Substrate Characterization and Outcomes of Ventricular Tachycardia Ablation in Amyloid Cardiomyopathy: A Multicenter Study.

BACKGROUND: Sustained ventricular tachycardia (VT) in cardiac amyloidosis is uncommon, and the substrate and outcomes of catheter ablation are not defined. METHODS: We included 22 consecutive patients (mean age, 68±10 years; male sex, 91%) with cardiac amyloidosis (ATTR [transthyretin], n=16; light chain, n=6) undergoing catheter ablation for VT/ventricular fibrillation (VF) between 2013 and 2023 in a retrospective, observational, international study. The primary efficacy outcome was recurrent VT/VF during follow-up, while the primary safety end point included major procedure-related adverse events. RESULTS: The indication for ablation was drug-refractory VT in 17 patients (77%), and premature ventricular complex-initiated polymorphic VT/VF in 5 patients (23%). Catheter ablation was performed using endocardial (n=17.77%) or endo-epicardial approaches (n=5.23%). Complete endocardial electroanatomical voltage maps of the left and right ventricles were obtained in 17 (77%) and 10 (45%) patients, respectively. Each patient had evidence of low-voltage areas, most commonly involving the interventricular septum (n=16); late potentials were recorded in 16 patients (73%). A median of 1 (1-2) VT was inducible per patient; 12 of the 26 mappable VTs (46%) originated from the interventricular septum. Complete procedural success was achieved in 16 patients (73%), with 4 (18%) major procedure-related adverse events. After a median follow-up of 32 (14-42) months, sustained VT/VF recurrence was observed in 9 patients (41%); survival free from VT/VF recurrence was 56% (95% CI, 36%-86%) at 36-month follow-up, and most patients remained on antiarrhythmic drugs. A significant reduction in per patient implantable cardioverter defibrillator therapies was noted in the 6-month period after ablation (before: 6 [4-9] versus after: 0 [0-0]; P<0.001). In multivariable analysis, complete procedural success was associated with reduced risk of recurrent VT/VF (hazard ratio, 0.002; P=0.034). CONCLUSIONS: Catheter ablation can achieve control of recurrent VT/VF in more than half of patients with cardiac amyloidosis, and the reduction in VT/VF burden post-ablation may be relevant for quality of life. Septal substrate and risk of procedure-related complications challenge successful management of patients with cardiac amyloidosis and VT/VF.

Case Report: Electroanatomic mapping as an early diagnostic tool in arrhythmogenic cardiomyopathy.

Background: Abnormal substrate on invasive electroanatomic mapping (EAM) correlates with areas of myocardial thinning and fibrofatty replacement in Arrhythmogenic Cardiomyopathy (ACM). However, EAM parameters are absent from all sets of diagnostic criteria for ACM. Case summary: A 41-year-old female with no significant family history was referred for evaluation of frequent premature ventricular complexes (PVCs). Twelve-lead ECG showed diffuse low-voltage QRS complexes. Holter monitor showed 28% burden of PVCs with various morphologies consistent with right ventricular (RV) inflow and outflow tract exits. Transthoracic echocardiogram revealed normal biventricular function and dimension. Cardiac magnetic resonance revealed a mildly increased indexed RV end-diastolic volume with normal RV systolic function and no dyssynchrony, akinesia, dyskinesia, or late gadolinium enhancement. Electrophysiologic study demonstrated 2 predominant PVC morphologies that were targeted with ablation, in addition to extensive abnormality with low-voltage and fractionated electrograms in the peri-tricuspid and right ventricular outflow tract free wall regions with septal sparing, suggestive of RV cardiomyopathy. Subsequent genetic testing revealed two pathogenic variants in the desmoplakin and plakophilin-2 genes, confirming the diagnosis of ACM. Conclusion: Advanced RV electropathy can precede RV structural changes in ACM. Invasive evaluation of the electroanatomic substrate should be considered in select cases even when imaging findings are not diagnostic. Future iterations of ACM guidelines may need to consider EAM substrate as one of the diagnostic criteria. A high index of diagnostic suspicion for ACM should be maintained in patients with multifocal RV ectopy.

