Connolly, Heidi M.

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: Carcinoid heart disease (CaHD) typically affects tricuspid and pulmonary valves and is associated with poor survival. To date, the role of right ventricular (RV) and atrial (RA) strain has not been evaluated in such cohort. Research Questions: To evaluate RV and RA strain patterns and assess their impact on survival and congestive heart failure (CHF) development. Methods: Retrospective study of CaHD patients (ICD 9/10 diagnosis of neuroendocrine tumor and echocardiographic evidence of CaHD prior to any surgical intervention; 2004-2019). Longitudinal strain was evaluated using speckle-tracking, RV/RA-focused view was used. RV strain was averaged from 3 and 6 segments for free wall (FWS) and global strain (GS), respectively. Auto-tracking with manual adjustment was done to ensure optimal tracking. The tracing of RV/RA endocardium was done with 15 points using the tricuspid valve annulus as a reference. The impact of strain parameters on mortality and CHF was evaluated with the Kaplan Meier and Cox proportional hazard analyses. Results: A total of 138 patients were included (mean age was 63 ± 10 years; 47% females). Median follow-up was 5.0 years (3.7-8.2). Significant RA and RV enlargement (72 and 79%, respectively) was more common than RV dysfunction (10%). The most common valvular disease > moderate was tricuspid regurgitation (TR; 97%) followed by pulmonary regurgitation (PR; 70%). RV GS mean was -21 + 6%, with FWS of -23 + 7%. The mean RA strain analysis revealed (93% sinus rhythm): a reservoir of 26 + 11%, a conduit of 14 + 8%, and an atrial contraction of 12 + 8%. Strain parameters were not associated with overall mortality. As opposed to PR/TR severity and RV/RA enlargement/dysfunction, patients with low RA reservoir strain (<23%) were more likely to develop CHF (adjusted-HR=1.80, p=0.04, 95% CI 1.04 - 3.134). Conclusions: Our findings suggests that CaHD patients have RV/RA dysfunction with overall reduced strain parameters. Patients with low RA reservoir had higher risk of CHF, but none of the RV/RA strain parameters were associated with excess mortality. This shows how strain analysis could complement other echocardiographic parameters in CaHD morbidity assessment.

Abstract Background Cardiac metastasis from neuroendocrine tumors (NET) is rare and has been thought to potentially result in life threatening sequalae. Peptide receptor radionucleotide therapy (PRRT), such as Lutetium-177 (Lu-177) DOTATATE, has been validated as effective treatment for patients with NET who have progressed on somatostatin analogue (SSA) therapy and more recently suggested for use in SAA-naïve higher risk grade 2 and grade 3 NETs. However, Lu-177 DOTATATE therapy has been found to have potentially serious adverse effects both locally and systemically. Overall, the clinical significance of cardiac metastasis of NET, as well as the safety and efficacy of Lu-177 DOTATATE in this cohort, has not been thoroughly evaluated. Purpose This study assessed the outcomes and clinical consequences of cardiac metastatic involvement in patients with NET. Furthermore, this study investigated the safety of Lu-177 DOTATATE therapy in patients with cardiac metastases from NET. Methods All patients who underwent 68Ga-DOTATATE positron emission tomography for evaluation of NET across three tertiary centers between 2016 and 2022 were retrospectively evaluated. Patients with evidence of cardiac metastasis were further evaluated. Baseline characteristics, treatment modality, and clinical outcomes including mortality, arrhythmia or conduction disease, carcinoid heart disease, and heart failure admissions were recorded. Patients with cardiac metastases were grouped and compared based on therapeutic modality (conservative therapy with surveillance or SSA, Lu-177 DOTATATE therapy, or surgical resection of metastases). Results From 3253 patients with NET, 51 patients were identified to have cardiac metastases (mean age 66.7 ± 12.2 years, 54% male). Three patients underwent surgical resection of cardiac metastases, and in two of whom this was concomitant while undergoing valve surgery for carcinoid heart disease. Patients with cardiac metastasis had significantly higher mortality than patients without cardiac metastasis (HR 2.12, 95%CI 1.00 – 4.52, p = 0.049, Figure 1A). Median follow-up from diagnosis of cardiac metastasis was 3.64 years [IQR 1.59 – 5.64]. There was no significant difference in clinical outcomes between patients that received Lu-177 DOTATATE therapy (n = 27) and conservative therapy (n = 21). Specifically, there was no significant difference in mortality risk at five years post the diagnosis of cardiac metastasis between these groups (p = 0.47, Figure 1B). Conclusion Patients with cardiac metastasis from NETs have worse clinical outcomes than NET patients without cardiac metastatic involvement. Lu-177 DOTATATE therapy appears to be safe in patients with cardiac metastasis from NET.Figure 1AFigure 1B

