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Background: Patients with Fontan palliation have reduced aerobic capacity because of impaired cardiac, pulmonary, and skeletal muscle function. However, the assessment of aerobic capacity in this population still relies on comparisons with people without cardiovascular disease, rather than comparison with the expected aerobic capacity of other Fontan patients. The purpose of this study was to determine the expected aerobic capacity of adults with Fontan palliation. Method: Adults with Fontan palliation who underwent cardiopulmonary exercise test at Mayo Clinic (2003-2023) were stratified into quartiles based on the predicted peak VO 2 . We assessed the correlates of predicted peak VO 2 , and the relationship between predicted peak VO 2 quartiles and cardiovascular outcomes (death/transplant). Results: Of 323 patients (age 29±9 years; 177 [55%] men), the median peak VO2 was 19.1 (15.2 - 23.9) ml/kg/min, and this corresponds to a predicted peak VO 2 of 51% (range 19 -88; interquartile range 41 - 62). The correlates of higher predicted peak VO 2 were smaller body mass index, higher systemic saturation, and lower Fontan pressures. The top, 2 nd ,3 rd , and bottom quartile of predicted peak VO 2 corresponds to predicted peak VO 2 of 63-88%, 51-62%, 41-50%, and 19-40%, respectively. Using the top quartile as the reference, the 3 rd quartile (HR 1.13, 95% CI 1.03-1.28, p=0.02), and 4 th quartile were associated with a higher risk of death/transplant (HR 1.32, 95% CI 1.16-1.69, p<0.001). Conclusions: The results of the current study would help calibrate the interpretation of exercise test data in adults with Fontan palliation and improve risk stratification in this population.

Background: Artificial intelligence (AI) can be used to predict a person’s age from the electrocardiogram (ECG) (AI-ECG age) and has been proposed as a measurement of biological age. The difference between AI-ECG age and chronological age (defined as delta-age) is an independent predictor of mortality in the general population. This study assessed the relationship between AI ECG estimated age and mortality among adults living with congenital heart disease (CHD). Methods: A previously validated neural network to estimate AI-ECG age was used to analyze standard digital 12-lead ECGs in a cohort of subjects aged >18 years seen in the adult CHD (ACHD) clinic between 1992 to 2023. A single ECG, collected during the year of the first visit to the ACHD clinic was analyzed to compute the delta-age.. A positive delta-age indicates an AI ECG estimated age higher than the subject’s chronological age. The relationship between the delta-age and mortality was evaluated using Cox proportional hazard models adjusting for influential clinical factors including chronologic age, sex, ACHD severity, NYHA class and history of arrhythmia. Results: Of 5,780 subjects tested (50% females), the mean chronological age was 39.1 ± 15.0 years. AI ECG estimated age was 52.3 ± 16.6 years. Complexity of CHD was classified as mild, moderate, and severe in 7.4%, 73.9% and 18.7% of patients respectively. Patients with severe CHD had the highest delta-age of 17.1 (±18.2) years followed by moderate 12.7 (±13.6) y and simple 7.7 (±11.5) y. Patients with single ventricle had the highest deviation in AI estimated age [median delta-age 21.0 (IQR 28.6) y] followed by those with a systemic right ventricle [median delta-age of 16.3 (IQR 29.3) y]. During a median follow-up of 6.4 y (25th – 75th centile 1.58 – 13.7 y), mortality occurred in 839 (14.5%) patients. After adjusting for chronological age, CHD severity, and other clinical variables, delta-age gap was associated with increased mortality risk (HR 1.06 (1.03 – 1.09) per 5-year increment in delta-age, p<0.005), Table 1. Conclusion: The difference between AI ECG and chronological age is an independent predictor of all-cause mortality in ACHD patients.

