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Sex and racial disparities in the presentation, diagnosis, and management of cardiac arrhythmias are recognized. Sex-specific differences in electrophysiological parameters are well known and are predominantly related to differences in ion channel expression and the influence of sex hormones. However, the relationship between hormonal or racial influence and arrhythmia mechanisms, presentation, and management needs to be better defined. Women and racial and ethnic groups are less likely to undergo catheter ablation procedures for treatment of cardiac arrhythmias. Underrepresentation of women and racial/ethnic groups in clinical trials has resulted in significant knowledge gaps. Whether sex and racial disparities in arrhythmia management reflect barriers in access to care, physician bias, patient values, and preferences or other factors requires further study. ispartof: HEART RHYTHM O2 vol:3 issue:6 pages:771-782 ispartof: location:United States status: published

Atrial fibrillation (AF) is prevalent in diabetes mellitus (DM); however, the basis for this is unknown. This study investigated AF susceptibility and atrial electrophysiology in type 1 diabetic Akita mice using in vivo intracardiac electrophysiology, high-resolution optical mapping in atrial preparations, and patch clamping in isolated atrial myocytes. qPCR and western blotting were used to assess ion channel expression. Akita mice were highly susceptible to AF in association with increased P-wave duration and slowed atrial conduction velocity. In a second model of type 1 DM, mice treated with streptozotocin (STZ) showed a similar increase in susceptibility to AF. Chronic insulin treatment reduced susceptibility and duration of AF and shortened P-wave duration in Akita mice. Atrial action potential (AP) morphology was altered in Akita mice due to a reduction in upstroke velocity and increases in AP duration. In Akita mice, atrial Na(+) current (I(Na)) and repolarizing K(+) current (I(K)) carried by voltage gated K(+) (K(v)1.5) channels were reduced. The reduction in I(Na) occurred in association with reduced expression of SCN5a and voltage gated Na(+) (Na(V)1.5) channels as well as a shift in I(Na) activation kinetics. Insulin potently and selectively increased I(Na) in Akita mice without affecting I(K). Chronic insulin treatment increased I(Na) in association with increased expression of Na(V)1.5. Acute insulin also increased I(Na), although to a smaller extent, due to enhanced insulin signaling via phosphatidylinositol 3,4,5-triphosphate (PIP(3)). Our study reveals a critical, selective role for insulin in regulating atrial I(Na), which impacts susceptibility to AF in type 1 DM.

Electrocardiograms (ECG) provide an effective, non-invasive approach for clinical diagnosis and monitoring treatment in patients with cardiac diseases including the most common cardiac arrhythmia, atrial fibrillation (AF). Portable ECG recording devices including Apple Watch and Kardia devices have been developed for AF detection. However, the efficacy of these smart devices has not been fully validated. We aimed to develop an open-source deep learning framework for automatic AF detection using the largest publicly available single-lead ECG dataset through a mobile Kardia device enhanced with style transfer-driven data augmentation. We developed and validated a 37-layer convolutional recurrent network (CRN) using 5,834 single-lead ECGs with a mean length of 30 seconds from the 2017 PhysioNet Challenge to automatically detect sinus rhythm and AF. To address the challenge of a lack of a large number of AF samples, we proposed a novel style transfer generator that fuses patient-specific clinical ECGs and mathematically modelled ECG features to synthesize realistic ECGs by five-fold. The differences between synthesized and clinical ECGs were analyzed by studying their average ECG morphologies and frequency distributions. Our results indicated the style transfer-driven data augmentation was not classifier-dependent. Validation on 2,917 clinical ECGs showed an F

There has been sustained focus on the secondary prevention of coronary heart disease and heart failure; yet, apart from stroke prevention, the evidence base for the secondary prevention of atrial fibrillation (AF) recurrence, AF progression, and AF‐related complications is modest. Although there are multiple observational studies, there are few large, robust, randomized trials providing definitive effective approaches for the secondary prevention of AF. Given the increasing incidence and prevalence of AF nationally and internationally, the AF field needs transformative research and a commitment to evidenced‐based secondary prevention strategies. We report on a National Heart, Lung, and Blood Institute virtual workshop directed at identifying knowledge gaps and research opportunities in the secondary prevention of AF. Once AF has been detected, lifestyle changes and novel models of care delivery may contribute to the prevention of AF recurrence, AF progression, and AF‐related complications. Although benefits seen in small subgroups, cohort studies, and selected randomized trials are impressive, the widespread effectiveness of AF secondary prevention strategies remains unknown, calling for development of scalable interventions suitable for diverse populations and for identification of subpopulations who may particularly benefit from intensive management. We identified critical research questions for 6 topics relevant to the secondary prevention of AF: (1) weight loss; (2) alcohol intake, smoking cessation, and diet; (3) cardiac rehabilitation; (4) approaches to sleep disorders; (5) integrated, team‐based care; and (6) nonanticoagulant pharmacotherapy. Our goal is to stimulate innovative research that will accelerate the generation of the evidence to effectively pursue the secondary prevention of AF.

