Dynamic exercise changes in venous pressure and liver stiffness in Fontan patients: effects of Treprostinil.

BACKGROUND: Systemic venous hypertension and low cardiac output are believed to be important mediators of liver injury after the Fontan procedure. Pulmonary vasodilators have the potential to improve such haemodynamics. The aim of this study was to assess the acute effects of exercise on liver stiffness and venous pressures and to assess the impact of inhaled Treprostinil on this response. METHODS: In this prospective, double-blind, placebo-controlled, crossover trial, 14 patients with a Fontan circulation were randomised to inhalation of placebo and Treprostinil. Incremental and constant work rate exercise tests were performed to assess the effect of Treprostinil on exercise tolerance. Venous pressures were measured throughout and liver stiffness at rest and immediately after peak exercise. RESULTS: Mean age was 27.8 ± 7.9 years and 66% were females. Exercise acutely increased liver stiffness by 30% (mean shear wave speed: 2.38 ± 0.71 versus 2.89 ± 0.51 ms, p = 0.02). Peripheral venous pressures increased acutely during both incremental (12.1 ± 2.4 versus 22.6 ± 8.0 mmHg, p < 0.001) and constant work rate exercise (12.5 ± 2.5 versus 23.4 ± 5.2 mmHg, p < 0.001). Overall, Treprostinil failed to attenuate exercise-induced increases in liver stiffness. Compared with placebo, Treprostinil did not significantly impact venous pressure responses, VO2peak, nor exercise endurance times. CONCLUSIONS: Peripheral venous pressure increased acutely during exercise by an average of 88% above baseline and was not altered by administration of inhaled Treprostinil. Liver stiffness measured immediately post-exercise increased acutely by an average of 30%, with no attenuation following Treprostinil inhalation.

Ebstein's Anomaly of the Tricuspid Valve: an Overview of Pathology and Management.

PURPOSE OF REVIEW: Ebstein's anomaly (EA) is a rare, but complex form of congenital heart disease consisting of a right ventricular myopathy and morphologic tricuspid valve disease leading to a high incidence of right ventricular dysfunction and arrhythmias. This review offers an updated overview of the current understanding and management of patients with EA with a focus on the adult population. RECENT FINDINGS: Increased understanding of anatomic accessory atrioventricular pathways in EA has resulted in an improvement in ablation techniques and long-term freedom of atrial arrhythmia recurrence. Despite an improvement in understanding and recognition of EA, significant disease heterogeneity and complex treatment options continue to challenge providers, with the best outcomes achieved at expert congenital heart disease centers.

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.

Corrected coronary opacification decrease from coronary computed tomography angiography: Validation with quantitative 13N-ammonia positron emission tomography.

BACKGROUND: To assess the functional relevance of a coronary artery stenosis, corrected coronary opacification (CCO) decrease derived from coronary computed tomography angiography (CCTA) has been proposed. The present study aims at validating CCO decrease with quantitative 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI). METHODS AND RESULTS: This retrospective study consists of 39 patients who underwent hybrid CCTA/PET-MPI. From CCTA, attenuation in the coronary lumen was measured before and after a stenosis and corrected to the aorta to calculate CCO and its decrease. Relative flow reserve (RFR) was calculated by dividing the stress myocardial blood flow (MBF) of a vessel territory subtended by a stenotic coronary by the stress MBF of the reference territories without stenoses. RFR was abnormal in 11 vessel territories (27%). CCO decrease yielded a sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for prediction of an abnormal RFR of 73%, 70%, 88%, 47%, and 70%, respectively. CONCLUSIONS: CCTA-derived CCO decrease has moderate diagnostic accuracy to predict an abnormal RFR in PET-MPI. However, its high negative predictive value to rule out functional relevance of a given lesion may confer clinical implications in the diagnostic work-up of patients with a coronary stenosis.

Outcome in middle-aged individuals with anomalous origin of the coronary artery from the opposite sinus: a matched cohort study.

