Mitochondrial dysfunction is associated with the severity of liver fibrosis in patients after the Fontan operation.

The gold standard for determining the severity of liver disease in Fontan patients is now liver biopsy. Since it is an invasive procedure, this study determined the possibility of applying mitochondrial function from isolated peripheral blood mononuclear cells (PBMCs) as a non-invasive indicator of liver fibrosis. Fontan patients (n = 37) without known liver disease were analysed cross-sectionally. Patients were classified according to their histology using the METAVIR score as follows; F0/F1-no/mild fibrosis; F2-moderate fibrosis; and F3/F4-cirrhosis. Peripheral blood mononuclear cells were assessed for mitochondrial activity and apoptosis. This study did not find any significant differences in cardiac function among the groups according to liver histology. Interestingly, our findings indicated a significant decrease in maximal respiration and spare respiratory capacity, in both the moderate (F2) and cirrhosis (F3/F4) groups compared with the group without significant fibrosis (F0/F1). Moreover, the cirrhosis group exhibited higher levels of apoptosis and lower levels of live cells, compared with both the moderate and no significant fibrosis groups. In conclusion, the degree of liver fibrosis in Fontan patients is strongly correlated with mitochondrial dysfunction in PBMCs. Mitochondrial function and apoptosis could potentially serve as novel markers for tracking the progression of liver fibrosis in these patients.

Achieving Consensus: Severity-Graded Definitions of Fontan-Associated Complications to Characterize Fontan Circulatory Failure.

BACKGROUND: Fontan physiology leads to chronic changes in other organ systems that may affect long-term survival and the success of heart transplantation. Inadequate assessment and treatment of the extra-cardiac effects of Fontan may contribute to poor outcomes. Severity-graded/ordinal consensus definitions of Fontan complications are lacking, which limits understanding of how Fontan-specific morbidity affects patients' outcomes. METHODS AND RESULTS: A panel of Fontan patient and physiology experts, including pediatric, adult congenital, heart failure, and critical-care cardiology as well as pediatric nephrology, hepatology and psychology, convened to develop definitions of Fontan complications. Definitions were created by using a severity-graded ordinal scale: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, disabling or life threatening. Following definition creation, a second panel of 21 experts in Fontan circulatory failure used a modified Delphi methodology to modify and vote on definitions until consensus (> 90% agreement without recommended further modification) was reached on final definitions. After 3 rounds of modifications and voting, consensus agreement was achieved on all Fontan-specific definitions. The defined complications and morbidities of Fontan include: anatomic Fontan pathway obstruction, cyanosis, systemic venous abnormalities resulting from venous insufficiency, atrial arrhythmia, ventricular arrhythmia, bradycardia, chronic pleural effusions, chronic ascites, protein-losing enteropathy, plastic bronchitis, hemoptysis and pulmonary hemorrhage, sleep apnea, Fontan-associated liver disease, portal and hepatic variceal disease, acute kidney injury affecting clinical treatment, polycythemia, thrombotic disease, recurrent or severe bacterial infection, skin atrophy, adrenal insufficiency, physical impact of previous stroke, mood/behavior disorder, and neurodevelopmental disorder. CONCLUSION: Consensus and severity-graded definitions of Fontan-specific cardiac and extra-cardiac complications were achieved and are available for use in research. They will allow future robust analyses of Fontan patient outcomes.

Durable ventricular assist device in adult patients with single ventricle: a systematic literature review.

The worldwide experience with mechanical circulatory support in adult patients with single ventricle and Fontan palliation is limited. We aimed to see the outcomes in such patients on durable left ventricular assist device. We systematically reviewed the English language literature found on PubMed and Google Scholar, searching the terms "Fontan," "single ventricle," "ventricular assist device," "LVAD," and "mechanical circulatory support," and selected all individual cases with reported outcomes. We identified 4 patients on pulsatile left ventricular assist device, all of whom were successfully bridged to transplant, and 15 patients on continuous flow LVAD, age 25.9 ± 5.8, predominantly males. Mean time on LVAD support was 718.6 ± 616.5 days, and only 2 patients (13.3%) died. Durable left ventricular assist device support in adult patients with Fontan provides excellent results and should be used more frequently.

Percutaneous pulmonary aspiration thrombectomy in an adolescent fontan patient using a large-bore system.