Introduction: The incidence and risk factors for atrial arrhythmia (AA) [atrial fibrillation (AF) and atrial flutter (AFL)] in adults with systemic right ventricle (SRV), specifically congenitally corrected-TGA (cc-TGA) and D-TGA palliated with atrial switch procedures, is not well understood. This study aims to better define these risks. Methods: Adults with SRV presenting to the Mayo Clinic between 1971 and 2022 were identified. Clinical characteristics, ECG and echocardiographic parameters were recorded at first evaluation. Sustained AA (> 30s) incidence at follow-up was documented using ECG. Cox regression analysis identified associations of incident AA. Results: Among 447 patients with SRV (mean age 34.7±14.8, 55.9% male, cc-TGA n=247; D-TGA post-atrial baffle n=200), AA was documented in 231 (51.6%) at a mean age of 37.5±18.8y. Isolated AF was observed in 88 (38.1%), isolated AFL in 71 (30.7%), and both AF and AFL in 72 (31.2%) patients. Univariate analysis showed significant predictors of AA as: age (HR:1.03, p<0.001), male sex (HR:1.49, p=0.026), NYHA class≥2 (HR:1.98, p<0.001), ventricular pacing (HR:1.64, p=0.019), QRS duration (HR:1.008, p<0.001), SRV enlargement (HR:1.73, p=0.01), SRV ejection fraction (HR:0.979,p=0.012), left atrial enlargement (HR:1.947, p=0.006), hypertension (HR:1.57, p=0.047), CKD (HR:0.991, p=0.021), and obesity (HR:1.66, p=0.023). In multivariable analysis, age (HR:1.032, p<0.001) and QRS duration (HR:1.007, p=0.013) were significant predictors of AA. Kaplan Meier analysis of time from first evaluation to incidence of AA is shown in the figure. AA was associated with heart failure in 56 (26.7%) patients. During 11.2±10.5 years of follow-up, mortality occurred in 50 (21.6%) with AA and 19 (8.8%) without AA. Conclusion: Atrial arrhythmia occurred in more than half of patients with SRV, predominantly in the third decade of life. Significant associations of AA included advancing age, longer QRS duration, enlargement of pulmonary venous atrium, reduced SRV function, hypertension and obesity. AA was associated with heart failure in one-fourth of patients and higher mortality. Close monitoring and early intervention in patients with risk factors may help mitigate the development of AA.

Introduction: Ebstein's anomaly (EA) is associated with ECG signature of right bundle branch block (RBBB). Patients with EA also have high incidence of accessory pathways (AP) and it has been hypothesized that the absence of RBBB on ECG may be associated with a higher prevalence of AP. This study aims to assess the prevalence of RBBB in patients with EA and examine the correlation between its absence and the presence of AP. Methods: Adults (age>18 years) with EA, identified using the Mayo Adult Congenital Heart Disease registry, were divided into 3 groups based on the QRS morphology of their first ECG. Those with prior AP ablation were excluded. The demographic characteristics, baseline ECG data, echocardiographic parameters and EP study data were retrospectively collected and compared between the three groups using Chi-square or ANOVA test as appropriate. Results: Of 596 patients with EA, 358(60.06%) patients had a RBBB, bifascicular block or an incomplete RBBB (group1) ; 18 (3.02%) patients had either a LBBB , ventricular pre-excitation, isolated left anterior or posterior fascicular block (group 2); and 220 (36.92%) patients had normal QRS (group 3). The characteristics of these groups are compared in the table. Patients with RBBB had larger RV size, reduced RV systolic function and higher likelihood of tricuspid valve surgery. EP study was performed in 51 (14%), 3 (17%) and 51 (23%) patients in groups 1, 2,and 3 respectively. One or more APs were noted in 11/51 (22%) and 14/51 (30%) patients with RBBB and normal QRS respectively (p=0.18). Additionally, in patients who did not undergo an EP study, supraventricular tachycardia was documented in 39/307 (13%), 2/15(13%) and 13/169 patients (8%) in group 1,2 and 3 respectively during followup . Conclusion: In a large cohort of adults with EA in a tertiary referral center, greater than one-third of patients had a normal QRS complex without RBBB. However, EP study did not reveal a significant difference in the prevalence of accessory pathways between patients with and without RBBB. In EA, the absence of RBBB may not increase the risk of an underlying accessory pathway.

