Fontan Patients Research Articles

Mild Acquired von Willebrand Syndrome and Cholestasis in Pediatric and Adult Patients with Fontan Circulation.

Background: Hemodynamic alterations in Fontan patients (FP) are associated with hemostatic dysbalance and Fontan-associated liver disease. Studies of other hepatopathologies indicate an interplay between cholestasis, tissue factor (TF), and von Willebrand factor (VWF). Hence, we hypothesized a relationship between the accumulation of bile acids (BA) and these hemostatic factors in FP. Methods: We included 34 FP (Phenprocoumon n = 15, acetylsalicylic acid (ASA) n = 16). BA were assessed by mass spectrometry. TF activity and VWF antigen (VWF:Ag) were determined by chromogenic assays. VWF collagen-binding activity (VWF:CB) was assessed via ELISA. Results: Cholestasis was observed in 6/34 FP (total BA ≥ 10 µM). BA levels and TF activity did not correlate (p = 0.724). Cholestatic FP had lower platelet counts (p = 0.013) from which 5/6 FP were not treated with ASA. VWF:Ag levels were increased in 9/34 FP and significantly lower in FP receiving ASA (p = 0.044). Acquired von Willebrand syndrome (AVWS) was observed in 10/34-FP, with a higher incidence in cholestatic FP (4/6) (p = 0.048). Conclusions: Cholestasis is unexpectedly infrequent in FP and seems to be less frequent under ASA therapy. Therefore, ASA may reduce the risk of advanced liver fibrosis. FP should be screened for AVWS to avoid bleeding events, especially in cholestatic states.

Magnetic resonance three-dimensional steady-state free precession imaging of the thoracic duct in patients with Fontan circulation and its relationship to outcomes

BackgroundLymphatic complications are common in patients with Fontan circulation. Three-dimensional balanced steady-state free precession (3D bSSFP) angiography by cardiovascular magnetic resonance (CMR) is widely used for cardiovascular anatomical assessment. We sought to determine the frequency of thoracic duct (TD) visualization using 3D bSSFP images and assess whether TD characteristics are associated with clinical outcomes. MethodsThis was a retrospective, single-center study of patients with Fontan circulation who underwent CMR. Frequency matching of age at CMR was used to construct a comparison group of patients with repaired tetralogy of Fallot (rTOF). TD characteristics included maximum diameter and a qualitative assessment of tortuosity. Clinical outcomes included protein-losing enteropathy (PLE), plastic bronchitis, listing for heart transplantation, and death. A composite outcome was defined as presence of any of these events. ResultsThe study included 189 Fontan patients (median age 16.1 years, IQR 11.0–23.2 years) and 36 rTOF patients (median age 15.7 years, IQR 11.1–23.7 years). The TD diameter was larger (median 2.50 vs. 1.95 mm, p = 0.002) and more often well visualized (65% vs. 22%, p < 0.001) in Fontan patients vs. rTOF patients. TD dimension increased mildly with age in Fontan patients, R = 0.19, p = 0.01. In Fontan patients, the TD diameter was larger in those with PLE vs. without PLE (age-adjusted mean 4.11 vs. 2.72, p = 0.005), and was more tortuous in those with NYHA class ≥ II vs. class I (moderate or greater tortuosity 75% vs. 28.5%, p = 0.02). Larger TD diameter was associated with a lower ventricular ejection fraction that was independent of age (partial correlation = − 0.22, p = 0.02). More tortuous TDs had a higher end-systolic volume (mean 70.0 mL/m2 vs. 57.3 mL/m2, p = 0.03), lower creatinine (mean 0.61 mg/dL vs. 0.70 mg/dL, p = 0.04), and a higher absolute lymphocyte count (mean 1.80 K cells/µL vs. 0.76 K cells/µL, p = 0.003). The composite outcome was present in 6% of Fontan patients and was not associated with TD diameter (p = 0.50) or tortuosity (p = 0.09). ConclusionsThe TD is well visualized in two-thirds of patients with Fontan circulation on 3D-bSSFP images. Larger TD diameter is associated with PLE and increased TD tortuosity is associated with an NYHA class ≥ II.

Clinical aspects and targeted inspiratory muscle training in children and adolescents with Fontan circulation: a randomized controlled trial.