AIMS: Anomalous origin of a coronary artery from the opposite sinus (ACAOS) has been associated with adverse cardiac events in the young. It remains unknown whether this holds true for middle-aged patients with uncorrected ACAOS as well. We assessed the outcome in middle-aged patients with newly diagnosed ACAOS by coronary computed tomography angiography (CCTA) compared with a matched cohort. METHODS AND RESULTS: We retrospectively identified 68 consecutive patients with ACAOS documented by CCTA. ACAOS with a course of the anomalous vessel between the aorta and pulmonary artery were classified as interarterial course (IAC). Each patient with ACAOS was matched to two controls without ACAOS. Major adverse cardiac events (i.e. myocardial infarction, revascularization and cardiac death) were recorded for all patients and controls. Two (3%) patients were lost to follow-up. Thus, 66 patients with ACAOS were included in the final analysis and matched with 132 controls. Mean age of patients was 56 ± 11 years, 73% were male and the mean follow-up was 49 months. Forty (65%) patients were classified as having ACAOS with IAC. The annual event rate of ACAOS vs. controls was 4.9 and 4.8%, the hazard ratio (HR) 0.94 (0.39-2.28, P = 0.89). The annual event rate of ACAOS with IAC compared with their matched controls was 5.2 and 4.3%, and the HR 1.01 (95% CI 0.39-2.58, P = 0.99). CONCLUSIONS: In middle-aged individuals with newly diagnosed ACAOS mid-term outcome is not statistically different to a matched control cohort without coronary artery anomalies, regardless of whether ACAOS with or without IAC variants are present.

Long-term prognostic performance of low-dose coronary computed tomography angiography with prospective electrocardiogram triggering.

OBJECTIVES: To assess long-term prognosis after low-dose 64-slice coronary computed tomography angiography (CCTA) using prospective electrocardiogram-triggering. METHODS: We included 434 consecutive patients with suspected or known coronary artery disease referred for low-dose CCTA. Patients were classified as normal, with non-obstructive or obstructive lesions, or previously revascularized. Coronary artery calcium score (CACS) was assessed in 223 patients. Follow-up was obtained regarding major adverse cardiac events (MACE): cardiac death, myocardial infarction and elective revascularization. We performed Kaplan-Meier analysis and Cox regressions. RESULTS: Mean effective radiation dose was 1.7 ± 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non-obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty-nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 ± 0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non-obstructive lesions, 30% with obstructive stenosis and 39% of those revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but 4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression identified obstructive stenosis, lesion burden in CCTA and CACS as independent MACE predictors (P ≤ 0.001). CONCLUSION: Low-dose CCTA with prospective electrocardiogram-triggering has an excellent long-term prognostic performance with a warranty period >6 years for patients with normal coronary arteries. KEY POINTS: • Coronary CT angiography (CCTA) has an excellent long-term prognostic performance. • CCTA can accurately stratify cardiac risk according to coronary lesion severity. • A normal CCTA predicts freedom from cardiac events for >6 years. • Patients with a coronary calcium score of 0 may experience cardiac events. • CCTA allows for reclassification of cardiac risk compared with ESC SCORE.

Hybrid CCTA/SPECT myocardial perfusion imaging findings in patients with anomalous origin of coronary arteries from the opposite sinus and suspected concomitant coronary artery disease.

BACKGROUND: Anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS) are associated with adverse cardiac events. Discrimination between ACAOS and coronary artery disease (CAD)-related perfusion defects may be difficult. The aim of the present study was to investigate the value of hybrid coronary computed tomography angiography (CCTA)/SPECT-MPI in patients with ACAOS and possible concomitant CAD. METHODS: We retrospectively identified 46 patients (mean age 56 ± 12 years) with ACAOS revealed by CCTA who underwent additional SPECT-MPI. ACAOS with an interarterial course were classified as malignant, whereas all other variants were considered benign. CCTA/SPECT-MPI hybrid imaging findings (ischemia or scar) were analyzed according to the territory subtended by an anomalous vessel or a stenotic coronary artery. RESULTS: Twenty-six (57%) patients presented with malignant ACAOS. Myocardial ischemia or scar was found only in patients who had concomitant obstructive CAD in the vessel matching the perfusion defect as evidenced by hybrid CCTA/SPECT imaging. CONCLUSION: Hybrid CCTA/SPECT-MPI represents a valuable non-invasive tool to discriminate the impact of ACAOS from concomitant CAD on myocardial ischemia. Our results suggest that in a middle-aged population myocardial ischemia due to ACAOS per se may be exceedingly rare and is more likely attributable to concomitant CAD.

