Fontan Patients Research Articles

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 < 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 < 0.001) and the ejection fraction (EF) (58,9 ± 4.5% vs 63.3 ± 3.9%, p < 0.002) were significantly lower in Fontan patients. Fontan patients with normal EF showed, however, significantly reduced values of MWI compared with CTRL (p<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.

Abstract 14263: Asessment of Pulmonary Vascular Reserve Using Pharmacologic Stress Testing in Patients With Fontan Physiology

Introduction: The presence of pulmonary vascular disease (PVD) may be under-recognized during standard hemodynamic evaluation in patients with Fontan physiology. Assessment of pulmonary vascular reserve (VR) (Δ pulmonary artery pressure/Δ cardiac index) utilizing pharmacologic stress testing could be a better way of identifying PVD in pediatric patients. The objective of this study is to diagnose Fontan patients with PVD utilizing pharmacologic stress testing. Hypothesis: Pharmacologic stress testing will unmask Fontan patients as having PVD. Methods: Single center record review of cardiac catheterizations with dobutamine administration in Fontan patients from January 2021 to June 2022. Following acquisition of baseline data on room air, a dobutamine infusion was started at 5 mcg/kg/min with dose escalation as needed until an appropriate heart rate response was achieved. Hemodynamics were reassessed at each dose interval, but data are reported at the highest cardiac index (CI). Abnormal VR was defined as &gt; 3 mmHg/l. Results: Eighteen Fontan patients (87% male) were included. Median age at the time of catheterization was 14 (IQR 11, 16) years with mean duration of Fontan circulation of 9.9 ± 3.9 years. The primary indication for catheterization was exercise intolerance (65%). Dobutamine administration did not result in a significant change in indexed pulmonary vascular resistance (PVRi) (2.1 ± 0.8 v 2.4 ± 1.31 iWU, p = 0.21) or Fontan pressure (12 [IQR 11, 14] v 14 (IQR 12, 15), p=1.0]. Eight patients had a PVRi ≥ 2.0 iWu at baseline; while 4 (22% of the cohort) had a PVRi &lt; 2.0 iWU at baseline but had an abnormal VR. Conclusions: PVD is common in Fontan patients but may be missed in some patients without pharmacologic stress testing. Accurate diagnosis of PVD will allow for optimization of Fontan circulation with pulmonary vasodilators.

Abstract 10776: A Supervised Classification Model Detects Fontan Patients Based on Clinical Notes With Higher Accuracy Than ICD Codes

Introduction: The Fontan operation palliates single ventricle heart defects. As native anatomy varies, Fontan cases cannot always be identified by ICD9 or 10CM codes. Hypothesis: We sought to train and evaluate a supervised machine learning (ML) system to identify Fontan cases based on unstructured clinical notes in a large database. Methods: 160 adult Fontan patients from validated clinical data at a single tertiary referral center with available text notes were studied. The imbalanced data set had more non-Fontan cases than Fontan patients; thus we created multiple datasets with different positive : negative case ratios ranging from 1:2 to 1:10. We used stratified 80-20 training-testing splits of data. Vectorized representations of text notes were used as features. We trained a Support Vector Machine (SVM) model, mostly used for text classification, to identify Fontan cases from notes. For each dataset, we performed random 80-20 data splitting 10 times and reported average F 1 score (harmonic mean of recall/sensitivity &amp; precision/positive predictive value) over the positive class. Results: The model achieved a mean F 1 score of 0.95 for the positive class on the data split with 1:2 positive-negative ratio. Increasing data imbalance from 1:2 to 1:10 did not substantially impact performance. The mean F 1 score over all data splits was 0.94, and SD 0.01. We also computed precision, recall, and F 1 score of ICD codes to identify Fontan patients. Performance comparisons between ICD codes only and Natural Language Processing (NLP)/ML are in Table 1. Conclusions: A supervised classification model more effectively detects Fontan patients based on clinical notes with higher accuracy than ICD codes. The model is robust and insensitive to data imbalance. Findings suggest our model may work effectively in real-world data. Since the sensitivity of ICD codes is high but PPV is low, it may be beneficial to apply ICD codes as a filter prior to applying NLP/ML to improve performance.