We describe the safe and effective percutaneous pulmonary thrombectomy in an 18-year-old female with a Fontan circulation using the FlowTriever® device (Inari Medical®, Irvine, US). Aspiration thrombectomy of both pulmonary arteries was performed using 24 and 16 F FlowTriever® catheters retrieving large amounts of thrombus material resulting in near total angiographic recanalization.

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

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

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.

Long-term incidence of arrhythmias in extracardiac conduit Fontan and comparison between systemic left and right ventricle.

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

Pacemaker-Related Factors and Outcomes of Fontan Patients　- Impact of Paced QRS Duration.

BACKGROUND: Permanent pacemaker (PPM) implantation has been identified as a risk factor for morbidity and mortality after Fontan operation. This study investigated the factors associated with outcomes in patients with Fontan physiology who underwent PPM implantation.Methods and Results: We retrospectively reviewed 508 patients who underwent Fontan surgery at Asan Medical Center between September 1992 and August 2022. Of these patients, 37 (7.3%) received PPM implantation. Five patients were excluded, leaving 32 patients, of whom 11 were categorized into the poor outcome group. Poor outcomes comprised death, heart transplantation, and "Fontan failure". Clinical, Fontan procedure-related, and PPM-related factors were compared between the poor and good outcome groups. Ventricular morphology, Fontan procedure-associated factors, pacing mode, high ventricular pacing rate, and time from first arrhythmia to PPM implantation did not differ significantly between the 2 groups. However, the poor outcome group exhibited a significantly longer mean paced QRS duration (P=0.044). Receiver operating characteristic curve analysis revealed a paced QRS duration cut-off value of 153 ms with an area under the curve of 0.73 (P=0.035). CONCLUSIONS: A longer paced QRS duration was associated with poor outcomes, indicating its potential to predict adverse outcomes among Fontan patients.

Importance of gamma-glutamyl transferase elevation in patients with Fontan-associated liver disease.

AIM: In patients with Fontan-associated liver disease (FALD), gamma-glutamyl transferase (GGT) levels are often elevated, however, its clinical importance is unclear. We investigated the relationship between the clinical course of FALD and GGT levels. METHODS: We enrolled 145 patients with FALD who underwent right-heart catheterization (RHC) and visited our department. Ursodeoxycholic acid (UDCA) was administered to 62 of the patients. Patients with GGT levels <50 and ≥50 U/L were compared. Follow-up RHC was undertaken in 76 patients. Cases in which GGT levels decreased by ≥10% or <50 U/L were defined as improved (n = 33). RESULTS: Patients with GGT levels ≥50 U/L had significantly lower levels of albumin and higher levels of alanine transaminase (ALT) but no significant differences in RHC factors. Over a 4.6-year period, 43.4% showed improvement in GGT levels. Improved cases had significantly lower total bilirubin (1.1 vs. 1.6 mg/dL), AST (22 vs. 28 U/L), and ALT (18 vs. 27 U/L) levels than nonimproved cases (n = 29, p < 0.05), and the change in platelet count (-0.5 vs. -3.0 × 10-4/µL) was significantly lower in the latter (p = 0.03). The improvement rate was significantly higher in UDCA-treated cases (55.2%) with GGT levels ≥50 U/L compared to cases not treated with UDCA (18.2%, p = 0.04). CONCLUSION: In cases of FALD with no improvement in GGT level, the platelet count decreased over time, suggesting progression of fibrosis. Physicians should be aware of the importance of a high GGT level in patients with FALD.

Ideal chest compression site for cardiopulmonary resuscitation in fontan circulation patients with dextrocardia.

BACKGROUND: We aimed to identify the ideal chest compression site for cardiopulmonary resuscitation (CPR) in patients with a single ventricle with dextrocardia corrected by Fontan surgery. METHODS: The most recent stored chest computed tomography images of all patients with a single ventricle who underwent Fontan surgery were retrospectively analysed. We reported that the ideal chest compression site is the largest part of the compressed single ventricle. To identify the ideal chest compression site, we measured the distance from the midline of the sternum to the point of the maximum sagittal area of the single ventricle as a deviation and calculated the area fraction of the compressed structures. RESULTS: 58 patients (67.2% male) were analysed. The mean right deviation from the midline of the sternum to the ideal compression site was similar to the mean sternum width (32.85 ± 15.61 vs. 31.05 ± 6.75 mm). When chest compression was performed at the ideal site, the area fraction of the single ventricle significantly increased by 7%, which was greater than that of conventional compression (0.15 ± 0.10 vs. 0.22 ± 0.11, P < 0.05). CONCLUSIONS: When performing CPR on a patient with Fontan circulation with dextrocardia, right-sided chest compression may be better than the conventional location.

