Electrical and structural remodeling of the heart can contribute to the development of cardiac arrhythmias. Ex vivo optical mapping has been used to visualize cardiac electrophysiological properties, activation and phase maps to further elucidate the mechanisms of atrial fibrillation and ventricular fibrillation initiation and persistence. Here we show an epicardial three-dimensional panoramic optical mapping tool integrated with micro-computed tomography automatically segmented with a deep learning model relying on a convolutional neural network to provide structural and electrical activation information in a single three-dimensional volume of a mouse heart. This technique allows for the acquisition and analysis of electrical activity of the entire epicardial surface with submillimeter spatial resolution and a temporal resolution of 1 ms. We establish the use of this method in transgenic mouse hearts with spontaneous atrial fibrillation and ventricular fibrillation, and mouse surgical models of myocardial infarction and left ventricular hypertrophy.

Background:There are limited data on changes in atrial fibrillation (AF) burden after antiarrhythmic drug (AAD) initiation. Objective:The purpose of this study was to quantify AF burden after AAD initiation in patients with cardiac implantable electronic devices (CIEDs). Methods:We conducted a retrospective study of all patients with CIEDs from 2 academic hospitals with new AAD initiation between April 2018 and March 2022. AF burden was quantified in patients with CIEDs at up to 6 months pre- and 12 months post-AAD initiation. Results:There were 128 patients (mean age 73.6 ± 12.2 years; 78 [61%] male) included in the analysis. The mean time to first AF burden measurement post-AAD initiation was 5.0 ± 6.8 months, and 98 (76.6%) patients had >1 post-AAD AF burden measurement. There was a significant reduction in AF burden at both the first and final interrogations post-AAD initiation relative to pre-AAD AF burden {pre: 5.9% (interquartile range [IQR] 1.3%-29.7%); first post: 0.2% (IQR 0%-2.9%); final: 0.1% (IQR 0%-1.5%)}. The median reduction in AF burden was 90.5% (IQR 2.7%-100%) at the first interrogation and 97.4% (IQR 35.7%-100%) at the final interrogation. A significant reduction in AF burden was seen at both time points in subgroups prescribed amiodarone and nonamiodarone AADs as well as in those with high (≥90%) and low (≤20%) baseline AF burden (P < .05 for all). In patients with AF >30 seconds after AAD initiation, the median reduction in AF burden was 72.1% (IQR 5.3%-96.9%) at the final interrogation. Conclusion:There was a median reduction in AF burden of 97.4% (IQR 35.7%-100%) after AAD initiation in patients with CIEDs at the final interrogation. Results are consistent in subgroups of AAD type and baseline AF burden.

BACKGROUND:The presence of double potentials (DPs)-2 discrete electrogram deflections separated by an isoelectric segment-is a validated indicator during ablation of scar-mediated atrial tachycardia (AT). A corridor of parallel DPs is often used as a marker of a line of conduction block, whereby DP duration decreases as one approaches the conducting gap. In this context, it is the spatial gradient of DP duration that is used for isthmus localization. Here, we calculate the DP duration gradient of atrial electroanatomic maps and assess how it compares with DP duration as a quantitative metric in isthmus identification. OBJECTIVE:The purpose of the study was to assess the utility of DP duration gradient for identifying AT isthmuses. METHODS:Patients undergoing ablation of scar-mediated AT were included if a complete high-density map was available. Isthmus points were identified by an electrophysiologist before analysis. As point clouds from the electroanatomic maps are irregular, calculations of DP gradients were interpolated to a regular grid via inverse distance weighting. Gradients were then back-interpolated onto the original point clouds for analysis. RESULTS:57 EAMs among 52 patients were available for analysis [13 (25.0%) female; median age 69.1 years]. Pooled isthmus points had higher DP gradient values than did nonisthmus points (Mann-Whitney, P < .001). In logistic regression, the DP gradient was more predictive of isthmus location than the DP duration (area under the curve 0.667; 95% confidence interval 0.660-0.673 vs area under the curve 0.621; 95% confidence interval 0.616-0.627; DeLong, P < .001.) CONCLUSION: DP gradient is a more accurate predictor of isthmus points than DP duration, and may be useful in identifying its location.

