Associations of Liver Stiffness Measured by Ultrasound Shear-Wave Elastography With Portal Hypertension and Circulatory Failure in Individuals With Fontan Circulation.

BACKGROUND. The Fontan operation palliates single-ventricle congenital heart disease but causes hepatic congestion with associated progressive hepatic fibrosis. OBJECTIVE. The purpose of this study was to evaluate associations between liver stiffness measured using ultrasound (US) shear-wave elastography (SWE) in patients with Fontan palliation and the occurrence of portal hypertension and Fontan circulatory failure during follow-up. METHODS. This retrospective study included 119 individuals 10 years old or older (median age, 19.1 years; 61 female patients, 58 male patients) with Fontan circulation who underwent liver US with 2D SWE from January 1, 2015, to January 1, 2022, and had 1 year or more of clinical follow-up (unless experiencing earlier outcome-related events). Median liver stiffness from the initial US examination was documented. Varices, ascites, splenomegaly, and thrombocytopenia (VAST) scores (range, 0-4) were determined as a marker of portal hypertension on initial US examination and 1 year or more of follow-up imaging (US, CT, or MRI). Composite clinical outcome for Fontan circulatory failure (death, mechanical circulatory support, cardiac transplant, or unexpected Fontan circulation-related hospitalization) was assessed. Analysis included the Wilcoxon rank sum test, logistic regression analysis with stepwise variable selection, and ROC analysis. RESULTS. Median initial liver stiffness was 2.22 m/s. Median initial VAST score was 0 (IQR, 0-1); median follow-up VAST score was 1 (IQR, 0-2) (p = .004). Fontan circulatory failure occurred in 37 of 119 (31%) patients (median follow-up, 3.4 years). Initial liver stiffness was higher in patients with a follow-up VAST score of 1 or greater (2.37 m/s) than in those with a follow-up VAST score of 0 (2.08 m/s) (p = .005), and initial liver stiffness was higher in patients with (2.43 m/s) than without (2.10 m/s) Fontan circulatory failure during follow-up (p < .001). Initial liver stiffness was the only significant independent predictor of Fontan circulatory failure (OR = 3.76; p < .001); age, sex, Fontan operation type, dominant ventricular morphology, and initial VAST score were not independent predictors. Initial liver stiffness had an AUC of 0.70 (sensitivity, 79%; specificity, 57%; threshold, > 2.11 m/s) for predicting a follow-up VAST score of 1 or greater and an AUC of 0.74 (sensitivity, 84%; specificity, 52%; threshold, > 2.12 m/s) for predicting Fontan circulatory failure. CONCLUSION. In patients with Fontan circulation, increased initial liver stiffness was associated with portal hypertension and circulatory failure during follow-up, although it had moderate performance in predicting these outcomes. CLINICAL IMPACT. US SWE may play a role in post-Fontan surveillance, supporting tailored medical and surgical care.

End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study.

BACKGROUND AND AIMS: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear. METHODS: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. RESULTS: From 558 patients (48% female, age at first visit 36 ± 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. CONCLUSIONS: Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.

Utility of a pharmacist-managed Anticoagulation Program in patients with congenital heart disease.

BACKGROUND: Warfarin remains the preferred anticoagulant for many patients with CHD. The complexity of management led our centre to shift from a nurse-physician-managed model with many providers to a pharmacist-managed model with a centralized anticoagulation team. We aim to describe the patient cohort managed by our Anticoagulation Program and evaluate the impact of implementation of this consistent, pharmacist-managed model on time in therapeutic range, an evidence-based marker for clinical outcomes. METHODS: A single-centre retrospective cohort study was conducted to evaluate the impact of the transition to a pharmacist-managed model to improve anticoagulation management at a tertiary pediatric heart centre. The percent time in therapeutic range for a cohort managed by both models was compared using a paired t-test. Patient characteristics and time in therapeutic range of the program were also described. RESULTS: After implementing the pharmacist-managed model, the time in therapeutic range for a cohort of 58 patients increased from 65.7 to 80.2% (p < .001), and our Anticoagulation Program consistently maintained this improvement from 2013 to 2022. The cohort of patients managed by the Anticoagulation Program in 2022 included 119 patients with a median age of 24 years (range 19 months-69 years) with the most common indication for warfarin being mechanical valve replacement (n = 81, 68%). CONCLUSIONS: Through a practice change incorporating a collaborative, centralized, pharmacist-managed model, this cohort of CHD patients on warfarin had a fifteen percent increase in time in therapeutic range, which was sustained for nine years.

