesia. The perinatal complications were heart failure, worsening valve regurgitation, and postoperative hematoma in three, four, and two patients, respectively. CONCLUSIONS: For C/S in women with Fontan circulation, regional anesthesia should be considered. Epidural labor analgesia can help prevent the decrease in pulmonary blood flow due to straining. We initiated labor analgesia or C/S with regional anesthesia at the appropriate time in four patients.

Intravenous iron infusion ameliorates anaemia and protein-losing enteropathy in patients after Fontan surgery: case series.

Protein-losing enteropathy is a severe complication of Fontan surgery and is associated with anaemia. Few studies have reported on the efficacy of an intravenous iron infusion for treating protein-losing enteropathy and low albuminemia after Fontan surgery. Herein, we present two cases of female patients who suffered from protein-losing enteropathy and low albuminemia following Fontan surgery, both of whom improved after an intravenous iron infusion.

[Imaging of congenital heart defects with a focus on magnetic resonance imaging and computed tomography]. / Bildgebung angeborener Herzfehler mit Fokus auf Magnetresonanz- und Computertomographie.

CLINICAL ISSUE: Due to advances in diagnostics and therapy, the survival rate of patients with congenital heart defects is continuously increasing. The aim of this review is to compare various imaging modalities that are used in the diagnosis of congenital heart defects. METHODS: Transthoracic echocardiography is the imaging method of choice in the presence of a congenital heart defect because of its wide availability and non-invasiveness. It can be complemented by transesophageal echocardiography, cardiac catheterization, computed tomography (CT), and magnetic resonance imaging (MRI) of the heart and vessels close to the heart. METHODICAL INNOVATIONS: The radiation exposure of CT examinations of the heart is continuously decreasing because of improved technologies. MRI is also being continuously optimized, e.g., by the acquisition of MR angiographies without contrast medium application or a thin three-dimensional (3D) visualization of the entire heart with the possibility of reconstruction in all spatial planes (whole-heart technique) as well as 2D to 4D flow. PRACTICAL RECOMMENDATION: Due to the complexity of congenital heart defects and the variety of possible pathologies, the choice of imaging modality and its exact performance has to be coordinated in an interdisciplinary context and individually adapted.

Long-Term Incidence of Arrhythmias in Extracardiac Conduit Fontan and Comparison Between Systemic Left and Right Ventricle.

AIMS: The extracardiac conduit-Fontan (ECC) has become the preferred technique for univentricular heart palliation, but there are currently no data on the incidence of long-term arrhythmias. This study investigated the incidence of arrhythmias and relation to single ventricle morphology in the long-term follow-up in ECC. METHODS AND RESULTS: All patients with ECC performed in our Centre between 1987 and 2017 were included (minimum follow-up 5 years). Of 353 consecutive patients, 303 [57.8% males, aging 8-50 (median 20) years at last follow-up] were considered and divided into 2 groups depending on left (194 in Group 1) or right (109 in Group 2) ventricular morphology. Eighty-five (28%) experienced ≥1 arrhythmic complications, with early and late arrhythmias in 17 (5.6%) and 73 (24.1%) patients, respectively. Notably, late bradyarrhythmias occurred after 6 years in 21 (11%) patients in Group 1, and in 15 (13.8%) in Group 2 [p=0.48]. Late tachyarrhythmias occurred in 55 (18.2%) patients after 12 years: 33 (17%) in Group 1 and 22 (20.2%) patients in Group 2 [p=0.5]. Ventricular tachycardias were documented after 12.5 years in 14 (7.2%) patients of Group 1 and 15 (13.8%) of Group 2 [p=0.06] with a higher incidence in Group 2 during the follow-up [p=0.005]. CONCLUSION: ECC is related to a significant arrhythmic risk in the long-term follow-up, higher than previously reported. Bradyarrhythmias occur earlier but are less frequent than tachyarrhythmias. Interestingly, patients with systemic right ventricle have a significantly higher incidence of ventricular tachycardias, especially in very long follow-up.

Anesthetic challenges in patients with multicompartmental lymphatic failure after Fontan palliation undergoing transcatheter thoracic duct decompression.

