Fontan Palliation Research Articles

The Fontan immunophenotype and post-transplant outcomes in children: A multi-institutional study.

Patients after Fontan palliation represent a growing pediatric population requiring heart transplant (HTx) and often have lymphopenia (L) and/or hypogammaglobinemia that may be exacerbated by protein-losing enteropathy (PLE, P). The post-HTx effects of this altered immune phenotype are not well studied. In this study of the Pediatric Heart Transplant Society Registry, 106 Fontan patients who underwent HTx between 2005 and 2018 were analyzed. The impact of lymphopenia and PLE on graft survival, infection, rejection, and malignancy was analyzed at 1 and 5 years post-HTx. The following combinations of lymphopenia and PLE were noted: +L+P, n=37; +L-P, n=23; -L+P, n=10; and -L-P, n=36. Graft survival between the groups was similar within the first year after transplant (+L+P: 86%, +L-P: 86%, -L+P: 87%, -L-P: 89%, p=.9). Freedom from first infection post-HTx was greatest among -L-P patients compared to patients with either PLE, lymphopenia, or both; with a 22.1% infection incidence in the -L-P group and 41.4% in all others. These patients had a significantly lower infection rate in the first year after HTx (+L+P: 1.03, +L-P: 1, -L+P: 1.3, -L-P: 0.3 infections/year, p < .001) and were similar to a non-single ventricle CHD control group (0.4 infections/year). Neither freedom from rejection nor freedom from malignancy 1 and 5 years post-HTx, differed among the groups. Fontan patients with altered immunophenotype, with lymphopenia and/or PLE, are at increased risk of infection post-HTx, although have similar early survival and freedom from rejection and malignancy. These data may encourage alternative immunosuppression strategies and enhanced monitoring for this growing subset of patients.

Preliminary Evaluation of Hemodynamic Effects of Fontan Palliation on Renal Artery Using Computational Fluid Dynamics

Background: The assessment of renal function is important to the prognosis of patients needing Fontan palliation due to the reconstructed compromised circulation. To know the relationship between the kidney perfusion and hemodynamic characteristics during surgical design could reduce the risk of acute kidney injury (AKI) and the postoperative complications. However, the issue is still unsolved because the current clinical evaluation methods are unable to predict the hemodynamic changes in renal artery (RA). Methods: We reconstructed a three-dimensional (3D) vascular model of a patient requiring Fontan palliation. The technique of computational fluid dynamics (CFD) was utilized to explore the changes of RA hemodynamics under different possible blood flow rates. The relationship between the kidney perfusion and hemodynamic characteristics was investigated. Results: The calculated results indicated the declined tendency of the pressure and pressure drop as the flow rate decreased. When the flow rate decreased to two-thirds of its baseline, both the pressure of left renal artery (LRA) and the pressure of right renal artery (RRA) dipped below 50%, and the pressure of RRA fell more quickly than that of LRA. Uneven distribution of WSS was observed on the trunk of RA, and the lowest WSS was found at the distal of RA. The average WSS in RA dropped to around 50% as the flow rate reached one-third of its baseline. Conclusions: As a promising approach, CFD can be utilized to quantitatively evaluate the hemodynamic characteristics of RA and contribute to offsetting the drawbacks of clinical assessments of renal function, to help realize better prognosis for the patients with Fontan palliation.

Cognitive function in adults with Fontan palliation versus acyanotic CHD patients and association with health-related quality of life.

Impairments and developmental delay are often reported in infants and young children with CHD. However, currently, there is no data regarding cognitive abilities assessed by standardised intelligence tests in adults with CHD. This study assesses the cognitive function in Fontan patients compared with acyanotic CHD patients whether restrictions in cognitive function are present in adulthood and its association with health-related quality of life. Forty-four adult CHD (female n = 21 (47.7%); mean age 34.7 ± 11.9 years), 22 with Fontan circulation and 22 with acyanotic CHD, underwent the Wechsler Intelligence Scale for adults as patients during routine follow-up in 2018. The Medical Outcomes Study Questionnaire Short-Form 36 Health Survey (SF-36) assessed health-related quality of life. Fontan patients showed significantly better results in the FSIQ (p = 0.020) and perceptual reasoning (p = 0.017) in comparison with patients with acyanotic CHD. All adult CHD patients showed normal IQ in subscales and full-scale IQ (FSIQ). In health-related quality of life, no association with cognitive function was found and no significant difference between both CHD groups, but trends to reduced values in acyanotic adult CHD. Interestingly, our study results in adult Fontan patients showed that it is possible to live an adult life with normal cognitive function and good health-related quality of life with a univentricular heart. Thus, this study could be a guidepost for more in-depth studies on cognitive function in Fontan survivors. In addition, the focus should be on health-related quality of life of adult CHD with simple CHD in particular, since a reduced health-related quality of life is not only medically based.

