Madhavan, Malini

Introduction: Atrial fibrillation (AF) is the most prevalent arrhythmia, placing a substantial burden on the healthcare system. Patients with AF are cared for in a variety of settings including primary care and cardiology clinics, while some require cardiac electrophysiology (EP) clinics offering specialized drugs or procedures. Appropriate triage of AF referrals to these specific clinics will lead to timely and appropriate care and reduce inefficiency in the health system. Goal: To develop a machine learning (ML) model to triage AF referrals to a large Cardiology center to either the Cardiology or EP clinic based on likelihood of requiring an invasive EP procedure or initiation of antiarrhythmic drug. Methods: We retrospectively analyzed 6,755 patients who were referred to CV with referral diagnosis of AF (mean age 70 ± 11 years, 66% male). We employed multiple input variables to predict the suitability for EP clinic defined as need for initiating an antiarrhythmic drug or an invasive EP procedure. These encompassed patient demographics, relevant comorbidities, medications, prior procedures, medical notes analyzed using natural language processing (NLP), and Holter monitoring data. Results: For internal referrals, XG boost model performed the best with AUC at 79%, accuracy at 72%, and F1 score at 68%. This model produces true positive (TP) at 68% and true negative (TN) at 74%, which was better in comparison with triaging using NLP only (AUC = 69%, TP = 58%, TN = 61%), Holter only (AUC = 52%, TP = 51%, TN = 77%), and NLP/Holter (AUC = 67%, TP = 60%, TN = 60%). When supplementing ML model with Holter readings on average HR ≥ 100 and maximum HR ≥ 150, the results can be improved to TP at 70% and TN at 73%. Conclusions: Our model effectively identifies patients who are more likely to require specialized EP care, enabling the automation and increased efficiency of the AF referral triage process. Prospective validation studies are paramount in determining the true value of this tool.

Introduction: The incidence and risk factors for sudden cardiac death (SCD) in patients with systemic right ventricle (sRV) and D-TGA palliated with atrial switch procedures is not well understood. Methods: This cohort was examined retrospectively for the composite end point of SCD, sustained ventricular tachycardia (VT) >30 s or appropriate ICD therapy for VT. Clinical characteristics of those with and without the end point were compared using the Kruskal-Wallis or Chi-square test as appropriate. Results: The composite end point occurred in 15 of 148 (10%) patients (63.5% male) at a mean age of 36.4 (SD 10.3) years. SCD occurred in 6 patients (n=2 successfully resuscitated), sustained VT in 6 patients and ICD therapy for VT in 3 patients who had previously received a primary prevention ICD. Patients with SCD/VT had lower sRV ejection fraction (EF) compared to patients without SCD/VT [28±11 vs 40±10%, P<0.001]. The odds ratio of SCD/VT in patients with sRVEF≤35% compared to sRVEF>35% was 13.3 (95% CI 2.8 - 64.4). Kaplan Meier analysis of time to SCD/VT stratified by sRV EF is presented in figure. QRS duration, QRS fragmentation, QTc and history of systemic AV valve surgery were not significantly associated with SCD/VT. Non-sustained ventricular tachycardia (NSVT) on Holter monitoring occurred more frequently in SCD/VT patients (80 vs 39%, p=0.003). All 11 survivors of SCD/VT received an ICD; appropriate ICD therapy occurred in 27% of these patients during follow-up. Conclusion: SCD or VT occurred in one-tenth of D-TGA patients palliated with atrial switch, predominantly in 3 rd and 4 th decade of life. Reduced sRV EF was the most important association and ICD implantation for primary prevention of SCD is a reasonable consideration in those with reduced sRV EF.