Abstract 15009: Detection of a Low Ventricular Stiffness With Preserved Ejection Fraction Phenotype in Single Ventricle Physiology

Introduction: Patients with single ventricle physiology frequently demonstrate decreased exercise tolerance after the Fontan operation. The objective of this study was to investigate the contribution of ventricular stiffness to exercise function in these patients. Hypothesis: We hypothesized that ventricular stiffness, both extremes of high and low stiffness, would be associated with exercise tolerance in Fontan patients. Methods: We previously validated an echocardiographic measure of ventricular stiffness, lateral Doppler E: tissue Doppler e’/end-diastolic volume (lateral E:e’/EDV) in children. Core-lab echocardiograms and exercise test results were obtained from the publicly-available Pediatric Heart Network Fontan Cross-sectional Study database. Exercise function was quantified as % predicted VO 2 . Ejection fraction (EF) was considered abnormal if &lt; 50%. Diastolic function was defined as high stiffness if the lateral E:e’/EDV was &gt; 90th percentile or low stiffness if &lt; 10th percentile. Patients were divided into four groups: 1 = normal EF and normal diastolic function, 2 = decreased EF with normal diastolic function, 3 = normal EF with high ventricular stiffness, and 4 = normal EF with low ventricular stiffness. Results: 239 patients (61% left, 29% right, 10% mixed ventricular dominance) had EF, lateral E:e’/EDV, and VO 2 measured. Differences between groups are reported in the Table. Conclusion: Single ventricle patients with both high and low stiffness and preserved EF had worse exercise capacity than patients with both normal and abnormal EF. To our knowledge, this is the first study detecting a low stiffness heart failure phenotype in single ventricle physiology. Future studies should further investigate the pathophysiologic mechanisms that lead to these extremes of stiffness in Fontan patients.

Abstract 15762: Model for Home-Based Physical Activity Program Utilizing Telemedicine for Fontan Patients

Introduction: Fontan patients have decreased exercise capacity. The COVID-19 pandemic exacerbated the variable adherence to hospital-based physical activity programs, which improve exercise capacity and attenuate the expected decline in aging Fontan patients. A positive pediatric exercise capacity trajectory has been reported to predict better adult Fontan outcomes. We designed and implemented a reimbursable 12-month, home-based, individualized physical activity program for Fontan patients utilizing a telemedicine model. Methods: Eligible participants must be able to complete a cardiopulmonary exercise test (CPET) and demonstrate ability to adhere to a 12-month exercise prescription. Assent and consent are obtained. CPET and informal surveys of physical activity self-efficacy are completed at enrollment and graduation. An individualized exercise prescription is provided, with focus on skeletal and respiratory muscle strength training and aerobic activities. Participants receive a Garmin© device to monitor adherence. A cardiologist, nurse coordinator, and exercise physiologists comprise the team and regularly communicate with participants, starting with weekly check-ins that gradually space out to monthly as participants gain confidence. Results: Since program initiation, 9 participants have completed the program and 3 remain active. For the 9 graduates, all scheduled in-person and telehealth visits were completed. At completion of the 12-month program compared to baseline, there was no difference in maximal or submaximal oxygen consumption (VO2), peak heart rate, or oxygen saturation, but there was a significant increase in systolic blood pressure (144 ± 16 vs 162 ± 15, p-value 0.004) and minute ventilation (68.8 ± 19.3 vs 76.8 ± 22.1, p-value 0.012) at peak exercise. Per subjective report, all graduates had increased confidence related to exercise. There were no adverse events in any participant. Conclusions: A novel, home-based, 12-month individualized physical activity program using telemedicine was successfully implemented, with no adverse events. A larger study is needed to better assess change in VO2 and other qualitative and quantitative parameters, although the lack of decline in exercise capacity is encouraging.