Adaptive Statistical Iterative Reconstruction-V: Impact on Image Quality in Ultralow-Dose Coronary Computed Tomography Angiography.

OBJECTIVE: The clinical utility of a latest generation iterative reconstruction algorithm (adaptive statistical iterative reconstruction [ASiR-V]) has yet to be elucidated for coronary computed tomography angiography (CCTA). This study evaluates the impact of ASiR-V on signal, noise and image quality in CCTA. METHODS: Sixty-five patients underwent clinically indicated CCTA on a 256-slice CT scanner using an ultralow-dose protocol. Data sets from each patient were reconstructed at 6 different levels of ASiR-V. Signal intensity was measured by placing a region of interest in the aortic root, LMA, and RCA. Similarly, noise was measured in the aortic root. Image quality was visually assessed by 2 readers. RESULTS: Median radiation dose was 0.49 mSv. Image noise decreased with increasing levels of ASiR-V resulting in a significant increase in signal-to-noise ratio in the RCA and LMA (P < 0.001). Correspondingly, image quality significantly increased with higher levels of ASiR-V (P < 0.001). CONCLUSIONS: ASiR-V yields substantial noise reduction and improved image quality enabling introduction of ultralow-dose CCTA.

MR-based attenuation correction for cardiac FDG PET on a hybrid PET/MRI scanner: comparison with standard CT attenuation correction.

PURPOSE: The aim of this study was to evaluate the feasibility of attenuation correction (AC) for cardiac (18)F-labelled fluorodeoxyglucose (FDG) positron emission tomography (PET) using MR-based attenuation maps. METHODS: We included 23 patients with no known cardiac history undergoing whole-body FDG PET/CT imaging for oncological indications on a PET/CT scanner using time-of-flight (TOF) and subsequent whole-body PET/MR imaging on an investigational hybrid PET/MRI scanner. Data sets from PET/MRI (with and without TOF) were reconstructed using MR AC and semi-quantitative segmental (20-segment model) myocardial tracer uptake (per cent of maximum) and compared to PET/CT which was reconstructed using CT AC and served as standard of reference. RESULTS: Excellent correlations were found for regional uptake values between PET/CT and PET/MRI with TOF (n = 460 segments in 23 patients; r = 0.913; p < 0.0001) with narrow Bland-Altman limits of agreement (-8.5 to +12.6 %). Correlation coefficients were slightly lower between PET/CT and PET/MRI without TOF (n = 460 segments in 23 patients; r = 0.851; p < 0.0001) with broader Bland-Altman limits of agreement (-12.5 to +15.0 %). PET/MRI with and without TOF showed minimal underestimation of tracer uptake (-2.08 and -1.29 %, respectively), compared to PET/CT. CONCLUSION: Relative myocardial FDG uptake obtained from MR-based attenuation corrected FDG PET is highly comparable to standard CT-based attenuation corrected FDG PET, suggesting interchangeability of both AC techniques.

Decreased clinical performance in TGA-ASO patients after RVOT interventions; a multicenter European collaboration.

BACKGROUND: In patients with transposition of the great arteries and an arterial switch operation (TGA-ASO) right ventricular outflow tract (RVOT) obstruction is a common complication requiring one or more RVOT interventions. OBJECTIVES: We aimed to assess cardiopulmonary exercise capacity and right ventricular function in patients stratified for type of RVOT intervention. METHODS: TGA-ASO patients (≥16 years) were stratified by type of RVOT intervention. The following outcome parameters were included: predicted (%) peak oxygen uptake (peak VO2), tricuspid annular plane systolic excursion (TAPSE), tricuspid Lateral Annular Systolic Velocity (TV S'), right ventricle (RV)-arterial coupling (defined as TAPSE/RV systolic pressure ratio), and N-terminal proBNP (NT-proBNP). RESULTS: 447 TGA patients with a mean age of 25.0 (interquartile range (IQR) 21-29) years were included. Patients without previous RVOT intervention (n = 338, 76%) had a significantly higher predicted peak VO2 (78.0 ± 17.4%) compared to patients with single approach catheter-based RVOT intervention (73.7 ± 12.7%), single approach surgical RVOT intervention (73.8 ± 28.1%), and patients with multiple approach RVOT intervention (66.2 ± 14.0%, p = 0.021). RV-arterial coupling was found to be significantly lower in patients with prior catheter-based and/or surgical RVOT intervention compared to patients without any RVOT intervention (p = 0.029). CONCLUSIONS: TGA patients after a successful arterial switch repair have a decreased exercise capacity. A considerable amount of TGA patients with either catheter or surgical RVOT intervention perform significantly worse compared to patients without RVOT interventions.