BACKGROUND:Atrial fibrillation (AF) occurs after heart transplantation (HT) and may increase morbidity and mortality; however, data on its incidence, predictors, and outcomes remain limited. OBJECTIVE:This study aimed to evaluate the incidence of AF and stroke after HT and identify predictors and outcomes of post-HT AF. METHODS:We conducted a retrospective study of adult patients who underwent HT at a high-volume center between January 1, 2005, and September 30, 2024. AF was classified as early (<30 days after HT) or late (≥30 days). Clinical variables for both the recipient and the donor were collected. Separate CHA2DS2-VASc scores were calculated using recipient and donor age. Predictors of early and late AF were assessed using univariate and multivariable logistic regression. RESULTS:Among 1072 patients (median age 55 years [interquartile range 45-63]; 75% male), AF occurred in 11% (n = 111), most commonly as late or combined early and late AF. Donor age, post-HT extracorporeal membrane oxygenation, and pericardial effusion predicted early AF, whereas rejection, cardiac allograft vasculopathy, and early AF predicted late AF. Stroke occurred in 9% of patients and was independently associated with pre-HT mechanical circulatory support and ischemic time but not AF. CHA2DS2-VASc scores incorporating recipient and donor factors predicted post-HT stroke; the donor-derived score also predicted AF. Survival was similar through 3 years after HT but was lower in patients with AF at 5 years (72% vs 86%; P < .01). CONCLUSION:AF after HT is associated with reduced long-term survival. Both donor and recipient factors contribute, and donor age-derived CHA2DS2-VASc scoring may aid risk stratification and surveillance.

Introduction Because ventricular tachycardia (VT) is often hemodynamically unstable, ablation is typically performed in the baseline rhythm. While prior studies have assessed the electrogram (EGM) features of VT isthmuses mapped in baseline rhythm, they have largely relied on proprietary or manual analysis. We hypothesized that EGM morphologic features could be automatically calculated using the information typically obtained during mapping, and could aid in detecting VT isthmus areas and their components during substrate mapping. Methods Patients undergoing ischemic VT ablation with detailed electroanatomic maps in both VT and a baseline rhythm were studied. Entrance, middle, exit, and adjacent bystander isthmus segments were determined in VT and registered to baseline rhythm maps. EGM features (voltage, velocity, signal duration, median vector angle difference (MVAD), number of deflections, and the maximum duration between electrogram segments) were assessed in both rhythms and compared between isthmus and non-isthmus regions and between isthmus segments. Results There were 25,284 points in baseline rhythm and 10,923 in VT among 10 patients (all men, median age 67.0 (8.5) years). Significant differences between isthmus and non-isthmus regions were present in all features for both rhythms except for MVAD, which was only significant in VT. Baseline rhythm conduction was progressively more directionally uniform from isthmus entrance to exit. A multivariable regression model of points in baseline rhythm demonstrated an AUC of 0.810 for predicting VT isthmus regions. Conclusion Automated EGM analysis can help identify isthmus in scar-related VT, different isthmus segments from each other, and may aid in targeting substrate for ablation.

Out-of-hospital cardiac arrest remains a leading cause of mortality in the United States, with survival critically dependent on timely bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use. Despite strong evidence supporting early intervention, bystander-initiated CPR remains suboptimal, with persistent racial, demographic, socioeconomic, literacy-related, and geographic disparities. National legislative efforts have been hampered by inadequate funding. To improve out-of-hospital cardiac arrest survival and address these disparities, the Institute of Medicine has identified US high school students as a prime target for CPR education and AED use. Although most US states have legislated mandates for CPR and AED education, there is no consistent, standardized implementation process. 1-time or didactic-only training, limited hands-on practice, lack of longitudinal reinforcement, and inequitable AED access undermine effectiveness. This Heart Rhythm Society Scientific Statement evaluates the current landscape of CPR and AED education for US high school students, including the effectiveness of state legislative mandates, implementation strategies, and disparities in access and outcomes. We identify critical gaps and propose evidence-based solutions and an implementation framework for uniform, effective, and equitable initial and longitudinal CPR and AED training aiming to transform generations of US high school students into lifesavers.

