Right Atrial Enlargement on Electrocardiogram in Previously Healthy Young Patients.

OBJECTIVES: To assess whether right atrial enlargement (RAE) on electrocardiogram (ECG) correlates with true RAE on echocardiogram in previously healthy young patients and to understand which patients with RAE on ECG may warrant additional testing. STUDY DESIGN: A single-center, retrospective review of previously healthy young patients with (1) ECGs that were read as RAE by a pediatric cardiologist and (2) echocardiograms obtained within 90 days of the ECG. ECGs were reviewed to confirm RAE and determine which leads met criteria. The echocardiograms were then reviewed and RA measurements with z scores obtained. A z score >2 was considered positive for RAE on echocardiogram. RESULTS: In total, 162 patients with median age 10.8 years were included in the study. A total of 23 patients had true RAE on echocardiogram, giving a positive predictive value (PPV) of 14%. In patients <1 year of age, the PPV increased to 35%. In patients older than 1 year, the PPV was low at 7%. Patients with true RAE were more likely to meet criteria for RAE in the anterior precordial leads (V1-V3) (48% vs 5%, P < .001) and meet criteria for right ventricular hypertrophy (22% vs 6%, P = .023). CONCLUSION: Our findings show that RAE on ECG has a low PPV for RAE on echocardiogram in previously healthy young patients. The highest yield for RAE on echocardiogram was observed in patients who were <1 year of age, had RAE in the anterior precordial leads, or displayed right ventricular hypertrophy on ECG.

From Other Journals: A Review of Recent Articles by Our Editorial Team.

In this review we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our hope is to provide a summary of the latest articles published recently in other journals in our field. The articles address: 1- The use of AI in fetal echocardiography, 2- The role of Apixaban in thromboembolism prevention in pediatric congenital heart disease, 3- Cardiovascular events in childhood cancer survivors, and lastly 4- the new consensus statement on cardiac catheterization for pediatrics and adults with congenital heart disease.

From Other Journals: A Review of Recent Articles by Our Editorial Team.

In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our hope is to provide a summary of the latest articles published recently in other journals in our field. The articles address (1) A new index for prenatal diagnosis of total anomalous pulmonary venous return, (2) Outcomes of patients with Tetralogy of Fallot after pulmonary valve replacement (PVR), and (3) Short-term outcomes of the self expanding Harmony valve for transcatheter PVR.

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.

Assessing Left Ventricular Pathology in Patients with Ebstein Anomaly Using Cardiovascular Magnetic Resonance: Looking Past the Right Heart.

Ebstein Anomaly (EA) is a malformation of the right heart, but there is data to suggest that the left ventricle (LV) can suffer from intrinsic structural and functional abnormalities which affect surgical outcomes. The LV in patients with EA is hypertrabeculated with abnormalities in LV function and strain. In this retrospective single-center study, patients with EA who underwent pre-operative cardiac MRI (CMR) between the periods of 2014-2024 were included along with a group of healthy-age-matched controls. Left ventricular and right ventricular volume, function and strain analyses were performed on standard SSFP imaging. LV noncompacted: compacted (NC/C) ratio and the displacement index of the tricuspid valve were measured. Forty-seven EA patients were included with mean age of 21.0 ± 17.6 years. Seventeen EA patients (36%) had mild pre-operative LV dysfunction on CMR and 1 (2.1%) had moderate LV dysfunction. Out of these 18 patients with LV dysfunction, only 2 were detected to have dysfunction on Echocardiogram. The global circumferential and longitudinal strain were significantly lower in the reduced LVEF group compared to those with preserved LVEF (- 14.8% vs. - 17%, p = 0.02 and - 11.9% vs. - 15.0%; p = 0.05; respectively) on CMR. A single EA patient met criteria for LVNC with a maximal NC/C ratio > 2.3. There was no statistically significant difference in NC/C ratio in the EA population (1.4 ± 0.6) vs. controls (1.1 ± 0.2), p = 0.17. There was an inverse correlation of LV ejection fraction with right ventricular end-diastolic volume and displacement index. All patients underwent the Da Silva Cone procedure at our center. Patients with preoperative LV dysfunction had longer duration of epinephrine use in the immediate postoperative period (33.7 ± 21.4 vs 10.2 ± 25.6 h, p = 0.02) and longer length of hospital stay (6.3 ± 3.2 vs 4.4 ± 1.2 days, p = 0.01). This is the largest study to date to evaluate preoperative LV structure and function in EA patients by CMR. In this cohort of 47 patients, preoperative LV dysfunction is fairly common and CMR has high sensitivity in detecting LV dysfunction as compared to Echo. True LV non-compaction was rare in this cohort. The presence of LV dysfunction is relevant to perioperative management and further study with larger cohorts and longer follow up are necessary.

