Atrial fibrillation (AF), the most common heart rhythm disorder, may cause stroke and heart failure. For patients with persistent AF with fibrosis proliferation, the standard AF treatment-pulmonary vein isolation-has poor outcomes, necessitating redo procedures, owing to insufficient understanding of what constitutes good targets in fibrotic substrates. Here we present a prospective clinical and personalized digital twin study that characterizes the arrhythmogenic properties of persistent AF substrates and uncovers locations possessing rotor-attracting capabilities. Among these, a portion needs to be ablated to render the substrate not inducible for rotors, but the rest (37%) lose rotor-attracting capabilities when another location is ablated. Leveraging digital twin mechanistic insights, we suggest ablation targets that eliminate arrhythmia propensity with minimum lesions while also minimizing the risk of iatrogenic tachycardia and AF recurrence. Our findings provide further evidence regarding the appropriate substrate ablation targets in persistent AF, opening the door for effective strategies to mitigate patients' AF burden. Sakata et al. performed a prospective personalized mechanistic computational (digital twin) study focused on characterizing the arrhythmogenic properties of the atrial fibrotic substrate in patients with persistent atrial fibrillation, and they introduce here a novel mechanism-oriented strategy for optimal ablation.

ABSTRACT Background Signal-averaged electrocardiogram (SAECG) records myocardial depolarization, and can detect inhomogeneous/slow conduction in fibrotic myocardium, which promotes reentrant ventricular arrhythmias (VAs). Hypertrophic cardiomyopathy (HCM) is associated with a high prevalence of cardiac fibrosis and VAs, but abnormal SAECG has low predictive power for VAs. We hypothesized that HCM-specific structural/electrical remodeling underlies this result. Methods We tested our hypothesis by retrospectively studying HCM patients (n=73) who underwent transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging within 12 months of SAECG and 12-lead ECG. Patients were divided into 2 groups (normal-SAECG, abnormal-SAECG) based on filtered-QRS duration ( fQRS d), root-mean-square-voltage ( RMS40 ) and low-amplitude (<40μV) signal of terminal 40ms of filtered-QRS (late potentials). Abnormal SAECG was defined as fQRS d >114ms, RMS40<20 μ V or LAS40>38ms . Results Abnormal SAECG was seen in ∼50% of HCM patients (37/73). In the abnormal-SAECG group, 78% (n=29) only had prolonged fQRS d, and 22% (n=8) had prolonged fQRS d plus late potentials ( RMS40<20 μ V or LAS40>38ms) . Mean fQRS d and LAS40 were significantly higher in the abnormal-SAECG group. The abnormal-SAECG group had significantly larger LA size, lower global-LV longitudinal systolic strain/strain rate and early-diastolic strain rate by TTE; higher LV-mass index (LVMI) and LV-scar burden by CMR; higher prevalence of repolarization abnormalities on 12-lead ECG. LVEF and adverse outcomes (VT/VF, heart failure, death) were similar in the 2 groups. Univariate analysis showed that fQRS d is positively correlated with LVMI, LV-scar mass, and negatively correlated with global-LV early diastolic strain rate. Conclusions In HCM, abnormal SAECG is associated with greater structural/electrical LV-remodeling, reflecting a severe global myopathy.

Background Although targeting atrial fibrillation (AF) drivers and substrates has been used as an effective adjunctive ablation strategy for patients with persistent AF (PsAF), it can result in iatrogenic scar-related atrial tachycardia (iAT) requiring additional ablation. Personalized atrial digital twins (DTs) have been used preprocedurally to devise ablation targeting that eliminate the fibrotic substrate arrhythmogenic propensity and could potentially be used to predict and prevent postablation iAT. Objectives In this study, the authors sought to explore possible alternative configurations of ablation lesions that could prevent iAT occurrence with the use of biatrial DTs of prospectively enrolled PsAF patients. Methods Biatrial DTs were generated from late gadolinium enhancement-magnetic resonance images of 37 consecutive PsAF patients, and the fibrotic substrate locations in the DT capable of sustaining reentries were determined. These locations were ablated in DTs by representing a single compound region of ablation with normal power (SSA), and postablation iAT occurrence was determined. At locations of iAT, ablation at the same DT target was repeated, but applying multiple lesions of reduced-strength (MRA) instead of SSA. Results Eighty-three locations in the fibrotic substrates of 28 personalized biatrial DTs were capable of sustaining reentries and were thus targeted for SSA ablation. Of these ablations, 45 resulted in iAT. Repeating the ablation at these targets with MRA instead of SSA resulted in the prevention of iAT occurrence at 15 locations (18% reduction in the rate of iAT occurrence). Conclusions Personalized atrial DTs enable preprocedure prediction of iAT occurrence after ablation in the fibrotic substrate. It also suggests MRA could be a potential strategy for preventing postablation AT.