Perioperative Characteristics and Outcomes of Fontan Versus Non-Fontan Patients Undergoing Combined Heart-Liver Transplantation: A Retrospective Cohort Study.

OBJECTIVES: Combined heart-liver transplantation (CHLT) is becoming increasingly frequent as a maturing population of patients with Fontan-palliated congenital heart disease develop advanced liver fibrosis or cirrhosis. The authors present their experience with CHLT for congenital and noncongenital indications, and identify characteristics associated with poor outcomes that may guide intervention in high-risk patients. DESIGN: This was a single-center retrospective cohort study. SETTING: This study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee. PARTICIPANTS: The study included 16 consecutive adult recipients of CHLT at the authors' institution between April 2017 and February 2022. INTERVENTIONS: Eleven patients underwent transplantation for Fontan indications, and 5 were transplanted for non-Fontan indications. MEASUREMENTS AND MAIN RESULTS: Compared with non-Fontan patients, Fontan recipients had longer cardiopulmonary bypass duration (199 v 119 minutes, p =m0.002), operative times (786 v 599 minutes, p = 0.01), and larger blood product transfusions (15.4 v 6.3 L, p = 0.18). Six of 16 patients required extracorporeal membrane oxygenation (ECMO), of whom 4 were Fontan patients who subsequently died. Patients who required ECMO had lower 5-hour lactate clearance (0.0 v 3.5 mmol/L, p = 0.001), higher number of vasoactive infusions, lower pulmonary artery pulsatility indices (0.58 v 1.77, p = 0.03), and higher peak inspiratory pressures (28.0 v 18.5 mmHg, p = 0.01) after liver reperfusion. CONCLUSIONS: Combined heart-liver transplantation in patients with Fontan-associated end-organ disease is particularly challenging and associated with higher recipient morbidity compared with non-Fontan-related CHLT. Early hemodynamic intervention for signs of ventricular dysfunction may improve outcomes in this growing high-risk population.

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

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

Vectorcardiography signs of a failing Fontan: Heart rate, PR interval, RtQRSvm, QRSvm and SPQRS-T angle as noninvasive markers of late Fontan complications and mortality.

BACKGROUND: Limited data exists on interpreting vectorcardiography (VCG) parameters in the Fontan population. OBJECTIVE: The purpose of this study was to demonstrate the associations between ECG/VCG parameters and Fontan failure (FF). METHODS/RESULTS: 107 patients with a Fontan operation after 1990 and without significant ventricular pacing were included. FF and Fontan survival (FS) groups were compared. The average follow-up after Fontan operation was 11.8 years ±7.1 years. 14 patients had FF (13.1%) which was defined as having protein-losing-enteropathy (1.9%), plastic bronchitis (2.8%), Fontan takedown (1.9%), heart transplant (5.6%), NYHA class III-IV (2.8%) or death (0.9%). A 12­lead ECG at last follow up or prior to FF was assessed for heart rate, PR interval, QRS duration, Qtc and left/right sided precordial measures (P-wave, QRS and T-wave vector magnitudes, spatial P-R and QRS-T angles). Transthoracic echocardiogram evaluated atrioventricular valve regurgitation and ventricular dysfunction at FF or last follow up. A cox multivariate regression analysis adjusted for LV dominance, ventricular dysfunction, HR, PR, QTc, Pvm, QRSvm, SPQRST-angle, RtPvm, RtQRSvm and RtTvm. Ventricular dysfunction, increased heart rate and prolonged PR interval were significantly associated to FF at the multivariate analysis. ROC analysis and Kaplan-meier analysis revealed an increased total mortality associated with a heart rate > 93 bpm, PR interval > 155 mv, QRSvm >1.91 mV, RtQRSvm >1.8 mV and SPQRST angle >92.3 mV with p values <0.001 to 0.018. CONCLUSION: We demonstrate the importance of ECG/VCG monitoring in the Fontan population and suggest specific indicators of late complications and mortality.