Augmented Biphasic Breathing Using Sniff and an Oral Positive Expiratory Pressure Device (Sniff-PEP) in Fontan Patients.

The use of an oral positive expiratory pressure device (oPEP) with sniff breathing (Sniff-PEP) mimics biphasic ventilation. Biphasic ventilation increases pulmonary blood flow and cardiac output in Fontan patients. The aim of this study was to assess the effect of Sniff-PEP on Fontan flow velocities. A single-center, pilot, prospective study was carried out in 15 subjects with Fontan circulation enrolled to use the oPEP device for 1 month. Subjects were instructed on Sniff-PEP and to use the device for 10-15 min 3-4 times a day. Measurements of flow velocity and cardiac output were measured via echocardiogram and quality of life assessments were performed at baseline and 4-6 weeks later. The mean age at enrollment was 19.9 ± 8.7 years (age range of 10-37 years). 7 patients (47%) had dominant left ventricle and 8 (53%) had an open fenestration. There was a statistically significant increase in flow velocities in the hepatic vein from 27.5 ± 7.6 to 35.1 ± 11.3 cm/s (p = 0.003), left pulmonary artery from 51.6 ± 16.6 to 57.6 ± 21.1 cm/s (p = 0.01), and right pulmonary artery from 43.1 ± 14.2 to 45.8 ± 17.2 cm/s (p = 0.04). With chronic use, the mean fenestration gradient slightly decreased from 4.5 ± 1.6 to 4.1 ± 1.9 mmHg but the difference was not statistically significant (p = 0.14). oPEP device therapy increased flow velocity in several areas in the Fontan circulation with acute use. Further studies are needed to assess the effects long term.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT03251742.

Prenatal Predictors for Pulmonary Balloon Valvuloplasty in the Newborn.

Pulmonary balloon valvuloplasty (PBV) is the treatment of choice for subjects with isolated pulmonary valve stenosis (IPS). The purpose of this study was to define fetal echocardiographic features associated with an inpatient PBV prior to newborn hospital discharge and characterize resource utilization of IPS fetuses among participating centers. Six center, retrospective case series of singleton fetuses identified between 2010 and 2020 with IPS. Third-trimester echocardiogram data was compared with postnatal data, included pulmonary valve Doppler velocities, pulmonary valve insufficiency and ductus arteriosus flow direction. Comparison between subjects who underwent inpatient PBV during their newborn hospital admission versus those infants referred for outpatient PBV after initial hospital discharge. We analyzed data by logistic regression, student t test and Chi-Square testing with a p value of ≤ 0.05 considered statistically significant. Forty-nine IPS fetuses were identified. Thirty-eight (78%) underwent inpatient PBV at 5 (range 1-58) days and 11 (22%) underwent outpatient PBV at 51.8 (11-174) days. Newborns requiring an inpatient PBV were more likely to have one or more characteristics on 3rd-trimester fetal echocardiogram: left to right or bidirectional ductus arteriosus flow (61% vs 0%), and/or a peak pulmonary valve velocity > 3.0 m/s (odds ratio 16.9, 95% confidence interval 3.02-94.17) with a sensitivity of 90.4% and specificity of 97.7%. Ductus arteriosus flow direction and pulmonary valve peak velocity in the 3rd trimester can successfully predict the need for newborn inpatient PBV. We speculate these findings may be useful in choosing delivery site for the pregnancy complicated by fetal IPS.

