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June 2012 Circulation: Arrhythmia and Electrophysiology Topic Review Circulation: Arrhythmia and Electrophysiology Editors’ Picks Most Read Articles on Arrhythmia Devices (Defibrillation, Pacing, Pacemakers, Heart Arrest, and Resuscitation) The Editors The following articles are being highlighted as part of Circulation: Arrhythmia and Electrophysiology’s Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in Circulation: Arrhythmia and Electrophysiology, Circulation, and the other Circulation subspecialty journals. The studies included in this article represent the most read manuscripts published on the topic of arrhythmia devices (defibrillation, pacing, pacemakers, heart arrest, and resuscitation) in 2010 and 2011. (Circ Arrhythm Electrophysiol. 2012;5:e69-e77.) Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017 Efficacy of Low Interatrial Septum and Right Atrial Appendage Pacing for Prevention of Permanent Atrial Fibrillation in Patients With Sinus Node Disease: Results From the Electrophysiology-Guided Pacing Site Selection (EPASS) Study failure (HF). The GREATER-EARTH trial tested the hypothesis that left ventricular (LV) pacing alone is superior to biventricular (BiV) pacing with regard to exercise tolerance (primary outcome) and LV structural remodeling (secondary outcomes). This multicenter, randomized, double-blind, crossover trial enrolled patients with an LV ejection fraction ≤35%, QRS duration ≥120 ms, and severely impaired exercise tolerance (6-minute walk distance ≤400 meters). A unique run-in period (with cardiac resynchronization therapy off) between implantation and the baseline assessment allowed for maturation of the system, identification of disqualifying issues, and optimization of medical therapy before randomization. The most marked clinical improvement occurred during this run-in phase and could be attributed, in part, to uptitration of β-blockers. Overall, the 2 pacing strategies resulted in similar improvements in exercise capacity and reverse LV remodeling. The most effective mode varied between patients, with some nonresponders to BiV pacing responding favorably to LV pacing, and vice versa. In addition to providing a rationale for a trial of crossover from 1 pacing mode to the other in initial nonresponders, results may prove relevant to future innovations in cardiac resynchronization therapy. Whereas, currently, there is little reason not to place a right ventricular (RV) lead in a cardiac resynchronization therapy system, because it is essential for defibrillation, the rationale for eliminating an RV lead will likely become increasingly relevant with the development of new LV leads (eg, multipolar or with defibrillation capacity) and novel implantation techniques. Roberto Verlato, MD; Giovanni Luca Botto, MD; Riccardo Massa, MD; Claudia Amellone, MD; Antonello Perucca, MD; Maria Grazia Bongiorni, MD; Emanuele Bertaglia, MD; Vigilio Ziacchi, MD; Marcello Piacenti, MD; Attilio Del Rosso, MD; Giovanni Russo, MD; Maria Stella Baccillieri, MD; Pietro Turrini, MD; and Giorgio Corbucci, PhD Summary: Patients with sinus node dysfunction may develop atrial fibrillation (AF). This study shows that pacing the interatrial septum can play a role in the prevention of permanent/persistent AF in patients with intra-atrial conduction delay to the posterior triangle of Koch. These patients can be identified by a quick electrophysiological study during the implanting procedure, as described in the report. The lead technology to permanently pace specific atrial sites is available, and the algorithms for continuous atrial pacing are also available. Finally, the pacemakers automatically store data about AF burden, simplifying the assessment of the development/progression of the disease. Conclusions: In patients with sinus node dysfunction and intra-atrial conduction delay, low interatrial septum pacing was superior to right atrial appendage pacing in preventing progression to persistent or permanent AF.1 Conclusions: LV pacing is not superior to BiV pacing; however, nonresponders to BiV pacing may respond favorably to LV pacing, suggesting a potential role as tiered therapy.2 Left Ventricular versus Simultaneous Biventricular Pacing in Patients With Heart Failure and a QRS Complex ≥120 Milliseconds Effect of Right Ventricular versus Biventricular Pacing on Electric Remodeling in the Normal Heart Bernard Thibault, MD; Anique Ducharme, MD, MSc; François Harel, MD, PhD; Michel White, MD; Eileen O’Meara, MD; Marie-Claude Guertin, PhD; Joel Lavoie, PhD; Nancy Frasure-Smith, PhD; Marc Dubuc, MD; Peter Guerra, MD; Laurent Macle, MD; Léna Rivard, MD; Denis Roy, MD; Mario Talajic, MD; Paul Khairy, MD, PhD; for the Evaluation of Resynchronization Therapy for Heart Failure (GREATER-EARTH) Investigators Samir Saba, MD; Haider Mehdi, PhD; Michael A. Mathier, MD; M. Zahadul Islam, MBBS; Guy Salama, PhD; and Barry London, MD, PhD Summary: Biventricular (BiV) pacing has been shown to have beneficial effects in a subset of patients with systolic heart failure (HF) and to prevent the deleterious effects of high-burden right Summary: Cardiac resynchronization therapy is an important adjunctive treatment modality for selected patients with heart Correspondence to The Editors, Circulation: Arrhythmia and Electrophysiology Editorial Office, 560 Harrison Ave, Suite 502, Boston, MA 02118. E-mail [email protected] © 2012 American Heart Association, Inc. Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org e69 DOI: 10.1161/CIRCEP.112.973305 e70 Circ Arrhythm Electrophysiol June 2012 ventricular (RV) pacing in patients with preserved left ventricular (LV) function. The mechanisms of these salutary effects are not fully elucidated. In this study, we examined the effect of BiV versus RV pacing on the normal heart in a rabbit model of epicardial pacing. After 4 weeks of pacing, the QT interval was significantly shorter in the BiV group compared with the RV or sham-operated (nonpaced) groups. Also, compared with rabbits in the RV group, rabbits in the BiV group had shorter RV-effective refractory period and shorter LV-paced QT interval during the drive train of stimuli and close to refractoriness. Also, protein expression of the KvLQT1 gene was significantly increased in the BiV group compared with the RV and control groups, whereas protein expression of SCN5A and connexin43 was significantly decreased in the RV compared with the other study groups. ERG protein expression was significantly increased in both pacing groups compared with the controls. These findings underscore the effect of the sites of pacing on electric remodeling in the normal heart and may have implications as to the effect of BiV pacing on arrhythmia incidence and burden. Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017 Conclusions: In this rabbit model, we demonstrate a direct effect of BiV but not RV pacing on shortening the native QT interval as well as the paced QT interval during burst pacing and close to the ventricular effective refractory period. These findings underscore the fact that the effect of BiV pacing is partially mediated through direct electric remodeling and may have implications as to the effect of BIV pacing on arrhythmia incidence and burden.3 Effect of Long-Term Right Ventricular Pacing in Young Adults With Structurally Normal Heart Sandeep Sagar, MD, PhD; Win-Kuang Shen, MD; Samuel J. Asirvatham, MD; Yong-Mei Cha, MD; Raul E. Espinosa, MD; Paul A. Friedman, MD; David O. Hodge, MS; Thomas M. Munger, MD; Coburn J. Porter, MD; Robert F. Rea, MD; David L. Hayes, MD; Arshad Jahangir, MD Summary: This study elucidates the long-term effect of right ventricular (RV) pacing on clinical outcomes in patients who underwent pacemaker implantation for symptomatic isolated congenital complete atrioventricular block (ICAVB). Over a mean follow-up of 20 years (longest, 39 years), the observed survival free of new heart failure (HF) after pacemaker implant in the overall ICAVB group was significantly worse than that of the age- and sex-specific Olmsted County, Minn, population rates. This difference was, however, attributable to the development of HF and ventricular dysfunction in those who had tested positive for antinuclear antibody (ANA) during adulthood, with no difference between patients with antibody-negative ICAVB and the Olmsted County population. The presence of a positive ANA was a strong predictor for the development of HF and death. These results suggest that, in young patients without structural heart disease, pacing from the RV position does not appear to have a detrimental effect on heart size or performance. The risk of HF after pacemaker implant is not solely the result of abnormal ventricular activation but, instead, an interaction between pacing and abnormal myocardial substrate. In patients with ICAVB, positive antibody status may predispose to cardiomyopathy and worse clinical outcomes. ANA testing should supplement the assessment of ventricular size and function by echocardiography to identify high-risk patients who might progress to HF. Conclusions: The natural history of patients with isolated congenital atrioventricular block who require pacing depends on their antibody status. ANA status was a predictor for the development of heart failure and death. Long-term RV pacing alone does not appear to be associated with development of heart failure, deterioration in ventricular function, or reduced survival in patients with Ab(–) isolated congenital atrioventricular block.4 Induction of Therapeutic Hypothermia by Paramedics After Resuscitation From Out-of-Hospital Ventricular Fibrillation Cardiac Arrest: A Randomized Controlled Trial Stephen A. Bernard, MD; Karen Smith, BSc, PhD; Peter Cameron, MD; Kevin Masci; David M. Taylor, MD; D. James Cooper, MD; Anne-Maree Kelly, MD; William Silvester, MB, BS; for the Rapid Infusion of Cold Hartmanns (RICH) Investigators Summary: The induction of therapeutic hypothermia after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest is recommended for the treatment of neurological injury by the American Heart Association; however, the optimal timing of this intervention is uncertain. Laboratory studies suggest that earlier cooling may improve neurological outcomes. This study reports the results of a randomized controlled trial in 234 patients comparing paramedic cooling after return of a circulation by use of a rapid infusion of large-volume, ice-cold intravenous fluid with cooling after hospital arrival. Paramedic cooling decreased core temperature by 0.8°C compared with patients allocated to hospital cooling, but the outcomes at hospital discharge were similar in both groups. Further research into cooling during cardiopulmonary resuscitation should be undertaken. Conclusions: In adults who have been resuscitated from out-ofhospital cardiac arrest with an initial cardiac rhythm of ventricular fibrillation, paramedic cooling with a rapid infusion of large-volume, ice-cold intravenous fluid decreased core temperature at hospital arrival but was not shown to improve outcome at hospital discharge compared with cooling commenced in the hospital.5 Dispatcher-Assisted Cardiopulmonary Resuscitation: Risks for Patients Not in Cardiac Arrest Lindsay White, MPH; Joseph Rogers, MS; Megan Bloomingdale; Carol Fahrenbruch, MSPH; Linda Culley, BA; Cleo Subido, RPL; Mickey Eisenberg, MD, PhD; Thomas Rea, MD, MPH Summary: Cardiopulmonary resuscitation (CPR) instructions pro vided over the telephone by the 911 emergency dispatcher can substantially increase bystander-initiated CPR and thereby increase the chance for survival from out-of-hospital cardiac arrest. Nevertheless, identification of cardiac arrest by dispatchers and bystanders can sometimes be challenging. A number of conditions can resemble cardiac arrest; consequently, patients who are not in cardiac arrest can receive CPR. The risk of bystander CPR for patients not in arrest is uncertain and has implications for how assertive dispatch is in instructing CPR. This article reports on a 2.5-year prospective study of dispatcher-assisted CPR in King County, Wash. Of the 1700 patients for whom dispatcher CPR instructions were initiated during the study period, 55% (938 of 1700) were in arrest, 45% (762 of 1700) were not in arrest, and 18% (313 of 1700) were not in arrest and progressed to receive bystander chest compressions. Of the patients not in arrest who received chest compressions, 12% experienced discomfort, and 2% sustained injuries likely or possibly caused by bystander CPR. The injuries were characterized most often by rib fracture, and no patients suffered visceral organ injury. The results of the present investigation indicate that the frequency of serious injury related to dispatcher-assisted bystander CPR among nonarrest patients is low. When coupled with the established benefits of bystander CPR among those with arrest, the results support an assertive program of dispatcher-assisted CPR. Conclusions: In this prospective study, the frequency of serious injury related to dispatcher-assisted bystander CPR among nonarrest patients was low. When coupled with the established benefits of bystander CPR among those with arrest, these results support an assertive program of dispatcher-assisted CPR.6 The Editors Most Read on Arrhythmia Devices e71 Permanent Pacemaker Insertion After CoreValve Transcatheter Aortic Valve Implantation: Incidence and Contributing Factors (the UK CoreValve Collaborative) Muhammed Khawaja, MBBS; Ronak Rajani, MD; Andrew C. Cook, PhD; Ali Khavandi, MD; Anouska Moynagh, MD; Saqib Chowdhary, MD; Mark S. Spence, MD; Sue Brown, BSC; Sohail Q. Khan, MD; Nicola Walker, MBChB, PhD; Uday Trivedi, MBBS; Nevil Hutchinson, MBBS; Adam J. De Belder, MD; Neil Moat, MBBS; Daniel J. Blackman, MD; Richard D. Levy, MD; Ganesh Manoharan, MD; David Roberts, MD; Saib S. Khogali, MD; Peter Crean, MD; Stephen J. Brecker, MD; Andreas