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.

Background There are limited data about the impact of timing of pulmonary valve replacement (PVR) on right heart reverse remodeling in patients with pulmonary regurgitation following intervention for isolated pulmonary valve stenosis (PS). This study compared differences in postprocedural right heart reverse remodeling after early versus late PVR (defined as PVR before versus after attainment of the conservative consensus criteria proposed by Bokma et al, 2018) in patients with prior intervention for PS, using patients with tetralogy of Fallot as the reference group. Method and Results Right atrial reservoir strain and right ventricular free wall strain was measured at baseline, 1 and 3 years after PVR. There were 114 patients with PS (early PVR, 87 [76%]; late PVR, 27 [24%]) and 291 patients with tetralogy of Fallot (early PVR, 197 [67%]; late PVR, 96 [33%]). The PS group had greater improvement in right atrial reservoir strain at 1 year (12%±4% versus 8%±4%; P <0.001) and 3 years (15%±6% versus 9%±6%; P <0.001), and a greater improvement in right ventricular free wall strain at 1 year (12%±4% versus 7%±3%, P =0.008) and 3‐years (16%±6% versus 12%±5%; P =0.01) after PVR compared with the tetralogy of Fallot group. There was no difference in right heart reverse remodeling between patients who underwent early versus later PVR within the PS group. In contrast, late PVR was associated with less right heart reverse remodeling within the tetralogy of Fallot group. Conclusions These data suggest that patients with palliated PS presenting pulmonary regurgitation have a more benign clinical course, and hence delaying PVR in this population may be appropriate.

Introduction: Carcinoid heart disease (CHD) is a rare sequelae of hormonally active neuroendocrine tumors that often requires cardiac surgical intervention. Little is reported on cardiac implantable electronic device (CIED) implantation in the CHD patient population. Hypothesis: We sought to establish the safety and efficacy of CIED implantation in patients with CHD. Methods: We retrospectively reviewed patients with a diagnosis of CHD who underwent CIED implantation at our institution (Mayo Clinic) and evaluated indications for implant, perioperative complications, and mortality. Results: A total of 27 patients with a cumulative follow up of 75 patient-years were identified during the study period. The most common indication for device implant was high grade atrioventricular block (n=18, 66.7%). 14 (51.8%) had baseline conduction disease and 26 (96.2%) underwent cardiac surgery prior to CIED implant. The majority of devices implanted were dual chamber permanent pacemakers (PPM) (n=17, 63.0%), while other devices included single chamber PPM, epicardial PPM, chronic resynchronization devices, and intracardiac defibrillators. Peri-operative complication occurred in 6 patients (22.2%), with 2 patients requiring ICU level care. No patient suffered carcinoid crisis during implantation and there was no peri-implant mortality. Long term, 3 patients required device extraction: 1 for infection, 1 for lead related pain, and 1 for generator migration. The median time to death from implant was 2.5 years, with one-year mortality at 15%. Conclusions: In this unique cohort of patients with CHD, CIED can be performed safely. CIED most often occurred in the post cardiac surgical period and carcinoid crisis was uncommon.