Isosorbide DiNitrate Effect on Hemodynamic Profile, Liver Stiffness, and Exercise Tolerance in Fontan Circulation (The NEET Clinical Trial).

After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2 years (range 11.2-39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO2 (1401 ± 428 to 1428 ± 436 mL/min, p = 0.128), but VO2 at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302 mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0 mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO2 at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer duration studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT04297241.

The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis.

The Pediatric Heart Network's Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT02741115) demonstrated improvements in some measures of exercise capacity and in the myocardial performance index following 6 months of treatment with udenafil (87.5 mg twice daily). In this post hoc analysis, we evaluate whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. The effect of udenafil on exercise was evaluated within subgroups defined by baseline characteristics, including peak oxygen consumption (VO2), serum brain-type natriuretic peptide level, weight, race, gender, and ventricular morphology. Differences among subgroups were evaluated using ANCOVA modeling with fixed factors for treatment arm and subgroup and the interaction between treatment arm and subgroup. Within-subgroup analyses demonstrated trends toward quantitative improvements in peak VO2, work rate at the ventilatory anaerobic threshold (VAT), VO2 at VAT, and ventilatory efficiency (VE/VCO2) for those randomized to udenafil compared to placebo in nearly all subgroups. There was no identified differential response to udenafil based on baseline peak VO2, baseline BNP level, weight, race and ethnicity, gender, or ventricular morphology, although participants in the lowest tertile of baseline peak VO2 trended toward larger improvements. The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115.

Outcomes after initial heart failure consultation in Fontan patients.

BACKGROUND: Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care. METHODS: This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as "too late" (death or declined for transplant due to being too sick) and/or "care escalation" (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. "Late referral" was defined as those referred too late and/or had care escalation. RESULTS: Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8-21.5, p=0.004). CONCLUSIONS: Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.

Abdominal CT and MRI Findings of Portal Hypertension in Children and Adults with Fontan Circulation.

Background Portal hypertension in the Fontan circulation is a function of elevated systemic venous pressure and liver fibrosis. Purpose To quantify the prevalence of radiologic evidence of portal hypertension and elevated VAST score (one point each for varices, ascites, splenomegaly, and thrombocytopenia) of 2 or greater in children and adults with Fontan circulation and to determine the association with hemodynamics and adverse outcomes. Materials and Methods This was a retrospective study of individuals with Fontan circulation who underwent abdominal MRI or CT for focal liver lesion surveillance between January 2012 and December 2019. Portal hypertension was defined as the presence of at least two of the following: varices, ascites, or splenomegaly. Fontan deterioration was defined as a composite of heart failure signs or symptoms requiring diuretic escalation, placement of a ventricular assist device, heart transplant, or death. Relationships between variables and the composite end point were assessed using univariable and multivariable logistic regression. Results A total of 123 patients (age range, 9-55 years; 32 children) were evaluated (median age, 23 years; IQR, 17-30 years; 63 male patients). Median time since diagnosis of Fontan circulation was 16 years (IQR, 12-23 years). Twenty-five of the 123 patients (20%) had radiologic evidence of portal hypertension, and 34 (28%) had a VAST score of 2 or greater. Fontan deterioration occurred in 25 of the 123 patients (20%); median follow-up duration was 0.4 year (IQR, 0.1-3.1 years). Compared with patients who had Fontan circulation without deterioration, patients with Fontan deterioration were more likely to have moderate or severe ventricular systolic dysfunction (P < .01), moderate or severe atrioventricular valve regurgitation (P < .01), higher Fontan pressure (P = .01), radiologic evidence of portal hypertension (P < .01), and VAST score of 2 or greater (P < .01). Conclusion Radiologic evidence of portal hypertension at abdominal imaging in children and adults with Fontan circulation was associated with higher venous pressures and an increased risk for Fontan deterioration. These characteristics may be used to identify patients who warrant comprehensive hemodynamic evaluation. © RSNA, 2022.