Large Right Atrial Size on Cardiac MRI is Associated with Post-operative Right Ventricular Dysfunction After the Cone Operation for Ebstein Anomaly.

The cone operation has revolutionized care for patients with Ebstein anomaly; however, acute post-operative right ventricular dysfunction (RVD) is common in this patient population. A single-center, retrospective review of 28 patients with Ebstein anomaly who underwent cardiac MRI (CMR) prior to cone reconstruction of the tricuspid valve was conducted. Measurements of atrial and ventricular size/function were assessed. Post-operative RVD was defined as the presence of moderate or severe systolic dysfunction on discharge echo. A two-tail t test was employed to compare the two groups. The average age at operation was 21.4 years (range 1.6-57.8) and 14 (50%) had RVD at discharge. Patients with post-operative RVD had significantly larger pre-operative right atrial (RA) maximum volume (p = 0.016) and RA minimum volume (p = 0.030). Patients with RVD had smaller pre-operative left atrial (LA) minimum volume (p = 0.012). Larger pre-operative right ventricular (RV) end-systolic volume (p = 0.046), lower RV ejection fraction (0.029), and smaller left ventricular (LV) end-diastolic volume (p = 0.049) were significantly associated with post-operative RVD. Post-operative RVD was associated with longer milrinone duration (p = 0.009) and higher maximum milrinone dose (p = 0.005) but was not associated with intensive care or hospital length of stay (p = 0.19 and 0.67, respectively). Increased RA and RV dilation and decreased LA and LV volumes are associated with the development of post-operative RVD following cone operation for Ebstein anomaly. Post-operative RVD affects milrinone dose and duration but is not associated with increased length of stay.

Arrhythmia Variant Associations and Reclassifications in the eMERGE-III Sequencing Study.

BACKGROUND: Sequencing Mendelian arrhythmia genes in individuals without an indication for arrhythmia genetic testing can identify carriers of pathogenic or likely pathogenic (P/LP) variants. However, the extent to which these variants are associated with clinically meaningful phenotypes before or after return of variant results is unclear. In addition, the majority of discovered variants are currently classified as variants of uncertain significance, limiting clinical actionability. METHODS: The eMERGE-III study (Electronic Medical Records and Genomics Phase III) is a multicenter prospective cohort that included 21 846 participants without previous indication for cardiac genetic testing. Participants were sequenced for 109 Mendelian disease genes, including 10 linked to arrhythmia syndromes. Variant carriers were assessed with electronic health record-derived phenotypes and follow-up clinical examination. Selected variants of uncertain significance (n=50) were characterized in vitro with automated electrophysiology experiments in HEK293 cells. RESULTS: As previously reported, 3.0% of participants had P/LP variants in the 109 genes. Herein, we report 120 participants (0.6%) with P/LP arrhythmia variants. Compared with noncarriers, arrhythmia P/LP carriers had a significantly higher burden of arrhythmia phenotypes in their electronic health records. Fifty-four participants had variant results returned. Nineteen of these 54 participants had inherited arrhythmia syndrome diagnoses (primarily long-QT syndrome), and 12 of these 19 diagnoses were made only after variant results were returned (0.05%). After in vitro functional evaluation of 50 variants of uncertain significance, we reclassified 11 variants: 3 to likely benign and 8 to P/LP. CONCLUSIONS: Genome sequencing in a large population without indication for arrhythmia genetic testing identified phenotype-positive carriers of variants in congenital arrhythmia syndrome disease genes. As the genomes of large numbers of people are sequenced, the disease risk from rare variants in arrhythmia genes can be assessed by integrating genomic screening, electronic health record phenotypes, and in vitro functional studies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier; NCT03394859.

Association of Childhood Blood Pressure with Left Atrial Size and Function: Study of High Blood Pressure in Pediatrics-Adult Hypertension in Youth (SHIP AHOY).