Abstract 15217: Intrahepatic Gene Expression Profile Differences in Patients With Fontan Associated Liver Disease

Introduction: Fontan associated liver disease (FALD) develops shortly after the Fontan palliation as the long-term consequence of chronically elevated central venous pressures. The molecular pathways underlying FALD remain largely unknown. We aimed to assess intrahepatic gene expression profile differences among these patients with advanced vs early fibrosis. Hypothesis: Advanced fibrosis in patients with Fontan circulation shows a specific gene expression profile with specific enriched pathways. Methods: This retrospective cohort study included adults with the Fontan circulation who had tissue available from at least one liver biopsy at the UCLA Adult Congenital Heart Disease Center. Clinical, laboratory, imaging and hemodynamic data prior to the liver biopsy were extracted from medical records. Patients were classified into early (F1-F2) or advanced fibrosis (F3-F4). RNA was isolated from formalin-fixed paraffin embedded liver tissue, RNA libraries were constructed using ribosomal RNA depletion method and sequencing was performed on Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were carried out using DESeq2 and Metascape. Results: Seventy-seven patients were included, 53% women, 50% White and 20% Hispanic. Most patients had either a lateral tunnel (40%) or atriopulmonary (24%) Fontan. Four patients had 2 liver biopsies and 1 had hepatocellular carcinoma. Early and advanced fibrosis were present in 43 (54%) and 37 (46%) samples, respectively. Both groups had similar age, comorbidities, NYHA class, liver function tests and liver ultrasound features. Patients with advanced fibrosis had higher BNP, Fontan, mean pulmonary artery and capillary wedge pressures. Samples with advanced fibrosis had 921 up-regulated genes compared to the ones with early fibrosis. The up-regulated genes were enriched in extracellular matrix organization, regulation of cell adhesion, response to wounding, TGF-beta signaling pathway and blood vessel morphogenesis. Conclusions: Advanced fibrosis in patients with Fontan circulation exhibits up-regulated genes compared to early fibrosis, including pathways related to inflammation, congestion and angiogenesis, adding further insight into FALD pathophysiology.

Abstract 14813: Insulin Resistances in Patients With Fontan Palliations

Introduction: Patients (pts) with single ventricles who have undergone Fontan palliation are surviving longer and at increased risk for acquired morbidly. Insulin resistance (IR) and abnormal glucose metabolism are known to be predictors of cardiac morbidity and mortality. Limited studies suggest that IR and metabolic syndrome occur in individuals following Fontan palliation. This study aimed to evaluate IR in Fontan pts. Methods: In this prospective, single-center, case-control study, Fontan pts and controls were recruited during clinic or catheterization visits between 6/2021 - 2/2022. Individuals with diabetes mellitus, pregnancy, steroid use, inotropic support, or surgery within the last 6 months were excluded. Control subjects were eligible if they had 2 ventricle circulation and did not have heart failure or systemic illness. Demographic and clinical data were collected via chart review. Fasting serum glucose and insulin were acquired at their visit. Group comparisons were made in IR via natural log-transformed homeostasis model assessment, ln(HOMA-IR), and QUICKI (1/[log(Insulin) + log(Glucose)]), without/with adjusting for age. Results: In total 89 pts (59 Fontan and 30 controls) were included, with median age of 20.2 yrs (interquartile range 15-28.1). Fontan pts showed significant elevation of ln(HOMA-IR) (0.82±0.62 vs 0.24±0.44) and decrease in QUICKI (0.34±0.03 vs 0.37±0.02) compared to controls (both p&lt;.0001); this remained significant even controlling for age (both p≤0.02). Analysis excluding Fontan pts with obesity still showed significant elevation of ln(HOMA-IR) and reduction of QUICKI in Fontan pts compared to controls when adjusting for age (both p&lt;0.05). With older age there was an increase in ln(HOMA-IR) (mean 0.2 in age &lt; 13 yrs vs. 0.53 in age 13-18 yrs vs. 0.78 in ag &gt; 18 yrs, p=0.01). Using a QUICKI &lt; 0.339 defining IR, there was an increase proportion of IR with older age (7% in age &lt; 13 yrs vs. 26% in age 13-18 yrs vs. 48% in age &gt; 18 yrs, p=0.01). Conclusions: Fontan pts had significant elevation in IR compared to controls using standard clinical IR serum testing that was independent of age. Additionally, IR continues to increase with age. Further evaluation is needed to understand risk for IR in pts undergoing Fontan palliation.