Baumbach, MD; Michael J. Mullen, MD; Jean-Claude Laborde, MD; and David Hildick-Smith, MD Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017 Summary: Transcatheter aortic valve implantation has entered mainstream interventional cardiology as a treatment for aortic stenosis in patients with prohibitively high operative risk. This is a growing cohort of patients globally, given the increased longevity and prevalence of significant comorbidities. The CoreValve Revalving system (CoreValve Medtronic) is 1 of the 2 prostheses currently in use, and it has been noted to be associated with an increased need for permanent pacemaker implantation. This study represents the largest analysis of the rates of permanent pacemaker implantation in patients receiving a CoreValve implant and uses clinical ECG data to create an electroanatomic model to explain the phenomenon. Consideration of these factors as addressed in this study has not only implications for the future designs of transcatheter aortic valve implantation devices but also immediate clinical impact on the standard of care of this increasingly numerous patient group. Conclusions: One third of patients undergoing a CoreValve transcatheter aortic valve implantation procedure require a permanent pacemaker within 30 days. Periprocedural atrioventricular block, balloon predilatation, use of the larger CoreValve prosthesis, increased interventricular septum diameter, and prolonged QRS duration were associated with the need for a permanent pacemaker.7 Inhaled Nitric Oxide Improves Outcomes After Successful Cardiopulmonary Resuscitation in Mice Shizuka Minamishima, MD; Kotaro Kida, MD, PhD; Kentaro Tokuda, MD; Huifang Wang, PhD; Patrick Y. Sips, PhD; Shizuko Kosugi, MD; Joseph B. Mandeville, PhD; Emmanuel S. Buys, PhD; Peter Brouckaert, MD, PhD; Philip K. Liu, PhD; Christina H. Liu, PhD; Kenneth D. Bloch, MD; and Fumito Ichinose, MD, PhD Summary: Sudden cardiac arrest is one of the leading causes of death worldwide. Despite advances in resuscitation techniques, <8% of the 300 000 adults who experience cardiac arrest in the United States each year survive to hospital discharge, and up to 60% of survivors have long-lasting neurological deficits. Although therapeutic hypothermia has proven effective in clinical studies, no pharmacological agent is available to improve outcome from cardiac arrest. Although originally developed as a selective pulmonary vasodilator, inhaled nitric oxide (NO) has been shown to have systemic effects in a variety of preclinical and clinical studies without causing systemic vasodilation. In the present study, we found that breathing a low concentration of NO, starting 1 hour after successful cardiopulmonary resuscitation for 23 hours, markedly improves long-term neurological and cardiac outcomes and survival in mice subjected to cardiac arrest and cardiopulmonary resuscitation. The ability of NO breathing to improve outcomes after cardiac arrest when begun after cardiopulmonary resuscitation, if extrapolated to human beings, makes inhaled NO a practical therapeutic approach that can be initiated after patients are transferred to a hospital. Furthermore, because inhaled NO does not cause systemic hypotension, in contrast to systemic NO donors, it is uniquely suited for the treatment of patients post cardiac arrest in whom blood pressure is often unstable. We anticipate that the established safety profile of NO inhalation will enable the rapid translation of findings in animal models to patients experiencing postcardiac arrest syndrome. Conclusions: These results suggest that NO inhalation after CA and successful cardiopulmonary resuscitation improves outcome via soluble guanylate cyclase-dependent mechanisms.8 Outcomes After In-Hospital Cardiac Arrest in Children With Cardiac Disease: A Report From Get With the Guidelines – Resuscitation Laura Ortmann, MD; Parthak Prodhan, MBBS; Jeffrey Gossett, MS; Stephen Schexnayder, MD; Robert Berg, MD; Vinay Nadkarni, MD; Adnan Bhutta, MBBS; for the American Heart Association’s Get With the Guidelines – Resuscitation (formerly National Registry of Cardiopulmonary Resuscitation) Investigators Summary: Survival after cardiac arrest is poor; however, small case series have suggested that children with cardiac disease who experience a cardiac arrest have better outcomes. Our study of 3323 pediatric patients using Get With the Guidelines – Resuscitation found that survival to hospital discharge was 37% in children with surgical cardiac disease compared with 28% in children with medical cardiac disease and 23% in children without cardiac disease. Although multiple previous studies have examined survival after cardiac arrest in pediatric patients, children undergoing cardiac surgery are a unique population, and their survival after arrest has not been well-studied. Children after cardiac surgery have a much higher risk of cardiac arrest compared with other pediatric populations, so this improved survival is encouraging for the providers who care for them. Notable is the higher odds of survival with the use of extracorporeal cardiopulmonary resuscitation, and this report adds to previous studies that have found extracorporeal cardiopulmonary resuscitation to be an effective rescue therapy. This study will be useful for medical providers when evaluating a patient’s prognosis and provides information for researchers wanting to study this unique group of patients. Conclusions: Children with surgical cardiac disease have significantly better survival to hospital discharge after an in-hospital cardiac arrest compared with children with medical cardiac disease and noncardiac disease.9 DEFI 2005: A Randomized Controlled Trial of the Effect of Automated External Defibrillator Cardiopulmonary Resuscitation Protocol on Outcome From Out-of-Hospital Cardiac Arrest Daniel Jost, MD; Hervé Degrange, MD; Catherine Verret, MD, PhD; Olivier Hersan, MD; Isabelle L. Banville, PhD; Fred W. Chapman, PhD; Paula Lank, RN, BSN; Jean Luc Petit, MD; Claude Fuilla, MD; René Migliani, MD, PhD; Jean Pierre Carpentier, MD, PhD; the DEFI 2005 Work Group Summary: The American Heart Association Guidelines 2005 for Emergency Cardiac Care made changes to the way that chest compressions, ventilations, and defibrillation countershocks are sequenced, in an effort to resuscitate more patients in cardiac arrest. These changes, which were based on theoretical considerations, experimental studies, and few clinical studies, aimed to increase cardiopulmonary resuscitation (CPR), in hopes of improving patient outcomes. Although several published articles have reported on the effect of increasing CPR in cohort studies, none has the evidence level of a randomized controlled trial. The results of this 18-month, 845-patient, randomized controlled trial on out-of-hospital ventricular fibrillation cardiac arrest are of particular interest and potential impact on the next cycle of the evidence review process of the International