BACKGROUND:Signal-averaged electrocardiogram (SAECG) records myocardial depolarization, and can detect inhomogeneous/slow conduction in fibrotic myocardium, which promotes reentrant ventricular arrhythmias (VAs). Hypertrophic cardiomyopathy (HCM) is associated with a high prevalence of cardiac fibrosis and VAs, but abnormal SAECG has low predictive power for VAs. We hypothesized that HCM-specific structural/electrical remodeling underlies this result. METHODS:We tested our hypothesis by retrospectively studying HCM patients (n = 73) who underwent transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging within 12 months of SAECG and 12‑lead ECG. Patients were divided into 2 groups (normal-SAECG, abnormal-SAECG) based on filtered-QRS duration (fQRSd), root-mean-square-voltage (RMS40) and low-amplitude (<40 μV) signal of terminal 40 ms of filtered-QRS (late potentials). Abnormal SAECG was defined as fQRSd > 114 ms, RMS40 < 20 μV or LAS40 > 38 ms. RESULTS:Abnormal SAECG was seen in ∼50 % of HCM patients (37/73). In the abnormal-SAECG group, 78 % (n = 29) only had prolonged fQRSd, and 22 % (n = 8) had prolonged fQRSd plus late potentials (RMS40 < 20 μV or LAS40 > 38 ms). Mean fQRSd and LAS40 were significantly higher in the abnormal-SAECG group. The abnormal-SAECG group had significantly larger LA size, lower global-LV longitudinal systolic strain/strain rate and early-diastolic strain rate by TTE; higher LV-mass index (LVMI) and LV-scar burden by CMR; higher prevalence of repolarization abnormalities on 12‑lead ECG. LVEF and adverse outcomes (VT/VF, heart failure, death) were similar in the 2 groups. Univariate analysis showed that fQRSd is positively correlated with LVMI, LV-scar mass, and negatively correlated with global-LV early diastolic strain rate. CONCLUSIONS:In HCM, abnormal SAECG is associated with greater structural/electrical LV-remodeling, reflecting a severe global myopathy.

Background In atrial fibrillation (AF) management, understanding left atrial (LA) substrate is crucial. While both electroanatomic mapping (EAM) and late gadolinium enhancement magnetic resonance imaging (LGE-MRI) are accepted methods for assessing the atrial substrate and are associated with ablation outcome, recent findings have highlighted discrepancies between low-voltage areas (LVAs) in EAM and LGE areas. Objective The purpose of this study was to explore the relationship between LGE regions and unipolar and bipolar LVAs using multipolar high-density mapping. Methods Twenty patients scheduled for AF ablation underwent preablation LGE-MRI. LA segmentation was conducted using a deep learning approach, which subsequently generated a 3-dimensional mesh integrating the LGE data. High-density EAM was performed in sinus rhythm for each patient. The electroanatomic map and LGE-MRI mesh were coregistered. LVAs were defined using cutoffs of 0.5 mV for bipolar voltage and 2.5 mV for unipolar voltage. The correspondence between LGE areas and LVAs in the LA was analyzed using confusion matrices and performance metrics. Results A considerable 87.3% of LGE regions overlapped with unipolar LVAs, compared with only 16.2% overlap observed with bipolar LVAs. Across all performance metrics, unipolar LVAs outperformed bipolar LVAs in identifying LGE areas (precision: 78.6% vs 61.1%; sensitivity: 87.3% vs 16.2%; F1 score: 81.3% vs 26.0%; accuracy: 74.0% vs 35.3%). Conclusion Our findings demonstrate that unipolar LVAs strongly correlate with LGE regions. These findings support the integration of unipolar mapping alongside bipolar mapping into clinical practice. This would offer a nuanced approach to diagnose and manage AF by revealing critical insights into the complex architecture of the atrial substrate.