Correction to: Outcomes of Patients With Hypoplastic Left Heart Syndrome Reaching Adulthood After Fontan Palliation: Multicenter Study.

Correction to: Outcomes of Patients With Hypoplastic Left Heart Syndrome Reaching Adulthood After Fontan Palliation: Multicenter Study.

Abstract 15303: Maternal Features for Live Births in Fontan Patients

Introduction: As the population of women with congenital heart disease with prior Fontan palliation (PFPs) increases, doubling in size over the next 20 years, there will be a concordant need for multidisciplinary obstetrics care. There is an increased prevalence of miscarriage, maternal and fetal complications including arrhythmias, heart failure, premature birth, and neonatal death. We sought to review our single center experience in the context of an established cardio-obstetrics multidisciplinary team. Methods: Single-center retrospective cohort study of PFPs with live births who received care at our cardio-obstetrics clinic. A chart review was performed to identify maternal characteristics as well as fetal outcomes. Descriptive statistics were calculated using R Studio Statistical Software version 1.2.5033.Result: Ten women with PFPs and live births were identified. None had more than one live pregnancy. The average number of pregnancies was 2 (range 1-6). The mean gestational age was 31.2 weeks (range 23-37). Five patients were primigravida. Six of the pregnancies were planned and eight received preconception counseling. Baseline NYHA was 50% class I and 50% class II. The most common maternal comorbidity in patients with a live pregnancy was atrial arrhythmia, and the most common pre-pregnancy medication was warfarin. Prematurity, low birth weight, and associated comorbidities (see table 1) were common in this population. The average birthweight was 1,589g (range 460g-2210g). Indication for delivery was more commonly obstetric than maternal concern. No maternal strokes, thromboembolic events, cardiac arrests, maternal or infant deaths and rehospitalizations were noted. Conclusion: Maternal and fetal complications in mothers with PFP are common. A multidisciplinary approach in a specialized cardio-obstetrics clinic has the potential to improve outcomes. Larger cohort and long term outcomes are needed in this patient population.

Acetaminophen pharmacokinetics in infants and children with congenital heart disease.

Acetaminophen is routinely used for perioperative analgesia in children undergoing major surgical procedures. There are few estimates of acetaminophen pharmacokinetic parameters in children with congenital heart disease, especially those with cyanotic heart disease. The current study prospectively investigated differences in acetaminophen pharmacokinetics following surgery using cardiopulmonary bypass in children with cyanotic and acyanotic congenital heart disease. Children (2-6 years, 9-23 kg) presenting for median sternotomy for Fontan palliation (cyanotic patients) or two ventricle surgical repair (acyanotic patients) were eligible for inclusion. A single intravenous dose of acetaminophen (15 mg/kg) was administered at the start of sternal closure after separation from cardiopulmonary bypass. The time-course of acetaminophen concentrations were described using non-linear mixed effects models. One and two-compartment disposition models with first-order elimination were tested. Pharmacokinetic parameter estimates were scaled using allometry and standardized to a 70 kg person. There were 208 acetaminophen concentrations assayed from 30 children, 15 with cyanotic, and 15 with acyanotic heart disease. A 2-compartment model best described acetaminophen PK. Parameter estimates (population parameter variability, PPV%; 95% confidence interval, CI) were clearance CL 15.3L.h-1.70 kg-1 (22.2%; 13.8-16.7), intercompartment clearance Q 45.4L.h-1.70 kg-1 (22.4%; 25.2-61.9), central volume of distribution V1 33.5L.70 kg-1 (23.2%; 25.9-38.8), peripheral volume of distribution V2 32.1L.70 kg-1 (21.7%; 25.9-38.8). Neither clearance nor volume parameters differed between cyanotic and acyanotic patients. Acetaminophen pharmacokinetics were characterized using a 2-compartment model with first-order elimination following cardiac bypass surgery in children. Population pharmacokinetic parameter estimates were similar to other studies in children. No differences were detected between patients with cyanotic and acyanotic heart disease.

Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure

Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.

Somatic growth in single ventricle patients: A systematic review and meta-analysis.

To map somatic growth patterns throughout Fontan palliation and summarise evidence on its key modifiers. Databases were searched for relevant articles published from January 2000 to December 2021. Height and weight z scores at each time point (birth, Glenn procedure, Fontan procedure and >5 years after Fontan completion) were pooled using a random effects meta-analysis. A random effects meta-regression model was fitted to model the trend in z scores over time. Nineteen studies fulfilled eligibility criteria, yielding a total of 2006 participants. The z scores for height and weight were markedly reduced from birth to the interstage period, but recovered by about 50% following the Glenn procedure. At >10 years after the Fontan procedure, the z scores for weight seemed to normalise despite persistent lower height, resulting in increased body mass index. The review revealed a number of modifiers of somatic growth, including aggressive nutritional management, timing of Glenn/Fontan, prompt resolution of complications and obesity prevention programmes in adolescence and adulthood. This review mapped the somatic growth of single ventricle patients and summarised key modifiers that may be amendable to improvement. These data provide guidance on strategies to further optimise somatic growth in this population and may serve as a benchmark for clinical follow-up.

Catheter ablation of atrial arrhythmias by using a multipolar grid-patterned high density mapping catheter in patients with congenital heart disease: a single-center experience

Abstract Objective Catheter ablation of arrhythmias in patients with congenital heart disease (CHD) remains challenging and time-consuming. A novel diagnostic catheter with a multipolar grid-patterned electrode configuration for high density mapping may reduce mapping time and enhance ablation success. Here we describe our experience of catheter ablation by using a multipolar grid-patterned mapping catheter in patients with CHD suffered from atrial tachycardia. Methods All patients with CHD underwent catheter ablation for atrial tachycardia by using multipolar grid-patterned high density mapping catheter between 04/2018 and 12/2021 were enrolled. Primary success was defined as non-inducibility of atrial tachycardia. Only the first catheter ablation was included in the study. Results A total of 37 consecutive patients (median age 34.2±33.0 years (range 7–65), female n=20) underwent 37 ablation procedures with initial high density mapping. The underlying heart defects were s/p ASD-closure (n=2), ASD-closure and corrected partial anomalous pulmonary venous return (n=2), corrected unroofed coronary sinus (n=1), pulmonary valve commissurotomy (n=2), repaired Tetralogy of Fallot (n=2), tricuspid and pulmonary valve replacement in PA/IVS (n=1), mitral valve replacement (n=1), Hypoplastic right heart syndrome (n=1), atrial switch procedure for dTGA (n=7), TA with Glenn shunt (n=1), Ross operation (n=1), Fontan palliation (tricuspid atresia n=6, DILV n=5, HLHS n=1, DORV n=1, dTGA n=1, criss-cross heart n=1, single ventricle n=1). A history of previous ablation was positive in 8 patients. During mapping of the cardiac chambers, the mean value of total collected points and used points were 32657.8±46171 and 3851.6±3295.5 respectively. Mean mapping and fluoroscopy time were 62.1±40.7 minute (range 3–178) and 11.4±8.5 minutes (range 0–32.2), respectively. There were 69 atrial tachycardia substrates in the 37 patients (median 2, range 1–4 per patient). All tachycardia substrates were completely ablated in 33/37 (89.2%) patients and partially in 4/37 (11.8%) patients. Acute success was achieved with successful ablation of 65 of 69 (94.2%) atrial substrates. During a median follow-up time of 20 months (range 5–49), recurrence rate was 5/65 (7.7%) atrial substrates in 5/37 (13.5%) patients. Comparison of 16 patients with Fontan palliation to the 23 patients without Fontan operation showed higher partially success rate in the patients with Fontan palliation (4/16 vs. 0/21, p=0.028). Conclusion In this series, high density mapping allowed elucidation of the tachycardia mechanism in all patients with a high primary ablation success, a limited radiation exposure and a low rate of arrhythmia recurrence. Funding Acknowledgement Type of funding sources: None.