OBJECTIVE(S): To evaluate the cross-sectional association of cardiovascular disease risk factors with left atrial (LA) size and function among healthy youth, aged 11-18 years, with a wide range of blood pressures (BPs). STUDY DESIGN: Echocardiographic images of youth enrolled in the Study of High Blood Pressure in Pediatrics: Adult Hypertension Onset in Youth study were analyzed for LA measurements. The association of casual BP, ambulatory BP, and other cardiovascular disease risk factors with LA size and function were determined using descriptive statistics and multivariable regression. Regression models adjusting for age, sex, race, and body mass index z score determined the independent association between ambulatory systolic BP indices (mean systolic BP/50th %ile systolic BP) and BP phenotypes with LA outcomes while exploratory analyses investigated for additional predictors of LA outcomes. RESULTS: The study population consisted of 347 youth: median age 15.7 years, 60% male and 40% non-White. Greater-risk casual systolic BP groups had worse cardiometabolic profiles but no differences in LA size and function. Each 0.1 increase in ambulatory systolic BP day or night index was associated with a 9.9 mL/m2 increase in LA volume/body surface area (LAV/BSA; 95th% CI 2.8-17.0, P = .006) and a 6.8 mL/m2 increase in LAV/BSA (95th% CI 0.8-12.8, P = .03), respectively. Ambulatory hypertension was associated with greater odds of abnormal LAV/BSA, defined as >75th %ile (2014 ambulatory BP monitoring criteria: OR 3.2 [95th% CI 1.4-7.2; P = .002]; 2022 ambulatory BP monitoring criteria: OR 2.1 [95th% CI 1.0-4.1; P = .008]). CONCLUSIONS: Increasing ambulatory systolic BP and ambulatory hypertension are independently associated with LAV/BSA.

Long-Term outcomes in adult patients with congenital heart disease considered for transplantation: A single center study.

BACKGROUND: Adult congenital heart disease (ACHD) patients pose unique challenges in identifying the time for transplantation and factors influencing outcomes. OBJECTIVE: To identify hemodynamic, functional, and laboratory parameters that correlate with 1- and 10-year outcomes in ACHD patients considered for transplantation. METHODS: A retrospective chart review of long-term outcomes in adult patients with congenital heart disease (CHD) evaluated for heart or heart + additional organ transplant between 2004 and 2014 at our center was performed. A machine learning decision tree model was used to evaluate multiple clinical parameters correlating with 1- and 10-year survival. RESULTS: We identified 58 patients meeting criteria. D-transposition of the great arteries (D-TGA) with atrial switch operation (20.7%), tetralogy of Fallot/pulmonary atresia (15.5%), and tricuspid atresia (13.8%) were the most common diagnosis for transplant. Single ventricle patients were most likely to be listed for transplantation (39.8% of evaluated patients). Among a comprehensive list of clinical factors, invasive hemodynamic parameters (pulmonary capillary wedge pressure (PCWP), systemic vascular pressure (SVP), and end diastolic pressures (EDP) most correlated with 1- and 10-year outcomes. Transplanted patients with SVP < 14 and non- transplanted patients with PCWP < 15 had 100% survival 1-year post-transplantation. CONCLUSION: For the first time, our study identifies that hemodynamic parameters most strongly correlate with 1- and 10-year outcomes in ACHD patients considered for transplantation, using a data-driven machine learning model.

From Other Journals: A Review of Recent Articles by Our Editorial Team.

This review is meant to highlight recent publications from other journals that are relevant to pediatric cardiologists. The articles chosen for this edition look at the outcomes of catheter-based interventions for aortic stenosis, the effect of atherosclerotic cardiovascular disease risk factors on the adult congenital heart disease population, the difference in mortality from congenital heart disease between rural and urban America, preoperative NT-proBNP as a predictor of Fontan outcomes, and an overview of the utilization and outcomes of the Rastelli, Nikaidoh, and REV procedures.

Persistent Patent Vertical Vein After Repair of Total Anomalous Pulmonary Venous Connection (TAPVR): A Rare Cause of Hypoxemia Post-Fontan Procedure.