Developing an adolescent and adult Fontan Management Programme.

Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.

Relation of Magnetic Resonance Elastography to Fontan Circulatory Failure in a Cohort of Pediatric and Adult Patients.

Elevated magnetic resonance elastography (MRE)-derived liver stiffness may be associated with worse outcomes in people with Fontan circulation. We sought to evaluate the association between liver stiffness and Fontan failure or portal hypertension. Single center cross-sectional retrospective study of people with Fontan circulation who underwent MRE between 2011 and 2020. The cohort was divided into adult (age ≥ 21 years) and pediatric (< 21 years) groups. Fontan circulatory failure (FF) was defined as any of the following: death, transplantation, ventricular assist device, heart failure symptoms requiring escalation of diuretics. Radiologic portal hypertension was defined as the presence of one or more of the following: splenomegaly, ascites, or gastrointestinal varices. 128 patients were included (average age = 22.6 ± 8.7 years) and 58 (45%) were children. Median liver stiffness was 4.3 kPa (interquartile range (IQR) 3.8-5.8) for the entire cohort. Thirty patients (23%) developed FF (16 adults, 14 children). Liver stiffness was higher in adults with FF compared to those without FF (4.9 (IQR 4.0-6.0) vs. 4.2 (IQR 3.8-4.7) kPa, p = 0.04). There was no difference in liver stiffness between pediatric patients with and without FF (4.4 (IQR 4.1-5.4) vs. 4.4 (IQR 3.8-5.0), p = 0.5). Adults with radiologic portal hypertension and adults with moderate or severe atrioventricular valve regurgitation had higher liver stiffness than adults without. MRE-derived liver stiffness is associated with atrioventricular valve regurgitation, portal hypertension, and poor clinical outcomes in adults with Fontan circulation. There was no association between liver stiffness and FF in pediatric patients. This difference may be due to the progressive nature of Fontan-associated liver disease.

Imaging of Fontan-associated liver disease.

The Fontan operation has dramatically altered the natural history of functionally single ventricle congenital heart disease. Patients who have undergone the Fontan operation are living longer and, thus, noncardiac morbidity resulting from the Fontan operation is increasingly being recognized. Fontan-associated liver disease (FALD), one of the chief morbidities following the Fontan operation, is believed to be a multifactorial process that manifests as hepatic congestion and fibrosis, portal hypertension, and development of focal liver lesions, including malignant tumors. This article reviews the imaging findings of FALD in the pediatric and young adult population, reviews the literature related to the imaging of FALD and discusses possible screening algorithms for this population. The need for further research to better understand the causes of FALD, to establish if early liver stiffness measurements (or their change over time) predict long-term outcomes and complications, and to define optimal liver screening procedures is highlighted.

Relation of visceral fat and haemodynamics in adults with Fontan circulation.

Being overweight is associated with reduced functional capacity in Fontan patients. Increased adiposity leads to accumulation of epicardial and intra-abdominal visceral fat, which produce proinflammatory cytokines and may affect endothelial function. This retrospective study to evaluate the association between visceral fat and Fontan haemodynamics included 23 Fontan patients >18 years old with MRI and catheterization data available. Epicardial fat volume indexed to body surface area was measured by cardiac MRI, and intra-abdominal visceral fat thickness and subcutaneous fat thickness were derived from abdominal MRI. Stepwise regression models were used to determine univariable and multivariable associations between fat measures and haemodynamics. Mean age was 28.2 ± 9.5 years and body mass index was 26 ± 4 kg/m2. Mean central venous pressure was 13 ± 3 mmHg and pulmonary vascular resistance index was 1.23WU·m2 (interquartile range: 0.95-1.56). Epicardial fat volume was associated with age (r2 = 0.37, p = 0.002), weight (r2 = 0.26, p = 0.013), body mass index (r2 = 0.27, p = 0.011), and intra-abdominal visceral fat (r2 = 0.30, p = 0.018). Subcutaneous fat thickness did not relate to these measures. There was modest correlation between epicardial fat volume and pulmonary vascular resistance (r2 = 0.27, p = 0.02) and a trend towards significant correlation between intra-abdominal fat thickness and pulmonary vascular resistance (r2 = 0.21, p = 0.06). Subcutaneous fat thickness was not associated with Fontan haemodynamics. In multivariable analysis, including age and visceral fat measures, epicardial fat was independently correlated with pulmonary vascular resistance (point estimate 0.13 ± 0.05 per 10 ml/m2 increase, p = 0.03). In conclusion, in adults with Fontan circulation, increased visceral fat is associated with higher pulmonary vascular resistance. Excess visceral fat may represent a therapeutic target to improve Fontan haemodynamics.