Objectives This study sought to evaluate the effect of cardiac resynchronization therapy with defibrillator (CRT-D) as compared with implantable cardioverter-defibrillator (ICD) on mortality, heart failure (HF) hospitalization, and ventricular arrhythmia in women versus men. Background CRT-D has demonstrated reduced mortality and HF hospitalizations with greater benefit observed in women compared with men. However, whether CRT-D prevented ventricular arrhythmias in women compared with men was unclear. Methods The RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study randomized 1,798 patients to an ICD or CRT-D. In this post hoc analysis, women and men were compared by randomized group. By using a multivariable model, the outcomes of death and HF hospitalization and incidence of ventricular arrhythmia were compared between men and women. Results There were 1,490 (83%) men (732, ICD; 758, CRT-D) and 308 (17%) women (172, ICD; 136, CRT-D) included in the analysis. Women with CRT-D had a significantly reduced incidence of death and HF hospitalization compared with men with CRT-D (hazard ratio: 0.52; 95% confidence interval: 0.33 to 0.81; p Conclusions Women have improved rates of death and HF hospitalization with CRT-D and were less likely to experience ventricular arrhythmia when compared with men, after adjusting for differences in baseline characteristics over a prolonged follow-up. Whether these improved outcomes reflect inherent sex differences in the underlying myocardial substrate resulting in an enhanced response to CRT-D requires further research.

Despite the increase in the number of female physicians across most specialties within cardiology, 10% of clinical cardiac electrophysiology (EP) fellows are women.This study sought to determine the factors that influence fellows-in-training (FITs) to pursue EP as a career choice and whether this differs by gender.The authors conducted an online multiple-choice survey through the American College of Cardiology to assess the decision factors that influence FITs in the United States and Canada to pursue cardiovascular subspecialties.A total of 933 (30.5%) FITs completed the survey; 129 anticipated specializing in EP, 259 in interventional cardiology (IC), and 545 in a different field or were unsure. A total of 1 in 7 (14%) FITs indicated an interest in EP. Of this group, more men chose EP than women (84% vs 16%; P 0.001). The most important factor that influenced FITs to pursue EP was a strong interest in the field. Women were more likely to be influenced by having a female role model (P = 0.001) compared with men. After excluding FITs interested in IC, women who deselected EP were more likely than men to be influenced by greater interest in another field (P = 0.004), radiation concerns (P = 0.001), lack of female role models (P = 0.001), a perceived "old boys' club" culture (P = 0.001) and discrimination/harassment concerns (P = 0.001).Women are more likely than men to be negatively influenced by many factors when it comes to pursuing EP as a career choice. Addressing those factors will help decrease the gender disparity in the field.

Background: Outcomes for patients with cardiac implantable electronic devices are better when follow-up incorporates remote monitoring technology in addition to in-clinic visits. For patients with implantable devices, we sought to determine the feasibility, safety and associated health care utilization of remote-only follow-up, along with its effects on patients’ quality of life and costs. Methods: This multicentre before-and-after pilot study involved patients with new or existing pacemakers or implantable cardioverter defibrillators. The “before” phase of the study spanned the period October 2015 to February 2017; the “after” phase spanned the period October 2016 to February 2018. The exposure was remote-only follow-up in combination with Remote View, a service that facilitates access to device data, allowing device settings to be viewed remotely to facilitate remote programming. Outcomes at 12 months were feasibility (adherence to remote monitoring), safety (rate of adverse events) and health care utilization (remote and in-clinic appointments). We also assessed quality of life, using 3 validated scales, and costs, taking into account both health care system and patient costs. Results: A total of 176 patients were enrolled. Adherence (defined as at least 1 successful remote transmission during follow-up) was 87% over a mean follow-up of 11.7 (standard deviation 2.2) months. There was a reduction in in-clinic visits at specialized sites among patients with both implantable defibrillators (26 v. 5, p < 0.001, n = 48) and pacemakers (42 v. 10, p < 0.001, n = 51). There was no significant change in visits to community sites for patients with defibrillators (13 v. 17, p = 0.3, n = 48). The composite rate of death, stroke, cardiovascular hospitalization and device-related hospitalization was 7% (n = 164). No adverse events were linked to the intervention. There was no change in quality-of-life scales between baseline and 12 months. Health care costs were reduced by 31% for patients with defibrillators and by 44% for those with pacemakers. Interpretation: This pilot study showed the feasibility of remote-only follow-up, with no increase in adverse clinical outcomes and no effect on quality of life, but with reductions in costs and health care utilization. These results support progression to a larger-scale study of whether superior effectiveness and reduced cost can be achieved, with preservation of safety, through use of remote-only follow-up. Trial registration: ClinicalTrials.gov, no. NCT02585817

Extracellular field shocks are applied between two extracellular electrodes placed on the body’s surface to convert ventricular fibrillation to sino-atrial rhythm. The basic question about the underlying mechanism relates to how electrical current flowing primarily through the extracellular space will flow across the cell membranes and affect the transmembrane potential of underlying cells. Experimental studies in whole hearts and cell cultures have shown that myocytes within the heart – at sites forming so-called virtual electrodes – can affect the shape of the action potential and/or excite the heart, and thereby interrupt reentrant circles and stop fibrillation. Small resistive obstacles formed by connective tissue or blood vessels in the order of few hundred micrometers in length may suffice to interrupt fibrillatory propagation. Overall, the connective tissue network, especially if it becomes more expressed in disease states or during evolving age, plays an important role in defibrillation.