Abstract 12163: Liver Disease in Right Heart Failure: Not Just Fontan Associated

Introduction: Hepatic fibrosis, cirrhosis, and hepatocellular carcinoma caused by the Fontan circulation, known as Fontan Associated Liver Disease (FALD), are due to low cardiac output and high venous pressure within the Fontan circuit. Hypothesis: We hypothesized that patients with congenital heart disease causing right heart dysfunction would have liver findings similar to FALD. Methods: We identified patients with the Fontan circulation or congenital heart disease associated with moderately depressed or dilated RV on echo or MRI, and/or increased right atrial pressure on cardiac cath. We defined hepatic congestion as increased kPA on Fibroscan, liver or IVC abnormalities on US, increased kPA or liver abnormalities on MRI elastography, and/or sinusoidal congestion on liver biopsy. The incidence of hepatic congestion was compared by chi squared analysis. Results: A total of 33 patients were identified for this study, 23 Fontan and 10 non-Fontan. Hepatic congestion was found in 25 patients (76%). Hepatic congestion was most often diagnosed by US in both Fontan (82.6%) and non-Fontan patients (40%). The most common findings on liver biopsy, including one non-Fontan Ebstein, were sinusoidal dilation, portal fibrosis, and perisinusoidal fibrosis. The incidence of hepatic congestion in Fontan was no different from non-Fontan however power was limited. Conclusions: Hepatic congestion was found in 83% of Fontan and 60% of non-Fontan patients. Fontan and non-Fontan patients alike are at risk for hepatic congestion and there is need for further evaluation to understand the clinical relevance of hepatic congestion caused right heart dysfunction.

Abstract 13950: Dynamic Myocardial Systolic and Diastolic Response to Exercise in Patients After the Fontan Operation

Background: Exercise capacity is one of the predictors of morbidity and mortality in patients after the Fontan circulation. The influence of myocardial systolic and diastolic functional reserve on exercise performance has not been well established in this population. This study aimed at studying the myocardial response to exercise in Fontan patients using exercise echocardiography. Methods: Twenty-three Fontan patients with baseline ejection fraction &gt;55% and 23 age and gender matched controls were included. A stepwise exercise stress echocardiography protocol was used. Tissue Doppler imaging (TDI) systolic (s’), and early diastolic (e’) velocities and myocardial acceleration during isovolumic contraction (IVA) were measured in the free wall of the dominant ventricle and interventricular septum and in the left ventricular free wall and septum of controls. Measurement was taken at rest and at incremental heart rate (HR). Changes in tissue Doppler velocities versus heart rate were studies and compared between patients and controls. Results: Resting HR was not significantly different between patients and controls but peak HR was lower in the Fontan group vs controls ( p &lt;0.001). At rest patients had significantly lower lateral and septal e’ and s’ compared to controls (lateral s’: 6.35±1.05 vs. 14.41± 1.88 cm/s; lateral e’: 9.38±1.71 vs.20.66±2.55 cm/s; septal s’: 5.30±2.46 vs. 11.58±2.26 cm/s; septal e’: 10.45±2.46 vs. 17.80±1.58 cm/s P &lt;0.001) except for IVA. At peak exercise, all variables were significantly lower in the patient group. During exercise, the slopes of lateral and septal s’ and IVA were significantly different between patients and controls except for e’. Conclusion: Our data suggest that patients with Fontan physiology have blunted systolic contractile response to exercise. Surprisingly our data suggest that the dynamic early diastolic myocardial reserve is preserved which suggest that early myocardial relaxation is not a limiting factor.

Abstract 10515: Mechanical Dyssynchrony in Patients With a Fontan Circulation and Its Relationship to Outcomes

Introduction: The prevalence and significance of mechanical dyssynchrony is not well known in the Fontan population. Methods: Single-center, retrospective analysis of CMRs in Fontan patients compared to healthy controls. Feature tracking was performed on all slices of a short-axis cine stack and dyssynchrony index (DI) was defined as the standard deviation of time-to-peak circumferential strain for all segments. A composite outcome was defined as death, heart transplant listing, or new ventricular arrhythmias. Results: A total of 512 cases (17±9 y) and 42 controls (16±9 y) were included. Figure 1 depicts differences in EDV i , EF, DI, and QRS duration between the cohorts. DI correlated with EDV i (r=0.35; p&lt;0.01), EF (r=-0.29; p&lt;0.01), and QRS duration (r=0.29; p&lt;0.01). At a median follow-up of 4.2 yrs, 10% had death or transplant listing and 4% had ventricular arrhythmias. RV dominance, EDV i , EF, DI, and QRS interval were associated with increased risk of the composite outcome (Table 1). Figure 2 demonstrates a significantly higher probability of the composite outcome in those with EDV i &gt;120 ml/m 2 and DI&gt;70 ms. Conclusion: Fontan patients have more mechanical dyssynchrony and longer QRS duration compared to controls. These abnormalities are more pronounced in RV or mixed ventricular morphology and are associated with a higher risk of ventricular arrhythmias, transplant listing, or death.