Background: We hypothesized that patients with coarctation of aorta (COA) and obesity would have more advanced cardiovascular remodeling and impaired aerobic capacity compared to COA patients without obesity. The purpose of this study was to assess the relationship between obesity, cardiovascular remodeling, and aerobic capacity in adults with repaired COA. Methods: The study comprised of 3 groups: (1) Obese COA group (n=177) (COA patients with body mass index [BMI] >30 kg/m2); (2) Non-obese COA group (n=572) (COA patients with BMI ≤30 kg/m2); (3) Control group (n=59) (subjects without structural heart disease and BMI ≤30 kg/m2). Cardiovascular remodeling was assessed using the following indices: (1) Arterial stiffness - total arterial compliance index (TACI). (2) Left ventricular hypertrophy - LV mass (LVM) and relative wall thickness (RWT). (3) LV diastolic function - Doppler-derived estimated LV end-diastolic pressure (LVEDP) and Tau. (4) Right ventricular-pulmonary artery coupling - RV free wall strain and right ventricle systolic pressure (RVFW/RVSP). Aerobic capacity was assessed using predicted peak oxygen consumption (VO2). Results: The obese COA group had higher LVM, RWT, LVEDP, and Tau, well as lower RVFWS/RVSP, TACI and peak VO2 compared to non-obese COA group and controls. There was a correlation between BMI and LVM (r=0.39, p<0.001), RWT (r=0.47, p<0.001), estimated LVEDP (r=0.43, p<0.001), tau (r=0.22, p=0.008), RVFWS/RVSP (r=- 0.24, p<0.001), and predicted peak VO2 (r= -0.48, p<0.001). Conclusions: These findings underscore the cardiovascular implications of obesity in the setting of COA, and provide opportunities for interventions to address obesity and improve outcomes in the COA population.

Background: Pulmonary hypertension (PH) and secondary right ventricle dysfunction is present in 20% of adults with coarctation of aorta (COA) based on echocardiographic studies. There are limited data about invasive hemodynamic characterization of PH in COA. The purpose of this study was to delineate the clinical features, hemodynamics, and outcomes of PH in COA. Method: Retrospective cohort study of adults with repaired COA that underwent right heart catheterization (RHC). PH was defined as pulmonary artery (PA) mean pressure >20 mmHg, and PH was classified as isolated precapillary PH and combined pre/postcapillary PH. Results: Of 99 COA patients that underwent RHC, 57 (58%) had PH. Of the patients with PH, 14 (25%) had isolated precapillary PH while 43 (75%) had postcapillary PH with or without precapillary disease. The correlates of PH were PA compliance (adjusted OR 0.79, 95% CI 0.71-0.86 per 1 ml/mmHg), left atrial reservoir strain (adjusted OR 0.95, 95% CI 0921-0.98 per 1%), and atrial fibrillation (adjusted OR 2.18, 95% CI 1.20-13.5). Higher PA mean pressure was associated with risk of cardiovascular events (adjusted HR 1.04, 95% CI 1.02-1.06 per 1 mmHg) and all-cause mortality (adjusted HR 1.05, 95% CI 1.02-1.08 per 1 mmHg). Conclusions: PH was present in over half of adults with COA referred for RHC, and one-quarter of the patients with PH presented with isolated precapillary PH suggesting an underlying PA vascular dysfunction as a contributing mechanism. Further studies are required to determine optimal therapies and strategies for prevention and treatment of PH in this population.