Intracardiac bone cement embolism resulting in ventricular perforation: an unusual cause of sudden chest pain.

Leakage of bone cement is a known complication after percutaneous kyphoplasty. In rare cases, bone cement can reach the venous system and cause life-threatening embolism. We present the case of a 73-year-old male, who was admitted to our hospital with new-onset chest pain and dyspnoea. He had a history of percutaneous kyphoplasty. Multimodal imaging showed intracardiac cement embolism in the right ventricle with penetration of the interventricular septum and perforation of the apex. The bone cement was successfully removed during open cardiac surgery.

Thromboprophylaxis in Patients With Fontan Circulation.

BACKGROUND: The optimal strategy for thromboprophylaxis in patients with a Fontan circulation is unknown. OBJECTIVES: The aim of this study was to compare the efficacy and safety of aspirin, warfarin, and nonvitamin K oral anticoagulants (NOACs) in a network meta-analysis. METHODS: Relevant studies published by February 2022 were included. The primary efficacy outcome was thromboembolic events; major bleeding was a secondary safety outcome. Frequentist network meta-analyses were conducted to estimate the incidence rate ratios (IRRs) of both outcomes. Ranking of treatments was performed based on probability (P) score. RESULTS: A total of 21 studies were included (26,546 patient-years). When compared with no thromboprophylaxis, NOAC (IRR: 0.11; 95% CI: 0.03-0.40), warfarin (IRR: 0.23; 95% CI: 0.14-0.37), and aspirin (IRR: 0.24; 95% CI: 0.15-0.39) were all associated with significantly lower rates of thromboembolic events. However, the network meta-analysis revealed no significant differences in the rates of major bleeding (NOAC: IRR: 1.45 [95% CI: 0.28-7.43]; warfarin: IRR: 1.38 [95% CI: 0.41-4.69]; and aspirin: IRR: 0.72 [95% CI: 0.20-2.58]). Rankings, which simultaneously analyze competing interventions, suggested that NOACs have the highest P score to prevent thromboembolic events (P score 0.921), followed by warfarin (P score 0.582), aspirin (P score 0.498), and no thromboprophylaxis (P score 0.001). Aspirin tended to have the most favorable overall profile. CONCLUSIONS: Aspirin, warfarin, and NOAC are associated with lower risk of thromboembolic events. Recognizing the limited number of patients and heterogeneity of studies using NOACs, the results support the safety and efficacy of NOACs in patients with a Fontan circulation.

Determinants of Advanced Liver Fibrosis in Adult Patients After Fontan Palliation: Usefulness of Ultrasound Transient Elastography.

BACKGROUND: Fontan-associated liver disease is an increasing concern. Our aim was to assess prevalence and predictors of advanced liver fibrosis with a specific focus on utility of liver stiffness measurement by ultrasound transient elastography. METHODS: A total of 97 adult Fontan patients (55% male, median age: 23.1 years, interquartile range [IQR]: 18.7-30.6); 92 (95%) were evaluated with transient elastography, and 50 (52%) underwent transjugular liver biopsy. Advanced liver fibrosis was defined as congestive hepatic fibrosis score 3 or 4. RESULTS: Only 4 patients (4%) had liver stiffness values < 10 kilopascal (kPa). Liver-stiffness measurements correlated weakly with peak oxygen uptake on exercise testing and Fontan pressure but not with Model for End-Stage Liver Disease excluding INR (MELD-XI) score or spleen size. Serial follow-up liver stiffness measurements in 73 clinically stable patients showed large variability among individual patients. Advanced liver fibrosis was present in 35 of 50 (70%) patients on liver biopsy and was associated to MELD-XI-Score ≥ 11 and splenomegaly but not to liver-stiffness measurements. Advanced liver fibrosis was not associated with patient age or time since Fontan operation but with younger age at completion of Fontan (3.7 years, IQR: 2.3-6.3 vs 6.8 years; IQR: 3.5-12.1; P = 0.037). CONCLUSIONS: In our cohort, advanced liver fibrosis was present in the majority of adult Fontan patients. Liver stiffness as measured by transient elastography was not associated with the degree of liver fibrosis. Because of its high variability on serial measurements, it seems not to be useful for clinical decision making. The unexpected finding that younger age at completion of Fontan was associated with advanced liver fibrosis merits further evaluation.