Lymphatic flow abnormalities are central to the development of protein losing enteropathy, plastic bronchitis, ascites and pleural effusions in patients palliated to the Fontan circulation. These complications can occur in isolation or multicompartmental (two or more). The treatment of multicompartmental lymphatic failure aims at improving thoracic duct drainage. Re-routing the innominate vein to the pulmonary venous atrium decompresses the thoracic duct, as atrial pressure is lower than systemic venous pressure in Fontan circulation. Transcatheter thoracic duct decompression is a new minimally invasive procedure that involves placing covered stents from the innominate vein to the atrium. Patients undergoing this procedure require multiple general anesthetics, presenting challenges in managing the sequelae of disordered lymphatic flow superimposed on Fontan physiology. We reviewed the first 20 patients at the Center for Lymphatic Imaging and Intervention at a tertiary care children's hospital presenting for transcatheter thoracic duct decompression between March 2018 and February 2023. The patients ranged in age from 3 to 26 years. The majority had failed prior catheter-based lymphatic intervention, including selective embolization of abnormal lympho-intestinal and lympho-bronchial connections to treat lymphatic failure in a single compartment. Fourteen had failure in three lymphatic compartments. Patients were functionally impaired (ASA 3-5) with significant comorbidities. Concurrent with thoracic duct decompression, three patients required fenestration closure for the resultant decrease in oxygen saturation. Ten patients had improvement in symptoms, seven had no changes and three have limited follow up. Five (25%) of these patients were deceased as of January 2024 due to non-lymphatic complications from Fontan failure.

The Prevalence of Scoliosis after Fontan Circulation Surgery Followed-Up to Adolescence.

Introduction: The advancement of surgical techniques and perioperative management for congenital heart disease (CHD) has increased life expectancy. The surgical creation of the Fontan circulation maintains pulmonary blood flow without relying on an effective pump from the abnormal heart, relying on peripheral vascular resistance to maintain effective flow through the lungs. Unfortunately, this delicate mechanism is compromised when scoliosis restricts ventilation, leading to Fontan failure and a poor prognosis for life. This report describes the prevalence of scoliosis with Fontan completion surgery and the role of screening and surgical correction. Methods: Ninety-six consecutive Japanese patients undergoing Fontan completion surgery for CHD between 2000 and 2017 were identified in our institutional records. The inclusion criterion was at least 7 years of follow-up after Fontan completion surgery, while the exclusion criteria were congenital, syndromic, and neuromuscular scoliosis. Radiographic and clinical parameters, including cardio-thoracic ratio (CTR) for cardiomegaly and cyanosis saturation, were compared between with and without scoliosis. Results: There were 23 and 40 patients in the scoliosis and no scoliosis groups, respectively. The mean age at the final follow-up was 18.5 and 16.7 years in the scoliosis and no scoliosis groups, respectively (p=0.02). Mean CTR was 43.7% and 39.4% in the scoliosis and no scoliosis groups (p=0.016), and the mean saturation in room air at the final follow-up was 88.8% and 93.2%, respectively (p=0.036). There were no significant differences to clarify the risk factors with multivariate logistic regression analysis. Conclusions: The prevalence of scoliosis with Fontan completion surgery was 36.5%. Screening for scoliosis is important for children with Fontan circulation surgery as part of their routine follow-up at least until they reach adolescence.Evidence Level: 4.

Evaluation of the total hydrodynamic energy loss using 4D flow MRI in a case with Fontan failure.

Fontan Failure (FF) is a common problem for single-ventricle patients as they reach adulthood. Although several mechanisms may cause FF, an optimized blood flow stream through the surgical conduits is essential to avoid excessive energy loss (EL). Recent clinical studies showed EL is related to the quality of life, exercise capacity, and hepatic function since the single-ventricle feeds pulmonary and systemic circulation serially. 4D flow MRI effectively estimates EL in Fontan circulation and allows clinicians to compare the effectiveness of the treatment strategy concerning pre-intervention. Here, we present 26-year-old women with FF who had normal cardiac catheterization findings and were treated according to high EL definitions that are measured through 4D flow MRI.

Impact of 4D-Flow CMR Parameters on Functional Evaluation of Fontan Circulation.