Liaison Committee on Resuscitation, leading to the American Heart Association 2010 guidelines. This randomized controlled trial demonstrated that, by following new automated external defibrillator prompts, basic life support-trained firefighters could shorten pauses in chest compressions and improve their overall CPR hands-on ratio from 48% to 61% during resuscitation of patients with ventricular fibrillation out-of-hospital cardiac arrest; however, this improvement in CPR metrics did not translate into e72 Circ Arrhythm Electrophysiol June 2012 measurable differences in rates of return of spontaneous circulation before advanced cardiac life support arrival, survival to hospital admission or discharge, or 1-year survival. The lack of benefit from increased CPR in this trial, combined with experience from this and other emergency medical systems, suggests that the survival rate may be further improved by efforts focused on other changes to community resuscitation such as increasing bystander CPR, shortening response times, or even providing more extensive and regular CPR training to rescuers. Conclusions: Following prompts from automated external defibrillators programmed with a protocol similar to AHA Guidelines 2005, firefighters shortened pauses in CPR and improved overall hands-on time, but survival to hospital admission of patients with ventricular fibrillation out-of-hospital cardiac arrest did not improve.10 Relationship Between Supranormal Oxygen Tension and Outcome After Resuscitation From Cardiac Arrest Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017 J. Hope Kilgannon, MD; Alan E. Jones, MD; Joseph E. Parrillo, MD; R. Phillip Dellinger, MD; Barry Milcarek, PhD; Krystal Hunter, MBA; Nathan I. Shapiro, MD; Stephen Trzeciak, MD, MPH; on behalf of the Emergency Medicine Shock Research Network (EMShockNet) Investigators Summary: Historically, the administration of supplemental oxygen has been considered a cornerstone of cardiopulmonary resuscitation for victims of cardiac arrest; however, laboratory experiments and recent clinical data suggest that, after a pulse is restored, excessive supplemental oxygen could be harmful. Supranormal oxygen tension can exacerbate oxygen-free radical formation and subsequent reperfusion injury; however, it is unclear if the risk of poor outcome is a threshold effect at a specific supranormal oxygen tension or is a dose-dependent association. The authors studied patients admitted to an intensive care unit after resuscitation from cardiac arrest at 120 US hospitals. After excluding patients with hypoxia, there were 4459 patients in the sample. The authors tested the association between postresuscitation arterial partial pressure of oxygen and in-hospital mortality. The median postresuscitation arterial partial pressure of oxygen was 231 (interquartile range 149 to 349) mm Hg. Fifty-four percent of the patients died. Over ascending ranges of oxygen tension, the authors found significant linear trends of increasing in-hospital mortality and decreasing survival as functionally independent. On multivariable analysis adjusted for patient-oriented covariates and potential hospital effects, a 100-mmHg increase in postresuscitation arterial partial pressure of oxygen was associated with a 24% increase in relative risk of death. The authors observed no evidence supporting a single threshold for harm from supranormal oxygen tension. In this large sample of patients postresuscitation, the authors found that the association between supranormal oxygen tension and risk of in-hospital death is a linear dose-dependent relationship. These data provide further support that supranormal oxygen tension may be harmful in patients resuscitated from cardiac arrest. Conclusions: In this large sample of patients postresuscitation, we found a dose-dependent association between supranormal oxygen tension and risk of in-hospital death.11 J Wave, QRS Slurring, and ST Elevation in Athletes With Cardiac Arrest in the Absence of Heart Disease: Marker of Risk or Innocent Bystander? Riccardo Cappato, MD; Francesco Furlanello, MD; Valerio Giovinazzo, MD; Tommaso Infusino, MD; Pierpaolo Lupo, MD; Mario Pittalis, MD; Sara Foresti, MD; Guido De Ambroggi, MD; Hussam Ali, MD; Elisabetta Bianco, MD; Roberto Riccamboni, MD; Gianfranco Butera, MD; Cristian Ricci, PhD; Marco Ranucci, MD; Antonio Pelliccia, MD; and Luigi De Ambroggi, MD Summary: The ECG pattern of early repolarization (ie, J wave, QRS slurring, and/or ST elevation) in the inferior and lateral ECG leads is a common finding in the general population and is even more frequently observed in athletes. Recent studies have suggested a potential proarrhythmic significance of these findings in the general population, but data are lacking in athletes. We investigated whether QRS-ST changes are markers of risk for cardiac arrest or sudden death in athletes without underlying heart disease. In a selected group of 21 young competitive athletes who had cardiac arrest in the absence of heart disease, the prevalence of J wave and/or QRS slurring in the inferior (II, III, and aVF) and lateral leads (V4 to V6) was significantly higher in cases than in control athletes. After sport discontinuation during 36-month follow-up, arrhythmia recurrences did not differ between subgroups with and without J wave or QRS slurring. Because of discrepancy between the frequency of early repolarization pattern on 12-lead ECG and the rarity of cardiac arrest/sudden death, the incidental finding of a J wave/QRS slurring in a healthy athlete should be considered as a marker that minimally increases the arrhythmic risk. The present findings provide novel insights on clinical profiles of athletes at possible risk of cardiac arrest. Conclusions: J wave and/or QRS slurring was found more frequently among athletes with cardiac arrest/sudden death than in control athletes. Nevertheless, the presence of this ECG pattern appears not to confer a higher risk for recurrent malignant ventricular arrhythmias.12 Mechanisms Underlying the Lack of Effect of Implantable Cardioverter-Defibrillator Therapy on Mortality in High-Risk Patients With Recent Myocardial Infarction: Insights from the Defibrillation in Acute Myocardial Infarction Trial (DINAMIT) Paul Dorian, MD, MSc; Stefan H. Hohnloser, MD; Kevin E. Thorpe, MMath; Robin S. Roberts, MTech; Karl-Heinz Kuck, MD; Michael Gent, DSc; and Stuart J. Connolly, MD Summary: In the Defibrillation in Acute Myocardial Infarction Trial (DINAMIT) study, implanted defibrillators did not reduce mortality in high-risk patients if implanted early after myocardial infarction. In patients randomized to an implantable cardioverter-defibrillator (ICD), sudden deaths were reduced, but nonarrhythmic mortality was increased. In an analysis of the potential causes of this finding, patients who are destined to receive therapy from their ICD (compared with those destined not to receive therapy) have clinical features that also increase