Effect of phosphodiesterase-5 inhibition on SystEmic Right VEntricular size and function. A multicentre, double-blind, randomized, placebo-controlled trial: SERVE.

AIMS: In adults with congenital heart disease and systemic right ventricles, progressive right ventricular systolic dysfunction is common and is associated with adverse outcomes. Our aim was to assess the impact of the phosphodiesterase-5-inhibitor tadalafil on right ventricular systolic function. METHODS AND RESULTS: This was a double-blind, randomized, placebo-controlled, multicentre superiority trial (NCT03049540) involving 100 adults with systemic right ventricles (33 women, mean age: 40.7 ± 10.7 years), comparing tadalafil 20 mg once daily versus placebo (1:1 ratio). The primary endpoint was the change in right ventricular end-systolic volume after 3 years of therapy. Secondary endpoints were changes in right ventricular ejection fraction, exercise capacity and N-terminal pro-B-type natriuretic peptide concentration. Primary endpoint assessment by intention to treat analysis at 3 years of follow-up was possible in 83 patients (42 patients in the tadalafil group and 41 patients in the placebo group). No significant changes over time in right ventricular end-systolic volumes were observed in the tadalafil and the placebo group, and no significant differences between treatment groups (3.4 ml, 95% confidence interval -4.3 to 11.0, p = 0.39). No significant changes over time were observed for the pre-specified secondary endpoints for the entire study population, without differences between the tadalafil and the placebo group. CONCLUSIONS: In this trial in adults with systemic right ventricles, right ventricular systolic function, exercise capacity and neuro-hormonal activation remained stable over a 3-year follow-up period. No significant treatment effect of tadalafil was observed. Further research is needed to find effective treatment for improvement of ventricular function in adults with systemic right ventricles.

Timing of Repair in Tetralogy of Fallot: Effects on Outcomes and Myocardial Health.

Early complete repair of tetralogy of Fallot (ToF) prior to 1 year of age has been demonstrated to be safe and has survival benefits over late repair. The age at repair of ToF affects long-term outcomes. This may largely be related to preserved, or comparatively better, myocardial health. Most studies advocate for an age of repair between 3 and 6 months and certainly below the age of 1 year. Patients with severe right ventricular outflow tract obstruction represent an exception to this rule and may require neonatal repair or surgical and catheter-based palliation before surgery. Older age at repair beyond the first birthday leads to unfavorable right ventricular remodeling with increased right ventricular stiffness and hypertrophy and is associated with increased long-term ventricular tachycardia and all-cause mortality. In this article, we review the short- and long-term benefits of early repair, with a focus on long-term morbidity. In conclusion, we emphasize the importance of myocardial health and the relationship to early repair and advocate for the use of magnetic resonance imaging in adult patients with repaired ToF to detect myocardial fibrosis.

Atrial function in the Fontan circulation: comparison with invasively assessed systemic ventricular filling pressure.

Abnormal atrial mechanics in biventricular circulations have been associated with elevated left heart filling pressures. Similar associations in the Fontan circulation are unknown. The aim of this study was to examine the relationship between atrial mechanics and invasively assessed hemodynamic parameters late after the Fontan operation. Thirty-nine Fontan patients with echocardiographic and invasive hemodynamic studies done within 48 h were included and were compared to 40 age-matched healthy controls. Atrial and ventricular strain measurements were measured offline using 2-dimensional speckle-tracking. Mean age was 10.2 ± 6.7 years and 24 (62%) were male. Atrial strain measures were lower in Fontan patients compared to healthy controls. There was no significant association between atrial strain measurements and Fontan systemic ventricular filling pressures (SVFP) as indicated by pulmonary artery occlusion pressures, direct left atrial pressure or systemic ventricular end-diastolic pressure. Global atrial strain was not correlated with segmental atrial strain in the pulmonary venous atrium. Global atrial reservoir strain was positively correlated with pulmonary vascular resistance (r = 0.508, p = 0.045). Global atrial conduit strain was positively correlated with E/A ratio of the AV valve inflow (r = 0.555, p = 0.002). Atrial and ventricular strain measurements were not significantly correlated. In patients with a Fontan, global atrial function is significantly depressed, and is uncoupled from segmental left lateral atrial function. Global as well as segmental atrial mechanics are not significantly associated with SVFPs in Fontan patients. Instead, global atrial reservoir function appears to parallel pulmonary vascular resistance.

