Warnes, Carole A.

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.

Introduction: The subcutaneous implantable cardioverter defibrillator (S-ICD) is an attractive option for patients with congenital heart disease (CHD) in whom a transvenous system is contraindicated. However, more than 10% of adult patients with CHD fail S-ICD screening due to a large T- to R-wave ratio. We hypothesized right-sternal electrodes may permit S-ICD placement in patients who fail left-sternal screen. Methods: We prospectively screened 40 patients with CHD for S-ICD using the standard proprietary approach. We also screened with right sternal electrodes (with left can electrode position). Results: The mean age of the cohort was 46+/-15 years; 24 males were enrolled. CHD anomalies consisted of tetralogy of Fallot (n=11), Ebstein’s anomaly (n=7), atrial septal defect (n=6), dextro-looped transposition of the great artery (n=5) and other (n=11). Left side screening ECG failed in 9 patients (23%), five of whom passed with right sternal electrodes, increasing the pass rate from 77% to 90%. Figure shows the screening ECG and chest x-ray of a patient who failed in all three vectors on the left side but passed in the alternative vector on the right side and underwent right sided implantation. Conclusions: The addition of right sternal electrodes during screening increases S-ICD eligibility and may avoid thoracotomy for high risk patients with CHD.

Background: Patients (pts) with protein losing enteropathy (PLE) following the Fontan operation (op) have a reported 50% mortality at 5 years (yrs) post diagnosis. We review our clinical outcomes in this pt population. Methods: From 1997 to 2010, 42 pts (55% M) with PLE following the Fontan op were identified from clinical databases. Data were collected by retrospective chart review. Results: Mean age at PLE diagnosis was 18.9 yrs + 11 (4.7-57.9 yrs) and initial Fontan op was 10.1 yrs + 10.8 (1.8-37.6 yrs). Mean time from Fontan op to PLE diagnosis was 8.4 yrs + 14.2 (30 days-27yrs). Types of Fontan op included: atriopulmonary connection (28, 67%), lateral tunnel or intraatrial conduit (6, 14%), or extracardiac conduit (8, 19%). Mean time from diagnosis to last follow-up was 8 yrs + 6 (1-22yrs). Survival was 88% at 5 yrs. There were 11 deaths, mean age 32 yrs + 7.7 (22-47 yrs). Mean time interval from diagnosis to death was 7.5 yrs + 5.4 (1-18yrs). Causes of death include: sepsis (7), complications after Fontan conversion (1), and unknown (3). Decreased survival was seen in pts with high Fontan pressure (mean >15mmHg, p=0.04), decreased ventricular function (EF < 55%, p=0.03), and NYHA class >2 at diagnosis (p=0.04). Pts who died had higher pulmonary vascular resistance (3.8 + 1.6 WU vs 2.1 + 1.1 WU, p=0.017), lower cardiac index (1.6 L/min/m 2 + 0.4 vs 2.7 L/min/m 2 + 0.7, p<0.0001), and lower mixed venous saturation (53% versus 66%, p=0.01) compared to survivors. All factors were obtained at initial PLE diagnosis. Pts treated with medical therapy only (n=15) resulted in symptomatic improvement in 7 pts (47%), no improvement in 5 (33%), and death in 3 (20%). Pts treated with medical + surgical/interventional catheterization procedures (n=27) resulted in symptomatic improvement in 10 pts (37%), no improvement in 9 (33%), and death in 8 (30%). Treatments used more in survivors included spironolactone (21, 68%), octreotide (7, 21%), sildenafil (6, 19%), fenestration creation (15, 48%), and relief of Fontan obstruction (7, 23%). Of the 31 survivors, 17 pts remain well-controlled. Conclusions: PLE remains difficult to treat, but in the current era, survival has improved with advances in treatment. Further study is needed to understand the mechanism of disease and ideal treatment strategy.