Since 1968, thousands of patients with a morphologically or functionally univentricular heart have been treated with a total cavopulmonary connection/Fontan operation. Because of the resulting passive pulmonary perfusion, blood flow is assisted by the pressure shift during respiration. Respiratory training is known to improve exercise capacity and cardiopulmonary function. However, there are limited data on whether respiratory training can also improve physical performance after Fontan surgery. The aim of the present study was to clarify the effects of six months of daily home-based inspiratory muscle training (IMT) aimed at increasing physical performance by strengthening respiratory muscles, improving lung function and peripheral oxygenation. In this non-blinded randomized controlled trial, the effects of IMT on lung capacity and exercise capacity were measured in a large cohort of 40 Fontan patients (25% female; 12.3±2.2 years) who were under regular follow-up by the outpatient clinic of the Department of Congenital Heart Defects and Pediatric Cardiology of the German Heart Center Munich. After a lung function test and a cardiopulmonary exercise test, patients were randomly assigned in a parallel arm design to either an intervention group (IG) or a control group (CG) via stratified and computer-generated letter randomization from May 2014 to May 2015. The IG completed a daily, telephone-monitored IMT of three sets of 30 repetitions for six months with an inspiratory resistive training device (POWERbreathe medic®), the CG continued their usual daily activities without an IMT until the second examination within the timeframe of November 2014 until November 2015. After six months of IMT, lung capacity values in the IG (n=18) did not increase significantly compared to the CG [n=19; ΔFVC: IG: 0.21±0.16 l vs. CG 0.22±0.31 l; P=0.946 (CI: -0.16, 0.17); ΔFEV1: CG: 0.14±0.30 vs. IG: 0.17±0.20 P=0.707 (CI: -0.20, 0.14)]. Exercise capacity did not improve significantly, yet the maximum workload achieved trended to improve with an increase of 14% in the IG vs. 6.5% in the CG [P=0.113 (CI: -15.8, 1.76)]. There was a significant increase of oxygen saturation at rest in the IG compared to the CG [IG: 3.31%±4.09% vs. CG: 0.17%±2.92%, P=0.014 (CI: -5.60, -0.68)]. Compared to the CG, the mean oxygen saturation at peak exercise no longer dropped below 90% in the IG. This observation is thus not statistically significant, yet of clinical relevance. The results of this study show benefits of an IMT in young Fontan patients. Even if some data are not statistically significant, they may still be clinically relevant and may contribute to a multidisciplinary approach in patient care. IMT should therefore be an additional target and integrated into the training program to improve the prognosis of Fontan patients. German Clinical Trials Register; DRKS.de; registration ID: DRKS00030340.

Ventricular dyssynchrony late after the Fontan operation is associated with decreased survival

BackgroundVentricular dyssynchrony and its relationship to clinical outcomes is not well characterized in patients following Fontan palliation. MethodsSingle-center retrospective analysis of cardiac magnetic resonance (CMR) imaging of patients with a Fontan circulation and an age-matched healthy comparison cohort as controls. Feature tracking was performed on all slices of a ventricular short-axis cine stack. Circumferential and radial strain, strain rate, and displacement were measured; and multiple dyssynchrony metrics were calculated based on timing of these measurements (including standard deviation of time-to-peak, maximum opposing wall delay, and maximum base-to-apex delay). Primary endpoint was a composite measure including time to death, heart transplant or heart transplant listing (D/HTx). ResultsA total of 503 cases (15 y; IQR 10, 21) and 42 controls (16 y; IQR 11, 20) were analyzed. Compared to controls, Fontan patients had increased dyssynchrony metrics, longer QRS duration, larger ventricular volumes, and worse systolic function. Dyssynchrony metrics were higher in patients with right ventricular (RV) or mixed morphology compared to those with LV morphology. At median follow-up of 4.3 years, 11% had D/HTx. Multiple risk factors for D/HTx were identified, including RV morphology, ventricular dilation, dysfunction, QRS prolongation, and dyssynchrony. Ventricular dilation and RV morphology were independently associated with D/HTx. ConclusionsCompared to control LVs, single right and mixed morphology ventricles in the Fontan circulation exhibit a higher degree of mechanical dyssynchrony as evaluated by CMR-FT. Dyssynchrony indices correlate with ventricular size and function and are associated with death or need for heart transplantation. These data add to the growing understanding regarding factors that can be used to risk-stratify patients with the Fontan circulation.

Systemic ventricular function in Fontan patients at rest and after exercise at altitude.