Hepatic Steatosis in Patients With Single Ventricle and a Fontan Circulation.

Background Hepatic steatosis, caused by nonalcoholic fatty liver disease, is a leading cause of chronic liver disease. The interplay between hepatic steatosis and the development of liver disease following the Fontan procedure is not well understood. This study examined the prevalence and associations of hepatic steatosis in patients with a Fontan circulation. Methods and Results This was a single-center retrospective study of 95 patients with a Fontan circulation with liver magnetic resonance imaging performed between 2012 and 2019. The average age at magnetic resonance imaging was 21.5±8.5 years. The percent liver fat signal was determined using magnetic resonance chemical shift-encoded proton density fat fraction imaging. Hepatic steatosis was defined as liver fat ≥5% and was present in 10.5% of the cohort. The presence of hepatic steatosis was associated with higher body mass index (29±4 versus 24±6 kg/m2, P=0.006), a higher frequency of obesity (50% versus 12%, P=0.015), lower high-density lipoprotein cholesterol (35±9 versus 43±14 mg/dL, P=0.050), and greater subcutaneous fat thickness (2.6±0.7 versus 1.8±1.0 cm, P=0.043). There was no association between hepatic steatosis and cardiovascular imaging or hemodynamic variables from cardiac catheterization. Conclusions Risk factors for hepatic steatosis in patients with Fontan circulation include obesity and dyslipidemia, similar to what is seen in the general population. Fontan hemodynamics were not associated with hepatic steatosis.

Hepatocellular carcinoma and the Fontan circulation: Clinical presentation and outcomes.

BACKGROUND: Fontan-associated liver disease (FALD) is universal in patients with a Fontan circulation. Hepatocellular carcinoma (HCC) is one of its severe expressions, and, though rare, frequently fatal. The purpose of this study was to describe the clinical presentation, risk factors, and outcomes of HCC in patients with a Fontan circulation. METHODS: A multicenter case series of Fontan patients with a diagnosis of HCC formed the basis of this study. The case series was extended by published cases and case reports. Clinical presentation, tumor characteristics, laboratory and hemodynamic findings as well as treatment types and outcomes, were described. RESULTS: Fifty-four Fontan patients (50% female) with a diagnosis of HCC were included. Mean age at HCC diagnosis was 30 ± 9.4 years and mean duration from Fontan surgery to HCC diagnosis was 21.6 ± 7.4 years. Median HCC size at the time of diagnosis was 4 cm with a range of 1 to 22 cm. The tumor was located in the right hepatic lobe in 65% of the patients. Fifty-one percent had liver cirrhosis at the time of HCC diagnosis. Fifty percent of the patients had no symptoms related to HCC and alpha-fetoprotein was normal in 26% of the cases. Twenty-six patients (48%) died during a median follow-up duration of 10.6 (range 1-50) months. CONCLUSIONS: HCC in Fontan patients occurs at a young age with a 1-year survival rate of only 50%. Meticulous liver surveillance is crucial to detect small tumors in the early stage.

Abdominal Skeletal Muscle Index as a Potential Novel Biomarker in Adult Fontan Patients.