We sought to evaluate the potential clinical role of 4D-flow cardiac magnetic resonance (CMR)-derived energetics and flow parameters in a cohort of patients' post-Fontan palliation. In patients with Fontan circulation who underwent 4D-Flow CMR, streamlines distribution was evaluated, as well a 4D-flow CMR-derived energetics parameters as kinetic energy (KE) and energy loss (EL) normalized by volume. EL/KE index as a marker of flow efficiency was also calculated. Cardiopulmonary exercise test (CPET) was also performed in a subgroup of patients. The population study included 55 patients (mean age 22 ± 11 years). The analysis of the streamlines revealed a preferential distribution of the right superior vena cava flow for the right pulmonary artery (62.5 ± 35.4%) and a mild preferential flow for the left pulmonary artery (52.3 ± 40.6%) of the inferior vena cave-pulmonary arteries (IVC-PA) conduit. Patients with heart failure (HF) presented lower IVC/PA-conduit flow (0.75 ± 0.5 vs 1.3 ± 0.5 l/min/m2, p = 0.004) and a higher mean flow-jet angle of the IVC-PA conduit (39.2 ± 22.8 vs 15.2 ± 8.9, p < 0.001) than the remaining patients. EL/KE index correlates inversely with VO2/kg/min: R: - 0.45, p = 0.01 peak, minute ventilation (VE) R: - 0.466, p < 0.01, maximal voluntary ventilation: R:0.44, p = 0.001 and positively with the physiological dead space to the tidal volume ratio (VD/VT) peak: R: 0.58, p < 0.01. From our data, lower blood flow in IVC/PA conduit and eccentric flow was associated with HF whereas higher EL/KE index was associated with reduced functional capacity and impaired lung function. Larger studies are needed to confirm our results and to further improve the prognostic role of the 4D-Flow CMR in this challenging population.

High-Risk Congenital Heart Disease in Pregnancy.

High-risk congenital heart disease (CHD) in pregnancy presents a complex clinical challenge. With improved medical care and increased survival rates, a growing population of adults with complex CHD are surviving to adulthood, including women of reproductive age. This chapter focuses on risk stratification and management of pregnant women with high-risk CHD, emphasizing the importance of considering both anatomical and physiological complexity. Maternal physiological changes, such as blood volume increase, cardiac output changes, and alterations in vascular resistance, can significantly impact high-risk CHD patients. Management of high-risk CHD in pregnancy necessitates a multidisciplinary approach and individualized care.

Detection of occult thrombosis in individuals with Fontan circulation by cardiac MRI.

OBJECTIVE: Identifying thrombus formation in Fontan circulation has been highly variable, with reports between 17 and 33%. Initially, thrombus detection was mainly done through echocardiograms. Delayed-enhancement cardiac MRI is emerging as a more effective imaging technique for thrombus identification. This study aims to determine the prevalence of occult cardiac thrombosis in patients undergoing clinically indicated cardiac MRI. METHODS: A retrospective chart review of children and adults in the Duke University Hospital Fontan registry who underwent delayed-enhancement cardiac MRI. Individuals were excluded if they never received a delayed-enhancement cardiac MRI or had insufficient data. Demographic characteristics, native heart anatomy, cardiac MRI measurements, and thromboembolic events were collected for all patients. RESULTS: In total, 119 unique individuals met inclusion criteria with a total of 171 scans. The median age at Fontan procedure was 3 (interquartile range 1, 4) years. The majority of patients had dominant systemic right ventricle. Cardiac function was relatively unchanged from the first cardiac MRI to the third cardiac MRI. While 36.4% had a thrombotic event by history, only 0.5% (1 patient) had an intracardiac thrombus detected by delayed-enhancement cardiac MRI. CONCLUSIONS: Despite previous echocardiographic reports of high prevalence of occult thrombosis in patients with Fontan circulation, we found very low prevalence using delayed-enhancement cardiac MRI. As more individuals are reaching adulthood after requiring early Fontan procedures in childhood, further work is needed to develop thrombus-screening protocols as a part of anticoagulation management.

The Lifesaving Impact of Transcatheter Interventions in the Early Post-Fontan Palliation Period.

Despite advancements in postoperative outcomes after Fontan surgery, there remains a risk of suboptimal outcomes and significant morbidity in the early postoperative period. Anatomical obstructions in the Fontan pathway can lead to prolonged pleural effusion or ascites, cyanosis, and low cardiac output syndrome (LCOS). Transcatheter interventions offer an alternative to early re-surgery for treating these complications. Over a 13-year period, early catheter angiography, performed within 30 days post-index procedure, was administered to 41 patients, identifying anatomical issues that necessitated re-intervention in 39 cases. This led to transcatheter interventions in 37 (10.4%) of the 344 Fontan surgery patients. The median age was 4.8 years (IQR: 4-9.4), and the median weight was 16.5 kg (IQR: 15-25.2), with females comprising 51.4% (19/37) of this group. The primary indications for the procedures were persistent pleural effusion or ascites in 27 patients (66%), LCOS in 8 patients (20%), and cyanosis in 6 patients (14%). Among the 37 undergoing transcatheter intervention, 30 were treated solely with this method and discharged, three died in ICU follow-up, and four required early re-surgery. No procedural mortality was observed. Our findings demonstrate that transcatheter interventions, including stent implantation, balloon angioplasty, and fenestration dilation, are safe and effective in the early post-Fontan period. Therefore, they should be considered an integral part of the management strategy for this patient group.