Hypertrophic cardiomyopathy detection with artificial intelligence electrocardiography in international cohorts: an external validation study.

Aims: Recently, deep learning artificial intelligence (AI) models have been trained to detect cardiovascular conditions, including hypertrophic cardiomyopathy (HCM), from the 12-lead electrocardiogram (ECG). In this external validation study, we sought to assess the performance of an AI-ECG algorithm for detecting HCM in diverse international cohorts. Methods and results: A convolutional neural network-based AI-ECG algorithm was developed previously in a single-centre North American HCM cohort (Mayo Clinic). This algorithm was applied to the raw 12-lead ECG data of patients with HCM and non-HCM controls from three external cohorts (Bern, Switzerland; Oxford, UK; and Seoul, South Korea). The algorithm's ability to distinguish HCM vs. non-HCM status from the ECG alone was examined. A total of 773 patients with HCM and 3867 non-HCM controls were included across three sites in the merged external validation cohort. The HCM study sample comprised 54.6% East Asian, 43.2% White, and 2.2% Black patients. Median AI-ECG probabilities of HCM were 85% for patients with HCM and 0.3% for controls (P < 0.001). Overall, the AI-ECG algorithm had an area under the receiver operating characteristic curve (AUC) of 0.922 [95% confidence interval (CI) 0.910-0.934], with diagnostic accuracy 86.9%, sensitivity 82.8%, and specificity 87.7% for HCM detection. In age- and sex-matched analysis (case-control ratio 1:2), the AUC was 0.921 (95% CI 0.909-0.934) with accuracy 88.5%, sensitivity 82.8%, and specificity 90.4%. Conclusion: The AI-ECG algorithm determined HCM status from the 12-lead ECG with high accuracy in diverse international cohorts, providing evidence for external validity. The value of this algorithm in improving HCM detection in clinical practice and screening settings requires prospective evaluation.

Secondary tricuspid regurgitation: incidence, types, and outcomes in atrial fibrillation vs. sinus rhythm.

BACKGROUND AND AIMS: Incidence and types of secondary tricuspid regurgitation (TR) are not well defined in atrial fibrillation (AFib) and sinus rhythm (SR). Atrial secondary TR (A-STR) is associated with pre-existing AFib; however, close to 50% of patients with A-STR do not have AFib. The aim of this study was to assess incidence, types, and outcomes of ≥ moderate TR in AFib vs. SR. METHODS: Adults with and without new-onset AFib without structural heart disease or ≥ moderate TR at baseline were followed for the development of ≥ moderate TR. Tricuspid regurgitation types were pacemaker, left-sided valve disease, left ventricular (LV) dysfunction, pulmonary hypertension (PH), isolated ventricular, and A-STR. RESULTS: Among 1359 patients with AFib and 20 438 in SR, 109 and 378 patients developed ≥ moderate TR, respectively. The individual types of TR occurred more frequently in AFib related to the higher pacemaker implantation rates (1.12 vs. 0.19 per 100 person-years, P < .001), larger right atrial size (median 78 vs. 53 mL, P < .001), and higher pulmonary pressures (median 30 vs. 28 mmHg, P < .001). The most common TR types irrespective of rhythm were LV dysfunction-TR and A-STR. Among patients in SR, those with A-STR were older, predominantly women with more diastolic abnormalities and higher pulmonary pressures. All types of secondary TR were associated with all-cause mortality, highest in PH-TR and LV dysfunction-TR. CONCLUSIONS: New-onset AFib vs. SR conferred a higher risk of the individual TR types related to sequelae of AFib and higher pacemaker implantation rates, although the distribution of TR types was similar. Secondary TR was universally associated with increased mortality.

Ten-Year Trend of Oral Anticoagulation Use in Postoperative and Nonpostoperative Atrial Fibrillation in Routine Clinical Practice.