Background: Remote monitoring is used to supplement in-clinic follow-up for patients with cardiac implantable electronic devices (CIEDs) every 6-12 months. There is a need to optimize remote management for CIEDs because of the consistent increases in CIED implants over the past decade. The objective of this study was to investigate real and perceived barriers to the use of remote patient management strategies in Canada and to better understand how remote models of care can be optimized. Methods: We surveyed 512 CIED patients and practitioners in 22 device clinics in Canada. Results: Device clinic surveys highlighted significant variation and inconsistency in follow-up care for in-clinic and remote visits across and within clinics. This survey showed that funding policies and management of additional workflow are barriers to optimal use and uptake. Despite this, device clinics perceive remote follow-up as a valuable resource and an efficient way to manage patient follow-up. Patients were broadly satisfied with their CIED follow-up care but identified barriers related to coordination of care, visit logistics, and information needs. Views varied as a function of clinical or sociodemographic characteristics. Most patients (n = 228; 91%) expressed a desire to receive a phone call from their device clinic after a remote transmission has been received. Conclusions: Lack of a unified, guideline-supported approach to follow-up after CIED implant, and discrepant funding policies across jurisdictions, are significant barriers to the use of remote patient management strategies in Canada. Efforts to increase or expand use of remote follow-up must recognize these barriers and the needs of specific subgroups of patients. Résumé: Introduction: La télésurveillance sert de complément à la consultation en clinique des patients porteurs d’un dispositif cardiaque électronique implantable (DCEI) tous les 6 à 12 mois. Il est nécessaire d’optimiser la prise en charge à distance des patients porteurs de DCEI en raison de la constante augmentation des implantations de DCEI au cours de la dernière décennie. L’objectif de la présente étude était d’examiner les obstacles réels et perçus à l’utilisation des stratégies de prise en charge à distance des patients du Canada et de mieux comprendre la façon d’optimiser les modèles de soins à distance. Méthodes: Nous avons interrogé 512 patients porteurs de DCEI et praticiens de 22 cliniques spécialisées en DCEI du Canada. Résultats: Les enquêtes des cliniques spécialisées en DCEI ont fait ressortir la variation importante et le manque d’uniformité dans les soins de suivi lors des consultations en clinique et à distance au sein de toutes les cliniques et entre elles. Cette enquête a montré que les politiques de financement et la gestion du flux de travail supplémentaire sont les obstacles qui empêchent l’utilisation optimale et l’adoption. Malgré cela, les cliniques spécialisées en DCEI perçoivent le suivi à distance comme une ressource très utile et un moyen efficace de prendre en charge le suivi du patient. Les patients étaient dans l’ensemble satisfaits de leurs soins de suivi relatifs à leur DCEI, mais relevaient des obstacles liés à la coordination des soins, à la logistique des consultations et à leurs besoins d’information. Les points de vue variaient en fonction des caractéristiques cliniques et sociodémographiques. La plupart des patients (n = 228 ; 91 %) ont fait part de leur souhait de recevoir un appel téléphonique de leur clinique spécialisée en DCEI après la réception de la transmission à distance. Conclusions: L’absence d’une approche unifiée et fondée sur les lignes directrices qui porte sur le suivi après l’implantation de DCEI, et la divergence des politiques de financement des provinces et territoires sont des obstacles importants à l’utilisation de stratégies de prise en charge à distance des patients au Canada. Les efforts visant à accroître ou à étendre l’utilisation du suivi à distance doivent tenir compte de ces obstacles et des besoins des sous-groupes particuliers de patients.

In clinical practice and for scientific purposes, cardiologists and primary care physicians perform risk assessment in patients with cardiac diseases or conditions with high risk of developing such. The European Heart Rhythm Association (EHRA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS) set down this expert consensus statement task force to summarize the consensus regarding risk assessment in cardiac arrhythmias. Objectives were to raise awareness of using the right risk assessment tool for a given outcome in a given population, and to provide physicians with practical proposals that may lead to rational and evidence-based risk assessment and improvement of patient care in this regard. A large variety of methods are used for risk assessment and choosing the best methods and tools hereof in a given situation is not simple. Even though parameters and test results found associated with increased risk of one outcome (e.g. death) may also be associated with higher risk of other adverse outcomes, specific risk assessment strategies should be used only for the purposes for which they are validated. The work of this task force is summarized in a row of consensus statement tables.

Atrial fibrillation is the most common sustained arrhythmia and is associated with significant morbidity, including an increased risk of stroke and death. The prevalence of atrial fibrillation is p...

Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, MACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair [¶][1] Sana M. Al-Khatib, MD, MHS, FACC, FAHA Joshua A. Beckman, MD, MS, FAHA Kim K. Birtcher, MS, PharmD, AACC Biykem Bozkurt, MD, PhD, FACC

Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, MACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair [¶][1] Sana M. Al-Khatib, MD, MHS, FACC, FAHA Joshua A. Beckman, MD, MS, FAHA Kim K. Birtcher, MS, PharmD, AACC Biykem Bozkurt, MD, PhD, FACC

Aims Implantable cardioverter-defibrillators (ICDs) are key in the prevention of sudden cardiac death, but outcomes may vary by type of device or programming [single chamber (SC) vs. dual chamber (DC)] in patients without a bradycardia pacing indication. We sought to meta-analyse patient outcomes of randomized trials of SC vs. DC devices or programming. Methods and results We searched PubMed, Embase, Scopus, Web of Science, and Cochrane trials databases for relevant studies excluding those published before 2000, involving children, or not available in English. Endpoints included mortality, inappropriate ICD therapies, and implant complications. Endpoints with at least three reporting studies were meta-analysed. We identified eight studies meeting inclusion criteria representing 2087 patients with 16.1 months mean follow-up. Mean age was 62.7 years (SD 1.92); in six studies reporting sex, most patients were male (85%). Comparing patients with a SC or DC ICD or programming, we found similar rates of mortality [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.54-1.68; P = 0.86] and inappropriate therapies (OR 1.46, 95% CI 0.97-2.19; P = 0.07) in five and six studies, respectively. In three studies of SC vs. DC ICDs (but not programming) rates of pneumothorax and lead dislodgement were not different (OR 2.12, 95% CI 0.18-24.72; P = 0.55 and OR 0.87, 95% CI 0.32-2.47; P = 0.83, respectively). Conclusion In this meta-analysis of randomized controlled trials comparing SC vs. DC ICD device or programming, there was no significant difference in inappropriate therapies, mortality, pneumothorax, or lead dislodgement. Future studies should compare these devices over longer follow-up and in specific patient populations.

Several well-designed and conducted randomized clinical trials (RCTs) have proven the survival benefit of implantable cardioverter defibrillators (ICDs). This benefit has been demonstrated in patients who survive a cardiac arrest due to a ventricular tachyarrhythmia or have sustained ventricular tachycardia not due to a transient or a reversible cause. The survival benefit of ICDs has also been shown in patients with significant systolic dysfunction (left ventricular ejection fraction (LVEF) ≤35%) due to ischemic or non-ischemic cardiomyopathy. The compelling evidence on the benefits of ICDs led the Centers for Medicare and Medicaid services (CMS) to cover secondary and primary prevention ICDs in Medicare beneficiaries. However, for primary prevention ICDs, CMS provides coverage with evidence development that requires clinicians to enter data on primary prevention ICD implants in Medicare beneficiaries into the National Cardiovascular Data Registry (NCDR) ICD Registry.

Key points Vagal reflexes slow heart rate and can change where the heartbeat originates within the sinoatrial node (SAN). The mechanisms responsible for this process - termed leading pacemaker (LP) shift - have not been investigated fully. We used optical mapping to measure the effects of baroreflex, chemoreflex and carbachol on pacemaker entrainment and electrical conduction across the SAN. All methods of stimulation triggered shifts in LP site from the central SAN to one or two caudal pacemaker regions. These shifts were associated with reduced current generation capacity centrally and increased electrical load caudally. Previous studies suggest LP shift is a rate-dependent phenomenon whereby acetylcholine slows central pacemaker rate disproportionately, enabling caudal cells that are less acetylcholine sensitive to assume control. However, our findings indicate the LP region is defined by both pacemaker rate and capacity to drive activation. Shifts in LP site provide an important homeostatic mechanism for rapid switches in heart rate. Abstract Reflex vagal activity causes abrupt heart rate slowing with concomitant caudal shifts of the leading pacemaker (LP) site within the sinoatrial node (SAN). However, neither the mechanisms responsible nor their dynamics have been investigated fully. Therefore, the objective of this study was to elucidate the mechanisms driving cholinergic LP shift. Optical maps of right atrial activation were acquired in a rat working heart-brainstem preparation during baroreflex and chemoreflex stimulation or with carbachol. All methods of stimulation triggered shifts in LP site from the central SAN to caudal pacemaker regions, which were positive for HCN4 and received uniform cholinergic innervation. During baroreflex onset, the capacity of the central region to drive activation declined with a decrease in amplitude and gradient of optical action potentials (OAPs) in the surrounding myocardium. Accompanying this decline, there was altered entrainment in the caudal SAN as shown by decreased conduction velocity, OAP amplitude, gradient and activation time. Atropine abolished these responses. Chemoreflex stimulation produced similar effects but central capacity to drive activation was preserved before the LP shift. In contrast, carbachol produced a prolonged period of reduced capacity to drive and altered entrainment. Previous studies suggest LP shift is a rate-dependent phenomenon whereby acetylcholine slows central pacemaker rate disproportionately, enabling caudal cells that are less acetylcholine sensitive to assume control. Our findings indicate that cholinergic LP shifts are also determined by altered electrical source-to-sink balance in the SAN. We conclude that the LP region is defined by both rate and capacity to drive atrial activation.