Background Little is known about outcomes following heart failure (HF) hospitalization among adults with congenital heart disease (CHD) in the United States. We aim to compare the outcomes of HF versus non‐HF hospitalizations in adults with CHD. Methods and Results Using a national deidentified administrative claims data set, patients with adult congenital heart disease (ACHD) hospitalized with and without HF (ACHDHF+, ACHDHF−) were characterized to determine the predictors of 90‐day and 1‐year mortality and quantify the risk of mortality, major adverse cardiac and cerebrovascular events, and health resource use. Cox proportional hazard regression was used to compare ACHDHF+ versus ACHDHF− for risk of events and health resource use. Of 26 454 unique ACHD admissions between January 1, 2010 and December 31, 2020, 5826 (22%) were ACHDHF+ and 20 628 (78%) were ACHDHF−. The ACHD HF+ hospitalizations increased from 6.6% to 14.0% ( P <0.0001). Over a mean follow‐up period of 2.23 ± 2.19 years, patients with ACHDHF+ had a higher risk of mortality (hazard ratio [HR], 1.86 [95% CI, 1.67–2.07], P <0.001), major adverse cardiac and cerebrovascular events (HR, 1.73 [95% CI, 1.63–1.83], P <0.001) and health resource use including rehospitalization (HR, 1.09 [95% CI, 1.05–1.14], P <0.001) and increased postacute care service use (HR, 1.56 [95% CI, 1.32–1.85], P <0.001). Cardiology clinic visits within 30 days of hospital admission were associated with lower 90‐day and 1‐year all‐cause mortality (odds ratio [OR], 0.62 [95% CI, 0.49–0.78], P <0.001; OR, 0.69 [95% CI, 0.58–0.83], P <0.001, respectively). Conclusions HF hospitalization is associated with increased risk of mortality and morbidity with high health resource use in patients with ACHD. Recent cardiology clinic attendance appears to mitigate these risks.

Introduction: Ebstein’s anomaly (EA) is a rare congenital anomaly of the tricuspid valve associated with heart failure and arrhythmias. Currently available imaging modalities like transthoracic echocardiography, cardiac magnetic resonance imaging (MRI), or computerized tomography (CT) are not viable for screening large asymptomatic populations. Hypothesis: A deep learning algorithm, implemented using a convolutional neural network (CNN) applied to the standard 12-lead ECG can be used as an accurate screening tool for EA in children and adults. Method: We identified 1,154 EA patients and 21,430 age- and sex-matched controls (1:20 ratio) between 1987 - 2020. A CNN was trained, validated and tested using digital 12-lead ECGs in 70%, 10% and 20% of the cohort respectively, divided by random shuffling. Results: The mean age was 26.68±19.23 years (41.8% aged < 18 years, 56.41% female) for the EA cohort and 28.36±18.65 years (37.2% aged <18 years, 55.67% female) for the control cohort. Following training and validation the area under the curve (AUC) for detecting EA in the testing cohort was 0.976 (95% CI 0.962 - 0.989) with prediction accuracy of 0.959. In subgroup analysis, the AUC was comparable in males (0.970, 95% CI 0.946-0.995) and females (0.979, 95% CI 0.964-0.994), those <18 (0.980, 95% CI 0.958-1.000) and ≥18 years old (0.972, 95% CI 0.954-0.989), as well as in those with right bundle branch block (RBBB) (0.969, 95% CI 0.950-0.989) and without RBBB (0.950, 95% CI 0.922-0.978) on ECG. Conclusion: Artificial intelligence enhanced ECG based detection of EA is possible with high diagnostic accuracy. Following further refinement and external validation, this algorithm can facilitate early detection of EA using ECGs, a widely available and inexpensive tool. Figure: Receiver operating characteristic (ROC) curve for the performance of the artificial intelligence CNN in detecting EA in the test cohort stratified by (A) age (< 18 and ≥ 18 years) and sex and (B) presence of RBBB.

Background: There are limited data about the stage D heart failure (advanced HF) in adults with congenital heart disease. Our study objectives were (1) to determine the incidence of new-onset advanced HF in patients and the relationship between advanced HF and all-cause mortality and (2) to determine the relationship between therapies for advanced HF and all-cause mortality. Methods: Retrospective cohort study of adults with congenital heart disease at Mayo Clinic (2003–2019). We defined advanced HF using the European Society of Cardiology diagnostic criteria for advanced HF. Therapies received by the patients with advanced HF were classified into 3 mutually exclusive groups (treatment pathways): (1) conventional cardiac intervention, (2) transplant listing, and (3) palliative care. Results: Of 5309 patients without advanced HF at baseline assessment, 432 (8%) developed advanced HF during follow-up (1.1%/y), and the incidence of advanced HF was higher in patients with severe or complex congenital heart disease. Onset of advanced HF was associated with 6-fold increase in the risk of mortality. Conventional cardiac intervention was associated with significantly higher risk of mortality as compared to transplant listing. The longer the interval from the initial onset of advanced HF to transplant evaluation, the lower the odds of being listed for transplant. Conclusions: Based on these data, we postulate that early identification of patients with advanced HF, and a timely referral for transplant evaluation (instead of conventional cardiac intervention) may offer the best chance of survival for these critically ill patients. Further studies are required to validate this postulation.