Use of a Postoperative Care Management Pathway Reduces the Incidence of Chylothorax Post-Fontan Palliation.

Pleural effusions and chylothorax are challenging morbidities post-Fontan palliation. We sought to evaluate the efficacy of our Fontan Care Pathway (FCP) in reducing the incidence of post-operative chylothorax and Time to Chest Tube Removal (TTCTR), and to determine risk factors associated with longer TTCTR. Between 2016 and 2022 our institutional approach to post-Fontan care fell into three categories: Group 1 (n = 36): no standardized approach; Group 2 (n = 30): a prophylactic chylothorax diet (fat content < 5%); Group 3 (n = 57): the FCP (a chylothorax diet, fluid restriction, supplemental O2 and aggressive diuresis). The incidence of chylothorax and TTCTR was compared between groups. Predictors of TTCTR were analyzed using linear regression modelling, adjusting for covariates. Chylothorax rate decreased in Group 3 compared to Groups 1 and 2 (9% vs. 28% and 33% respectively, p = 0.011), without alteration in TTCTR. Univariate factors associated with median TTCTR included chylothorax (+ 13.7 days, p = 0.001), additional procedures at time of Fontan (+ 2.4 days per procedure p = 0.017), Fontan revision or takedown (+ 11.7 days, p = 0.018) and minor/major complications (+ 5.1, p = 0.01 and + 15.8, p < 0.001, respectively). On multivariable analysis, chylothorax (+ 6.5 days, p = 0.005) and major complications (+ 15.8 days, p = 0.001) were associated with increased TTCTR. When chylothorax was excluded from multivariable analysis, the FCP showed a significant decrease in TTCTR (- 3.3 days, p = 0.034). A bundled therapy approach was associated with reduced laboratory confirmed chylothorax post-Fontan, whereas diet change alone was not. Additional studies in this area, with larger sample sizes are warranted.

Thrombocytopenia is Associated with Higher Fontan Pressure and Increased Morbidity in Patients with Fontan Circulation.

After the Fontan procedure, patients require lifelong follow-up due to significant late morbidity and mortality. Thrombocytopenia is seen frequently post-Fontan, likely due to secondary hypersplenism from elevated Fontan pressure. We investigated platelet counts in patients with a Fontan circulation and assessed associations with catheterization data and clinical outcomes. This retrospective study included 92 patients (33% female) post-Fontan who had a complete blood count performed between January 2011 and July 2023. The age at evaluation was 24.0 ± 8.9 years. Outcomes measured included elevated Fontan pressure (≥ 15 mmHg), Fontan-associated liver disease (FALD), unscheduled admissions, transplant, and death. Participants with thrombocytopenia (≤ 150,000/µL) had significantly higher rates of elevated Fontan pressure (OR 8.1, 95% CI 1.3-52.7, p = 0.03), FALD (OR 4.1, 95% CI 1.6-10.6, p = 0.004), and unscheduled admissions (362 ± 577 versus 115 ± 185 admissions per 1000 patient-years, p = 0.02). Thrombocytopenia post-Fontan is associated with elevated Fontan pressure, FALD, and increased morbidity. Platelet count could serve as a non-invasive factor in identifying patients at risk of decompensation.

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

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

"Fontan Conduit Stent-Angioplasty and Progression of Fontan-Associated Liver Disease".