A number of clinical studies have reported that diabetes mellitus (DM) is an independent risk factor for Atrial fibrillation (AF). After adjustment for other known risk factors including age, sex, and cardiovascular risk factors, DM remains a significant if modest risk factor for development of AF. The mechanisms underlying the increased susceptibility to AF in DM are incompletely understood, but are thought to involve electrical, structural, and autonomic remodeling in the atria. Electrical remodeling in DM may involve alterations in gap junction function that affect atrial conduction velocity due to changes in expression or localization of connexins. Electrical remodeling can also occur due to changes in atrial action potential morphology in association with changes in ionic currents, such as sodium or potassium currents, that can affect conduction velocity or susceptibility to triggered activity. Structural remodeling in DM results in atrial fibrosis, which can alter conduction patterns and susceptibility to re-entry in the atria. In addition, increases in atrial adipose tissue, especially in Type II DM, can lead to disruptions in atrial conduction velocity or conduction patterns that may affect arrhythmogenesis. Whether the insulin resistance in type II DM activates unique intracellular signaling pathways independent of obesity requires further investigation. In addition, the relationship between incident AF and glycemic control requires further study.

This study sought to evaluate the effect of cardiac resynchronization therapy with defibrillator (CRT-D) as compared with implantable cardioverter-defibrillator (ICD) on mortality, heart failure (HF) hospitalization, and ventricular arrhythmia in women versus men.CRT-D has demonstrated reduced mortality and HF hospitalizations with greater benefit observed in women compared with men. However, whether CRT-D prevented ventricular arrhythmias in women compared with men was unclear.The RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study randomized 1,798 patients to an ICD or CRT-D. In this post hoc analysis, women and men were compared by randomized group. By using a multivariable model, the outcomes of death and HF hospitalization and incidence of ventricular arrhythmia were compared between men and women.There were 1,490 (83%) men (732, ICD; 758, CRT-D) and 308 (17%) women (172, ICD; 136, CRT-D) included in the analysis. Women with CRT-D had a significantly reduced incidence of death and HF hospitalization compared with men with CRT-D (hazard ratio: 0.52; 95% confidence interval: 0.33 to 0.81; p 0.001) on multivariable analysis. Women with a primary prevention indication and CRT-D had the lowest rate of ventricular arrhythmia compared with men (hazard ratio: 0.59; 95% confidence interval: 0.39 to 0.91; p = 0.016).Women have improved rates of death and HF hospitalization with CRT-D and were less likely to experience ventricular arrhythmia when compared with men, after adjusting for differences in baseline characteristics over a prolonged follow-up. Whether these improved outcomes reflect inherent sex differences in the underlying myocardial substrate resulting in an enhanced response to CRT-D requires further research.

This article summarizes recommendations for the clinical use of antiarrhythmic drugs for the treatment and prevention of atrial and ventricular arrhythmias based on current guideline and consensus documents. The choice of antiarrhythmic drug is based on the efficacy and safety profile and influenced by the presence or absence of structural heart disease. Because of its adverse side-effect profile, amiodarone is recommended for the management of atrial fibrillation only when other agents have failed or are contraindicated. For treatment of symptomatic ventricular arrhythmias in the setting of structural heart disease, amiodarone is generally the preferred agent.

The optimal follow-up of patients with pacemakers requires an integrated approach and a trained healthcare team. This chapter summarizes the goals of pacemaker follow-up, the paradigms of pacemaker follow-up, the frequency and standard protocol of pacemaker follow-up, management of the data, and the roles and responsibilities of the personnel involved in pacemaker follow-up. In-person follow-up is recommended within 72 h of device implant, within 2–12 weeks following implantation, and annually thereafter. Remote follow-up strategies offer the potential benefits of early detection of device complications, early detection of significant arrhythmias, and facilitate accelerated follow-up for monitoring indicators of normal battery depletion or to monitor device performance in the event of a health advisory/recall. For stable patients annual follow-up may be sufficient. A trained healthcare team with delegated responsibilities can allow for more efficient follow-up protocols.