BACKGROUND: Fontan palliation results in a chronic multisystem disorder with diminished exercise capacity and increased risk of muscle wasting. The aims of this study were to assess the feasibility of skeletal muscle mass measurements in Fontan patients undergoing magnetic resonance imaging liver surveillance to compare muscle mass with a historic control and to assess its correlation with cardiorespiratory fitness. METHODS: Skeletal muscle area (SMA) and skeletal muscle index (SMI) were measured at T12 and L3. A young, healthy historic cohort was used as a comparison group. RESULTS: Forty patients with a Fontan circulation (mean age, 25.5 ± 7.9 years; 50% were men) were included. Measurements of SMA and SMI were feasible and highly reproducible. Mean SMA and SMI were significantly lower in women compared with men at both T12 (SMA: 25.1 ± 4.9 cm2 vs 33.5 ± 8.4 cm2, P < 0.001; SMI: 9.7 ± 2.1 cm2/m2 vs 11.3 ± 2.7 cm2/m2, P = 0.045) and L3 (SMA: 121 ± 12 cm2 vs 162 ± 24 cm2, P < 0.001; SMI: 46.9 ± 7.0 cm2/m2 vs 54.5 ± 7.4 cm2/m2, P = 0.002). Mean SMI at L3 was significantly lower in the male Fontan population compared with the healthy historic cohort (54.5 ± 7.4 cm2/m2 vs 60.9 ± 7.8 cm2/m2, P < 0.001), but was similar for women (46.9 ± 7.0 cm2/m2 vs 47.5 ± 6.6 cm2/m2, P = 0.692). SMI at L3, but not at T12, was positively correlated with peak oxygen consumption, oxygen pulse, and workload. Four patients (10%) met criteria for muscle wasting in the sarcopenic range based on L3 measurements. CONCLUSIONS: Abdominal skeletal muscle mass can be reproducibly determined on surveillance liver magnetic resonance imaging scans. Muscle wasting appears to occur commonly in Fontan patients. Further research is needed to better define the value of SMI as a biomarker in the Fontan population.

CONTEXTE: L'intervention palliative de Fontan engendre une atteinte multiviscérale chronique, notamment une diminution de la capacité à l'effort et une hausse du risque d'atrophie musculaire. L'étude visait à évaluer la possibilité de mesurer la masse musculaire squelettique des patients ayant subi une intervention de Fontan et faisant l'objet d'une surveillance du foie par imagerie par résonance magnétique, afin de comparer les résultats à ceux d'une cohorte historique témoin et d'en évaluer la corrélation avec la capacité cardiorespiratoire. MÉTHODOLOGIE: La surface musculaire squelettique (SMS) et l'indice musculaire squelettique (IMS) ont été mesurés en T12 et en L3. Une cohorte historique de sujets jeunes et en santé a servi de groupe témoin. RÉSULTATS: Quarante patients ayant subi une intervention de Fontan (âge moyen, 25,5 ± 7,9 ans; 50 % des sujets étaient de sexe masculin) ont été admis dans l'étude. Il a été possible d'obtenir des mesures de la SMS et de l'IMS hautement reproductibles. Les valeurs moyennes de la SMS et de l'IMS étaient significativement plus faibles chez les femmes que chez les hommes, tant en T12 (SMS : 25,1 ± 4,9 cm2 vs 33,5 ± 8,4 cm2, p < 0,001; IMS : 9,7 ± 2,1 cm2/m2 vs 11,3 ± 2,7 cm2/m2, p = 0,045) qu'en L3 (SMS : 121 ± 12 cm2 vs 162 ± 24 cm2, p < 0,001; IMS : 46,9 ± 7,0 cm2/m2 vs 54,5 ± 7,4 cm2/m2, p = 0,002). L'IMS moyen en L3 était significativement plus bas chez les hommes ayant subi une intervention de Fontan que chez ceux de la cohorte historique de témoins en santé (54,5 ± 7,4 cm2/m2 vs 60,9 ± 7,8 cm2/m2, p < 0,001), mais comparable chez les femmes (46,9 ± 7,0 cm2/m2 vs 47,5 ± 6,6 cm2/m2, p = 0,692). L'IMS mesuré en L3 était corrélé positivement avec la consommation maximale d'oxygène, le pouls d'oxygène et la charge d'effort, ce qui n'était pas le cas de l'IMS mesuré en T12. Selon les mesures effectuées en L3, quatre patients (10 %) répondaient aux critères d'atrophie musculaire de la sarcopénie. CONCLUSIONS: La masse musculaire squelettique abdominale peut être déterminée de façon reproductible à partir des clichés d'imagerie par résonance magnétique obtenus aux fins de la surveillance du foie. Il semble que les patients ayant subi une intervention de Fontan présentent fréquemment une atrophie musculaire. Des recherches plus poussées s'imposent afin de mieux définir l'utilité de l'IMS comme biomarqueur au sein de la population des patients ayant subi une intervention de Fontan.