Vertical vein (VV) ligation during total anomalous pulmonary venous return (TAPVR) repair is controversial. While some surgeons prefer ligation of the VV to prevent adverse sequelae of shunting across it and to promote flow through the newly created anastomosis, others leave it to serve as a "pop off valve" to the left heart structures, which are believed to be hypoplastic and noncompliant, presumably contributing to a more favorable post-operative outcome. We report two patients post-Fontan procedure, who underwent cardiac catheterization to explore the etiology of hypoxia and were found to have a persistent VV responsible for right to left shunting. Both patients underwent closure of the VV with improvement in the cyanosis and clinical course. These cases provide evidence supporting surgical ligation of the VV at the time of TAPVR repair, especially in patients with single ventricle.

Abnormal Global Longitudinal Strain During Anthracycline Treatment Predicts Future Cardiotoxicity in Children.

Global longitudinal strain (GLS) is a sensitive predictor of cardiotoxicity in adults with cancer. However, the significance of abnormal GLS during childhood cancer treatment is less well-understood. The objective was to evaluate the use of GLS for predicting later cardiac dysfunction in pediatric cancer survivors exposed to high-dose anthracyclines. This was a retrospective study of pediatric patients exposed to a doxorubicin isotoxic equivalent dose of ≥ 225 mg/m2. Transthoracic echocardiograms (TTE) were obtained prior to chemotherapy (T1), during anthracycline therapy (T2), and following completion of therapy (T3). Cardiotoxicity was defined as meeting at least one of the following criteria after anthracycline therapy: a decrease in left ventricle ejection fraction (LVEF) by 10% from baseline to a value < 55%, fractional shortening < 28%, or a decrease in GLS by ≥ 15% from baseline. Nineteen of 57 (33%) patients met criteria for cardiotoxicity at T3. Cardiotoxicity was associated with a lower LVEF at T2 (p = 0.0003) and a decrease in GLS by ≥ 15% at T2 compared to baseline (p = < 0.0001). ROC analysis revealed that the best predictor of cardiotoxicity at T3 was the percent change in GLS at T2 compared to baseline (AUC 0.87). A subgroup analysis revealed that a decrease in GLS by ≥ 15% from baseline at 0-6 months from completion of anthracycline therapy was associated with cardiotoxicity > 1-year post-treatment (p = 0.017). A decline in GLS during chemotherapy was the best predictor of cardiotoxicity post-treatment. GLS serves as an important marker of cardiac function in pediatric patients undergoing treatment with anthracyclines.

From Other Journals: A Review of Recent Articles by Our Editorial Team.

In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. This review includes (1) Fetal diagnosis, associated anomalies, and factors affecting outcomes in fetal congenitally corrected transposition of the great arteries (ccTGA), (2) The impact of Fontan-associated liver disease on heart and heart/liver transplant, (3) 1-year outcomes of the Harmony transcatheter pulmonary valve, (4) Risk factors associated with major adverse cardiac events in patients with pulmonary atresia and intact ventricular septum undergoing intervention, and (5) Benefits of pulmonary valve replacement in tetralogy of Fallot patients.

Association Between Seasonal Fontan Timing, Viral Infection Burden, and Post-Operative Length of Stay.

The Fontan procedure (FP) is typically a semi-elective surgery performed between 2 and 5 years of age to complete staged single ventricle palliation. Optimal timing for the FP, particularly in relation to seasonal infectious burden, remains unclear. We queried the Pediatric Health Information System (PHIS) database for all admissions for viral respiratory infections (VRI) from January 2006 to September 2015 and separately for all admissions with a primary procedure code of FP. The PHIS query generated 2,767,142 admissions for VRI and 6349 admissions for the FP from 45 children's hospitals. Of all FP, 2124 (33.5%) were performed from October through March. The median length of stay after Fontan procedure was 9 days (IQR 7-15). Median length of stay after FP was correlated with VRI burden (correlation coefficient = 0.3, p = 0.03). April through August (weeks 18 through 35) had the lowest VRI admission burden and FP length of stay was significantly shorter during this time (13.6 ± 14.8 days vs 14.9 ± 20.3 days, p = 0.03). The FP is frequently performed during the viral respiratory season. This timing is associated with an increased post-operative length of stay after the FP. For elective FP, ideal timing that avoids the viral respiratory season and minimizes post-operative LOS is April through August.