Background:Conventional transvenous dual-chamber pacemakers may have deleterious effects on the left ventricle, such as pacing-induced cardiomyopathy for those with a high pacing burden. Although the effect of right ventricular (RV) pacing on left ventricular function has been well studied, its impact on RV remodelling and function is not well established. Methods:This systematic review and meta-analysis were constructed according to PRISMA guidelines. We searched Embase, PubMed and SCOPUS using MeSH terms, associated keywords and Boolean operators from inception to March 2024. Relevant studies reported on at least one component of RV function following RV pacing, including: change in RV ejection fraction (RVEF), pulmonary artery systolic pressure (sPAP), tricuspid annular plane systolic excursion (TAPSE), RV volume, tissue Doppler-derived tricuspid lateral annular systolic velocity (S'), 2D fractional area change (FAC), RV index of myocardial performance (RIMP) and tricuspid regurgitation. Results:In all, 18 studies, enrolling 1,220 patients, were examined to analyse the effect of RV pacing on RV echocardiographic parameters. The meta-analysis revealed that RV pacing influenced several echocardiographic parameters. RVEF showed a pooled mean difference of 2.28% (95% CI [-1.2818, 5.8385]; p=0.21), whereas TAPSE (-0.0444 cm; 95% CI [-0.1976, 0.1089]; p=0.57) and RIMP (-0.0714; 95% CI [-0.2888, 0.1459]; p=0.52) exhibited small, non-significant reductions in pooled mean difference. In contrast, S' pooled mean difference decreased significantly (-1.3522 cm/s; 95% CI [-2.3647, -0.3396]; p=0.0089), but there were no significant changes in FAC% (-0.1208 %; 95% CI [-3.6630, 3.4215]; p=0.95) or sPAP (3.7282 mmHg; 95% CI [-6.0651, 13.5216]; p=0.46) pooled mean difference. Heterogeneity was high across all RV function parameters examined, with I² values exceeding 89%. Length of treatment was not significantly associated with changes in RVEF (p=0.21), TAPSE (p=0.53), S' (p=0.22), or FAC% (p=0.68), but significantly influenced RIMP (p=0.01). Site of pacing significantly affected TAPSE (p=0.0198), S' (p=0.0124), FAC% (p=0.0014) and sPAP (p=0.0006). Apical pacing was consistently associated with the worst outcomes across parameters, including the greatest negative impact on TAPSE, S' and sPAP, whereas left bundle branch area pacing (LBBAP) generally showed better outcomes, including the least impact on sPAP. Conclusion:RV pacing is associated with significant reductions in S' and notable effects on other echocardiographic parameters, with heterogeneity largely driven by the site of pacing. Apical pacing had the most detrimental effects across multiple parameters, whereas LBBAP was generally associated with better outcomes. Further studies are needed to address residual heterogeneity and examine additional covariates.

Background:Early sinus node dysfunction (SND) occurs in 2%-4% of patients following heart transplantation (HT). Objective:The purpose of the current study was to examine characteristics of patients requiring terbutaline for SND post-HT and clinical and hemodynamic outcomes. Methods:A retrospective study was conducted at 2 centers to identify HT recipients from January 2020 to June 2025 started on terbutaline for early SND. Data was collected regarding recipient and donor characteristics and compared between terbutaline and no terbutaline groups. For the terbutaline group, additional information was obtained regarding changes in hemodynamics, dosing, and tolerability. Response to terbutaline after steady-state dosing and sinus node recovery were assessed. Results:450 individuals underwent bicaval HT (median age 56 years, 75% male, 23% black, 18% Hispanic). Of these, 30 (6.7%) were initiated on terbutaline an average of 7 days post-HT. Demographics, pre-transplant mechanical circulatory support, or pre-transplant amiodarone exposure were similar between groups. Older donor age, longer ischemic time, and Organ Care System use were significantly associated with terbutaline use. Heart rate and cardiac index by Fick significantly increased after starting terbutaline with significant individual variability. 50% were classified as having sinus node recovery; 2 patients ultimately needed a permanent pacemaker. Conclusion:Despite individual variability in heart rate response with terbutaline, early SND was able to be managed pharmacologically in most patients and need for permanent pacemaker remained low.