BACKGROUND: The outcomes of catheter ablation for atrial fibrillation in adults with congenital heart disease are not well described. METHODS: In a retrospective study of adult patients with congenital heart disease who underwent catheter ablation for atrial fibrillation between 2000 and 2020 at Mayo Clinic, procedural characteristics and outcomes were collected. The primary outcomes were atrial arrhythmia (AA) recurrence following a 3-month blanking period and repeat ablation. An arrhythmia clinical severity score was assessed pre- and post-ablation based on the duration of arrhythmia episodes, symptoms, cardioversion frequency, and antiarrhythmic drug use. RESULTS: One hundred forty-five patients (age, 57±12 years; 28% female; 63% paroxysmal atrial fibrillation) underwent 198 ablations with a median follow-up of 26 months (interquartile range, 14–69). One hundred ten, 26, and 9 patients had simple, moderate, and complex congenital heart disease, respectively. All patients underwent pulmonary vein isolation, and non–pulmonary vein targets were ablated in 79 (54%). AA recurrence at 12 months was 37% (95% CI, 29%–45%). On univariate analysis, increasing left atrial volume index was associated with higher odds of AA recurrence (odds ratio, 1.03 [1.00–1.06] per 1 mL/m 2 increment; P =0.05). Noninducibility of atrial flutter was predictive of decreased odds of AA recurrence (odds ratio, 0.43 [0.21–0.90]; P =0.03). A second ablation was performed in 43 patients after a median of 20 (interquartile range, 8–37) months. Arrhythmia clinical severity scores improved following ablation, reflecting a decrease in symptoms, cardioversions, and antiarrhythmic drugs. CONCLUSIONS: Catheter ablation of atrial fibrillation is feasible and effective in patients with adult congenital heart disease and reduces symptoms. Recurrence of AA frequently requires repeat ablation.

Background: Patients with ccTGA have a high incidence of atrial arrhythmias and premature failure of the systemic right ventricle. We sought to better define this risk. Methods: A retrospective review of all clinical data for patients with ccTGA followed at a large tertiary care institution was performed. The primary outcome was a composite of death and cardiac transplantation. Results: A cohort of 165 patients (age 41±16 years, 53% male) were followed for 11±8 years; 41 patients died, 7 underwent cardiac transplantation, and 4 underwent VAD placement. Male sex (HR 2.7, p=0.002), older age (HR 1.04, p<0.001), clinical heart failure symptoms (HR 7, p<0.001), heart failure hospitalization (HR 4.9, p<0.001), syncope (HR 1.8, p=0.04) and pulmonary hypertension (HR 2.77, p<0.001) were significant predictors of the primary outcome. Atrial fibrillation (HR 3.5, p=0.002), atrial flutter (HR 3.05, p=0.04), and prolonged QRS duration (HR 1.01, p=0.004) on the first ECG, as well as right and left atrial enlargement (HR 4, p<0.001 and 3.7, p<0.003) and severe systemic AV valve regurgitation (HR 3.8, p=0.03) on the first echocardiogram were associated with poor outcomes. Atrial arrhythmias occurred in 110(67%) patients: atrial fibrillation in 75(45%), atrial flutter in 50(30%), and supraventricular tachycardia in 16(9.7%) patients. Arrhythmias were largely asymptomatic in 109(66%) patients, while 25(14.5%) experienced palpitations, dizziness or presyncope, and 10(6%) presented with decompensated heart failure. Cardioversion and antiarrhythmic therapy were utilized in 53(32%) patients. Surgical pulmonary vein isolation or atrial MAZE were performed in 15(9%) patients, cryoablation of the CTI in 3 patients, and surgical ablation of an accessory pathway in 2 patients. One or more catheter ablation procedures were also performed in 18(11%) patients. Conclusions: Atrial fibrillation and flutter, heart failure, prolonged QRS duration, systemic AV valve regurgitation and pulmonary hypertension predict worse outcomes in ccTGA. Although asymptomatic in a majority of patients, atrial arrhythmias are associated with significant morbidity and mortality. Whether a rhythm control strategy even in asymptomatic patients may improve outcomes remains unknown.

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.

Abstract Background In contrast to bloodstream infection due to a variety of bacteria in patients with cardiovascular implantable electronic devices (CIED), there are limited data regarding candidemia and risk of CIED infection. Methods All patients with candidemia and a CIED at Mayo Clinic Rochester between 2012 and 2019 were reviewed. Cardiovascular implantable electronic device infection was defined by (1) clinical signs of pocket site infection or (2) echocardiographic evidence of lead vegetations. Results A total of 23 patients with candidemia had underlying CIED; 9 (39.1%) cases were community onset. None of the patients had pocket site infection. The duration between CIED placement and candidemia was prolonged (median 3.5 years; interquartile range, 2.0–6.5). Only 7 (30.4%) patients underwent transesophageal echocardiography and 2 of 7 (28.6%) had lead masses. Only the 2 patients with lead masses underwent CIED extraction, but device cultures were negative for Candida species. Two (33.3%) of 6 other patients who were managed as candidemia without device infection subsequently developed relapsing candidemia. Cardiovascular implantable electronic device removal was done in both patients and device cultures grew Candida species. Although 17.4% of patients were ultimately confirmed to have CIED infection, CIED infection status was undefined in 52.2%. Overall, 17 (73.9%) patients died within 90 days of diagnosis of candidemia. Conclusions Although current international guidelines recommend CIED removal in patients with candidemia, the optimal management strategy remains undefined. This is problematic because candidemia alone is associated with increased morbidity and mortality as seen in this cohort. Moreover, inappropriate device removal or retention can both result in increased patient morbidity and mortality.