BACKGROUND: The study aimed to describe the patterns and trends of initiation, discontinuation, and adherence of oral anticoagulation (OAC) in patients with new-onset postoperative atrial fibrillation (POAF), and compare with patients newly diagnosed with non-POAF. METHODS AND RESULTS: This retrospective cohort study identified patients newly diagnosed with atrial fibrillation or flutter between 2012 and 2021 using administrative claims data from OptumLabs Data Warehouse. The POAF cohort included 118 366 patients newly diagnosed with atrial fibrillation or flutter within 30 days after surgery. The non-POAF cohort included the remaining 315 832 patients who were newly diagnosed with atrial fibrillation or flutter but not within 30 days after a surgery. OAC initiation increased from 28.9% to 44.0% from 2012 to 2021 in POAF, and 37.8% to 59.9% in non-POAF; 12-month medication adherence increased from 47.0% to 61.8% in POAF, and 59.7% to 70.4% in non-POAF. The median time to OAC discontinuation was 177 days for POAF, and 242 days for non-POAF. Patients who saw a cardiologist within 90 days of the first atrial fibrillation or flutter diagnosis, regardless of POAF or non-POAF, were more likely to initiate OAC (odds ratio, 2.92 [95% CI, 2.87-2.98]; P <0.0001), adhere to OAC (odds ratio, 1.08 [95% CI, 1.04-1.13]; P <0.0001), and less likely to discontinue (odds ratio, 0.83 [95% CI, 0.82-0.85]; P <0.0001) than patients who saw a surgeon or other specialties. CONCLUSIONS: The use of and adherence to OAC were higher in non-POAF patients than in POAF patients, but they increased over time in both groups. Patients managed by cardiologists were more likely to use and adhere to OAC, regardless of POAF or non-POAF.

A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome.

Importance: Sudden death and cardiac arrest frequently occur without explanation, even after a thorough clinical evaluation. Calcium release deficiency syndrome (CRDS), a life-threatening genetic arrhythmia syndrome, is undetectable with standard testing and leads to unexplained cardiac arrest. Objective: To explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS. Design, Setting, and Participants: An international, multicenter, case-control study including individual cases of CRDS, 3 patient control groups (individuals with suspected supraventricular tachycardia; survivors of unexplained cardiac arrest [UCA]; and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia [CPVT]), and genetic mouse models (CRDS, wild type, and CPVT were used to define the cellular mechanism) conducted at 10 centers in 7 countries. Patient tracings were recorded between June 2005 and December 2023, and the analyses were performed from April 2023 to December 2023. Intervention: Brief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing). Main Outcomes and Measures: Change in QT interval and change in T-wave amplitude (defined as the difference between their absolute values on the postpause sinus beat and the last beat prior to tachycardia). Results: Among 10 case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, 10 control patients who experienced UCA, and 3 control patients with genotype-positive CPVT, the median change in T-wave amplitude on the postpause sinus beat (after brief ventricular tachycardia at ≥150 beats/min) was higher in patients with CRDS (P < .001). The smallest change in T-wave amplitude was 0.250 mV for a CRDS case patient compared with the largest change in T-wave amplitude of 0.160 mV for a control patient, indicating 100% discrimination. Although the median change in QT interval was longer in CRDS cases (P = .002), an overlap between the cases and controls was present. The genetic mouse models recapitulated the findings observed in humans and suggested the repolarization response was secondary to a pathologically large systolic release of calcium from the sarcoplasmic reticulum. Conclusions and Relevance: There is a unique repolarization response on an electrocardiogram after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls. If these findings are confirmed in larger studies, this easy to perform maneuver may serve as an effective clinical diagnostic test for CRDS and become an important part of the evaluation of cardiac arrest.

Atrial Fibrillation Substrate and Catheter Ablation Outcomes in MYBPC3- and MYH7-Mediated Hypertrophic Cardiomyopathy.