Abstract Background Congenital Heart Disease (CHD) is associated with development of atrial fibrillation (AF) at an early age. With increased survival of this cohort into adulthood, the prevalence of concurrent CHD and AF is expected to increase over the next several decades. Little is known about the utility of clinical risk factors or prediction models in determining bleeding or stroke rates in adults with CHD and AF. Purpose This study aims to measure the performance of the CHADSVASC and HASBLED scores in a cohort of people with CHD. The association between traditional stroke and bleeding risk factors, as well as CHD-specific factors, will be quantified. Methods Patients age 18 or older attending one of three centers in the USA were included in this study if they had a history of AF on ECG, holter monitor or device interrogation, in addition to a diagnosis of Tetralogy of Fallot (TOF), Double Outlet Right Ventricle (DORV), or Pulmonary Atresia with Intact Ventricular Septum (PA-IVS). Outcomes were major bleeding event, and stroke rate. Analysis was conducted using cox univariable regression controlling for current age. Receiver operator curve and c-statistics were produced for the CHADSVASC and HASBLED scores respectively. Results 326 people were included in this study, of whom 161 (49.5%) had TOF secondary to Pulmonic Stenosis, 126 (38.8%) had TOF secondary to Pulmonary Atresia, 25 (7.7%) had DORV, and 155 (47.7%) had PA-IVS. 227 people used warfarin (79.4%), 28 (9.8%) used apixaban, 9 (3.1%) used Rivaroxaban, 3 (1%) used Edoxaban, and 5 (1.7%) used Enoxaparin for a period of at least 30 days during the study. 13 (4.5%) people didn’t receive anticoagulation during the study. 26 people had a stroke (8.8%) while 85 people (28.6%) had a major bleeding event. Only the CHADSVASC score was significantly associated with stroke rates (HR 2.103, 95% CI 1.555 to 2.844, p&lt;0.001). Clinical variables, such as subtype of CHD, prior conduit placement or unifocalization were not associated with stroke or major bleeding events. C-statistic for the CHADSVASC score in predicting stroke events was 0.755 (Figure 1). C-statistic for the HASBLED score in predicting major bleeding was 0.442 (Figure 2). Conclusions Among people with CHD and AF, the CHADSVASC score can robustly predict stroke events. Other clinical variables are less valuable in predicting either bleeding or strokes. The HASBLED score likely doesn’t have a role in predicting major bleeding episodes in this cohort.

Abstract Aims The effects of obesity on Fontan haemodynamics are poorly understood. Accordingly, we assessed its impact on exercise invasive haemodynamics and exercise capacity. Methods and results Seventy-seven adults post-Fontan undergoing exercise cardiac catheterization (supine cycle protocol) were retrospectively identified using an institutional database and categorized according to the presence of obesity [body mass index (BMI) &gt; 30 kg/m2] and overweight/normal BMI (BMI ≤ 30 kg/m2). There were 18 individuals with obesity (BMI 36.4 ± 3 kg/m2) and 59 with overweight/normal BMI (BMI 24.1 ± 3.6 kg/m2). Peak oxygen consumption (VO2) on non-invasive cardiopulmonary exercise testing was lower in patients with obesity (15.6 ± 3.5 vs. 19.6 ± 5.8 mL/kg/min, P = 0.04). At rest, systemic flow (Qs) [7.0 (4.8; 8.3) vs. 4.8 (3.9; 5.8) L/min, P = 0.001], pulmonary artery (PA) pressure (16.3 ± 3.5 vs. 13.1 ± 3.5 mmHg, P = 0.002), and PA wedge pressure (PAWP) (11.7 ± 4.4 vs. 8.9 ± 3.1 mmHg, P = 0.01) were higher, while arterial O2 saturation was lower [89.5% (86.5; 92.3) vs. 93% (90; 95)] in obesity compared with overweight/normal BMI. Similarly, patients with obesity had higher exercise PA pressure (29.7 ± 6.5 vs. 24.7 ± 6.8 mmHg, P = 0.01) and PAWP (23.0 ± 6.5 vs. 19.8 ± 7.3 mmHg, P = 0.047), but lower arterial O2 saturation [82.4 ± 7.0% vs. 89% (85; 92), P = 0.003]. Conclusion Adults post-Fontan with obesity have worse aerobic capacity, increased Qs, higher filling pressures, and decreased arterial O2 saturation compared with those with overweight/normal BMI, both at rest and during exercise, mirroring the findings observed in the obesity phenotype of heart failure with preserved ejection fraction. Whether treating obesity and its cardiometabolic sequelae in Fontan patients will improve haemodynamics and outcomes requires further study.