Abstract Background Cardiovascular implantable electronic devices (CIED) infection carries significant morbidity, mortality, and financial burden. Bacteremia in patients with CIED increases risk of CIED infection. While several investigations have examined Staphylococcus aureus bacteremia and risk of CIED infection, data regarding non-S. aureus gram-positive coccal (non-SA GPC) bacteremia in patients with CIED has been both limited and dated. The current study examined the clinical characteristics of patients with CIED who developed non-SA GPC bacteremia and their proclivity of CIED infection. Methods We reviewed all patients with CIED who developed non-SA GPC bacteremia at Mayo Clinic between 2012–2019. Cases with a left ventricular assist device, non-hospitalization, and contaminated blood culture were excluded. The 2019 European Heart Rhythm Association International Consensus Document was used to define CIED infection. Results A total of 160 patients with CIED developed non-SA GPC bacteremia during the period. Ninety (56.2%) patients had CIED infection, with 60 (37.5%) classified as definite and 30 (18.8%) possible. This included 41/64 (64.1%) patients with coagulase-negative Staphylococcus (CoNS), 30/41 (73.2%) patients with Enterococcus, 13/19 (68.4%) patients with viridans group streptococci (VGS), and 6/36 (16.6%) patients with other non-SA GPC. The odds of CIED infection (with 95% CI) for CoNS, Enterococcus, and VGS bacteremia were 8.9 (3.2–24.6), 13.6 (4.5–41.6), and 10.8 (2.9–40.0) -fold higher, respectively, as compared to other non-SA GPC. Among those with infected CIED, 51 (56.7%) patients underwent complete device extraction after a median of 6 (IQR 3.5–10) days. In an unadjusted analysis of patients with CIED infection, the reduction in one-year mortality following device removal was not statistically significant (HR 0.59, 95% CI 0.26–1.33, p=0.198). Conclusion The overall prevalence of CIED infection following non-SA GPC bacteremia was higher than previously reported, particularly that due to CoNS, Enterococcus, and VGS. Further study with a larger cohort is needed to demonstrate the survival benefit from CIED extraction in patients with infected CIED due to non-SA GPC. Disclosures Larry M. Baddour, M.D., Boston Scientific: Advisor/Consultant|Botanix Pharmaceuticals: Advisor/Consultant|Roivant Sciences: Advisor/Consultant|UpToDate, Inc.: Royalty payments - authorship duties Rizwan Sohail, M.D., Aziyo Biologics: Advisor/Consultant|Boston Scientific: Advisor/Consultant|Medtronic: Advisor/Consultant|Philips: Advisor/Consultant|Philips: Honoraria Malini Madhavan, M.B.B.S., Biosense Webster: Advisor/Consultant|Biotronik Inc: Advisor/Consultant|Boston Scientific: Grant/Research Support|Convatec: Advisor/Consultant.

Objective Supraventricular arrhythmias are common in adults with Ebstein anomaly (EA). However, there are limited data about prognostic implications of atrial fibrillation (AF) in this population. Accordingly, our aim was to assess the clinical profile and burden of AF in adults with EA, and the relationship between AF and outcomes. Methods and results Six hundred eighty-two consecutive adults with a median age of 36 (24–49) years from Mayo Clinic, Minnesota, USA, between 2003 and 2020 were included. Sustained episodes of AF, clinical, echocardiographic, rhythm and surgical data were collected. Prevalence of AF at baseline was 18% (126 patients); the first episode occurred at a mean age of 43±17 years. Patients with AF were older, were more likely men, and had hypertension, renal dysfunction, cardiac devices, and more advanced right-sided and left-sided remodelling. During a median follow-up of 156 (81–240) months, 62 patients (11%) developed incident AF. At the last encounter, prevalence of AF was 28% (188 patients); of those, 63 (34%) had recurrent AF. Hospitalisation for heart failure (HF) occurred in 51 patients (7%). AF (HR 2.32, 95% CI 1.18 to 4.47; p=0.01) was independently associated with hospitalisation for HF. All-cause death occurred in 53 patients (8%); it was more frequent in those with AF in the univariable analysis, although it did not remain significant in the multivariable analysis. Conclusions AF in EA develops at relatively young ages with one-third of the cohort exhibiting a recurrent pattern. Patients with AF had a higher prevalence of comorbidities and worse right-sided and left-sided cardiac remodelling. AF was independently associated with HF hospitalisation.

