Egbe, Alexander C.

Abstract Aims Systemic ventricular (SV) strain imaging improves early detection of systolic dysfunction in patients with congenital heart disease and biventricular circulation. However, its role for risk stratification in the Fontan population has not been systematically studied. We hypothesized that among Fontan patients with normal SV ejection fraction (Echo_EF) at baseline, those with reduced SV longitudinal strain (Echo_LS) would have a higher risk of progressive SV systolic dysfunction, greater neurohormonal activation, and cardiovascular events (heart failure hospitalization/death/transplant) during follow-up. Methods and results We studied adults with Fontan palliation and normal SV systolic function (Echo_EF >50%) at baseline who underwent follow-up echocardiogram >36 months after the baseline echocardiogram. Echo_LS was assessed from the apical 4-chamber window using speckle tracking echocardiography. Patients were divided into reduced vs. normal Echo_LS groups, using −18% as the cut-off point. Echo_LS, Echo_EF, and NT-proBNP were assessed at baseline and follow-up encounters. Of 272 patients (age, 28 ± 8 years), 98 (36%) and 174 (64%) had reduced vs. normal Echo_LS. The reduced_Echo_LS group had progressive SV systolic dysfunction [worse temporal decline in Echo_EF (relative_Δ_Echo_EF −12.8% vs. −2.1%, P < 0.001)], and higher prevalence of new-onset SV systolic dysfunction [30% (29/98) vs. 8% (13/174), P < 0.001]. The reduced Echo_LS group also had greater neurohormonal activation [relative Δ_ NT-proBNP 36 (95%CI, 27–43) % vs. 17 (95%CI, 11–23) %, P < 0.001], and higher risk of cardiovascular events (adjusted hazard ratio 1.84, P = 0.009). Conclusion Echo_LS improves risk stratification in Fontan patients with normal Echo_EF and may provide an opportunity for early interventions to improve outcomes.

Background Atrial dysfunction is a risk factor for atrial arrhythmia and can be detected by atrial strain imaging in patients with biventricular circulation. However, the role of atrial strain imaging for risk stratification of atrial arrhythmia in patients with Fontan palliation has not been studied, despite the high prevalence and prognostic implications of atrial arrhythmia in this population. We hypothesized that pulmonary venous atrial strain was associated with new‐onset and recurrent atrial arrhythmia in Fontan physiology. Method and Results This is a retrospective study of adults with Fontan palliation and no prior history of atrial arrhythmia who underwent atrial strain imaging by speckle tracking echocardiography (2003–2023). New‐onset and recurrent atrial arrhythmias were ascertained from baseline encounter to last follow‐up. Of 404 patients, atrial reservoir strain assessment was feasible in 329 patients (81%), with modest intra‐ and interobserver agreement. The median atrial reservoir strain was 18% (interquartile range, 13%–24%), and atrial dysfunction (atrial reservoir strain <28%) was present in 294 (89%). Atrial reservoir strain <15% was associated with new‐onset atrial arrhythmia (adjusted hazard ratio [HR], 1.59 [95% CI, 1.09–2.34]; P =0.009), and recurrent atrial arrhythmia (adjusted HR, 2.01 [95% CI, 1.06–3.93]; P =0.003). Rhythm control therapy was associated with lower risk of recurrence compared with rate control therapy (adjusted HR, 0.92 [95% CI, 0.86–0.98]; P =0.003). Conclusions Atrial dysfunction was common and was associated with new‐onset and recurrent atrial arrhythmias. The higher prevalence of atrial arrhythmias in patients with reduced atrial strain and the apparent protective effect of rhythm control therapy suggest that rhythm control therapy may be the preferred treatment in patients with reduced atrial strain.

BACKGROUND: Bioprosthetic valve dysfunction and reoperations/reinterventions are common after aortic valve replacement (AVR) with bioprosthetic valves, leading to cycles of left ventricular (LV) pressure overload and unloading. The purpose of this study was to compare postoperative changes in LV structure and function and their relationship to clinical outcomes in young patients who underwent AVR with bioprosthetic valves (Bio_AVR group) versus mechanical prosthetic valves (Mech_AVR group). METHODS: Retrospective study of adults with congenital heart disease who underwent AVR at Mayo Clinic (2003–2023). The Bio_AVR group was matched 1:2 to the Mech_AVR group. LV indices (LV mass index, relative wall thickness, LV global longitudinal strain, averaged e′, and averaged E/e′) and clinical indices (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and New York Heart Association class) were assessed preoperatively, and at 1, 5, and 10 years post-AVR. RESULTS: We studied 151 and 302 patients in the Bio_AVR and Mech_AVR groups, respectively (age 38±16 years, 58% males). Both groups had similar LV and clinical indices at baseline and 1 year post-AVR. However, the Bio_AVR group had higher LV mass index, relative wall thickness, and averaged E/e′, and lower averaged e′ and LV global longitudinal strain at 5 and 10 years post-AVR. Of 51 patients from the Bio_AVR group who underwent a second AVR, there was less robust improvement in LV indices and clinical indices after the second AVR compared with the first AVR. CONCLUSIONS: AVR with a bioprosthetic valve was associated with progressive LV hypertrophy and dysfunction, and worsening clinical status compared with mechanical prosthetic valves. This provides further evidence against the use of bioprosthetic AVR in young patients.