Reduced protein expression of the cardiac ryanodine receptor type 2 (RyR2) is thought to affect the susceptibility to stress-induced ventricular tachyarrhythmia (VT) and cardiac alternans, but direct evidence for the role of RyR2 protein expression in VT and cardiac alternans is lacking. Here, we used a mouse model (crrm1) that expresses a reduced level of the RyR2 protein to determine the impact of reduced RyR2 protein expression on the susceptibility to VT, cardiac alternans, cardiac hypertrophy, and sudden death. Electrocardiographic analysis revealed that after the injection of relatively high doses of caffeine and epinephrine (agents commonly used for stress test), wild-type (WT) mice displayed long-lasting VTs, whereas the crrm1 mutant mice exhibited no VTs at all, indicating that the crrm1 mutant mice are resistant to stress-induced VTs. Intact heart Ca2+ imaging and action potential (AP) recordings showed that the crrm1 mutant mice are more susceptible to fast-pacing induced Ca2+ alternans and AP duration alternans compared with WT mice. The crrm1 mutant mice also showed an increased heart-to-body-weight ratio and incidence of sudden death at young ages. Furthermore, the crrm1 mutant hearts displayed altered Ca2+ transients with increased time-to-peak and decay time (T50), increased ventricular wall thickness and ventricular cell area compared with WT hearts. These results indicate that reduced RyR2 protein expression suppresses stress-induced VTs, but enhances the susceptibility to cardiac alternans, hypertrophy, and sudden death., This work was supported by research grants from the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canada Foundation for Innovation, and the Heart and Stroke Foundation Chair in Cardiovascular Research (to S.R.W.C.). The present study was also supported by the Spanish Ministry of Economy and Competitiveness [SAF2014-58286-C2-1-R] (L.H.-M.) and [DPI2013-44584-R] (R.B.).

Multi-electrode basket catheters are used for 3D mapping of complex focal arrhythmias in real-time, but full contact is hard to achieve for all electrodes in the atria. We have developed a novel inverse mapping approach, which enables endocardial potentials to be recovered from noncontact recordings and report on its efficacy. Intra-atrial electrograms were acquired with 64 channel Constellation™ catheters in 4 anesthetized sheep in sinus rhythm (SR), atrial pacing (AP) and atrial fibrillation (AF), with catheters of different dimension at various locations in right and/or left atria (RA, LA). Atrial endocardial potentials were recovered from noncontact recordings using finite-element and meshless inverse methods. Inverse mapping reproduced contact electrograms, recorded separately at distributed sites, with excellent accuracy in SR and AP [CC 0.8+0.18, time delay 1+3 ms, relative RMS error 0.53+0.17, n=96]. Moreover, repeatable activation time maps were obtained in SR and AP. Focal activity was identified in AF and precise noncontact region-of-interest mapping was also demonstrated.

Sex-specific differences in the epidemiology, pathophysiology, clinical presentation, clinical treatment, and clinical outcomes of atrial fibrillation (AF), sustained ventricular arrhythmias, and sudden cardiac death are recognized. Sex hormones cause differences in cardiac electrophysiological parameters between men and women that may affect the risk for arrhythmias. The incidence and prevalence of AF is lower in women than in men. However, because women live longer and AF prevalence increases with age, the absolute number of women with AF exceeds that of men. Women with AF are more symptomatic, present with more atypical symptoms, and report worse quality of life in comparison with men. Female sex is an independent risk factor for death or stroke attributable to AF. Oral anticoagulation therapy for stroke prevention has similar efficacy for men and women, but older women treated with warfarin have a higher residual risk of stroke in comparison with men. Women with AF are less likely to receive rhythm control antiarrhythmic drug therapy, electric cardioversion, or catheter ablation in comparison with men. The incidence and prevalence of sustained ventricular arrhythmias and sudden cardiac death are lower in women than in men. Women receiving implantable cardioverter defibrillators for primary prevention of sudden cardiac death are less likely to experience sustained ventricular arrhythmias in comparison with men. In contrast, women receiving a cardiac resynchronization therapy implantable cardioverter defibrillator for the treatment of heart failure are more likely to benefit than men. Women are less likely to be referred for implantable cardioverter defibrillator therapy despite current guideline recommendations. Women are more likely to experience a significant complication related to implantable cardioverter defibrillator implantation in comparison with men. Whether sex differences in treatment decisions reflect patient preferences or treatment biases requires further study.

Sudden cardiac arrest (SCA) remains an important public health challenge. Despite a dramatic decrease in the age-adjusted risk of SCA, the cumulative number of fatal SCAs in the United States remains large. Estimates range from 450 000 fatal SCAs per year; a figure in the range of 300 000 to 370 000 per year is likely the best current estimate.1 SCA appears to account for ≈50% of all cardiovascular deaths,2 and it is estimated that 50% of the SCAs are the first clinical expression of previously undiagnosed heart disease.2,3 Most out-of-hospital cardiac arrests (80%) occur in private homes or other living facilities.4 Electric mechanisms associated with SCA are broadly classified into tachyarrhythmic and nontachyarrhythmic categories, the latter including pulseless electric activity (PEA; formerly referred to as electromechanical dissociation), asystole, extreme bradycardia, and other mechanisms often associated with noncardiac factors (Table). The first approaches to the problem of SCA focused on ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT). An early impact on the prevention and treatment of VF and VT was realized in patients with acute coronary syndromes >50 years ago,5 followed by the development of strategies for responding to out-of-hospital cardiac arrest, implantable cardioverter-defibrillators, and defibrillation by lay responders. View this table: Table. Tachyarrhythmic and Nontachyarrhythmic Cardiac Arrest Data from the Seattle emergency rescue system6 and elsewhere7–9 have identified progressive reductions in the number of responses to SCA over 2 to 3 decades. This change was due primarily to a reduction in the number of ventricular tachyarrhythmic events identified by emergency medical services responders. In the Seattle data, the incidences of PEA and asystole had not changed over the 3 decades of observation and therefore have emerged as proportionately more frequent mechanisms than VT/VF. Whether this also reflects the …