their risk of nonsudden death, including risks related to heart failure and recurrent ischemic events. During followup, patients who receive therapy from their ICD are more likely to have intercurrent cardiac clinical adverse events both before and after ICD therapy compared with patients who receive no therapy or do not have an ICD. In an early postmyocardial infarction setting, the same clinical circumstances that increase the risk of ventricular arrhythmias also increase the risk of nonsudden death; in addition, ICD therapies themselves may increase the risk of subsequent death. These findings underscore the limitations of a strategy of ICD implantation in certain high-risk groups, especially early after acute myocardial infarction. Conclusions: In patients receiving ICDs early after myocardial infarction, those factors that are associated with arrhythmia requiring ICD therapy are also associated with a high risk of nonsudden death, negating the benefit of ICDs in this setting.13 Low-Energy Multistage Atrial Defibrillation Therapy Terminates Atrial Fibrillation With Less Energy Than a Single Shock Wenwen Li, PhD; Ajit H. Janardhan, MD, PhD; Vadim V. Fedorov, PhD; Qun Sha, MD; Richard B. Schuessler, PhD; and Igor R. Efimov, PhD Summary: Atrial fibrillation (AF) is the most common tachyarrhythmia worldwide, and the number of Americans with this condition is expected to grow as the population ages. Patients with The Editors Most Read on Arrhythmia Devices e73 Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017 AF experience increased rates of thromboembolic stroke, congestive heart failure, cognitive dysfunction, and mortality. For symptomatic patients, cardioversion of AF to sinus rhythm using a single high-voltage external shock remains a mainstay of therapy. External cardioversion is painful, necessitating costly anesthesia and careful periprocedural patient monitoring. Previous attempts to design an implantable device that converts AF to sinus rhythm safely have been hampered primarily because of the discomfort associated with shocks. Defibrillating AF with a conventional, single biphasic shock remains significantly above the human pain threshold; however, prior studies in rabbits and dogs showed that atrial defibrillation could be achieved with significantly lower energy if multiple shocks are used rather than a single biphasic shock. The goal of this study was to further reduce the atrial defibrillation threshold in vivo, using a more clinically relevant canine model of AF. Here we introduce a novel multiple-shock, multistage electrotherapy that significantly reduces the atrial defibrillation threshold below single biphasic and multiple-shock therapies. Importantly, the novel electrotherapy tested here cardioverts AF at an energy that is likely at or below the human pain threshold (0.19±0.12 J). The findings give clinicians hope that multiple-stage electrotherapy may eventually allow pain-free cardioversion of AF and opens (or reopens) the door to the possibility of an implantable device that achieves pain-free defibrillation of AF in humans. Conclusions: Three-stage electrotherapy significantly reduces the AF defibrillation threshold and opens the door to low-energy atrial defibrillation at or below the pain threshold.14 Differences Between Out-of-Hospital Cardiac Arrest in Residential and Public Locations and Implications for Public-Access Defibrillation Fredrik Folke, MD; Gunnar H. Gislason, MD, PhD; Freddy K. Lippert, MD; Søren L. Nielsen, MD; Peter Weeke, MD; Morten L. Hansen, MD, PhD; Emil L. Fosbøl, MD, PhD; Søren S. Andersen, MD; Søren Rasmussen, MSc, PhD; Tina K. Schramm, MD; Lars Køber, MD, DMSc; and Christian Torp-Pedersen, MD, DMSc Summary: Whereas a tremendous amount of resources has focused on deployment of automated external defibrillators (AEDs) in public locations, the majority of out-of-hospital cardiac arrests (OHCAs) take place in residential areas and remain not covered by publicly placed AEDs. Furthermore, little is known about how to identify residential areas with the highest risk of OHCA, let alone the possible cost of public-access defibrillation in such areas. We therefore performed a systematic analysis of OHCAs in residential areas of Copenhagen to examine whether high-risk areas of OHCA suitable for AED placement could be identified. Using simple demographic characteristics of a city center, we were able to identify residential areas characterized by having at least 1 OHCA every 4.3 to 5.6 years within a 100 ×100-m area. These areas comprised <3% of all residential quarters but included up to 9% of all residential cardiac arrests. The estimated cost of AED deployment in selected residential areas was below $100 000 per quality-adjusted life-year but likely to exceed the corresponding cost for AED deployment in public locations. Furthermore, individuals with OHCAs in residential locations were more likely to have characteristics associated with a poor outcome compared with public ones in that the patients were older and more often male, the ambulance response interval was longer, arrests occurred more often at night, and the patients had ventricular fibrillation less often. Therefore, if future public-access defibrillation programs in residential areas are to succeed without excessive costs, strategic placement of AEDs in selected residential areas is a necessity. Conclusions: On the basis of simple demographic characteristics of a city center, we could identify residential areas suitable for automated external defibrillator placement. Individuals with OHCA in residential locations were more likely to have characteristics associated with poor outcome compared with public cardiac arrests.15 Chest Compressions Cause Recurrence of Ventricular Fibrillation After the First Successful Conversion by Defibrillation in Out-of-Hospital Cardiac Arrest Jocelyn Berdowski, MSc, MSE; Jan G.P. Tijssen, PhD; and Rudolph W. Koster, MD, PhD Summary: The current guidelines (GL) for cardiopulmonary resuscitation issued in 2005 advise to immediately resume cardiopulmonary resuscitation (CPR) after a defibrillation shock by abandoning postshock rhythm analysis and checking for signs of life to minimize CPR interruption. This shortens the delay to CPR resumption by about half a minute. At the same time, the CPR cycle is extended from 1 to 2 minutes. This study analyzed the relation among CPR resumption, ventricular fibrillation (VF) recurrence, and VF duration after a first successful shock during randomized treatment with resuscitation GL2000 or GL2005. Our study demonstrated a close relation between initiation of chest compressions and recurrence of VF. In the first 2 seconds of CPR resumption, the hazard of VF recurrence was 15 times larger than before the start of CPR, regardless of the preceding rhythm or guideline used. The hazard remained increased during the first 8 seconds of CPR. VF recurred in 72% of cases in both groups. Because of earlier resumption