Background:Accurate identification of macro-reentrant atrial tachycardia (AT) circuits is critical for successful ablation but remains challenging with conventional mapping techniques. The aim of this study was to automatically detect macro-reentrant AT loops from high-density local activation time (LAT) maps. Methods:We developed an algorithm for automated detection of macro-reentrant AT circuits using LAT-derived directed graphs. Compared to previous graph-based approaches, the algorithm is designed to identify the fastest-conducting reentrant pathways and cluster them by rotational orientation (clockwise vs. counterclockwise) to distinguish single- from dual-loop circuits. The algorithm was applied retrospectively to 60 macro-reentrant scar-related AT cases mapped with CARTO or Ensite from two institutions. The results were compared with blinded expert electrophysiologist annotations of loop location and single- vs. dual-loop classification. Results:The 60 cases included 16 right atrial and 44 left atrial ATs from 51 patients. Expert review identified 57% single-loop and 43% dual-loop circuits. Compared with expert annotation, the algorithm correctly identified anatomical loop locations with 88% accuracy and correctly distinguished single- vs. dual-loop ATs in 93% of cases. Conclusion:Our LAT graph-based algorithm automatically identified single- and dual-loop macro-reentrant AT circuits. Localizing these pathways may provide insight into circuit mechanisms and help guide ablation. CLINICAL PERSPECTIVE:What is Known: Accurate characterization of macro-reentrant atrial tachycardias (ATs) is essential for effective catheter ablation, yet identifying these circuits from local activation time (LAT) maps remains challenging and operator dependent. What the Study Adds: We developed and validated a graph-based algorithm that automatically identifies macro-reentrant AT circuits from LAT maps with high agreement compared to expert electrophysiologist annotation.The algorithm localizes reentrant loop pathways and distinguishes single- from dual-loop circuits.Localizing these pathways may provide insight into circuit mechanisms and help guide ablation.

Rapid technological advancements in noninvasive and invasive imaging including echocardiography, computed tomography, magnetic resonance imaging and positron emission tomography have allowed for improved anatomical visualization and precise measurement of cardiac structure and function. These imaging modalities allow for evaluation of how cardiac substrate changes, such as myocardial wall thickness, fibrosis, scarring and chamber enlargement and/or dilation, have an important role in arrhythmia initiation and perpetuation. Here, we review the various imaging techniques and modalities used by clinical and basic electrophysiologists to study cardiac arrhythmia mechanisms, periprocedural planning, risk stratification and precise delivery of ablation therapy. We also review the use of artificial intelligence and machine learning to improve identification of areas for triggered activity and isthmuses in reentrant arrhythmias, which may be favorable ablation targets. Rogers et al. review the current imaging modalities to investigate the mechanisms of cardiac arrhythmias and discuss the future impact of machine learning and artificial intelligence on digital imaging.

Atrial fibrillation (AF) is a prevalent arrhythmia with known detriments such as heart failure, stroke, and cognitive decline even in patients without prior stroke. The mechanisms by which AF leads to cognitive dysfunction are yet unknown, and there is a lack of animal models to study this disease process. We previously developed a murine model of spontaneous and prolonged episodes of AF, a double transgenic mouse model with cardiac-specific expression of a gain-of-function mutant voltage-gated sodium channel (DTG-AF mice). Herein, we show, for the first time to our knowledge, a murine model of AF without any cerebral infarcts exhibiting cognitive dysfunction, including impaired visual learning and cognitive flexibility on touch screen testing. Mesenteric resistance arterial function of DTG-AF mice showed significant loss of myogenic tone, increased wall thickness and distensibility, and mitochondrial dysfunction. Brain pial arteries also showed increased wall thickness and mitochondrial enlargement. Furthermore, DTG-AF mice have decreased brain perfusion on laser speckle contrast imaging compared with controls. Cumulatively, these findings demonstrate that AF leads to vascular structural and functional alterations necessary for dynamic cerebral autoregulation, resulting in increased cerebral stress and cognitive dysfunction. Expression of mitochondrial catalase (mCAT) to reduce mitochondrial reactive oxygen species (ROS) was sufficient to prevent vascular dysfunction due to AF, restore perfusion, and improve cognitive flexibility.