Physical activity at high altitude is expected to pose risks for patients with Fontan circulation and to impair systemic ventricular function. This study aims to determine the effect of high-altitude hypoxia on ventricular function in Fontan patients at rest and after exercise. We hypothesize that systemic ventricular function deteriorates under hypoxic conditions in Fontan patients. In this prospective study, 21 Fontan patients (NYHA class I-II) and 21 age-, gender- and body mass index-matched healthy controls were enrolled (median age 17.9 and 16.9 years). Transthoracic echocardiography was performed at rest, after peak (PE) and after continuous exercise (CE) in normoxia and hypoxia at simulated altitude (2,500 m above sea level). The effect of hypoxia on echocardiographic parameters was quantified by linear mixed-effects models and the difference between normoxia and hypoxia (Δ= hypoxia-normoxia). At rest, cardiac output (CO) estimated by outflow tract velocity time integral × heart rate and annular plane systolic excursion (APSE) were lower in hypoxia compared to normoxia in Fontan patients (CO: Δ = -12.0%, n.s.; APSE: Δ = -9.6%, p < 0.001), an increase was observed in controls (CO: Δ = 8.5%, n.s.; APSE: Δ = 2.5%, n.s.). Other parameters of systolic and diastolic function did not show relevant changes. After exercise under hypoxic conditions, Fontan patients did not show relevant deterioration of systolic function compared to normoxia. Late, active diastolic filling reflected by A-wave velocity remained unchanged in Fontan patients, but increased in controls. Under hypoxic conditions, CO and workload were higher after CE than PE in Fontan patients (CO: PE Δ = 1,530 vs. CE 1630), whereas controls showed higher work load and CO estimates after PE than CE as expected (CO: PE Δ = 2,302 vs. CE 2149). Fontan patients clinically tolerated short-term altitude exposure up to two hours and exercise and showed no consistent deterioration of systolic systemic ventricular function, but parameters of myocardial contractility, heart rate and cardiac output did not increase as observed in controls. This is likely to be multifactorial and may include intrinsic cardiac dysfunction as well as preload inadequacy and the lack of augmented atrial contraction. CE may be better tolerated than PE.

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.

Haemodynamic and prognostic associations of liver fibrosis scores in Fontan-associated liver disease

ObjectivesFontan-associated liver disease (FALD) is universal post-Fontan palliation; however, its impact on survival remains controversial and current diagnostic tools have limitations. We aimed to assess the prognostic role of liver...

Utility of the Total Thrombus-Formation Analysis System as a Tool for Evaluating Thrombogenicity and Monitoring Antithrombotic Therapy in Pediatric Fontan Patients.

There is no consensus regarding thromboprophylaxis after Fontan procedure, and novel tools to assess thrombogenicity are needed to establish optimal thromboprophylaxis. The Total Thrombus-formation Analysis System (T-TAS) was developed for the quantitative analysis of thrombus formation using microchips with thrombogenic surfaces. This prospective study evaluated the utility of T-TAS in the assessment of thrombogenicity in pediatric Fontan patients. The participants included 20 consecutive Fontan patients who underwent cardiac catheterization and 30 healthy controls. Blood samples collected without and with antithrombotic therapy (aspirin or aspirin and warfarin) were used for T-TAS to compute the area under the curve (AUC) in the atheroma (AR10-AUC30) and platelet (PL18-AUC10) chips. A higher AUC indicates higher thrombogenicity. T-TAS values showed that patients in the Fontan group without antithrombotic therapy had lower thrombogenicity than those in the control group [PL18-AUC10, median (interquartile range) 356 (313-394) vs. 408 (392-424); AR10-AUC30, median (interquartile range) 1270 (1178-1351) vs. 1382 (1338-1421)]. Aspirin and warfarin therapies significantly decreased PL18-AUC10 and AR10-AUC30, respectively, compared with those of patients without antithrombotic therapy (P < 0.001 for each comparison). Subgroup analysis divided by low (< 9mmHg) or high (≥ 9mmHg) central venous pressure (CVP) showed that CVP affects the reduction in AR10-AUC30 with antithrombotic therapy. T-TAS may be a useful tool for monitoring thrombogenicity and antithrombotic therapy in Fontan patients.

T1 mapping of the myocardium and liver in the single ventricle population.