Lymphopenia and immunoglobulin deficiency in adult patients with a Fontan circulation

Abstract Background Patients with a functionally univentricular heart and a Fontan palliation are prone to a wide range of extra-cardiac complications. Lymphopenia and immunoglobulin deficiency are insufficiently characterized in this population. Purpose The aim of this study was to analyze prevalence and associations of lymphopenia and immunoglobulin deficiency in a cohort of adult Fontan patients. Methods Ninety-five consecutive patients with a Fontan circulation that were seen at our institution between 2011 and 2021 were screened. Laboratory results and clinical characteristics were extracted from the patient's charts. Results Fifty-five patients (47% male) underwent evaluation of lymphocyte and/or immunoglobulin subpopulations at a mean age of 28.9±9.7 years. Baseline characteristics are depicted in the Table. Seven patients (7/55, 12.7%) had immunoglobulin G (IgG) levels below the lower limit of normal (i.e. &amp;lt;7.0 g/l). Patients with IgG deficiency had a higher prevalence of protein-losing enteropathy (43% versus 4%, p=0.001). Fifteen patients (15/52, 28.8%) had lymphocyte counts below the lower limit of normal (i.e. &amp;lt;850/μl). Lymphocyte counts and lymphocyte subpopulations were comparable in groups with and without protein-losing enteropathy. There was a moderately positive correlation between absolute lymphocyte counts and IgG levels (r=0.301, p=0.032). In a subgroup of 24 patients that underwent liver biopsy, there was no difference in terms of absolute lymphocyte counts and immunoglobulin subpopulations in patients with a low (i.e. 1–2) and high (i.e. 3–4) congestive hepatic fibrosis score. Conclusion IgG deficiency is present in 13% of patients with a Fontan circulation and seems to be associated with the presence of protein-losing enteropathy. Lymphopenia is more common and occurs in a quarter of all patients with a Fontan circulation; however, its etiology is likely more complex and multifactorial. Funding Acknowledgement Type of funding sources: None.

Social life in adult patients after Fontan procedure

BackgroundLittle is known about the social life in adult patients after Fontan palliation. The study aimed to assess the long-term social life of patients after Fontan surgery, including school achievement, employment, and marital status.ResultsWe conducted a cross-sectional study on patients aged 18 years or above who had a Fontan operation for a single ventricle pathology. Our outcomes were the academic performance and marital and employment status of adult Fontan patients. Patients or their families were interviewed directly or by phone, and a set of questions were asked to address their educational level, employment, and marital status. Ninety-nine patients were included in the study. Their median age was 21 years (min–max: 18–41), and 60% were females (n= 59). The most common diagnoses were double inlet left ventricle (n= 24, 24%), tricuspid atresia (n= 21, 21%), and the unbalanced atrioventricular canal (n= 21, 21%). Fourteen patients (14%) were married, and 6 of them had children (two were females). Eleven percent were college graduates (either diploma or bachelor’s degree), and 47% were high school graduates.ConclusionsFontan operation could negatively affect the social life of the patients. It may affect employment patterns, educational levels, and marital status.

Staged Ventricular Septation in Double-Inlet Ventricle - A Strategy to Avoid Fontan?

Single-stage ventricular septation for double-inlet left or right ventricle (DILV or DIRV) has historically been associated with poor outcomes. We hypothesize that staged ventricular septation may demonstrate favorable clinical outcomes to be an alternative to Fontan palliation. This single-center retrospective study reviewed patients with DILV or DIRV who underwent staged ventricular septation between 2015-2021. The strategy involves pulmonary artery banding or Norwood procedure during infancy (stage 1), followed by partial ventricular septation to anchor the septum, while maintaining systemic RV pressure to avoid septal shift (stage 2). Residual septal defects are closed with pulmonary artery band removal at stage 3. Results are reported as median (interquartile range). Twelve patients underwent partial ventricular septation. At a median follow-up time of 17 months (8-30) after stage 2, there were no interstage deaths or cardiac transplants; LV dysfunction was observed in one patient. Hemodynamic evaluation after stage 2 demonstrated median left atrial pressure of 9.5 mm Hg (8.9-11.5), cardiac index of 3.4 L/min/m2 (3.2-3.6), and RV and LV indexed end-diastolic volumes of 52 ml/m2 (41-67) and 105 ml/m2 (81-115), respectively. Five patients have progressed to stage 3; one required pacemaker for complete heart block. Unplanned reintervention was required in 4 patients after stage 1, 2 patients after stage 2, and 3 patients after stage 3. Staged ventricular septation is an alternative to single-ventricle palliation in a subset of double-inlet ventricle patients and is associated with acceptable early outcomes. Further studies are necessary to determine long-term outcomes.