and longer duration of CPR, the patient treated with GL2005 had VF recurrence significantly sooner and stayed in VF longer as well: a median of 40 seconds in the first CPR cycle. From a metabolic point of view, prolonged VF is more energy-consuming than asystole. This could possibly explain why the application of GL2005 did not show improved survival in all published literature. Further research is needed to determine whether prolonged VF recurrence during CPR influences survival. Conclusions: Early CPR resumption after defibrillation causes early VF recurrence.16 Modulation of Calcium-Activated Potassium Channels Induces Cardiogenesis of Pluripotent Stem Cells and Enrichment of Pacemaker-Like Cells Alexander Kleger, MD, PhD; Thomas Seufferlein, MD; Daniela Malan, PhD; Michael Tischendorf; Alexander Storch, MD; Anne Wolheim; Stephan Latz; Stephanie Protze; Marc Porzner, MD; Christian Proepper, PhD; Cornelia Brunner, PhD; Sarah-Fee Katz; Ganesh Varma Pusapati, PhD; Lars Bullinger, MD; Wolfgang-Michael Franz, MD; Ralf Koehntop; Klaudia Giehl, PhD; Andreas Spyrantis, PhD; Oliver Wittekindt, PhD; Quiong Lin; Martin Zenke, PhD; Bernd K. Fleischmann, MD; Maria Wartenberg, PhD; Anna M. Wobus, PhD; Tobias M. Boeckers, MD; and Stefan Liebau, MD Summary: It is well-accepted that embryonic stem cells represent a particularly attractive source for ex vivo generation of cardiomyocytes. Considering the feasibility of in vitro model systems for pharmacological screenings, toxicological, or even potential cell therapeutic applications, major obstacles need to be overcome. Pharmaceutical model systems require a (1) high purity of the cell system; (2) specifically, differentiated cell subtypes, such as cardiac pacemaker-like cells; and (3) absence of unphysiological alterations due to genetically engineered cell genomes. Relative to the future potential for cell therapeutic applications, furthermore, in vivo improvement of (1) contractile heart function; (2) prevention of arrhythmias caused by insufficient graft guidance; (3) potential teratoma formation; and (4) immunotolerance are the crucial premises. The differentiation system presented here provides an interesting tool for applications in biomedical engineering, pathophysiological, and toxicological studies and even potential therapeutic applications. Here we provide a new cardiac differentiation system exclusive of genetic manipulation and lineage selection and thus fulfilling most of these criteria. Conclusions: SKCa activation drives the fate of pluripotent cells toward mesoderm commitment and cardiomyocyte specification, e74 Circ Arrhythm Electrophysiol June 2012 preferentially into nodal-like cardiomyocytes. This provides a novel strategy for the enrichment of cardiomyocytes and, in particular, the generation of a specific subtype of cardiomyocytes, pacemaker-like cells, without genetic modification.17 Safety of Pacemaker Reuse: A Meta-Analysis With Implications for Underserved Nations Timir S. Baman, MD; Pascal Meier, MD; Joshua Romero, BA; Lindsey Gakenheimer; James N. Kirkpatrick, MD; Patricia Sovitch, NP; Hakan Oral, MD; and Kim A. Eagle, MD Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017 Summary: A great disparity in medical health care is clearly evident in the field of cardiac electrophysiology (specifically, pacemaker implantation) in which the specialty is either severely underdeveloped or entirely nonexistent in many low- and middle-income countries. In an effort to promote cost savings, as well as to provide care to those with no other means of acquiring a device, a number of articles in a wide variety of international settings have been published describing the safety and efficacy of pacemaker reuse. The aim of this meta-analysis is to assess the safety of pacemaker reuse. Pooled individual patient data (n=2270) from 18 trials were included in the analysis. The results demonstrate that there is no significant difference in infection rate between pacemaker reuse and new device implantation (P=0.58); however, there was an increased risk for malfunction in the reuse group (P=0.002). This difference was mainly driven by abnormalities in set screws, which possibly occurred during device extraction as well as nonspecific device “technical errors.” Overall, pacemaker reuse was associated with an overall low rate of infection (<2%) and device malfunction (<1%) and may represent a viable option for patients in underserved nations with symptomatic bradycardia and no other means of obtaining a device. We believe that postmortem pacemaker reuse is a safe, feasible, and ethically responsible means of delivering electrophysiological health care to those in great need. Conclusions: This study suggests that pacemaker reuse has an overall low rate of infection and device malfunction and may be a safe and efficacious means of treating patients in underserved nations with symptomatic bradyarrhythmias and no other method of obtaining a device; however, the results also denote a higher rate of device malfunction as compared with new device implantation. Patients with highly symptomatic conduction disease may benefit from pacemaker reuse; however, they should be closely monitored for device malfunction, especially during implantation.18 Extraction of Old Pacemaker or Cardioverter-Defibrillator Leads by Laser Sheath versus Femoral Approach Pierre Bordachar, MD; Pascal Defaye, MD; Eric Peyrouse, MD; Serge Boveda, MD; Bilel Mokrani, MD; Christelle Marquié, MD; Laurent Barandon, MD, PhD; Emilie Marcant Fossaert, MD; Stephane Garrigue, MD; Sylvain Reuter, MD; Julien Laborderie, MD; Eloi Marijon, MD; Jean-Claude Deharo, MD; Peggy Jacon, MD; Salem Kacet, MD; Sylvain Ploux, MD; Antoine Deplagne, MD; Michel Haissaguerre, MD; Jacques Clementy, MD; Philippe Ritter, MD; and Didier Klug, MD Summary: Some operators routinely extract chronically implanted transvenous leads using a femoral approach, whereas others prefer a superior approach. This prospective study compared the safety and effectiveness of laser sheaths versus femoral snare extractions. We undertook a (1) prospective single-center randomized study to compare the safety and effectiveness of laser sheath versus femoral snare extractions and the radiation exposure associated with each; and (2) nonrandomized comparison of registries from several French centers specializing in lead extractions from the femoral or superior approach. Regardless of the technique implemented, complete or partial extractions were achieved in >95% of procedures. The rates of mortality and of major complications, although low, were not negligible and indicate that these procedures must be performed by a trained team working in an environment equipped with immediate surgical backup. We found no significant difference between the proximal approach, using laser, and the femoral approach, using snares, with respect to procedural success and complication rates; however, procedures performed using the femoral approach