Lymphopenia in adults after the Fontan operation: prevalence and associations.

Lymphopenia is common in adults who have had a Fontan operation although its aetiology and clinical implications remain unknown. Previous work suggests an association between lymphopenia and both liver disease and splenomegaly. The objective of this study was to assess the prevalence of lymphopenia in adults with a Fontan circulation and evaluate its associations with risk factors and clinical outcomes. Using a retrospective cohort study design, we studied 73 adult Fontan patients (age 25.0 ± 8.4 years) who had a complete blood count and abdominal imaging performed. Patients with protein-losing enteropathy were excluded. Clinical data were extracted from hospital records. The mean white blood cell count was 6580 ± 220/ml with a mean lymphocyte count of 1223 ± 508/ml. Lymphopenia, defined as lymphocyte count <1000/ml, was present in 23 (32%) patients. Patients with lymphopenia had a lower total white blood cell count (5556 ± 2517 versus 7136 ± 1924/ml, p = 0.009) and a lower platelet count (162 ± 69 versus 208 ± 69 k/ml, p = 0.008). Lymphopenia was also associated with findings of portal hypertension, including splenomegaly (36 versus 14%, p = 0.04), varices (22 versus 6%, p = 0.04), and ascites (39 versus 14%, p = 0.02). Lymphopenia did not correlate with any cardiac imaging, haemodynamic or exercise testing variables. In conclusion, lymphopenia is common in adult Fontan patients and is associated with markers of portal hypertension. Larger studies are needed to better define the relationship between lymphopenia and clinical outcomes.

The Fontan outcomes network: first steps towards building a lifespan registry for individuals with Fontan circulation in the United States.

The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.

Echocardiographic predictors of elevated left ventricular end diastolic pressure in adolescent and adult patients with repaired tetralogy of Fallot.

Elevated left ventricular end diastolic pressure is a risk factor for ventricular arrhythmias in patients with tetralogy of Fallot. The objective of this retrospective study was to identify echocardiographic measures associated with left ventricular end diastolic pressure >12 mmHg in this population. Repaired tetralogy of Fallot patients age ≥13 years, who underwent a left heart catheterisation within 7 days of having an echocardiogram were evaluated. Univariate comparison was made in echocardiographic and clinical variables between patients with left ventricular end diastolic pressure >12 versus ≤12 mmHg. Ninety-four patients (54% male) with a median age of 24.6 years were included. Thirty-four (36%) had left ventricular end diastolic pressure >12 mmHg. Patients with left ventricular end diastolic pressure >12mmHg were older (median 32.9 versus 24.0 years, p = 0.02), more likely to have a history of an aortopulmonary shunt (62% versus 38%, p = 0.03), and have a diagnosis of hypertension (24% versus 7%, p = 0.03) compared to those with left ventricular end diastolic pressure ≤12 mmHg. There were no significant differences in mitral valve E/A ratio, annular e' velocity, or E/e' ratio between patients with left ventricular end diastolic pressure >12 versus ≤12 mmHg. Patients with left ventricular end diastolic pressure >12mmHg had larger left atrial area (mean 17.7 versus 14.0 cm2, p = 0.03) and larger left atrium anterior-posterior diameter (mean 36.0 versus 30.6 mm, p = 0.004). In conclusion, typical echocardiographic measures of left ventricular diastolic dysfunction may not be reliable in tetralogy of Fallot patients. Prospective studies with the use of novel echocardiographic measures are needed.

The Effect of Udenafil on Heart Rate and Blood Pressure in Adolescents With the Fontan Circulation.