Background The objective of this international multicenter study was to investigate both early and late outcomes of cardiac resynchronization therapy (CRT) in patients with a systemic right ventricle (SRV) and to identify predictors for congestive heart failure readmissions and mortality. Methods and Results This retrospective international multicenter study included 13 centers. The study population comprised 80 adult patients with SRV (48.9% women) with a mean age of 45±14 (range, 18–77) years at initiation of CRT. Median follow‐up time was 4.1 (25th–75th percentile, 1.3–8.3) years. Underlying congenital heart disease consisted of congenitally corrected transposition of the great arteries and dextro‐transposition of the great arteries in 63 (78.8%) and 17 (21.3%) patients, respectively. CRT resulted in significant improvement in functional class (before CRT: III, 25th–75th percentile, II–III; after CRT: II, 25th–75th percentile, II–III; P =0.005) and QRS duration (before CRT: 176±27; after CRT: 150±24 milliseconds; P =0.003) in patients with pre‐CRT ventricular pacing who underwent an upgrade to a CRT device (n=49). These improvements persisted during long‐term follow‐up with a marginal but significant increase in SRV function (before CRT; 30%, 25th–75th percentile, 25–35; after CRT: 31%, 25th–75th percentile, 21–38; P =0.049). In contrast, no beneficial change in the above‐mentioned variables was observed in patients who underwent de novo CRT (n=31). A quarter of all patients were readmitted for heart failure during follow‐up, and mortality at latest follow‐up was 21.3%. Conclusions This international experience with CRT in patients with an SRV demonstrated that CRT in selected patients with SRV dysfunction and pacing‐induced dyssynchrony yielded consistent improvement in QRS duration and New York Heart Association functional status, with a marginal increase in SRV function.

Background: Mitral annular disjunction (MAD) has recently been recognized as an arrhythmogenic entity. Data on the electrophysiological substrate as well as the outcomes of catheter ablation of ventricular arrhythmias in patients with MAD is limited. Methods: Forty patients with MAD (mean age 47±15 years; 70% female) underwent catheter ablation for ventricular arrhythmias. Detailed clinical, electrocardiographic, cardiac imaging, and procedural data were collected. Clinical outcomes were compared between patients who had substrate modification in the MAD area and those who did not. Results: Twenty-three (57.5%) patients had ablation for premature ventricular contractions, 10 (25%) patients for sustained ventricular tachycardia, and 7 (17.5%) patients for premature ventricular contraction-triggered ventricular fibrillation. Mean end-systolic MAD length was 10.58±3.49 mm on transthoracic echocardiography. Seventeen (42.5%) patients had preprocedural cardiac magnetic resonance imaging, and 5 (29%) patients had late gadolinium enhancement. Among the 18 (45%) patients who had abnormal local electrograms (low voltage, long-duration, fractionated, isolated mid-diastolic potentials) during electroanatomical mapping, 10 (25%) patients had abnormal electrograms in the anterolateral mitral annulus and/or MAD area. Substrate modification was performed in 10 (25%) patients. Catheter ablation was acutely successful in 36 (90%) patients (elimination of premature ventricular contraction or noninducibility of ventricular tachycardia). After a median follow-up duration of 54.08 (interquartile range, 10.67–89.79) months, premature ventricular contraction burden decreased from a median of 9.75% (interquartile range, 3.25–14) before the ablation to a median of 4% (interquartile range, 1–7.75) after the ablation ( P =0.03 [95% CI, 0.055–6.5]). Eight (20.5%) patients had repeat ablation for ventricular arrhythmias. Substrate modification of the MAD was associated with a trend toward lower rates of repeat ablation (0% versus 26.7%; P =0.16). Conclusions: Patients with MAD have a complex arrhythmogenic substrate, and catheter ablation is effective in reducing recurrence of ventricular arrhythmias. Substrate mapping and ablation may be considered in these patients.