Fontan associated liver disease (FALD) is an increasingly recognized complication of the single ventricle circulation characterized by hepatic venous congestion leading to hepatic fibrosis. Within the Fontan myocardium, fibrotic myocardial remodeling may occur and lead to ventricular dysfunction. Magnetic resonance imaging (MRI) T1 mapping can characterize both myocardial and liver properties. The aim of this study was to compare myocardial and liver T1 between single ventricle patients with and without a Fontan and biventricular controls. A retrospective study of 3 groups of patients: 16 single ventricle patients before Fontan (SVpre 2 newborns, 9 pre-Glenn, 5 pre-Fontan, 31% single right ventricle [SRV]), 16 Fontans (56% SRV) and 10 repaired d-transposition of the great arteries (TGA). Native modified Look-Locker inversion T1 times were measured in the myocardium and liver. Cardiac MRI parameters, myocardial and liver T1 values were compared in the three groups. Correlations were assessed between liver T1 and cardiac parameters. Myocardial T1 was higher in SVpre (1,056 ± 48ms) and Fontans (1,047 ± 41ms) compared to TGA (1,012 ± 48ms, P < 0.05). Increased liver T1 was found in both SVpre (683 ± 82ms) and Fontan (727 ± 49ms) patients compared to TGA patients (587 ± 58ms, P < 0.001). There was no difference between single left ventricle (SLV) versus SRV myocardial or liver T1. Liver T1 showed moderate correlations with myocardial T1 (r = 0.48, confidence interval [CI] 0.26-0.72) and ejection fraction (r = -0.36, CI -0.66-0.95) but not with other volumetric parameters. Increased liver T1 at both pre- and post-Fontan stages suggests there are intrinsic liver abnormalities early in the course of single ventricle palliation. Increased myocardial T1 and its relationship to liver T1 suggest a combination of edema from passive venous congestion and/or myocardial fibrosis occurring in this population. Liver T1 may provide an earlier marker of liver disease warranting further study.

1115 NON-INVASIVE MYOCARDIAL WORK INDICES IN PATIENTS WITH FONTAN CIRCULATION

Abstract Background Although the Fontan operation has contributed greatly to the improvement of survival in patients with a single ventricle, cardiac function and exercise capacity may deteriorate over time. However, there have been no quantitative analyses of the effects of Fontan circulation on myocardial work (MW). Recently, a novel non-invasive method for calculating MW has been introduced on the basis of speckle tracking analysis with the estimation of left ventricular (LV) pressure from brachial artery cuff pressure. Purpose Aim of this study was to evaluate the diagnostic performance of the non-invasive myocardial work indices in predicting subclinical myocardial work impairment in Fontan patients. Methods A total of 69 patients were included and compared with healthy age- and sex- matched controls (CTRL). Ventricular systolic function and global longitudinal strain (GLS) were assessed. Cardiopulmonary exercise test was performed. Global myocardial work index (MWI) was calculated as the area of the LV pressure strain loops. From MWI, global constructive work (MCW), wasted work (MWW) and work efficiency (MWE) were estimated. Results The two groups were comparable for blood pressure, weight and height. Mean age of Fontan patients was 21.0±9.2 years. MWI (1162 ± 364 mmHg% vs 1777 ± 240 mmHg%, p &amp;lt; 0.001), MCW (1554 ± 450 mmHg% vs 2102 ± 221 mmHg%, p = 0.001) and MWE (90 ± 6% vs 96 ± 2% p = 0.001) were significantly reduced in Fontan patients compared with healthy CTRL. Moreover, GLS (-13,9 ± 3,1% vs -21,2 ± 1.5%, p &amp;lt; 0.001) and the ejection fraction (EF) (58,9 ± 4.5% vs 63.3 ± 3.9%, p &amp;lt; 0.002) were significantly lower in Fontan patients. Fontan patients with normal EF showed, however, significantly reduced values of MWI compared with CTRL (p&amp;lt;0.05). Fontan patients with functional right ventricle showed significantly reduced MWE compared with patients with functional left ventricle (p=0.030). In univariate analysis, peak VO2 was significantly associated with age, SatO2, MWI. In multivariate regression, lower peak VO2 was associated with older age (p = 0.003) and lower MWI (p = 0.026). Conclusions Fontan physiology is associated with disadvantageous ventricular work. In Fontan patients, estimation of MWI may be a more sensitive indicator of myocardial work impairment compared with EF and is able to predict exercise capacity.

Dissimilarity in coagulation system in adults after fontan surgery based on thrombin generations.