Transvenous retrograde thoracic duct embolization for effective treatment of recurrent plastic bronchitis after Fontan palliation

Plastic bronchitis (PB) is a rare but potentially detrimental complication of the Fontan circulation. Retrograde transvenous thoracic duct embolization (TDE) has been proposed as a treatment strategy for lymphatic dysfunction. A 5.5-year-old patient (16 kg/105 cm) was referred to our institution for severe PB refractory to conservative treatment 3 months after completion of Fontan palliation. CT-scan showed multiple bilateral areas of patchy consolidation and ground-glass opacity with obstruction of the right main and right lower bronchi. Bi-inguinal transnodal fluoroscopy-guided lymphangiogram confirmed the diffuse and abnormal lymphatic leak originating from the thoracic duct into the chest, predominantly right-sided, and showed the TD ostium near the left venous angle. There was no opacification of any target central lymphatic vessel for direct transabdominal puncture. Retrograde approach from the femoral vein was adopted to catheterize the thoracic duct and selectively embolize its distal portion using intercalation of microcoils and liquid embolic adhesive. Recurrence of symptoms after 2 months indicated a redo catheterization that revealed the persistence of dilated peribronchial lymphatic network with a minimal residual leak across the previously embolized caudal section of the TD. Complete occlusion of the TD over its entire length was performed using the same technique. The procedure was technically successful and the patient was uneventfully discharged after 2 days. There was no cast recurrence or procedure-related complications and sustained clinical improvement at 18-month of postoperative follow-up. Fluoroscopy-guided lymphangiography was essential to understand the anatomy and flow pattern of the lymphatic system and to plan the lymphatic intervention. End-to-end TDE is an effective minimally invasive treatment in Fontan patients with PB and can be necessary in case of relapse after selectively embolizing the TD distal section.

Ventricular Flow Profile in Young Patients With Single Left Ventricle Fontan Using Echocardiographic Contrast Particle Imaging Velocimetry

The modern Fontan palliation directs systemic venous blood from the superior and inferior vena cava to the pulmonary arteries, bypassing the heart. Its success depends on low pulmonary vascular resistance and optimal systolic and diastolic ventricular function.1,2 Diastolic dysfunction in Fontan circulation is a well-known phenomenon, but its clinical impact remains underappreciated. Assessment of diastolic dysfunction in Fontan patients is challenging but might be enhanced by novel, advanced imaging techniques.

Subcutaneous Treprostinil Improves Surgical Candidacy for Next Stage Palliation in Single Ventricle Patients With High-Risk Hemodynamics

Single ventricle (SV) patients with pulmonary vascular disease (SV-PVD) are considered poor surgical candidates for Glenn or Fontan palliation. Given limited options for Stage 1 (S1) and Stage 2 (S2) SV patients with SV-PVD, we report on the use of subcutaneous treprostinil (TRE) to treat SV-PVD in this population. This single-center, retrospective cohort study examined SV patients who were not candidates for subsequent surgical palliation due to SV-PVD and were treated with TRE. The primary outcome was ability to progress to the next surgical stage; secondary outcomes included changes in hemodynamics after TRE initiation. Between 3/2014 and 8/2021, 17 SV patients received TRE for SV-PVD: 11 after S1 and 6 after S2 (median PVR 4.1 [IQR 3.2-4.8] WU*m2 and 5.0 [IQR 1.5-6.1] WU*m2, respectively). Nine of 11 (82%) S1 progressed to S2, and 2 (18%) underwent heart transplant (HTx). Three of 6 (50%) S2 progressed to Fontan, 1 underwent HTx and 2 are awaiting Fontan on TRE. TRE significantly decreased PVR in S1 patients with median post-treatment PVR of 2.0 (IQR 1.5-2.6) WU*m2. TRE can allow for further surgical palliation in select pre-Fontan patients with SV-PVD, obviating the need for HTx. Improvement in PVR was significant in S1 patients and persisted beyond discontinuation of therapy for most patients.