[Figure][1] It is increasingly uncommon for someone to make an expensive purchase or choose a contractor for a major project without some thoughtful research. Decisions about health care and who provides it should be no different, but reliable information about the quality of health care

William A. Zoghbi MD, FACC ACC President The unstated rationale for public reporting is that this information has impacts on market forces, payers, and practitioners to improve health care quality and reduce costs. In one of the first public reporting efforts, the Health Care Financing Administration (HCFA) published hospital mortality rates for Medicare patients undergoing coronary artery bypass graft surgery (CABG) (1). These data, derived from administrative and claims information, were not originally intended for this use and the report was criticized by hospitals and providers because they feared that the risk adjustment models were inadequate. Although adjustments were made, the usefulness of these reports has never been established, and many express negative opinions about these data (2). The HCFA experience led to the development of several private quality improvement registries and public state-wide reporting systems, such as the Northern New England Cardiovascular Study Group and the Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database (3). New York, Pennsylvania, Massachusetts, and California subsequently developed public reporting mechanisms for cardiac surgical outcomes (4–7). Some states even report physician-specific data and have expanded reporting to include percutaneous coronary interventions (PCI) (8). In 2005, the Centers for Medicare and Medicaid Services (CMS) launched the Hospital Compare website to publicly report hospital quality information derived from several sources (9). Certain core measures are reported for cardiac patients along with risk-adjusted mortality and readmission rates for acute myocardial infarction and heart failure derived from Medicare enrollment and claims data. The site also reports the results of patient surveys about their hospitalization and is considering adding measures from the Hospital Value Based Purchasing Program. The number of resources currently devoted to public reporting is unknown, but public reporti ng initiatives continue to proliferate with additional state initiatives, reports from payers that focus on costs, and reports from business consumer groups (10). There are now several internet-based forums where patients can report their individual experiences with physicians, both good and bad, in an unregulated and nonscientific manner. This, in turn, has resulted in some physicians requiring patients to agree to not participate in such activities before any treatment is provided. January 2011, under the authority of the Patient Protection and Affordable Care Act of 2010 (PPACA), CMS implemented the Physician Compare website (11). Several benchmarks for this effort were established: 1) providing information on the performance of physicians (and other health care providers) enrolled in Medicare; 2) reporting to Congress on the plans to use these data for value-based purchasing and consumer choice; and 3) demonstrating how financial incentives will be applied to beneficiaries who use “high-quality physicians.”

Beat-to-beat alternations in the amplitude of the cytosolic Ca2+ transient (Ca2+ alternans) are thought to be the primary cause of cardiac alternans that can lead to cardiac arrhythmias and sudden death. Despite its important role in arrhythmogenesis, the mechanism underlying Ca2+ alternans remains poorly understood. Here, we investigated the role of cardiac ryanodine receptor (RyR2), the major Ca2+ release channel responsible for cytosolic Ca2+ transients, in cardiac alternans. Using a unique mouse model harboring a suppression-of-function (SOF) RyR2 mutation (E4872Q), we assessed the effect of genetically suppressing RyR2 function on Ca2+ and action potential duration (APD) alternans in intact hearts, and electrocardiogram (ECG) alternans in vivo. We found that RyR2-SOF hearts displayed prolonged sarcoplasmic reticulum Ca2+ release refractoriness and enhanced propensity for Ca2+ alternans. RyR2-SOF hearts/mice also exhibited increased propensity for APD and ECG alternans. Caffeine, which enhances RyR2 activity and the propensity for catecholaminergic polymorphic ventricular tachycardia (CPVT), suppressed Ca2+ alternans in RyR2-SOF hearts, whereas carvedilol, a β-blocker that suppresses RyR2 activity and CPVT, promoted Ca2+ alternans in these hearts. Thus, RyR2 function is an important determinant of Ca2+, APD, and ECG alternans. Our data also indicate that the activity of RyR2 influences the propensity for cardiac alternans and CPVT in an opposite manner. Therefore, overly suppressing or enhancing RyR2 function is pro-arrhythmic.

h i Sudden cardiac death due to ventricular arrhythmias in the setting of underlying disease remains a substantial problem both within the U.S. and worldwide. Nearly 300,000 individuals in the U.S. die suddenly each year. In many, the terminal event is the first manifestation of underlying cardiac disease, even though this is present in the majority of cases. It is estimated that only 30%–50% among those at risk for sudden cardiac death, meeting defined primary prevention guidelines for the implantation of an ICD, receive appropriate risk counseling and potentially life saving medical or device treatment. The substantially lower implant rates in women and minorities further underscore the disparities in ICD use within North America. The strongest evidence guiding clinical decision-making for these patients is based on the outcomes of large-scale, multi-center randomized clinical trials that examine the impact of drug and device therapy in patients with significant left ventricular (LV) dysfunction. The SCD-HeFT and ADIT II trials clearly demonstrated enhanced survival with device therapy in patients with either ischemic or non-ischemic disease and ventricular dysfunction indicated