BACKGROUND: The effects of disease-causing MYBPC3 or MYH7 genetic variants on atrial myopathy, atrial fibrillation (AF) clinical course, and catheter ablation efficacy remain unclear. OBJECTIVES: The aim of this study was to characterize the atrial substrate of patients with MYBPC3- or MYH7-mediated hypertrophic cardiomyopathy (HCM) and its impact on catheter ablation outcomes. METHODS: A retrospective single-center study of patients with HCM who underwent genetic testing and catheter ablation for AF was performed. Patients with MYBPC3- or MYH7-mediated HCM formed the gene-positive cohort; those without disease-causative genetic variants formed the control cohort. High-density electroanatomical mapping was performed using a 3-dimensional mapping system, followed by radiofrequency ablation. RESULTS: Twelve patients were included in the gene-positive cohort (mean age 55.6 ± 9.9 years, 83% men, 50% MYBPC3, 50% MYH7, mean ejection fraction 59.3% ± 13.7%, mean left atrial [LA] volume index 51.7 ± 13.1 mL/m2, mean LA pressure 20.2 ± 5.4 mm Hg) and 15 patients in the control arm (mean age 61.5 ± 12.6 years, 60% men, mean ejection fraction 64.9% ± 5.1%, mean LA volume index 54.1 ± 12.8 mL/m2, mean LA pressure 19.6 ± 5.41 mm Hg). Electroanatomical mapping demonstrated normal voltage in 87.7% ± 5.03% of the LA in the gene-positive cohort and 94.3% ± 3.58% of the LA in the control cohort (P < 0.001). Of the abnormal regions, intermediate scar (0.1-0.5 mV) accounted for 6.33% ± 1.97% in the gene-positive cohort and 3.07% ± 2.46% in the control cohort (P < 0.01). Dense scar (<0.1 mV) accounted for 5.93% ± 3.20% in the gene-positive cohort and 2.61% ± 2.19% in the control cohort (P < 0.01). Freedom from AF at 12 months was similar between the gene-positive (75%) and control (73%) cohorts (P = 0.92), though a greater number of procedures were required in the gene-positive cohort. CONCLUSIONS: Patients with MYBPC3- or MYH7-mediated HCM undergoing AF ablation have appreciably more low-amplitude LA signals, suggestive of fibrosis. However, catheter ablation remains an effective rhythm-control strategy.

Mitral valve prolapse: arrhythmic risk during pregnancy and postpartum.

BACKGROUND AND AIMS: Arrhythmic mitral valve prolapse (AMVP) is linked to life-threatening ventricular arrhythmias (VAs), and young women are considered at high risk. Cases of AMVP in women with malignant VA during pregnancy have emerged, but the arrhythmic risk during pregnancy is unknown. The authors aimed to describe features of women with high-risk AMVP who developed malignant VA during the perinatal period and to assess if pregnancy and the postpartum period were associated with a higher risk of malignant VA. METHODS: This retrospective international multi-centre case series included high-risk women with AMVP who experienced malignant VA and at least one pregnancy. Malignant VA included ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock from an implantable cardioverter defibrillator. The authors compared the incidence of malignant VA in non-pregnant periods and perinatal period; the latter defined as occurring during pregnancy and within 6 months after delivery. RESULTS: The authors included 18 women with AMVP from 11 centres. During 7.5 (interquartile range 5.8-16.6) years of follow-up, 37 malignant VAs occurred, of which 18 were pregnancy related occurring in 13 (72%) unique patients. Pregnancy and 6 months after delivery showed increased incidence rate of malignant VA compared to the non-pregnancy period (univariate incidence rate ratio 2.66, 95% confidence interval 1.23-5.76). CONCLUSIONS: The perinatal period could impose increased risk of malignant VA in women with high-risk AMVP. The data may provide general guidance for pre-conception counselling and for nuanced shared decision-making between patients and clinicians.