The Fontan procedure is the treatment of choice in congenital cardiac malformations defined as the single ventricle. Those patients are at high risk of thromboembolism, but the exact mechanism of this is poorly understood.The aim of this study was to evaluate an involvement of thrombin generations and microparticles in prothrombotic state in adults with Fontan circulation. Study included hospitalized patients after Fontan procedure and healthy volunteers. We assessed laboratory tests including thrombin generation by Calibrated Automated Thrombography in three variants (platelet poor plasma (impact of coagulation factors), platelet rich plasma (influence of platelets) and related with microparticles). The technique allows for a comprehensive evaluation of the coagulation system. The study groups consisted of 81 adult Fontan patients (41 females (50.6%); median age 22 interquartile range [20-27] years) and 54 control subjects. In patients with Fontan circulation higher values of endogenous thrombin potential and peak values were observed for both platelet poor plasma (+17% and +33%) and microparticles (+29% and 41%) compared to controls (all p < 0.05). Moreover, in Fontan group we found 64.9% shorter lag time and 70.4% time to peak for microparticles variant (both p < 0.001). Contrary, analysis in the platelet rich plasma showed 17.1% reduced endogenous thrombin potential in Fontan. Further, there were no differences in thrombin synthesis in platelet rich plasma in Fontan patients receiving aspirin or those with thrombocytopaenia (all p > 0.05). This study for the first time showed that thrombin generation associated with microparticles may be an important contributor to prothrombotic state in Fontan population.

Invited Commentary to 'Hemodynamic performance of 16-20mm extracardiac Goretex conduits in adolescent Fontan patients at rest and during simulated exercise'.

Invited Commentary to 'Hemodynamic performance of 16-20mm extracardiac Goretex conduits in adolescent Fontan patients at rest and during simulated exercise'.

Role of Cardiovascular Imaging in the Follow-Up of Patients with Fontan Circulation.

Since its first description in 1971, the Fontan procedure and its modifications have led to a substantial improvement in the survival rates of patients with a variety of types of complex Congenital Heart Disease (CHD) characterised by the presence of a single, dominant ventricle. However, despite the significant improvement of the prognosis over the years, Fontan patients are still exposed to several cardiovascular and systemic complications. It is, therefore, important to fully understand the pitfalls hidden behind a Fontan anatomy and the potential predictors of ventricular failure. Cardiovascular imaging plays a key role in this context, allowing for the early identification of complications with important prognostic implications. Echocardiography remains the first-line imaging modality for serial evaluation of Fontan patients. However, there is a growing role of cardiovascular magnetic resonance and cardiac computed tomography from pre-operative assessment to longitudinal follow-up. The aim of this paper will be to provide a comprehensive overview of the role, strengths, and weaknesses of each imaging modality in the assessment of congenital cardiac conditions palliated with the Fontan procedure.

Fontan-associated Liver Disease in Adults: What a Cardiologist Needs to Know. A Comprehensive Review for Clinical Practitioners

Nowadays most patients with a univentricular heart after Fontan repair survive until adulthood. One of the hallmarks of Fontan circulation is permanently elevated central venous pressure, which leads to congestive hepatopathy. Subsequently, liver fibrosis, cirrhosis, or hepatocellular carcinoma may occur, all of them constituting an entity called Fontan-associated liver disease (FALD). Given that these complications convey poor prognosis, the need for life-long hepatic surveillance is not in doubt. Many serum biomarkers and sophisticated imaging techniques have been proposed to avoid invasive liver biopsy in this cohort, but none proved to be a relevant surrogate of liver fibrosis seen in histopathological specimens. The surveillance models proposed to date require an extensive diagnostic work-up, which can be problematic, particularly in resource-depleted countries. Moreover, the question of combined heart–liver transplant is gaining more attention in the Fontan cohort. The aim of this study is to provide practical information on the pathophysiology of FALD and to propose a simplified framework for the routine assessment of liver status in Fontan patients that would be helpful in the decision-making process.

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.