were longer and were associated with a longer exposure of the operators and patients to fluoroscopy. Conclusions: Old transvenous leads were extracted with similar success and complication rates by the femoral and laser approaches; however, the femoral approach was associated with longer procedures and a longer duration of fluoroscopic exposure.19 Complication Rates Associated With Pacemaker or Implantable Cardioverter-Defibrillator Generator Replacements and Upgrade Procedures: Results From the REPLACE Registry Jeanne E. Poole, MD; Marye J. Gleva, MD; Theofanie Mela, MD; Mina K. Chung, MD; Daniel Z. Uslan, MD; Richard Borge, MD; Venkateshwar Gottipaty, MD, PhD; Timothy Shinn, MD; Dan Dan, MD; Leon A. Feldman, MD; Hanscy Seide, MD; Stuart A. Winston, DO; John J. Gallagher, MD; Jonathan J. Langberg, MD; Kevin Mitchell, RN, BS; Richard Holcomb, PhD; for the REPLACE Registry Investigators Summary: Cardiac implantable electronic device use is increasing worldwide. Improvements in medical therapy will result in many patients requiring subsequent procedures for generator replacement or “upgrades” to multilead systems. Although data from retrospective series have been available, REPLACE is the first prospective multicenter trial to examine complications related to generator replacement. The 2 patient populations studied included patients who needed only a generator replacement and those who required a lead addition or revision for advanced therapy. This study examined a broad range of major and minor complications. Major complications with planned generator replacements alone were modest; however, when a transvenous lead addition or revision was combined with a generator replacement, the risk was markedly higher, especially for left ventricular leads. Our results support the use and development of devices with long battery life to minimize the lifetime surgical risk for a patient. The choice of device for each patient must be carefully considered. Mitigation of leadrelated risks is also important. Using the fewest leads necessary for the clinical need of the patient is critical. The risk associated with upgrade procedures is concerning and favors performing indicated complex procedures before the development of advanced end-stage medical and cardiac disease, situations in which the risk may be prohibitive. Finally, our results provide insight into procedural outcomes for the next phase of life for patients who receive cardiac implantable electronic devices and a more robust analysis that can be used to establish a benchmark for comparative performance in this time of healthcare reform. Conclusions: Pacemaker and implantable cardioverter-defibrillator generator replacements are associated with a notable complication risk, particularly those with lead additions. These data support careful decision-making before device replacement, when managing device advisories and when considering upgrades to more complex systems.20 cAMP Sensitivity of HCN Pacemaker Channels Determines Basal Heart Rate but Is Not Critical for Autonomic Rate Control Patrick A. Schweizer, MD, MSc; Nana Duhme, MSc; Dierk Thomas, MD; Rüdiger Becker, MD; Jörg Zehelein, MD; Andreas Draguhn, MD; Claus Bruehl, PhD; Hugo A. Katus, MD; and Michael Koenen, PhD Summary: Pharmacological If inhibition is clinically used to treat patients with stable angina and sinus tachycardia; however, the role of If in sinus node function and, particularly, mechanisms underlying autonomic heart rate regulation are incompletely understood. According to the BEAUTIFUL study, blockage of If current in patients The Editors Most Read on Arrhythmia Devices e75 with stable coronary artery disease and left ventricular systolic dysfunction reduced resting heart rate by 6 bpm (8%), a minor effect related to the reduction of 21 bpm (31%) observed in HCN4-695X carriers. Our results suggest that mutant carriers might tolerate sinus bradycardia owing to their preserved ability to accelerate heart rate according to physical requirements. Thus, cardiac-specific blockage of If may allow for significant reduction of basal heart rate without adversely affecting chronotropic competence. This suggestion has important clinical implications. Improvements in drug selectivity will reduce extracardiac side effects, as well as nonspecific channel inhibition, and may offer a more effective blockage of If pacemaker currents in the future. On the other hand, as shown in the present study, functional inactivation of If might unmask arrhythmogenic potential during adrenergic stimulation. These considerations are relevant to safety concerns other than bradycardia associated with high-dose If-blockage. Conclusions: In humans, cAMP responsiveness of If determines basal heart rate but is not critical for maximum heart rate, heart rate variability, or chronotropic competence. Furthermore, cAMP-activated If may stabilize heart rhythm during chronotropic response.21 Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017 Utility of the Ventricular Fibrillation Waveform to Predict a Return of Spontaneous Circulation and Distinguish Acute From Post Myocardial Infarction or Normal Swine in Ventricular Fibrillation Cardiac Arrest Julia H. Indik, MD, PhD; Daniel Allen, BS; Michael Gura, MS; Christian Dameff, MS; Ronald W. Hilwig, DVM, MS, PhD; and Karl B. Kern, MD Summary: Ventricular fibrillation (VF) and pulseless ventricular tachycardia are the initial rhythm in about one quarter of cardiac arrests. Although the performance of effective chest compressions with minimal to no interruptions is well-known to be a critical component in resuscitation, the optimal duration of chest compressions before defibrillation shocks is unclear. It is unknown if the timing of shocks and chest compressions should be the same for patients with acute myocardial infarction (MI) as those with a history of MI or even those without any cardiovascular disease. Furthermore, it is recognized that patients with acute MI resuscitated from cardiac arrest caused by VF may not show ST-segment elevation, complicating decisions of whether to send patients for emergent cardiac catheterization once a perfusing rhythm has been restored. This investigation explores the evolution of the VF waveform parameters of amplitude spectral area and slope in acute MI, post MI, and control swine. We find that amplitude spectral area and slope predict the restoration of a perfusing rhythm after a shock, independent of the underlying myocardium, and, furthermore, with well-performed chest compressions, amplitude spectral area at a threshold of 33.5 mV-Hz showed a sensitivity of 83% to distinguish an acute from a nonacute MI state. Conclusions: In a swine model of VF cardiac arrest, amplitude spectral area, and slope predict return of spontaneous circulation independent of myocardial substrate. Furthermore, with chest compressions, the VF waveform evolves differently and may offer a means to distinguish an acute MI.22 Amiodarone Versus