Unlocking the potential of artificial intelligence in electrocardiogram biometrics: age-related changes, anomaly detection, and data authenticity in mobile health platforms.

Aims: Mobile devices such as smartphones and watches can now record single-lead electrocardiograms (ECGs), making wearables a potential screening tool for cardiac and wellness monitoring outside of healthcare settings. Because friends and family often share their smart phones and devices, confirmation that a sample is from a given patient is important before it is added to the electronic health record. Methods and results: We sought to determine whether the application of Siamese neural network would permit the diagnostic ECG sample to serve as both a medical test and biometric identifier. When using similarity scores to discriminate whether a pair of ECGs came from the same patient or different patients, inputs of single-lead and 12-lead medians produced an area under the curve of 0.94 and 0.97, respectively. Conclusion: The similar performance of the single-lead and 12-lead configurations underscores the potential use of mobile devices to monitor cardiac health.

Interventional cardiologists' perspectives and knowledge towards artificial intelligence.

BACKGROUND: Artificial intelligence (AI) is increasingly utilized in interventional cardiology (IC) and holds the potential to revolutionize the field. METHODS: We conducted a global, web-based, anonymous survey of IC fellows and attendings to assess the knowledge and perceptions of interventional cardiologists regarding AI use in IC. RESULTS: A total of 521 interventional cardiologists participated in the survey. The median age range of participants was 36 to 45 years, most (51.5%) practice in the United States, and 7.5% were women. Most (84.7%) could explain well or somehow knew what AI is about, and 63.7% were optimistic/very optimistic about AI in IC. However, 73.5% believed that physicians know too little about AI to use it on patients and most (46.1%) agreed that training will be necessary. Only 22.1% were currently implementing AI in their personal clinical practice, while 60.6% estimated implementation of AI in their practice during the next 5 years. Most agreed that AI will increase diagnostic efficiency, diagnostic accuracy, treatment selection, and healthcare expenditure, and decrease medical errors. The most tried AI-powered tools were image analysis (57.3%), ECG analysis (61.7%), and AI-powered algorithms (45.9%). Interventional cardiologists practicing in academic hospitals were more likely to have AI tools currently implemented in their clinical practice and to use them, women had a higher likelihood of expressing concerns regarding AI, and younger interventional cardiologists were more optimistic about AI integration in IC. CONCLUSIONS: Our survey suggests a positive attitude of interventional cardiologists regarding AI implementation in the field of IC.

Arrhythmic manifestations and outcomes of definite and probable cardiac sarcoidosis.

BACKGROUND: The 2014 Heart Rhythm Society consensus statement defines histological (definite) and clinical (probable) diagnostic categories of cardiac sarcoidosis (CS), but few studies have compared their arrhythmic phenotypes and outcomes. OBJECTIVE: The purpose of this study was to evaluate the electrophysiological/arrhythmic phenotype and outcomes of patients with definite and probable CS. METHODS: We analyzed the arrhythmic/electrophysiological phenotype in a single-center North American cohort of 388 patients (median age 56 years; 39% female, n = 151) diagnosed with definite (n = 58) or probable (n = 330) CS (2000-2022). The primary composite outcome was survival to first ventricular tachycardia/fibrillation (VT/VF) event or sudden cardiac death. Key secondary outcomes were also assessed. RESULTS: At index evaluation, in situ cardiac implantable electronic devices and antiarrhythmic drug use were more common in definite CS. At a median follow-up of 3.1 years, the primary outcome occurred in 22 patients with definite CS (38%) and 127 patients with probable CS (38%) (log-rank, P = .55). In multivariable analysis, only a higher ratio of the 18F-fluorodeoxyglucose maximum standardized uptake value of the myocardium to the maximum standardized uptake value of the blood pool (hazard ratio 1.09; 95% confidence interval 1.03-1.15; P = .003, per 1 unit increase) was associated with the primary outcome. During follow-up, patients with definite CS had a higher burden of device-treated VT/VF events (mean 2.86 events per patient-year vs 1.56 events per patient-year) and a higher rate of progression to heart transplant/left ventricular assist device implantation but no difference in all-cause mortality compared with patients with probable CS. CONCLUSION: Patients with definite and probable CS had similarly high risks of first sustained VT/VF/sudden cardiac death and all-cause mortality, though patients with definite CS had a higher overall arrhythmia burden. Both CS diagnostic groups as defined by the 2014 Heart Rhythm Society criteria require an aggressive approach to prevent arrhythmic complications.