Ion channels orchestrate electrical signaling in excitable cells. In nature, ion channel function is customized by modulatory proteins that have evolved to fulfill distinct physiological needs. Yet, engineering synthetic modulators that precisely tune ion channel function is challenging. One example involves the voltage-gated sodium (NaV) channel that initiates the action potential and whose dysfunction amplifies the late/persistent sodium current (INaL), a commonality that underlies various human diseases, including cardiac arrhythmias and epilepsy. Here, using a computational protein design platform, we engineered a de novo peptide modulator, engineered late-current inhibitor X by inactivation-gate release (ELIXIR), that binds NaV channels with submicromolar affinity. Functional analysis revealed unexpected selectivity in inhibiting “pathogenic” INaL and confirmed its effectiveness in reversing NaV dysfunction linked to both cardiac arrhythmias and epilepsy in cellular and murine models. These findings exemplify the efficacy of de novo protein design for engineering synthetic ion channel modulators and set the stage for the rational design of future therapeutic approaches.

BACKGROUND:Decision making regarding new pacemaker implantation after transcatheter tricuspid valve intervention (TTVI), including transcatheter edge-to-edge repair (TEER) or transcatheter tricuspid valve replacement (TTVR), is complex owing to anatomic and TTVI-related challenges. OBJECTIVE:This study aimed to evaluate the feasibility of nontransvalvular pacing strategies, including coronary sinus (CS) or leadless pacemaker (LP) placement, after TTVI. METHODS:Consecutive patients undergoing TTVI at a single institution were retrospectively studied for new pacemaker indications and pacing strategy. Procedural challenges and outcomes associated with nontransvalvular pacemaker implantation were assessed. RESULTS:Among 137 patients who underwent TTVI (69 TTVR; 68 TEER) at a single center, 34 patients (25%) were excluded for preexisting pacemaker, and 15 of 103 patients (15%) subsequently developed an indication for pacing after TEER (n = 5 of 53; 9%) or TTVR (n = 10 of 50; 20%). An alternative pacing strategy was attempted after TEER and TTVR. After TEER (n = 5), CS lead placement was 50% successful (2 of 4) and 1 LP attempt was unsuccessful (0 of 1). After TTVR (n = 10), CS lead placement was 75% successful (6 of 8) and LP placement was 100% successful (2 of 2) on the initial attempt. CS lead placement was limited by CS anatomy, whereas LP placement was limited by TTVR interaction. A transvenous pacemaker was successfully placed if needed. No pacemaker device-related adverse event occurred in any patient peri-procedurally or at 1-year follow-up. CONCLUSION:Alternative nontransvalvular pacing strategies may be feasible and safe in patients who require pacing after TTVI. Preprocedural planning with a multidisciplinary approach can help optimize procedural success. Further studies and longer-term follow-up are warranted.

BACKGROUND:The anatomical relationship between the tricuspid annulus and the conduction system increases the risk for new-onset conductance disturbance (NOCD) following transcatheter tricuspid valve replacement (TTVR). OBJECTIVES:The aim of this study was to describe the incidence and types of NOCD and potential risk factors. METHODS:This was a single-center, retrospective analysis of TTVR patients. The primary endpoint was 30-day NOCD incidence. Subgroups with (NOCD+) and without (NOCD-) conduction disturbances were compared. Echocardiographic measures of tricuspid valve and right ventricular size, morphology, and function as well as post-TTVR computed tomographic device position within the annulus were assessed. RESULTS:A total of 70 patients were included in this analysis, of whom 31 (44.3%) developed NOCD, which included right bundle branch block, complete atrioventricular block and slow atrial fibrillation. New permanent pacemaker implantation was required in 8 patients (14%) within 30 days. Baseline absolute right ventricle free wall longitudinal strain was significantly higher in NOCD+ patients (29.7% ± 5.4% vs 25.1% ± 6.4%; P = 0.002). Type IIIB leaflet morphology was more prevalent in NOCD+ patients (48.4% vs 25.6%; P = 0.049). No difference was found regarding membranous septum (MS) dimensions or device oversizing. The postprocedural incidence of white blood cell count peak >13 × 109/L was higher in NOCD+ patients (51.6% vs 28.2%; P = 0.046). By logistic regression, the primary outcome was associated with baseline absolute right ventricle free wall longitudinal strain ≥29% and contact of subvalvular device component with the MS on follow-up computed tomography. CONCLUSIONS:NOCD incidence was 44.6% after TTVR in a highly selected patient population. Baseline hyperdynamic right ventricular function and contact of the device with the MS were independently associated with NOCD at 30 days. Further studies are warranted.