Background— T-wave alternans (TWA) increases before ventricular tachycardia (VT) or fibrillation (VF), suggesting that it may warn of VT/VF in implantable cardioverter-defibrillator patients. Recently, we described a method for measuring alternans and nonalternans variability (TWA/V) from electrograms (EGMs) stored in implantable cardioverter-defibrillators before VT/VF. The goal of this prospective, multicenter study was to determine whether EGM TWA/V was greater before VT/VF than at baseline. Methods and Results— We enrolled 63 implantable cardioverter-defibrillator patients. TWA/V was computed from stored EGMs before spontaneous VT/VF and from sequential windows of 8 pairs of beats using 4 different control recordings: baseline rhythm, rapid pacing at 105 bpm, segments of ambulatory Holter EGMs matched to the time of VT/VF episodes, and EGMs before spontaneous supraventricular tachycardia. During follow-up, 28 patients had 166 episodes of VT/VF. TWA/V was greater before VT/VF (62.9±3.1 μV; n=28) than during baseline rhythm (12.8±1.8 μV; P P P P P Conclusions— In implantable cardioverter-defibrillator patients, EGM TWA/V is greater before spontaneous VT/VF than in control recordings. Future implantable cardioverter-defibrillators that measure EGM TWA/V continuously may warn patients and initiate pacing therapies to prevent VT/VF.

Background Recent economic trends influenced by healthcare reform, an aging population, changes in physician reimbursement, and increasing competition will have a significant impact on the electrophysiology workforce. Therefore, there is an important need to obtain information about the EP workforce to assess training of arrhythmic healthcare providers in order the meet the requisite societal need. This report summarizes the data collected by the HRS Workforce Study Task Force in relation to physician workforce issues. Objective The HRS Workforce Study Task Force was charged with conducting a comprehensive study to assess changes in the field of electrophysiology since the last workforce study conducted in 2001 and to identify the population and distribution of professionals who treat patients with heart rhythm disorders. Methods A series of comprehensive questionnaires were designed by the HRS Workforce Study Task Force to conduct online surveys with physicians, basic science researchers, and allied professionals. Data collected in the physician survey included: personal demographics and professional profile characteristics such as primary work setting and areas of affiliation; workload characteristics such as hours worked, time spent by activity, workload relative to capacity, competition for patients, volume by specific procedure, sources of referrals, income levels, personal mobility, and anticipated future changes in the respondent's practice. Survey responses were collated and analyzed by the Workforce Study Task Force. Results Work capacity is expected to increase to offset some of the economic drivers; however, recruitment of new EPs could be challenging and uncertain. Specifically, geographic mobility (>50 miles) appears to be minimal at present overall and unlikely to significantly change for the majority of physicians once they have established themselves in a given community following the completion of their training. Practice time is predominantly spent performing device implantations, device follow-ups and ablations. These activities are being tasked upon younger physicians, thereby suggesting a need for trained allied professionals to assume a greater role in device management. The perception of competition varied by respondent age and geographic location but, in general, was felt to be at least moderate by most respondents. Furthermore, there are concerns that increasing competition may dilute operator experience and potentially lower high quality outcomes if increasing competition leads to lower procedural volumes. Conclusion Based on findings from this study, the task force identified specific workforce (supply) trends and the key drivers of current and future challenges. Although specific areas will require further analysis, overall, the current EP workforce is stable, with the exception of geographic dispersion. However, the workforce must adapt to the key economic drivers (demand) and address future recruitment challenges.

Background— Atrial fibrillation (AF) is commonly associated with impaired quality of life. There is no simple validated scale to quantify the functional illness burden of AF. The Canadian Cardiovascular Society Severity in Atrial Fibrillation (CCS-SAF) scale is a bedside scale that ranges from class 0 to 4, from no effect on functional quality of life to a severe effect on life quality. This study was performed to validate the scale. Methods and Results— In 484 patients with documented AF (62.2�12.5 years of age, 67% men; 62% paroxysmal and 38% persistent/permanent), the SAF class was assessed and 2 validated quality-of-life questionnaires were administered: the SF-36 generic scale and the disease-specific AFSS (University of Toronto Atrial Fibrillation Severity Scale). There is a significant linear graded correlation between the SAF class and measures of symptom severity, physical and emotional components of quality of life, general well-being, and health care consumption related to AF. Patients with SAF class 0 had age- and sex-standardized SF-36 scores of 0.15�0.16 and −0.04�0.31 (SD units), that is, units away from the mean population score for the mental and physical summary scores, respectively. For each unit increase in SAF class, there is a 0.36 and 0.40 SD unit decrease in the SF-36 score for the physical and mental components. As the SAF class increases from 0 to 4, the symptom severity score (range, 0 to 35) increases from 4.2�5.0 to 18.4�7.8 ( P Conclusions— The CCS-SAF scale is a simple semiquantitative scale that closely approximates patient-reported subjective measures of quality of life in AF and may be practical for clinical use.