Coupled waveform patterns in the arterial and venous fontan circulation are related to parameters of pulmonary, lymphatic and cardiac function

The lack of a sub-pulmonary ventricle in patients with a Fontan circulation contributes to circulatory decline, largely related to increased central venous pressure. Our group has determined that single-site waveform analysis correlates with clinical features of Fontan patients. The goal of this study was to determine if multi-site waveform analysis yielded additional associations with functional status or cardiac performance. Patients with a Fontan circulation (N = 95) that underwent free-breathing cardiac MRI were included in this study. Volumetric flow rate curves were sampled in the ascending aorta, superior vena cava, inferior vena cava and left pulmonary artery. Flow curves were interpolated to equal temporal phases and were then used to create three data matrices of arterial and venous waveforms. Principal component analysis was performed on each matrix and principal components that accounted for >10% variance were correlated to traditional clinical indices. Results indicate correlation of inferior and superior vena cava waveform patterns to parameters of pulmonary (RV/TLC %, lowest SaO2%), lymphatic (cystatin-c, BUN, alkaline phosphatase) and to ventricular function (CI, EF, EDVi, ESVi and VVCR). This study demonstrates that coupled waveform analysis of arterial and venous vessels relays additional information about Fontan patient status.

Selective Use of Pulmonary Vasodilators in Patients with Fontan Physiology.

Fontan-associated liver disease is a well-known sequela following the Fontan procedure for patients living with single-ventricle heart disease. Pulmonary vasodilators, such as phosphodiesterase type 5 inhibitors, have emerged as a potential therapeutic option for lowering central venous pressures by reducing pulmonary vascular resistance. We performed a single-center retrospective review of Fontan patients who were placed on pulmonary vasodilator therapy with prehemodynamic and posthemodynamic, MR elastography, and histologic assessments. A total of 125 patients with Fontan circulation underwent surveillance with cardiac catheterization during the review period. Fifty-three (42%) patients who did not have increased end-diastolic pressures at the time of cardiac catheterization were started on phosphodiesterase type 5 inhibitor therapy. Nine patients (17%) underwent posttherapy follow-up catheterization. The mean Fontan pressure decreased from 15.4 ± 3.3 mmHg to 13.3 ± 2.5 mmHg (p=0.026), after initiation of pulmonary vasodilatory therapy. There was no change in end-diastolic pressure, transpulmonary gradient, wedge pressure, pulmonary vascular resistance, cardiac index, or saturation. Eleven patients (21%) underwent pretherapy MR elastography testing with posttherapy follow-up MR elastography. We found no improvement in liver stiffness score following the application of pulmonary vasodilators. Three patients underwent pretherapy and posttherapy liver biopsies, with variable histological changes observed within the hepatic parenchyma. These data demonstrate indeterminate results for the selective use of pulmonary vasodilators but highlight the need for large prospective randomized control trials of pulmonary vasodilator therapies to fully assess the benefit of such therapies in Fontan-associated liver disease.

Abstract 10960: The Thoracic Duct is Well-Visualized on 3D-BSSFP Imaging in Patients With Fontan Circulation and Its Size and Tortuosity Are Associated With Worse Outcomes

Introduction: Lymphatic complications are common in patients with Fontan circulation. 3D balanced steady-state free precession (3D-bSSFP) angiography by cardiovascular magnetic resonance (CMR) is widely adopted for cardiovascular anatomical assessment. We sought to determine the frequency of thoracic duct visualization using 3D bSSFP images and assess whether thoracic duct characteristics are markers of poor clinical outcomes. Methods: This was a retrospective, single-center study of patients with Fontan circulation who underwent CMR. Patients with repaired tetralogy of Fallot (rTOF) were included as a comparison. Thoracic duct characteristics included maximum diameter and a qualitative assessment of tortuosity (Figure). Clinical outcomes included protein-losing enteropathy (PLE), plastic bronchitis, listing for heart transplant, or death. A composite outcome was defined as presence of any of the above. Results: The study group was comprised of 189 Fontan patients and 36 rTOF patients (median age at CMR 16 years, IQR: 11-23 years). The thoracic duct diameter was larger (median 2.50 vs 1.95 mm, p&lt;0.01) and more often well-visualized (65% vs 22%, p&lt;0.01) in Fontan patients vs the rTOF group. The thoracic duct diameter was larger in Fontan patients with PLE (median 4.0 vs 2.5 mm, p=0.02) vs Fontan patients without PLE, and was more tortuous in Fontan patients with congestive heart failure (CHF) vs Fontan patients without CHF (moderate or greater tortuosity in 75% vs 28.5%, p=0.02). Larger thoracic duct diameter was associated with a lower ejection fraction (R= -0.24, p&lt;0.01). The composite outcome was present in 6% of Fontan patients and was not associated with thoracic duct diameter (p=0.72) or tortuosity (p=0.09). Conclusions: The thoracic duct can be well visualized in 2/3 of patients with Fontan circulation on 3D-bSSFP images. Larger thoracic duct dimension and increased tortuosity are associated with co-morbidities experienced by Fontan patients.