Abstract 13035: Mechanical Circulatory Support is a Viable Solution for Adults With Failing Fontan Circulation

Mechanical circulatory support (MCS) is rarely used in adults with congenital heart disease and even more uncommon among those with single ventricle (e.g. Fontan) circulation. As survivorship among Fontan patients increases, evaluation for MCS is warranted. This systematic review’s objective is to study the outcomes of adult Fontan patients supported by MCS. METHODS We searched the literature in English in PubMed and Google Scholar in May 21 &amp; 2, 2022 using MeSH terms: "VAD," "Fontan," and "circulatory assist device." The search yielded 2785 results. After screening for title, abstract, patient age (&gt;18 y/o), and extractable individual patient data, 23 reports met the criteria. Ultimately, 15 full texts were reviewed and included in this report. RESULTS We identified 18 patients on MCS, including 7 on short-term devices (Impella), 4 on paracorporeal pulsatile devices (PPDs), and 7 on durable continuous flow ventricular assist devices (VADs). Short-term pumps were used for cardiogenic shock (5, with 3 survivors) or support of high-risk ablation procedures. PPDs were used as a bridge to transplantation, mean patient age of 23.5±3.4 years old; all survived after a mean time on MCS of 172±158 days.In the VAD cohort (7 patients, 85.7% males, age 25.1±4.0), 5 received Heartmate 3, one received Heartmate II, and one Heartware (Table 1). Indications for VAD included cardiogenic shock (4 patients, 2 on VA ECMO) or heart failure. VADs dramatically increased cardiac index from 1.6±0.14 to 3.6±0.1 L/min/m2, p=0.0003, and decreased Fontan pressure from 21.4±3.3 to 13.0±1.4 mmHg, p=0.02. Heartmate 3 mean speed was 6460±568.3 rpm. All patients survived, with mean time on VAD lasting 459.5±452.2 days. CONCLUSIONS Implanted mostly for catastrophic indications, adult Fontan patients demonstrated improved hemodynamics and excellent survival following MCS use. These improvements are promising, and earlier implantation prior to catastrophic events may lead to better outcomes.

Abstract 15324: The Fontan Circulation Shows Decreased Cell Survival and Oxidative Damage

Introduction: Single ventricle congenital heart disease such as hypoplastic left heart syndrome (HLHS) with a Fontan circulation accounts for the largest group of children hospitalized with circulation failure, with an in-hospital mortality of 20-50%. We sought to (i) evaluate the mechanisms underlying circulation failure and (ii) identify novel therapeutic targets. Methods: Blood was collected from patients with HLHS s/p Fontan and from controls with normal cardiac anatomy and function (N=5/group). Plasma microvesicles (MV) were isolated and proteomics assessed using data independent acquisition mass spectroscopy. Dysregulated proteins with a fold change &gt;1.5 or &lt; -1.5, p&lt;0.05 were evaluated using Ingenuity pathway analysis. Results: Age of Fontan patients vs. controls was 17.04±2 vs. 15.7±2.5, p=0.4; 20% were male in both groups. 60% of Fontan patients were in NYHA class II/III, 40% in NYHA class IV; 80% had Fontan-associated liver disease. Circulating MVs were released from cardiomyocytes, endothelial cells, and hepatocytes based on cell surface markers. Upregulated proteins (N=27) implicated cell death pathways (Solute carrier family 2, Angiotensinogen, CD14); while downregulated proteins (N=88) implicated impaired cell survival (tyrosine-protein kinase Yes, endothelial growth factors). MVs contained mitochondria and endoplasmic reticulum proteins implicating upregulation in reactive oxygen species signaling (catalase A, S100A8) and downregulation in antioxidant enzymes (GPX1, PRDX 5). Conclusion: Circulating MVs from patients with HLHS s/p Fontan are released from the heart, blood vessels, and liver providing a noninvasive signature of organ remodeling. The MV protein cargo implicates heightened cell death, oxidative damage and impaired cell survival, thereby providing insight into the mechanisms of Fontan associated circulation failure. Figure: Decreased Cell Survival and Oxidative Damage in the Fontan Circulation