Background: Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, electrical remodeling and fibrosis that lead to inhomogeneous ventricular depolarization and arrhythmias. Signal averaged ECG (SAECG) is useful for non-invasive risk stratification in ischemic cardiomyopathy. However, the association between SAECG and structural remodeling in HCM has not been investigated. Methods: We retrospectively studied 594 HCM patients from the Johns Hopkins HCM Registry, who underwent echocardiography and cardiac magnetic resonance (CMR) imaging within 12 months of SAECG or 12-lead ECG. Seventy-three patients underwent SAECG and were divided into 2 groups (Normal-SAECG, Abnormal-SAECG) based on filtered QRS duration and/or presence of late potentials . Results: Abnormal SAECG was seen in 50% of HCM patients (37/73). Of the 37 HCM patients with abnormal SAECG, 29 patients only had prolonged filtered QRS duration ( fQRS> 114ms ), and 8 patients had prolonged fQRS duration as well as late potentials ( LAS40 >38ms; RMS40 <20μV). Mean fQRS and LAS40 were significantly higher in the Abnormal-SAECG group ( fQRS : 125.7 vs 107msec, p<0.0001; LAS40 : 31.2 vs 22.9msec; p=0.002; RMS40 : 40 vs 54μV; p=0.07). HCM patients with abnormal SAECG also had 1) larger left atrial size (p=0.03), lower global LV peak systolic strain (p=0.04), systolic strain rate (p=0.008), early diastolic strain rate (p=0.01) by ECHO; 2) greater LV mass index (p=0.004) 3) Higher prevalence and amount of late gadolinium enhancement (LGE) reflecting LV-scar (p=0.045 and 0.01) by CMR; 4) higher prevalence of repolarization abnormalities on 12-lead ECG (p=0.02). Adverse outcomes (sustained-VT/VF, heart failure, death) were similar in the 2 groups. Filtered QRS duration (SAECG) was positively correlated with LV mass index (r=0.43, p=0.0002), QRS duration on 12-lead ECG (r=0.67, p=0.000), and negatively correlated with global LV early diastolic strain rate (r= -0.34, p=0.009) in our HCM cohort. Conclusion: In HCM, prolonged filtered QRS on SAECG reflects a greater degree of structural remodeling characterized by more LV hypertrophy, larger LA size, worse cardiac mechanics, and higher prevalence and amount of fibrosis.

BACKGROUND Among patients with heart failure undergoing car-diac resynchronization therapy (CRT), patients with a minimal change in left ventricular ejection fraction (LVEF) have recently been defined as "nonprogressors" rather than as "nonresponders." Little is known regarding long-term outcomes of nonprogressors.OBJECTIVE We sought to evaluate outcomes in patients undergo-ing CRT on the basis of echocardiographically determined response status.METHODS We reviewed the medical charts of patients with an LVEF of <35% and a QRS duration of >120 ms undergoing CRT at the Cleveland Clinic, Johns Hopkins Hospital, and Johns Hopkins Bay -view Medical Center between 2003 and 2014. Response to CRT was defined on the basis of LVEF change as follows: super -responders >20%, responders 6%-19%, nonprogressors 0%-5%, and progressors <0%. Survival free of left ventricular assist device (LVAD) implantation and heart transplantation was compared on the basis of response classification.RESULTS A total of 1058 patients were included and had a mean follow-up 8.7 & PLUSMN; 5.4 years, over which time there were 606 end points (37 LVAD implants, 32 heart transplants, and 537 deaths). Survival free of LVAD and heart transplant differed significantly be-tween response groups after CRT both in the mid-term (4 years) and in the long-term (8.7 & PLUSMN; 5.4 years), with super-responders achieving the best outcomes and progressors the worst (P < .001). In multi-variate analysis, nonprogressors had superior outcomes to progres-sors (P = .02) at 4 years of follow-up. Over the duration of follow-up (8.7 & PLUSMN; 5.4 years), there was no significant difference in survival between those 2 groups (P = .18).CONCLUSION Nonprogressors to CRT have superior medium-term outcomes but similar long-term outcomes to progressors and infe-rior outcomes to responders and super-responders.