The purpose of this study was to describe procedural outcomes, hemodynamic improvement, regression of left ventricular (LV) mass hypertrophy, and cardiovascular. The primary outcomes were procedural complications, reinterventions, and hemodynamic improvement after coarctation of aorta (COA) repair. The secondary outcomes were improvement in the severity of hypertension, regression of LV mass index, and incidence of cardiovascular events (atrial fibrillation, ventricular tachycardia, heart failure hospitalization, and cardiovascular death) after COA repair. Secondary outcomes were assessed only in patients with isolated COA who had clinical and imaging follow-up at 1 year and 3 years postintervention. Of 172 patients that underwent COA repair (surgical 161; transcatheter 11), there were no procedural deaths, and all patients had residual COA gradient <20 mm Hg. Of 128 patients that met criteria for secondary outcomes assessment, 39 (36%) had a reduction in the intensity of antihypertension therapy, and cardiovascular events occurred in 16 (13%) patients. There was no significant reduction in the overall prevalence of hypertension (stage 1 and stage 2) over time (78% versus 70% versus 73%, P =0.4 at baseline, 1 year and 3 years). Postintervention hypertension (both stage 1 and 2) were independent risk factors for suboptimal left ventricular mass index regression and cardiovascular events. Persistent hypertension was common after repair of native COA in adults and was associated with suboptimal left ventricular mass index regression and cardiovascular events. These results suggest that optimal blood pressure control with medical therapy after COA repair may result in improved clinical outcomes.

Objective To review the long-term functional outcomes of patients with Ebstein anomaly who had cardiac surgery at our institution. Methods From April 1, 1972 to January 1, 2006, 539 patients with Ebstein anomaly had 604 cardiac operations at Mayo Clinic Rochester. The 506 late survivors form the basis of this report. Patient records were reviewed and all patients were mailed a medical questionnaire or contacted by telephone. Patients who had associated complex congenital heart disease were excluded (pulmonary atresia, conotruncal abnormalities, and atrioventricular discordance and ventriculoarterial discordance). Results At the initial operation at our institution, the mean age was 24 years (range 8 days to 79 years) and 53% were female. Survival at 5, 10, 15, and 20 years was 94%, 90%, 86%, and 76%. Survival free of late reoperation was 86%, 74%, 62%, and 46% at 5, 10, 15, and 20 years respectively. Surveys were returned by 285 patients. Two hundred and thirty-seven (83%) of patients were in NYHA class I or II and 34% were taking no cardiac medication. Five patients (2%) reported having endocarditis, 1 patient (<1%) reported a stroke, and 103 patients (36%) had atrial fibrillation or flutter. There were a total of 202 pregnancies among 82 women. Recurrence of congenital heart disease was low. Only 9/232 (0.04%) of liveborn children had congenital heart disease. Conclusions Patients have good long term survival and functional outcomes, after operation for Ebstein anomaly. Atrial arrhythmias are relatively common both before and after operation. Pregnancy appears to be well tolerated with low recurrence risk of congenital heart disease.

Background Coarctation of the aorta is commonly associated with recoarctation or additional cardiovascular disorders that require intervention. The best surgical approach in such patients is uncertain. Ascending-to-descending aortic bypass graft via the posterior pericardium (CoA bypass) allows simultaneous intracardiac repair or an alternative approach for the patient with complex coarctation. Methods and Results Between 1985 and 2000, 18 patients (13 males and 5 females, mean age 43±13 years) with coarctation of the aorta underwent CoA bypass through median sternotomy. Before operation, average New York Heart Association class was II (range I to IV), and 15 patients (83%) had systemic hypertension. One or more previous cardiovascular operations had been performed in 12 patients (67%); 10 patients had ≥1 prior coarctation repair. Two patients had prior noncoarctation cardiovascular surgery. Concomitant procedures performed in 14 patients (78%) included the following: aortic valve replacement in 9; coronary artery bypass surgery in 3; mitral valve repair in 2; and septal myectomy, mitral valve replacement, aortoplasty, subaortic stenosis resection, ventricular septal defect closure, and ascending aorta replacement in 1 patient each. All patients survived the operation and were alive with patent CoA bypass at a mean follow-up of 45 months. No graft-related complications occurred, and there were no instances of stroke or paraplegia. Systolic blood pressure fell from 159 mm Hg before surgery to 125 mm Hg after surgery. Conclusions CoA bypass via median sternotomy can be performed with low morbidity and mortality. Although management must be individualized, extra-anatomic CoA bypass via the posterior pericardium is an excellent single-stage approach for patients with complex coarctation or recoarctation and concomitant cardiovascular disorders.