BACKGROUND:Patients with atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular mortality compared to patients with AF alone. Consequently, employing rhythm control strategies such as AF catheter ablation could offer substantial benefits to patients with COPD. However, the impact of COPD on AF ablation outcomes is not well established. METHODS:In this single-center case control study, we retrospectively analyzed 200 patients with AF and COPD, 52 of whom underwent AF catheter ablation. Those who underwent ablation were matched with a control group of patients with AF but without COPD who underwent ablation. Ablation outcomes were compared between the groups. Univariate and multivariable analysis were conducted for prediction of AF recurrence. RESULTS:Compared to the controls, cases with COPD were more likely to have AF recurrence following catheter ablation (OR 13.42, P-value = 0.0001). Multivariable analysis revealed predictors of AF recurrence following catheter ablation included decreased use of loop diuretics and amiodarone. Patients with severe or very severe COPD were more likely to have left atrial enlargement than patients with mild or moderate COPD (OR 2.28, P-value = 0.026). CONCLUSION:Patients with AF and COPD were more likely than patients with AF but without COPD to experience AF recurrence following catheter ablation. Predictors of AF recurrence included decreased use of loop diuretics and amiodarone. Our study demonstrates that while ablation in patients with COPD is safe, ablation in patients with COPD is associated with higher AF recurrence rates.

Voltage substrate mapping is a promising tool for the treatment of atrial fibrillation (AF). It is helpful to detect atrial fibrosis, which includes areas with low bipolar voltage, heterogeneous conduction properties, and shortened effective refractory period. The voltage amplitude is typically defined as the maximal peak-to-peak level within a specified time window of interest. Contemporary electroanatomic mapping platforms now enable many thousands of data points to be mapped, so that a geometric model of the atrial endocardium is constructable over a short period of time. This mapping procedure is often done with bipolar electrodes to cancel the far-field signal. The recording site coordinates are projected onto an atrial shell, with interpolation of the voltage data across the shell surface. The amplitude of the recorded bipolar electrogram depicted on the three-dimensional shell provides detailed information for substrate mapping. Wherever there are areas of low peak-to-peak voltage, it is thought to mark the presence of abnormal tissue properties and conduction. However, uncontrolled variables and environmental factors affecting voltage level include the oncoming electrical activation wavefront direction, the catheter incidence angle, the force applied to the catheter, and the region-variable shape and structure of atrial tissue. Techniques and settings to acquire atrial voltage data for AF analysis have not been standardized. Methods to characterize atrial electrograms are also presently limited. These factors affect quality and reproducibility of the mapping results. Herein, voltage substrate mapping and its variables pertaining to AF and radiofrequency ablation are described and discussed, with suggestions for future work efforts.

BackgroundRegular interaction with patients with cardiac implantable electronic devices (CIEDs) provides CIED clinic personnel with unique insights into patient-related barriers and challenges to remote monitoring (RM) implementation.MethodsUsing a global network, an international survey was administered to CIED clinic personnel. Qualitative questions gathered information on perceived challenges with patient connectivity and patient-level barriers associated with RM implementation.ResultsA total of 339 responses from 302 unique centres were included in the analysis. Respondents most often were cardiac electrophysiologists (57.8%), followed by nurses (17.1%) and nurse practitioners (7.7%). Most respondents (84.7%) reported at least one challenge in daily RM management. The biggest challenge was the increasing data volume and data variability (38.3%), followed by staff shortage (33.8%), difficulties with billing for technical activities (20.2%), and insufficient RM reimbursement (16.0%). Patient connectivity was identified as a major barrier by 72.7% of respondents. The main concerns were patient literacy (80.8%), followed by a lack of patient understanding of RM importance (65.8%), the lack of required bandwidth or technology to support RM (49.6%), and the cost to the patient (47.9%). Subgroup analyses showed that patient connectivity was often identified as a major barrier by non-MD CIED clinic staff, respondents working in office-based CIED clinics, and respondents from clinics with a per-patient payment reimbursement model.ConclusionsThere are many patient-related barriers identified by non-MD CIED clinic staff. Dedicated strategies to optimise the utilisation and adherence of RM of patients with CIEDs are urgently needed to improve clinical outcomes.