A nation's health and economic development are inextricably and synergistically connected. Stark differences exist between wealthy and developing nations in the use of cardiac implantable electronic devices (CIEDs). Cardiovascular disease is now the leading cause of death in low- and middle-income countries (LMIC), with a significant burden from rhythm-related diseases. As science, technology, education, and regulatory frameworks have improved, CIED recycling for exportation and reuse in LMIC has become possible and primed for widespread adoption. In our manuscript, we outline the science and regulatory pathways regarding CIED reuse. We propose a pathway to advance this technology that includes creating a task force to establish standards for CIED reuse, leveraging profes- sional organizations in areas of need to foster the professional skills for CIED reuse, collaborating with regulatory agencies to create more efficient regulatory expectations and bring the concept to scale, and establishing a global CIED reuse registry for quality assurance and future science.

Radiographic identification of the cardiac implantable electronic device (CIED) manufacturer facilitates urgent interrogation of an unknown CIED. In the past, we relied on visualizing a manufacturer-specific X-ray logo. Recently, a free smartphone application ("Pacemaker-ID") was made available. A photograph of a chest X-ray was subjected to an artificial intelligence (AI) algorithm that uses manufacturer characteristics (canister shape, battery design) for identification. We sought to externally validate the accuracy of this smartphone application as a point-of-care (POC) diagnostic tool, compare on-axis to off-axis photo accuracy, and compare it to X-ray logo visualization for manufacturer identification. We reviewed operative reports and chest X-rays in 156 pacemaker and 144 defibrillator patients to visualize X-ray logos and to test the application with 3 standard (on-axis) and 4 non-standard (off-axis) photos (20° cranial; caudal, leftward, and rightward). Contingency tables were created and chi-squared analyses (P < .05) were completed for manufacturer and CIED type. The accuracy of the application was 91.7% and 86.3% with single and serial application(s), respectively; 80.7% with off-axis photos; and helpful for all manufacturers (range, 85.4%-96.6%). Overall, the application proved superior to the X-ray logo, visualized in 56% overall (P < .0001) but varied significantly by manufacturer (range, 7.7%-94.8%; P < .00001). The accuracy of the Pacemaker-ID application is consistent with reports from its creators and superior to X-ray logo visualization. The accuracy of the application as a POC tool can be enhanced and maintained with further AI training using recent CIED models. Some manufacturers can enhance their X-ray logos by improving placement and design.

Radiographic identification of an unknown CIED's manufacturer can facilitate urgent interrogation. In the past, we relied on visualizing a manufacturer-specific X-ray logo. Recently, a free smartphone app ("Pacemaker-ID") was made available. A photo of a chest X-ray is subjected to an AI algorithm that uses manufacturer-specific characteristics (shape, battery design) for identification with a reported accuracy of 89%.

RationalePatients with ischemic cardiomyopathy (ICMP) are at high risk for malignant arrhythmias, largely due to electrophysiological remodeling of the non-infarcted myocardium. The electrophysiological properties of the non-infarcted myocardium of patients with ICMP remain largely unknown.ObjectivesTo assess the pro-arrhythmic behavior of non-infarcted myocardium in ICMP patients and couple computational simulations with machine learning to establish a methodology for the development of disease-specific action potential models based on clinically measured action potential duration restitution (APDR) data.Methods and ResultsWe enrolled 22 patients undergoing left-sided ablation (10 ICMP) and compared APDRs between ICMP and structurally normal left ventricles (SNLVs). APDRs were clinically assessed with a decremental pacing protocol. Using genetic algorithms (GAs), we constructed populations of action potential models that incorporate the cohort-specific APDRs. The variability in the populations of ICMP and SNLV models was captured by clustering models based on their similarity using unsupervised machine learning. The pro-arrhythmic potential of ICMP and SNLV models was assessed in cell- and tissue-level simulations. Clinical measurements established that ICMP patients have a steeper APDR slope compared to SNLV (by 38%, p < 0.01). In cell-level simulations, APD alternans were induced in ICMP models at a longer cycle length compared to SNLV models (385–400 vs 355 ms). In tissue-level simulations, ICMP models were more susceptible for sustained functional re-entry compared to SNLV models.ConclusionMyocardial remodeling in ICMP patients is manifested as a steeper APDR compared to SNLV, which underlies the greater arrhythmogenic propensity in these patients, as demonstrated by cell- and tissue-level simulations using action potential models developed by GAs from clinical measurements. The methodology presented here captures the uncertainty inherent to GAs model development and provides a blueprint for use in future studies aimed at evaluating electrophysiological remodeling resulting from other cardiac diseases.