The Fontan Udenafil Exercise Longitudinal (FUEL) trial showed that treatment with udenafil was associated with improved exercise performance at the ventilatory anaerobic threshold in children with Fontan physiology. However, it is not known how the initiation of phosphodiesterase 5 inhibitor therapy affects heart rate and blood pressure in this population. These data may help inform patient selection and monitoring after the initiation of udenafil therapy. The purpose of this study is to evaluate the effects of udenafil on vital signs in the cohort of patients enrolled in the FUEL trial. This international, multicenter, randomized, double-blind, placebo-controlled trial of udenafil included adolescents with single ventricle congenital heart disease who had undergone Fontan palliation. Changes in vital signs (heart rate [HR], systolic [SBP] and diastolic blood pressure [DBP]) were compared both to subject baseline and between the treatment and the placebo groups. Additional exploratory analyses were performed to evaluate changes in vital signs for prespecified subpopulations believed to be most sensitive to udenafil initiation. Baseline characteristics were similar between the treatment and placebo cohorts (n = 200 for each). The groups demonstrated a decrease in HR, SBP, and DBP 2 hours after drug/placebo administration, except SBP in the placebo group. There was an increase in SBP from baseline to after 6-min walk test in the treatment and placebo groups, and the treatment group showed an increase in HR (87.4 ± 15.0 to 93.1 ± 19.4 beats/min, p <0.01) after exercise. When comparing changes from baseline to the 26-week study visit, small decreases in both SBP (-1.9 ± 12.3 mm Hg, p = 0.03) and DBP (-3.0 ± 9.6 mm Hg, p <0.01) were seen in the treatment group. There were no clinically significant differences between treatment and placebo group in change in HR or blood pressure in the youngest age quartile, lightest weight quartile, or those on afterload-reducing agents. In conclusion, initiation of treatment with udenafil in patients with Fontan circulation was not associated with clinically significant changes in vital signs, implying that for patients similar to those enrolled in the FUEL trial, udenafil can be started without the requirement for additional monitoring after initial administration.

Exercise Pathophysiology and Testing in Individuals With a Fontan Circulation.

The Fontan circulation, a surgical palliation for single-ventricle congenital heart disease, profoundly impacts the cardiopulmonary response to exercise. Reliant on passive pulmonary blood flow, the Fontan circulation has limited capacity to augment cardiac output as necessary to supply working muscles during exercise. Cardiopulmonary exercise testing (CPET) objectively assesses cardiorespiratory fitness and provides insight into the etiology of exercise intolerance. Furthermore, CPET variables, such as peak oxygen consumption and submaximal variables, have prognostic value and may be used as meaningful endpoints in research studies. CPET is also useful in clinical research applications to assess the effect of pharmacologic or other interventions. Medical therapies to improve exercise tolerance in individuals with a Fontan circulation, such as pulmonary vasodilators, may modestly improve peak oxygen consumption. Exercise training focused on aerobic fitness and lower extremity strength may have a more consistent and larger impact on these measures of aerobic fitness. CPET is a valuable diagnostic and prognostic tool for those with a Fontan circulation. Newer ancillary assessments, such as noninvasive peripheral venous pressure monitoring and cardiac output measurements, hold promise to provide a more nuanced insight into the underlying pathophysiology.

La circulation de Fontan, une solution chirurgicale palliative aux cardiopathies congénitales univentriculaires, a de profondes répercussions sur la réponse cardiorespiratoire à l'exercice physique. Puisqu'elle repose sur un flux sanguin pulmonaire passif, la circulation de Fontan présente une capacité limitée à accroître le débit cardiaque au besoin pour assurer l'approvisionnement des muscles durant l'effort physique. L'épreuve d'effort cardiorespiratoire (EECR) permet de mesurer la capacité cardiorespiratoire de manière objective et de mieux comprendre les causes de l'intolérance à l'effort. En outre, les variables mesurées lors de l'EECR, comme la consommation maximale d'oxygène (VO2) et les variables sous-maximales, ont une valeur pronostique et pourraient constituer des critères d'évaluation pertinents dans les travaux de recherche.L'EECR possède également des applications utiles en recherche clinique pour évaluer les effets des interventions pharmacologiques ou d'autre nature. Les traitements médicaux qui visent à améliorer la tolérance à l'effort chez les personnes ayant une circulation de Fontan, comme les vasodilatateurs pulmonaires, pourraient entraîner une modeste augmentation de la valeur maximale de VO2. L'entraînement physique axé sur la capacité aérobique et sur la force des membres inférieurs pourrait avoir un effet plus constant et important sur ces mesures de la capacité aérobique. L'EECR est un précieux outil diagnostique et pronostique pour l'évaluation des patients ayant une circulation de Fontan. Des méthodes d'évaluation complémentaires plus récentes, comme la surveillance non invasive de la pression veineuse périphérique et les mesures du débit cardiaque, sont des avenues prometteuses vers une compréhension plus nuancée des mécanismes physiopathologiques sous-jacents.