Patients with Fontan circulation insidiously develop congestive hepatopathy related to chronically reduced cardiac output and central venous hypertension, also known as Fontan-associated liver disease (FALD). Fontan pathway obstruction is increasingly detected and may accelerate FALD. The impact of conduit stent angioplasty on FALD is unknown. Retrospective, single-center review of patients with Fontan circulation who underwent conduit stent angioplasty at cardiac catheterization over 5-year period. Demographics and cardiac histories were reviewed. Labs, liver ultrasound elastography, echocardiogram, hemodynamic and angiographic data at catheterization were recorded pre- and post-stent angioplasty. Primary outcome was change in hepatic function via MELD-XI scores and liver stiffness (kPa), with secondary outcomes of ventricular function, BNP, and repeat catheterization hemodynamics. 33 patients underwent Fontan conduit stent angioplasty, 19.3 ± 7.0 years from Fontan operation. Original conduit diameter was 19.1 ± 1.9 mm. Prior to angioplasty, conduit size was reduced to a cross-sectional area 132 (91, 173) mm2 and increased to 314 (255, 363) mm2 post-stent. Subjects' baseline median MELD-XI of 11 (9, 12) increased to 12 (9, 13) at 19 ± 15.5 months post-angioplasty (n = 22, p = 0.053). There was no significant change in liver stiffness at 12.1 ± 8.9 months post-angioplasty (n = 15, p = 0.13). Median total bilirubin significantly increased (1.4 [0.9, 1.8]), from baseline 1.1 [0.7, 1.5], p = 0.04), as did median BNP (41 [0, 148] from baseline 34 [15, 79]; p = 0.02). There were no significant changes in ventricular function or repeat invasive hemodynamics (n = 8 subjects). Mid-term follow-up of Fontan subjects post-conduit stent angioplasty did not show improvements in non-invasive markers of FALD.

Cardiac and Liver Fibrosis Assessed by Multiparametric MRI in Patients with Fontan Circulation.

The abnormal hemodynamics in Fontan circulation due to persistently increased systemic venous pressure results in hepatic venous congestion and Fontan-associated liver disease. Combined assessment of cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in this context have not been fully explored. To evaluate cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in patients who have undergone Fontan procedures. Thirty-eight patients and 23 controls underwent cardiac and liver MRI examinations in a 3.0-T scanner. Mann-Whitney, Fisher exact test, and Spearman's correlation were applied to evaluate myocardial volumes, function, native cardiac and liver T1 mapping, ECVs and liver stiffness. The mean native cardiac T1 value (p = 0.018), cardiac ECV (p < 0.001), liver native T1 (p < 0.001), liver ECV (p < 0.001), and liver stiffness (p < 0.001) were higher in patients than controls. The indexed end-diastolic volume (EDVi) correlated with the myocardial ECV (r = 0.356; p = 0.033), native liver T1 (r = 0.571; p < 0.001), and with liver stiffness (r = 0.391; p = 0.015). In addition, liver stiffness correlated with liver ECV (r = 0.361; p = 0.031) and native liver T1 (r = 0.458; p = 0.004). An association between cardiac remodeling and cardiac and liver fibrosis were found in this population. The usefulness of MRI to follow cardiac and liver involvement in these patients is critical to improve treatment strategies and to prevent the need for combined liver and heart transplantation.

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

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

Long-Term Renal Involvement in Association with Fontan Circulation.

Multiorgan dysfunction is a concern of Fontan patients. To clarify the pathophysiology of Fontan nephropathy, we characterize renal disease in the long-term observational study. Medical records of 128 consecutive Fontan patients [median age: 22 (range 15-37) years old] treated between 2009 and 2018 were reviewed to investigate the incidence of nephropathy and its association with other clinical variables. Thirty-seven patients (29%) showed proteinuria (n = 34) or < 90 mL/min/1.73 m2 of estimated glomerular filtration rate (eGFR) (n = 7), including 4 overlapping cases. Ninety-six patients (75%) had liver dysfunction (Forns index > 4.21). Patients with proteinuria received the Fontan procedure at an older age [78 (26-194) vs. 56 (8-292) months old, p = 0.02] and had a higher cardiac index [3.11 (1.49-6.35) vs. 2.71 (1.40-4.95) L/min/m2, p = 0.02], central venous pressure [12 (7-19) vs. 9 (5-19) mmHg, p < 0.001], and proportion with > 4.21 of Forns index (88% vs. 70%, p = 0.04) than those without proteinuria. The mean renal perfusion pressure was lower in patients with a reduced eGFR than those without it [55 (44-65) vs. 65 (45-102) mmHg, p = 0.03], but no other variables differed significantly. A multivariable analysis revealed that proteinuria was associated with an increased cardiac index (unit odds ratio 2.02, 95% confidence interval 1.12-3.65, p = 0.02). Seven patients with severe proteinuria had a lower oxygen saturation than those with no or mild proteinuria (p = 0.01, 0.03). Proteinuria or a decreased eGFR differentially occurred in approximately 30% of Fontan patients. Suboptimal Fontan circulation may contribute to the development of proteinuria and reduced eGFR.