Background Pacemaker battery depletion triggers alert for replacement notification and results in automatic reprogramming, which has been shown to be associated with relevant cardiorespiratory symptoms and adverse clinical events. Objective Determine if electrocardiogram (ECG) pacing features may be predictive of pacemaker battery depletion and clinical risk. Methods This is an ECG substudy of a cohort analysis of 298 subjects referred for pacemaker generator replacement from 2006 to 2017. Electronic medical record review was performed; clinical, ECG, and pacemaker characteristics were abstracted. We applied two ECG prediction rules for pacemaker battery depletion that are relevant to all major pacemaker manufacturers except Boston Scientific and MicroPort: (1) atrial pacing not at a multiple of 10 and (2) nonsynchronous ventricular pacing not at a multiple of 10, to determine diagnostic sensitivity, specificity, and risk in applicable ECG subjects. Results We excluded 32 subjects not at replacement notification or duplicate surgeries. Overall, 176 of 266 subjects (66.2%) demonstrated atrial pacing or nonsynchronous ventricular pacing on preoperative ECG. When utilizing both rules, 139 of 176 preoperative ECGs and 12 of 163 postoperative ECGs met criteria for battery depletion yielding reasonable sensitivity (79.0%), high specificity (92.6%), and a positive likelihood ratio of 11.6:1. These rules were associated with significant increase in cardiorespiratory symptoms (P < .001) and adverse clinical events (P < .025). Conclusions The "Rules of Ten" provided reasonable sensitivity and specificity for detecting replacement notification in pacemaker subjects with an applicable ECG. This ECG tool may help clinicians identify most patients with pacemaker battery depletion at significant clinical risk.

BACKGROUND:An estimated 1 million patients require cardiac implantable electronic devices (CIEDs) but go without annually. This disparity exists in low-to-middle-income nations largely owing to the cost of CIED hardware. Humanitarian reuse of CIEDs has been shown to be safe and feasible. However, recent publications have raised concern that promotion of CIED reuse may foster a CIED "black market," to the dismay of manufacturers, regulators, and clinicians alike.OBJECTIVE:To determine if unregulated CIED sales for potential human use is a real issue by investigating unregulated public online CIED sale listings in the United States of America.METHODS:An observational study was undertaken over 6 months using multiple internet search engines from May 1 to November 1, 2019. We cataloged usable CIEDs (still in packaging, manufactured <7 years) and pricing. Manufacturers were contacted to determine status of sellers and unregulated CIEDs using model/serial numbers.RESULTS:In total, 58 CIEDs-47 implantable cardioverter-defibrillators and 11 permanent pacemakers-from 4 manufacturers were listed for sale on 3 websites. During the study period, 8 of 11 pacemakers and 37 of 47 implantable cardioverter-defibrillators were sold (price range: $100-$1500 [US dollars]). No new listings were seen in the last 3 months of observation, possibly owing to concomitant industry investigation.CONCLUSION:There does exist a public online market for unregulated CIED sales in the United States. This specific market seems to be small and unlikely to significantly expand with active monitoring by manufacturers and regulators.