Quantification of ventricular stress in univentricular hearts during early childhood using age-independent zlog-NT-proBNP.

BACKGROUND: Children with univentricular hearts (UVH) undergo up to three palliative surgical procedures to achieve complete circulatory separation (Fontan circulation). As a marker of cardiac wall stress, NT-proBNP is a promising tool to assess systemic ventricular load in these patients. However, different reference intervals (RI) apply to each stage, as NT-proBNP is highly age-dependent. METHODS: Children undergoing systemic-to-pulmonary (SP) shunt placement (stage 1), bidirectional cavopulmonary shunt (BCPS, stage 2) or total cavopulmonary connection (TCPC, stage 3) between 2011 and 2021 with NT-proBNP measurement within 7 days before surgery were included. Furthermore, outpatients after TCPC with NT-proBNP measurement were enrolled. Biomarker levels were evaluated using its age-adjusted z-score ("zlog-NT-proBNP"; age-independent RI, -1.96 to +1.96), allowing comparison between different stages and revealing changes in systemic ventricular load independent of the marked physiological decline in RI with age. RESULTS: Overall, 289 children (227 before, 62 after TCPC) met the eligibility criteria. Median time between blood sampling and surgery (SP shunt/BCPS/TCPC) was 2 [1-3] days and 3.2 [2.0-4.5] years after TCPC. Age-adjusted zlog-NT-proBNP levels were 3.47 [2.79-3.93] in children with native UVH (before SP shunt), 3.10 [1.89-3.58] at stage 1 (before BCPS), 1.08 [0.51-1.88] at stage 2 (before TCPC), and 1.09 [0.72-1.75] at stage 3 (after TCPC/Fontan completion). Consequently, BCPS revealed the strongest decrease (median - 2.02 logarithmized standard deviations, p < 0.001). CONCLUSIONS: In children with UVH undergoing staged Fontan palliation, zlog-NT-proBNP is a highly promising tool for course assessment of systemic ventricular load, independent of the age-related decline in physiological NT-proBNP concentration.

Objective Quantification of Bilateral Bubble Contrast Echocardiography Correlates with Systemic Oxygenation in Patients with Single Ventricle Circulation.

Bubble contrast echocardiography is commonly used to diagnose pulmonary arteriovenous malformations (PAVMs) in single ventricle congenital heart disease (CHD), yet previous studies inconsistently report a correlation between bubble echoes and oxygenation. In this study, we sought to re-evaluate the correlation between bubble echoes and oxygenation by assessing total bilateral shunting and unilateral shunting. We conducted a single-center, retrospective study of patients with single ventricle CHD and previous Glenn palliation who underwent a cardiac catheterization and bubble echocardiogram during the same procedure from 2011 to 2020. Spearman's rank correlation was performed to examine the relationship between total bilateral shunting and measures of systemic oxygenation, as well as unilateral shunting and ipsilateral pulmonary vein oxygenation. For all patients (n = 72), total bilateral shunting moderately correlated with peripheral oxygen saturation (SpO2) (rs = -0.44, p < 0.0001). For patients with Glenn/Kawashima circulation (n = 49), total bilateral shunting was moderately correlated (SpO2: rs = -0.38, p < 0.01). In contrast, unilateral shunting did not correlate with ipsilateral pulmonary vein oxygenation for any vein measured (p = 0.16-p > 0.99). In conclusion, the total burden of bilateral bubble shunting correlated with systemic oxygenation and may better reflect the total PAVM burden from all lung segments. Unilateral correlation may be adversely influenced by non-standardized approaches to pulmonary vein sampling.

Dielectric elastomer actuator-based valveless pump as Fontan failure assist device: introduction and preliminary study.