Artificial intelligence-enhanced electrocardiogram for arrhythmogenic right ventricular cardiomyopathy detection.

Aims: ECG abnormalities are often the first signs of arrhythmogenic right ventricular cardiomyopathy (ARVC) and we hypothesized that an artificial intelligence (AI)-enhanced ECG could help identify patients with ARVC and serve as a valuable disease-detection tool. Methods and results: We created a convolutional neural network to detect ARVC using a 12-lead ECG. All patients with ARVC who met the 2010 task force criteria and had disease-causative genetic variants were included. All case ECGs were randomly assigned in an 8:1:1 ratio into training, validation, and testing groups. The case ECGs were age- and sex-matched with control ECGs at our institution in a 1:100 ratio. Seventy-seven patients (51% male; mean age 47.2 ± 19.9), including 56 patients with PKP2, 7 with DSG2, 6 with DSC2, 6 with DSP, and 2 with JUP were included. The model was trained using 61 case ECGs and 5009 control ECGs; validated with 7 case ECGs and 678 control ECGs and tested in 22 case ECGs and 1256 control ECGs. The sensitivity, specificity, positive and negative predictive values of the model were 77.3, 62.9, 3.32, and 99.4%, respectively. The area under the curve for rhythm ECG and median beat ECG was 0.75 and 0.76, respectively. Conclusion: Our study found that the model performed well in excluding ARVC and supports the concept that the AI ECG can serve as a biomarker for ARVC if a larger cohort were available for network training. A multicentre study including patients with ARVC from other centres would be the next step in refining, testing, and validating this algorithm.

Ventricular Tachycardia Ablation in Patients With Desmoplakin Cardiomyopathy.

BACKGROUND: Desmoplakin (DSP) pathogenic variants are rare causes of arrhythmogenic cardiomyopathy and often involve the right and left ventricles. Ventricular tachycardia (VT) ablations may be required in these patients, but procedural characteristics have not been reported. OBJECTIVES: In this study, the authors sought to report a multicenter experience of VT ablation in patients with DSP pathogenic variants. METHODS: VT ablations performed in patients with known DSP pathogenic variants were analyzed across 6 centers in 3 countries. Patient characteristics and acute and long-term procedural outcomes were reported. RESULTS: A total of 20 patients (13 men, median age 43 years [Q1-Q3: 41.5-53.0 years], left ventricular ejection fraction 43.0% [Q1-Q3: 41.5%-53.0%], 11 previous failed ablations) were referred for VT ablation procedures. All patients had symptomatic VTs, with ICD therapy in 19 patients. Epicardial procedures were performed in 16 of the 20 patients. VT target sites were located in the right ventricular (RV) endocardium (n = 11), the RV epicardium (n = 4), the left ventricular (LV) endocardium (n = 2) and the LV epicardium (n = 7). In 3 patients, the VT target sites were in close proximity to coronary arteries, limiting ablation. During follow-up, VTs recurred in 11 patients, and repeated ablations were performed in 9 patients. Allowing for multiple procedures, 19 of the 20 patients remained free of VT recurrence after a median follow-up of 18 months [Q1-Q3: 5-60 months]. CONCLUSIONS: Patients with DSP cardiomyopathy often have biventricular involvement, and ablation procedures often require ablation in both ventricles and the epicardium. Recurrences are not uncommon, and the pathologic substrate can be located in close proximity to epicardial coronary arteries, limiting the success rate of ablations.