BACKGROUND: Exercise-induced hypertension (EIH) is common in adults with coarctation of the aorta (COA), but there are limited data about hemodynamics and outcomes in such patients. The purpose of this study was to assess changes in arterial load during exercise in patients with COA with versus without EIH, and the relationship to clinical outcomes. METHODS: We compared Doppler-derived arterial load indices (effective arterial elastance index, total arterial compliance index, systemic vascular resistance index), and clinical indices of disease severity (pulmonary congestion, aerobic capacity, and cardiovascular biomarkers) between adults with repaired COA and healthy controls. EIH was defined as systolic blood pressure (BP) at peak exercise >210 mm Hg in men or >190 mm Hg in women. RESULTS: In this prospective cohort study, we assessed patients with COA (n=41, age 43±14 years, 26 [63%] men) and healthy controls (n=41). Although both groups had similar resting systolic BP, the COA group had higher Doppler-derived arterial load indices at rest, as well as a greater rise in systolic BP and Doppler-derived arterial load indices at each stage of exercise, leading to a higher prevalence of EIH in the COA group (37% versus 10%; P =0.004). Compared with patients with COA without EIH (n=26, 63%), those with EIH had higher arterial load at rest and during exercise, as well as worse cardiac dysfunction, pulmonary congestion, and biomarkers of cardiovascular remodeling, despite no significant differences in resting systolic BP. CONCLUSIONS: BP assessment during exercise can improve risk stratification and identify patients who may benefit from intensification of medical therapy.

Abstract Aims Pulmonary regurgitation (PR) after reparative intervention for congenital heart disease has been studied extensively. However, the burden, distribution of causes, and outcome of PR in adults is unknown. The study aimed to evaluate the prevalence, types, and outcomes of moderate/severe PR in adults in the community setting. Methods and results A total of 398 adult residents of Olmsted County who had clinically indicated echocardiography 2004–2023 at Mayo Clinic, Rochester, and had moderate or severe PR were identified retrospectively. The median age was 77 years, 48% were females, and 61 (51%) had severe PR. The age- and sex-adjusted US prevalence was 0.11% (vs. 0.67% for ≥moderate tricuspid regurgitation). Moderate/severe PR was due to pulmonary hypertension in 77%, congenital/iatrogenic in 11%, primary pulmonary valve disease in 2% (88% due to carcinoid), and idiopathic isolated in 10%. In contrast, severe PR was due to congenital/iatrogenic disease in 52%, pulmonary hypertension in 39%, primary PR in 5%, and isolated idiopathic in 3%. The all-cause mortality rate per 100 person-year was 73 in primary (mostly carcinoid) PR, 16 in pulmonary hypertension–related PR (not different vs. propensity-matched patients without PR), and 6 in isolated idiopathic PR (not different vs. matched patients without PR). Conclusion Moderate or severe PR had a lower prevalence vs. TR. The most frequent cause was pulmonary hypertension for ≥moderate PR and congenital/iatrogenic for severe PR. Mortality in patients with acquired ≥moderate PR appeared to be related to the underlying cause, with no excess mortality compared with matched patients without PR. Whether specifically severe PR confers excess mortality requires future investigation.

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. METHODS: Adults with Fontan palliation who underwent a cardiopulmonary exercise test at Mayo Clinic (2003–2023) were stratified into quartiles based on the predicted peak oxygen consumption (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 VO 2 was 19.1 (15.2–23.9) mL/kg per minute, and this corresponds to a predicted peak VO 2 of 51% (range, 19–88; interquartile range, 41–62). After multivariable adjustments, the correlates of predicted peak VO 2 were body mass index (β±SE, −2.61±0.95; 2.61% decrease in predicted peak VO 2 per 5 kg/m 2 increase in body mass index; P =0.009), systemic saturation (β±SE, 3.65±0.85; 3.65% increase in predicted peak VO 2 per 5% increase in oxygen saturation; P <0.001), and Fontan pressure (β±SE, −1.24±0.22; 1.24% decrease in predicted peak VO 2 per 1 mm Hg increase in Fontan pressures; P <0.001). There was a 47% increase in the risk for death/transplant from a higher predicted peak VO 2 quartile to the next lower quartile (adjusted hazard ratio, 1.47 [95% CI, 1.09–2.05]; P =0.01). 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. It also underscores the need to maintain normal Fontan hemodynamics and body weight, which are important determinants of aerobic capacity.

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.