Background The purpose of this study was to describe the correlates and outcomes in adults with unrepaired partial anomalous pulmonary venous return and intact atrial septum (PAPVR‐IAS). Methods and Results We identified adults with PAPVR‐IAS who received care at the Mayo Clinic, while those with unrepaired PAPVR‐IAS comprised the reference group. Clinical indices (New York Heart Association class, peak oxygen consumption, and NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]) and echo‐derived right heart indices (right atrial [RA] volume, RA reservoir strain, right ventricular [RV] free wall strain, RV end‐diastolic area, and RV systolic pressure) were assessed at baseline and 3‐year and 5‐year follow‐up. There were 80 patients and 38 patients with unrepaired versus repaired PAPVR‐IAS, respectively. The clinical predictors of surgical repair were the number of anomalous veins, RA volume, and RV end‐diastolic area. The PAPVR‐IAS risk score, derived from these clinical predictors, was associated with surgical repair (adjusted odds ratio, 1.37 [95% CI, 1.24–1.65] per unit increase in risk score; area under the curve, 0.742). Among patients with unrepaired PAPVR‐IAS with 3‐year (n=73) and 5‐year follow‐up (n=36), there was no temporal change in clinical indices (New York Heart Association class, predicted peak oxygen consumption, and NT‐proBNP) and right heart indices (RA volume index, RA reservoir strain, RV end‐diastolic area index, RV free wall strain, and RV systolic pressure). Conclusions The PAPVR‐IAS risk score can be used to assess the odds of requiring surgical repair. Furthermore, there was no temporal deterioration in clinical and right heart indices during follow‐up in adults with unrepaired PAPVR‐IAS.

Abstract Aims Women with congenital heart disease (CHD) are at risk of pregnancy-related adverse outcomes (PRAO). The purpose of this study was to assess temporal changes in cardiac structure and function (cardiac remodelling) during pregnancy, and the association with PRAO in women with CHD. Methods and results Retrospective study of pregnant women with CHD and serial echocardiograms (2003–2021). Cardiac structure and function were assessed at pre-specified time points: prepregnancy, early pregnancy, late pregnancy, and postnatal period. PRAO was defined as the composite of maternal cardiovascular, obstetric, and neonatal complications. The study comprised 81 women with CHD (age, 29 ± 5 years). Compared to the baseline echocardiogram, there was a relative increase in right ventricular systolic pressure (RVSP) (relative change 13 ± 5%, P &lt; 0.001, in early pregnancy; and 18 ± 5%, P &lt; 0.001, in late pregnancy). There was a relative decrease in right ventricle free wall strain (RVFWS) (relative change −11 ± 3%, P &lt; 0.001, in late pregnancy; and −11 ± 4%, P = 0.003, in postnatal period), and a relative decrease in RVFWS/RVSP (relative change, −10 ± 5%, P = 0.02 in early pregnancy, −26 ± 7%, P &lt; 0.001, in late pregnancy, and −14 ± 5%, P &lt; 0.001, in postnatal period). Baseline right ventricular to pulmonary arterial (RV–PA) coupling, and temporal change in RV–PA coupling were associated with PRAO, after adjustment for maternal age and severity of cardiovascular disease. Conclusion Women with CHD had a temporal decrease in RV systolic function and RV–PA coupling, and these changes were associated with PRAO. Further studies are required to delineate the aetiology of deterioration in RV–PA coupling during pregnancy, and the long-term implications of right heart dysfunction observed in the postnatal period.