Longitudinal Assessment of Cardiac Function Following Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Multisystem inflammatory syndrome in children (MIS-C) after COVID-19 is commonly associated with cardiac involvement. Studies found myocardial dysfunction, as measured by decreased ejection fraction and abnormal strain, to be common early in illness. However, there is limited data on longitudinal cardiac outcomes. We aim to describe the evolution of cardiac findings in pediatric MIS-C from acute illness through at least 2-month follow-up. A retrospective single-center review of 36 patients admitted with MIS-C from April 2020 through September 2021 was performed. Echocardiographic data including cardiac function and global longitudinal strain (GLS) were analyzed at initial presentation, discharge, 2-4-week follow-up, and at least 2-month follow-up. Patients with mild and severe disease, normal and abnormal left ventricular ejection fraction (LVEF), and normal and abnormal GLS at presentation were compared. On presentation, 42% of patients with MIS-C had decreased LVEF < 55%. In patients in whom GLS was obtained (N = 18), 44% were abnormal (GLS < |- 18|%). Of patients with normal LVEF, 22% had abnormal GLS. There were no significant differences in troponin or brain natriuretic peptide between those with normal and abnormal LVEF. In most MIS-C patients with initial LVEF < 55% (90%), LVEF normalized upon discharge. At 2-month follow-up, all patients had normal LVEF with 21% having persistently abnormal GLS. Myocardial systolic dysfunction and abnormal deformation were common findings in MIS-C at presentation. While EF often normalized by 2 months, persistently abnormal GLS was more common, suggesting ongoing subclinical dysfunction. Our study offers an optimistic outlook for recovery in patients with MIS-C and carditis, however ongoing investigation for longitudinal effects is warranted.

Multimodality Imaging in Ebstein Anomaly.

Ebstein anomaly is the most common form of tricuspid valve congenital anomalies. The tricuspid valve is abnormal with different degrees of displacement of the septal leaflet and abnormal rotation of the valve towards the right ventricular outflow tract. In severe forms, it results in significant tricuspid regurgitation and requires surgical repair. There is an increased interest in understanding the anatomy of the tricuspid valve in this lesion as the surgical repair has evolved with the invention and wide adoption of the cone operation. Multimodality imaging plays an important role in diagnosis, follow-up, surgical planning and post-operative care. This review provides anatomical tips for the cardiac imagers caring for patients with Ebstein anomaly and will help provide image-based personalized medicine.

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 prognostic role of liver volumetry in Fontan patients.

BACKGROUND AND HYPOTHESES: High venous pressures and associated hepatic congestion are important drivers for Fontan-associated liver disease. The prognostic significance of hepatomegaly as a marker of congestion however is not well defined and is further explored in this research study. METHODS: Fontan patients who have had liver ultrasound scans were identified from the Prince Sultan Cardiac Centre Fontan Database and had their anatomic, surgical, clinical histories abstracted from the electronic medical records following institutional ethics approval. Liver volumes were determined retrospectively from reviewing individual US images, and these, divided into tertiles, were analysed in the context of the predefined endpoints of (i) Primary - death or heart or liver transplantation, or (ii) Secondary - combined endpoint of death, transplantation, arrhythmia, or protein-losing enteropathy. RESULTS: Mean indexed liver volumes for the entire cohort (n = 199) were 1065.1 ± 312.1 ml/m2, range 387 to 2071 ml/m2. Patients with the largest liver volumes (highest tertile) were less likely to have a functioning fenestration compared to those in the lowest tertile 44% versus 56% p = 0.016 and experienced the highest burden of mortality and heart or heart-liver transplantation, p = 0.016, and were more likely to reach the composite endpoint of death, protein-losing enteropathy, arrhythmia, or transplantation, p = 0.010. Liver volumes had an overall predictive accuracy for the combined outcome of 61% (CI 53%, 67%, p = 0.009). CONCLUSIONS: Liver volumetry may serve as a potentially important congestion biomarker for adverse outcomes after the Fontan operation.