Cardiac Transplantation of the Fontan Patient with a Prior Norwood Procedure

Single-ventricle palliation starting with a Norwood procedure which culminates in a failed Fontan palliation poses certain unique operative challenges for cardiac transplantation. In this manuscript, we describe some of these challenges and our particular approach in management. Single-ventricle palliation starting with a Norwood procedure which culminates in a failed Fontan palliation poses certain unique operative challenges for cardiac transplantation. In this manuscript, we describe some of these challenges and our particular approach in management. Commentary: Transplantation After Norwood Palliation: Proper Preparation Minimizes the RiskOperative Techniques in Thoracic and Cardiovascular SurgeryPreviewAs the population with a Fontan circulation continues to grow, there is an increasing rate of patients with Fontan failure being referred for heart transplantation.1 Importantly, there has been an increase in the proportion of patients with hypoplastic left heart syndrome surviving to achieve Fontan completion, and these patients represent the highest complexity for heart transplantation due to their aortic arch and pulmonary artery anatomy. The mortality rate for transplantation in patients with single ventricle palliation has been reported to be as high as 20-30%,2-4 and it is likely that many have been denied transplantation due to the perceived extremely high risk. Full-Text PDF

Single ventricular strain measures correlate with peak oxygen consumption in children and adolescents with Fontan circulation.

Children with a single ventricle post-Fontan palliation are at increased risk of poor outcomes with peak oxygen consumption acting as a surrogate outcome marker. The purpose of this study is to evaluate the relationship between peak oxygen consumption and echocardiographic measures of ventricular function and deformation, including ventricular global longitudinal strain and dyssynchrony, in children and adolescents following Fontan palliation. Patients (age 8-21 years) with single ventricle post-Fontan palliation were prospectively recruited and participated in an echocardiogram, including views optimised for two-dimensional speckle tracking, and a cardiopulmonary exercise test on a cycle ergometer to maximal volitional fatigue. Thirty-eight patients (mean age 13.7 ± 2.3 years) post-Fontan palliation had either a single left ventricular (n = 20), single right ventricular (n = 14), or biventricular (n = 4) morphology. Peak oxygen consumption (24.9 ± 5.6 ml/kg/minute) was correlated with global longitudinal strain (r = -0.435, p = 0.007), a strain discoordination time to peak index (r = -0.48, p = 0.003), and the presence of an electro-mechanical dyssynchrony strain pattern (p = 0.008). On multivariate regression modelling, these three variables were associated with peak oxygen consumption independently of age and sex. The single right ventricular group had evidence of possible diastolic dysfunction by E/e' compared to the single left ventricular and biventricular groups (p = 0.001). Strain analysis measures are correlated with peak oxygen consumption in this cohort of children, adolescents, and young adults following Fontan palliation, suggesting that ventricular mechanics may influence the efficiency of the Fontan circulation.

Into the Blue: First in Man Data on Diving Physiology in Fontan Patients.

Swimming and diving are popular recreational activities. As congenital heart disease, especially patients with univentricular hearts after Fontan palliation are thought to have reduced physiologic capacities for compensation of submersion-associated physiologic demands, current guidelines put restraints on this group of patients. Although these restrictions on doctoral advice place a significant burden on affected patients, it is especially interesting that these guideline recommendations are merely based on physiologic assumptions, i.e., expert consensus. A recent study by Paech et al. presented the first in vivo data on the effects of immersion in Fontan patients, stating no major adverse events in their study group as well as comparable physiologic adaption as reported in the literature for healthy people. Yet, submersion was not reflected in this study, and the current study therefore aimed to conduct a first study for the evaluation of the effects of submersion and apnea diving in Fontan patients. A control group of healthy adults as well as patients recruited from the Heart Center Leipzig, Department of pediatric cardiology underwent a standardized diving protocol including a static as well as dynamic apnea phase. Physiologic data were recorded. This study presents the first structured data on diving physiology in Fontan patients compared to healthy probands. There were no adverse events. The physiologic response to diving seems to be comparable between healthy probands and Fontan patients. Although, healthy probands did reach a much better performance, the basic mechanisms of physiologic adaption seem comparable.