OBJECTIVES This study aimed to determine the tong-term outcomes and predictors of left ventricular (LV) ejection fraction (LVEF) improvement in patients with severe cardiomyopathies undergoing cardiac resynchronization therapy (CRT). BACKGROUND Whether patients with severe LV dysfunction benefit from CRT or have reached a point in disease severity past the point at which CRT is beneficial is unknown. METHODS We collected clinical and echocardiographic data on 420 patients with an LVEF of <= 15% and a QRS duration of <= 120 ms undergoing CRT at the Cleveland Clinic and 2 hospitals in the Johns Hopkins Health System between April 2003 and May 2014. Multivariate models were created to determine factors associated with response to CRT, defined as an absolute improvement in LVEF of >5% and survival free of LVAD and heart transplant. Procedure-related deaths were also collected. RESULTS A total of 298 patients had pre- and appropriately timed post-CRT echocardiograms, of whom 145 (48.7%) met the criteria for response. In multivariate analysis, LV size and left bundle branch block (LBBB) were associated with response. Among the most dilated quintile (LV end-diastolic diameter [LVEDD] of >7.8 cm), 30.4% met the criteria for response. In multivariate analysis, smaller LV end-diastolic dysfunction and presence of LBBB were associated with improved survival free of heart failure and LVAD over a mean follow-up period of 5.2 years. There were no procedure-related deaths. CONCLUSIONS Patients with severe LV dysfunction respond to CRT, although at a lower rate compared to traditional CRT candidates. Smatter LV size and LBBB are important predictors of positive outcomes in this population. Even among the most dilated patients, 30.4% realized a meaningful improvement in LVEF with CRT. The CRT implant procedure itself appears well tolerated. (C) 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation.

Our world is faced with a global pandemic that threatens to overwhelm many national health care systems for a prolonged period. Consequently, the elective long-term cardiac implantable electronic device (CIED) management of millions of patients is potentially compromised, raising the likelihood of patients experiencing major adverse events owing to loss of CIED therapy. This review gives practical guidance to health care providers to help promptly recognize the requirement for expert consultation for urgent interrogation and/or surgery in CIED patients.

Background: Cardiac resynchronization therapy (CRT) has significant nonresponse rates. We assessed whether machine learning (ML) could predict CRT response beyond current guidelines. Methods: We analyzed CRT patients from Cleveland Clinic and Johns Hopkins. A training cohort was created from all Johns Hopkins patients and an equal number of randomly sampled Cleveland Clinic patients. All remaining patients comprised the testing cohort. Response was defined as ≥10% increase in left ventricular ejection fraction. ML models were developed to predict CRT response using different combinations of classification algorithms and clinical variable sets on the training cohort. The model with the highest area under the curve was evaluated on the testing cohort. Probability of response was used to predict survival free from a composite end point of death, heart transplant, or placement of left ventricular assist device. Predictions were compared with current guidelines. Results: Nine hundred twenty-five patients were included. On the training cohort (n=470: 235, Johns Hopkins; 235, Cleveland Clinic), the best ML model was a naive Bayes classifier including 9 variables (QRS morphology, QRS duration, New York Heart Association classification, left ventricular ejection fraction and end-diastolic diameter, sex, ischemic cardiomyopathy, atrial fibrillation, and epicardial left ventricular lead). On the testing cohort (n=455, Cleveland Clinic), ML demonstrated better response prediction than guidelines (area under the curve, 0.70 versus 0.65; P =0.012) and greater discrimination of event-free survival (concordance index, 0.61 versus 0.56; P <0.001). The fourth quartile of the ML model had the greatest risk of reaching the composite end point, whereas the first quartile had the least (hazard ratio, 0.34; P <0.001). Conclusions: ML with 9 variables incrementally improved prediction of echocardiographic CRT response and survival beyond guidelines. Performance was not improved by incorporating more variables. The model offers potential for improved shared decision-making in CRT (online calculator: http://riskcalc.org:3838/CRTResponseScore ). Significant remaining limitations confirm the need to identify better variables to predict CRT response.

Ablation of atrial vagal ganglia has been associated with improved pulmonary vein isolation (PVI) outcomes. Disruption of vagal reflexes results in heart rate (HR) increase. We investigated the association between HR change after PVI and freedom from atrial fibrillation (AF) at 1 year.

Key Teaching Points•Transseptal puncture, which is widely used for ablation of left-sided arrhythmias, can be challenging.•Excessive tenting and difficulties in reaching the interatrial septum are among the possible challenges.•Application of a curled force-sensing ablation catheter upon the fossa ovalis ("reverse tenting") can readily facilitate the second transseptal puncture. •Transseptal puncture, which is widely used for ablation of left-sided arrhythmias, can be challenging.•Excessive tenting and difficulties in reaching the interatrial septum are among the possible challenges.•Application of a curled force-sensing ablation catheter upon the fossa ovalis ("reverse tenting") can readily facilitate the second transseptal puncture.