OBJECTIVES: Fontan failure refers to a condition in which the Fontan circulation, a surgical procedure used to treat certain congenital heart defects, becomes insufficient, leading to compromised cardiac function and potential complications. This in vitro study therefore investigates the feasibility of bladeless impedance-driven cavopulmonary assist device via dielectric elastomer actuator (DEA) as a means to address Fontan failure. METHODS: A cavopulmonary assist device, constructed using DEA technologies and employing the impedance pump concept, is subjected to in vitro testing within a closed-loop setup. This study aims to assess the device's functionality and performance under controlled conditions, providing valuable insights into its potential application as a cavopulmonary assistive technology. RESULTS: The DEA-based pump, measuring 50 mm in length and 30 mm in diameter, is capable of achieving substantial flow rates within a closed-loop setup, reaching up to 1.20 l/min at an activation frequency of 4 Hz. It also provides a broad range of working internal pressures (<10 to >20 mmHg). Lastly, the properties of the flow (direction, magnitude, etc.) can be controlled by adjusting the input signal parameters (frequency, amplitude, etc.). CONCLUSIONS: In summary, the results suggest that the valveless impedance-driven pump utilizing DEA technology is promising in the context of cavopulmonary assist devices. Further research and development in this area may lead to innovative and potentially more effective solutions for assisting the right heart, ultimately benefiting patients with heart-related health issues overall, with a particular focus on those experiencing Fontan failure.

Trends and outcomes of heart transplantation in adults with congenital heart disease.

OBJECTIVES: Heart transplantation for adult congenital heart disease is complicated and associated with challenging pretransplant support, long waiting and high early post-transplant mortality. We explored if surgical and medical advances and allocation system changes have affected outcomes. METHODS: From United Network for Organ Sharing database, adults with congenital heart disease listed for heart transplantation were queried. To explore practice and outcome trends, patients were divided into 4 eras (eras 1-3: nearly 3 equal periods from 1992 to 2018, era 4: after 2018, corresponding with new allocation system). Univariate and multivariable analysis was performed to evaluate outcomes. RESULTS: A total of 2737 patients were listed. There was gradual increase in listed and transplanted patients, along with significant increase in use of mechanical support, simultaneous kidney and liver transplantation. While proportion of transplanted remained constant, there was decrease in proportion delisted/died after listing (P = 0.01) and waiting list duration (P = 0.01), especially in era 4. Thirty-day post-transplant mortality remains high; however, it has significantly improved starting era 3 (P = 0.01). Current survival at 1-year and 5-years is 85% and 65%, with improvement mainly related to decreased early death. On multivariable analysis, factors associated with survival were lower glomerular filtration rate (hazard ratio = 0.99, P = 0.042), bilirubin (hazard ratio = 1.17, P<0.001) and mechanical ventilation (hazard ratio = 2.3, P=0.004). CONCLUSIONS: Heart transplantation in adults with congenital heart disease is increasing, along with added complexity, higher usage of pretransplant mechanical support and simultaneous organ transplantation. Despite that, more complex patients do not experience worse outcomes. Early mortality improved but remains high. New donor allocation system allowed shorter waiting time and higher proportion transplanted without altering early mortality.

Pulmonary vascular disease and optical coherence tomography imaging in patients with Fontan palliation.

INTRODUCTION: The Fontan procedure is the palliative procedure of choice for patients with single ventricle physiology. Pulmonary vascular disease (PVD) is an important contributor to Fontan circulatory failure. AREAS COVERED: We review the pathophysiology of PVD in patients with Fontan palliation and share our initial experience with optical coherence tomography (OCT) in supplementing standard hemodynamics in characterizing Fontan-associated PVD. In the absence of a sub-pulmonary ventricle, low pulmonary vascular resistance (PVR; ≤2 WU/m2) is required to sustain optimal pulmonary blood flow. PVD is associated with adverse pulmonary artery (PA) remodeling resulting from the non-pulsatile low-shear low-flow circulation. Predisposing factors to PVD include impaired PA growth, endothelial dysfunction, hypercoagulable state, and increased ventricular end-diastolic pressure. OCT parameters that show promise in characterizing Fontan-associated PVD include the PA intima-to-media ratio and wall area ratio (i.e. difference between the whole-vessel area and the luminal area divided by the whole-vessel area). EXPERT OPINION: OCT carries potential in characterizing PVD in patients with Fontan palliation. PA remodeling is marked by intimal hyperplasia, with medial regression. Further studies are required to determine the role of OCT in informing management decisions and assessing therapeutic responses.