Abstract 11319: Post-Operative Dialysis in Failing Fontan Patients Undergoing Heart Transplant: How Well Does the Pre-Transplant Creatinine Clearance Risk-Stratify Patients?

Introduction: The need for dialysis early post-heart transplant (HT) can be suprisng when it occurs in the setting of purportedly normal renal function pre-HT, as has been described in failing Fontan (FF) patients. Hypothesis: We hypothesized that FF patients may have an increased incidence of post-operative dialysis (POD). Methods: The Pediatric Heart Transplant Society (PHTS) database was used to identify all children ≥2 years of age with failing Fontan (FF) physiology or cardiomyopathy (CM, benchmark lesion) who underwent isolated HT from 2005-2019. The primary endpoint was POD, defined as any form of dialysis within the first 30 days post-HT. Pre-transplant estimated glomerular filtration rate (eGFR) was calculated using the modified Schwartz formula, and a subset of patients with provided supplemental data additionally had renal function evaluated by a non-creatinine-based method. Results: Of 2003 children who met the inclusion criteria, 263 had FF (13%) and 1740 had CM (87%). Whereas the mean ages were similar (FF 11.2 vs CM 12.2 years, P=0.3), FF patients were 11% shorter (134 vs. 148, P&lt;0.001) and 9 kg lighter (31.2 vs. 40.2, P&lt;0.001), and had a lower serum creatinine (0.57 vs. 0.64 mg/dl, P=0.001) but similar eGFR pre-transplant (110.2 vs. 106.7 L/min/1.73m 2 , P=0.26). In a subset of 22 FF patients with available results from 24-hour urine collection or nuclear medicine scan, the Schwartz formula overestimated the GFR in 15/22 patients by an average of 40.2 ml/min/1.73 m2 (range 2.6 to 91.8). Overall, compared to CM patients, FF patients had a 4.7-fold higher risk of requiring POD (3.8% vs. 0.8%, P&lt;0.001). Of those who required POD, the difference in 30 day post-HT mortality was not significant (40% vs. 14%, 0.3). Multivariable analysis revealed that pre-HT ECMO and longer CPB times were independently associated with POD; there was a trend toward association of higher pre-HT eGFR (P=0.06). Conclusions: Fontan patients have a ~5-fold higher risk of post-operative dialysis compared to cardiomyopathy patients, and despite a normal or even supraphysiological pre-transplant estimated CrCl. Non-creatinine-based methods independent of malnutrition status should be considered in the FF population.

Abstract 13884: Cardiopulmonary Exercise Testing Delineates Underlying Mechanisms of “Good” and “Poor” Exercise Performance in Post-Fontan Patients

Background: Fontan patients have limited exercise capacity primarily due to an absence of subpulmonary ventricle by which ventricular filling is hindered in response to incremental exercise. Little is understood as to how to improve exercise performance in Fontan patients. Methods: Cardiopulmonary exercise testing (CPET) in Fontan patients were studied retrospectively. The patients were divided into “Good” and “Poor” performance by peak oxygen consumption (pVO2) at 35 and 30 ml/kg/min for males and females, respectively. Data are shown as mean ± standard deviation. Results: Table 1 presents demographic data and CPET results of males and females with “Good” and “Poor” exercise performance (total 36 patients). Ventilatory anaerobic threshold (VAT) and peak work rate (pWR) were significantly lower in male “Poor” group than in male “Good” group whereas no significant difference was noted in female groups other than pVO2. A specific trend of each group emerged when weight (kg)-pVO2 (L/min) and maximum minute ventilation (maxVE: L/min)-pVO2 (L/min) relationship were assessed, which indicated that “Good” Fontan had higher skeletal muscle mass effects in given weight and better ventilatory efficiency for oxygenation, respectively, than “Poor” group (Figure 1). Conclusions: Under the same single ventricle physiology which mitigates ventricular filling, some Fontan patients showed better exercise performance than others due to higher skeletal muscle mass effects and better ventilatory efficiency for oxygenation. A simple method of plotting of 2 CPET parameters may be useful in assessing improvement in exercise performance by muscle and breathing training in Fontan patients.