Occult Diastolic Dysfunction and Adverse Clinical Outcomes in Adolescents and Young Adults With Fontan Circulation.

Background In Fontan circulation, diastolic dysfunction portends a worse clinical outcome but may be concealed during routine assessment. Invasive evaluation with rapid volume expansion (RVE) can identify patients with occult diastolic dysfunction (ODD). We sought to evaluate the association between ODD and adverse clinical outcomes at medium-term follow-up. Methods and Results We conducted a single-center observational study of patients with Fontan circulation who underwent clinical catheterization with RVE from 2012 to 2017. ODD was defined as post-RVE end-diastolic pressure ≥15 mm Hg. A composite adverse clinical outcome included mortality, cardiac transplant, ventricular assist device, plastic bronchitis, protein-losing enteropathy, arrhythmia, stroke/thrombus, or cardiac-related hospital admission. Proportional hazards regression was used to compare the ODD-positive and ODD-negative groups for risk of the composite adverse clinical outcome. Eighty-nine patients with Fontan circulation (47% female patients) were included at a median age of 14 years. ODD was identified in 31%. Fontan duration was longer in the ODD group (P=0.001). The composite adverse clinical outcome occurred more frequently in the ODD group (52 versus 26%, P=0.03) during a median follow-up duration of 2.9 years after catheterization. ODD (hazard ratio [HR], 2.68 [95% CI, 1.28-5.66]; P=0.02) and Fontan duration (HR, 1.07 [95% CI, 1.02-1.12]; P=0.003) were associated with the composite adverse clinical outcome. When stratified by Fontan duration, ODD remained significantly associated with the hazard of adverse clinical outcomes in patients with a Fontan duration ≥10 years (HR, 2.57 [95% CI, 1.03-6.57]; P=0.04). Conclusions Cardiac catheterization with rapid volume expansion reveals a significant incidence of ODD, which relates to Fontan duration. ODD is associated with an increased hazard of adverse clinical outcomes during medium-term follow-up, especially in patients with longer Fontan duration. ODD may portend a worse prognosis in Fontan circulation.

Single Center Experience With Durable Continuous Flow Single Ventricle Assist Device: A Viable Option in Fontan Circulatory Failure.

Ventricular assist devices are increasingly used for patients with single ventricle physiology. We describe the use of durable, continuous flow, single ventricular assist device (SVAD) therapy in Fontan circulatory failure patients. Retrospective, single-center review of patients with Fontan circulation implanted with a SVAD between 2017 and 2022. Patient characteristics and outcomes were obtained by chart review. Nine patients underwent SVAD implantation (median age 24 years). Most patients had a total cavopulmonary connection; one had an atriopulmonary Fontan. Five patients had a systemic right ventricle. SVAD was most often utilized as bridge to candidacy (67%). Eight patients had at least moderate systemic ventricular systolic dysfunction. SVAD support continued for a median of 65 days (longest duration, 1,105 days) and one patient remains on support at time of submission. Of five patients discharged home, median length of stay after SVAD was 24 days. Six patients were transplanted (median 96 days from SVAD). Two patients died from pretransplant multisystem organ failure before transplant. All transplanted patients remain alive (median time since transplant 593 days). Continuous flow SVAD therapy can be effective for patients with Fontan circulatory failure and systolic dysfunction. Further studies should investigate feasibility and optimal SVAD timing with more advanced Fontan associated end-organ dysfunction.