Procainamide for the Acute Treatment of Recurrent Supraventricular Tachycardia in Pediatric Patients Philip M. Chang, MD; Michael J. Silka, MD; David Y. Moromisato, MD; and Yaniv Bar-Cohen, MD Summary: Relative efficacy of different pharmacological approaches to the management of recurrent supraventricular arrhythmias in pediatric patients is largely unknown because systematic comparisons between the various antiarrhythmic agents are limited, the number of patient cohorts available for study is small, and the end points for treatment are variable. This retrospective singleinstitution study included 37 patients (median age, 34 days; the majority with congenital heart disease) with recurrent supraventricular tachycardia. The majority had atrial arrhythmias, and a quarter had reentry using an accessory pathway. Intravenous administration of procainamide was more effective than intravenous amiodarone, without substantial differences in the incidence of adverse events, a somewhat surprising finding given the general perception of amiodarone therapy. The findings suggest that intravenous procainamide warrants an important role in the management of pediatric patients with recurrent supraventricular arrhythmias. Conclusions: In this cohort, procainamide achieved greater success compared with amiodarone in the management of recurrent supraventricular tachycardia without statistically significant differences in adverse event frequency.23 Determination of Inadvertent Atrial Capture During Para-Hisian Pacing Manoj Obeyesekere, MBBS; Peter Leong-Sit, MD; Allan Skanes, MD; Andrew Krahn, MD; Raymond Yee, MD; Lorne J. Gula, MD; Matthew Bennett, MD; and George J. Klein, MD Summary: The para-Hisian pacing maneuver is very useful in clinical electrophysiology, but care must be taken to avoid technical and interpretative pitfalls. Inadvertent atrial capture during the maneuver may give the erroneous impression of retrograde conduction over a septal accessory pathway in the absence of an accessory pathway or retrograde conduction over the atrioventricular (AV) node in the presence of an accessory pathway. Intuitively, direct atrial capture should give a very short stimulus-to-atrial interval. A stimulus-to–atrial interval at the proximal coronary sinus (stim-PCS) of <60 ms (or <70 ms at the high right atrium [stim-HRA]) is observed only with direct atrial capture. A stim-PCS of >90 ms (or stim-HRA >100 ms) is observed only in the absence of atrial capture. An overlap zone between these values exists where atrial capture cannot be excluded or confirmed. A change of stimulus-to-atrial interval of 20 ms using a small catheter adjustment to lose or obtain atrial capture deliberately reliably ensures that inadvertent atrial capture has not occurred. Conclusions: Stim-PCS and stim-HRA can be used to monitor for inadvertent atrial capture during para-Hisian pacing. A stim-PCS <60 ms (or stim-HRA <70 ms) and stim-PCS >90 ms (or stim-HRA >100 ms) were observed only with and without atrial capture, respectively, but there was significant overlap between these values. Deliberate atrial capture and loss of capture reliably identifies atrial capture regardless of intervals.24 Comparison of a Novel, Single-Lead Atrial Sensing System With a Dual-Chamber Implantable Cardioverter-Defibrillator System in Patients Without Antibradycardia Pacing Indications: Results of a Randomized Study Christian Sticherling, MD; Markus Zabel, MD; Sebastian Spencker, MD; Udo Meyerfeldt, MD; Lars Eckardt, MD; Steffen Behrens, MD; Michael Niehaus, MD; for the ADRIA Investigators Summary: Supraventricular tachyarrhythmias are a frequent cause for inappropriate therapy in patients with implantable cardioverterdefibrillators (ICDs). Atrial sensing and electrogram recordings are potentially helpful to discriminate supraventricular from ventricular tachycardias. The present study compared a novel, ICD system that incorporates an atrial sensing bipole in the single ICD lead (A+ICD, 124 patients) with a conventional, dual-chamber ICD system with a separate atrial lead (125 patients) in patients without bradycardia pacing indications. Both systems correctly identified all ventricular tachycardia episodes, and supraventricular e76 Circ Arrhythm Electrophysiol June 2012 tachyarrhythmia discrimination with the A+ system was not i nferior to that of the conventional system. The A+ system was faster to implant. This single-lead system offers potentially useful atrial sensing without the need to implant an additional atrial lead. Conclusions: The novel A+-ICD system can be implanted faster and is equivalent to a standard DR-ICD with regard to the detection of ventricular tachyarrhythmias and supraventricular tachyarrhythmias. It represents a useful alternative to obtain atrial sensing.25 New Criteria During Right Ventricular Pacing to Determine the Mechanism of Supraventricular Tachycardia Soufian T. AlMahameed, MD; Alfred E. Buxton, MD; and Gregory F. Michaud, MD Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017 Summary: Rapid accurate distinction of atrioventricular nodal reentry from orthodromic atrioventricular reentry tachycardia is critical to successful catheter ablation for these supraventricular tachycardias (SVT). Right ventricular pacing that entrains SVT is often used to make this distinction but is not helpful when pacing fails to entrain or terminates SVT. We developed and tested 2 new criteria for distinguishing these SVTs using right ventricular pacing trains that do not require entrainment. From right ventricular pacing trains, the transition zone is defined from the first QRS complex that is fusion between SVT and pacing to the first paced complex that has a stable QRS morphology (either completely paced or constantly fused). During the transition zone, advance of the stimulus-atrial interval or a fixed stimulus-atrial indicates orthodromic atrioventricular reentry tachycardia. In 92 patients with SVT of various mechanisms, these criteria showed excellent diagnostic accuracy and could be applied regardless of whether pacing terminated SVT. Conclusions: During right ventricular pacing, within 40 milliseconds of the tachycardia cycle length, orthodromic atrioventricular reentry tachycardia is the likely mechanism when atrial timing is perturbed or a fixed stimulus-atrial interval is established within the transition zone.26 References 1. 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Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017 Circulation: Arrhythmia and Electrophysiology Editors' Picks: Most Read Articles on Arrhythmia Devices (Defibrillation, Pacing, Pacemakers, Heart Arrest, and Resuscitation) Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017 Circ Arrhythm Electrophysiol. 2012;5:e69-e77 doi: 10.1161/CIRCEP.112.973305 Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2012 American Heart Association, Inc. All rights reserved. Print ISSN: 1941-3149. 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