Implantable cardioverter-defibrillator (ICD) implantation is a guideline-recommended indication for primary prevention of sudden cardiac death (SCD) in high-risk patients. ICD implantation is lower in women than in men, a difference that has persisted over the last two decades. The goal of this review is to explore potential factors in under- utilization of ICDs in women and to provide information on gender differences in mortality benefit of ICDs. Epidemiological evidence shows that women with cardiovascular disease tend to present at an older age, have more non-ischemic cardiomyopathy, and develop fewer ventricular arrhythmias than men. Significant gender differences in participants of ICD clinical trials challenge the applicability of mortality benefit of ICDs in women. Studies of cardiac resynchronization therapy (CRT) devices have shown improved survival in women over men, a fact that is not reflected in the number of CRTs implanted in women. A gender gap in the implantation of ICDs for primary prevention of SCD continues to exist. Understanding of differences in epidemiology and physiology between women and men is an important step in providing appropriate device therapy to patients at risk of SCD.

Journal of Cardiovascular ElectrophysiologyVolume 28, Issue 7 p. 742-744 EDITORIAL COMMENT Selectivity: Who really should be offered AF ablations? Jane Chen MD, Corresponding Author Jane Chen MD janechenep@gmail.com orcid.org/0000-0003-3232-2613 Orlando VA Medical Center, Orlando, FL, USA Correspondence Jane Chen, MD, Orlando VA Medical Center, 13800 Veterans Way, Orlando, Florida 32827, USA Email: janechenep@gmail.comSearch for more papers by this author Jane Chen MD, Corresponding Author Jane Chen MD janechenep@gmail.com orcid.org/0000-0003-3232-2613 Orlando VA Medical Center, Orlando, FL, USA Correspondence Jane Chen, MD, Orlando VA Medical Center, 13800 Veterans Way, Orlando, Florida 32827, USA Email: janechenep@gmail.comSearch for more papers by this author First published: 09 May 2017 https://doi.org/10.1111/jce.13251 Disclosures: None. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume28, Issue7July 2017Pages 742-744 RelatedInformation

Heart failure (HF) is associated with metabolic perturbations, particularly of fatty acids (FAs), which remain to be better understood in humans. This study aimed at testing the hypothesis that HF patients with reduced ejection fraction display systemic perturbations in levels of energy-related metabolites, especially those reflecting dysregulation of FA metabolism, namely, acylcarnitines (ACs). Circulating metabolites were assessed using mass spectrometry (MS)-based methods in two cohorts. The main cohort consisted of 72 control subjects and 68 HF patients exhibiting depressed left ventricular ejection fraction (25.9 ± 6.9%) and mostly of ischemic etiology with ≥2 comorbidities. HF patients displayed marginal changes in plasma levels of tricarboxylic acid cycle-related metabolites or indexes of mitochondrial or cytosolic redox status. They had, however, 22-79% higher circulating ACs, irrespective of chain length (P < 0.0001, adjusted for sex, age, renal function, and insulin resistance, determined by shotgun MS/MS), which reflects defective mitochondrial β-oxidation, and were significantly associated with levels of NH2-terminal pro-B-type natriuretic peptide levels, a disease severity marker. Subsequent extended liquid chromatography-tandem MS analysis of 53 plasma ACs in a subset group from the primary cohort confirmed and further substantiated with a comprehensive lipidomic analysis in a validation cohort revealed in HF patients a more complex circulating AC profile. The latter included dicarboxylic-ACs and dihydroxy-ACs as well as very long chain (VLC) ACs or sphingolipids with VLCFAs (>20 carbons), which are proxies of dysregulated FA metabolism in peroxisomes. Our study identified alterations in circulating ACs in HF patients that are independent of biological traits and associated with disease severity markers. These alterations reflect dysfunctional FA metabolism in mitochondria but also beyond, namely, in peroxisomes, suggesting a novel mechanism contributing to global lipid perturbations in human HF.NEW & NOTEWORTHY Mass spectrometry-based profiling of circulating energy metabolites, including acylcarnitines, in two cohorts of heart failure versus control subjects revealed multiple alterations in fatty acid metabolism in peroxisomes in addition to mitochondria, thereby highlighting a novel mechanism contributing to global lipid perturbations in heart failure.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/acylcarnitines-in-human-heart-failure/.

24 Heart failure (HF) is associated with metabolic perturbations, particularly of fatty acids (FA), which 25 remain to be better understood in humans. This study aimed at testing the hypothesis that HF patients with 26 reduced ejection fraction, display systemic perturbations in levels of energy-related metabolites, especially 27 those reflecting dysregulation of FA metabolism, namely acylcarnitines (ACs). Circulating metabolites 28 were assessed using mass spectrometry (MS)-based methods in two cohorts. The main cohort consisted of 29 72 controls and 68 HF patients, exhibiting depressed left ventricular ejection fraction (25.96.9%) and 30 mostly of ischemic etiology with  2 comorbidities. HF patients displayed marginal changes in plasma 31 levels of Krebs cycle-related metabolites or indices of mitochondrial or cytosolic redox status. They had, 32 however, 22-79% higher circulating ACs, irrespective of chain length (p<0.0001; adjusted for sex, age, 33 renal function and insulin resistance; determined by tandem MS), which reflect defective mitochondrial β34 oxidation and were significantly associated with levels of NT-Pro-BNP levels, a disease severity marker. 35 Subsequent extended LC-MS/MS analysis of 53 plasma ACs in a subset group from the primary cohort, 36 confirmed and further substantiated with a comprehensive lipidomic analysis in a validation cohort, 37 revealed in HF patients a more complex circulating AC profile. The latter included dicarboxylic-ACs and 38 dihydroxy-ACs as well as AC or sphingolipids with very-long chain (VLC)-FAs (>20 carbons), which are 39 proxies of dysregulated FA metabolism in peroxisomes. Our study identified alterations in circulating ACs 40 in HF patients, which are independent of biological traits and associated with disease severity markers. 41 These alterations reflect dysfunctional FA metabolism in mitochondria, but also beyond, namely in 42 peroxisomes, suggesting a novel mechanism contributing to global lipid perturbations in human HF. 43 44

Cardiovascular implantable electronic devices, such as pacemakers, defibrillators, and cardiac resynchronization devices, are in widespread use. These devices have sophisticated monitoring capabilities that can help in the management of disease processes. Remote monitoring of such devices, using transmitters that can receive and directly download information stored on the devices from patients’ homes to physicians’ offices, can reduce office visits and decrease time to detection of clinically relevant events. This article explores the utility of such remote monitoring.

A 40-year-old woman with nonischemic cardiomyopathy and a left ventricular (LV) ejection fraction of 35% was referred for recurrent ventricular tachycardia (VT). She experienced 248 VT episodes treated by antitachycardia pacing (ATP) over 14 days. In 2005, she received an implantable cardioverter-defibrillator for an episode of syncope and nonsustained VT. She later underwent an invasive electrophysiology study (EPS) with inducible VT and an ablation of the AV nodal reentrant tachycardia. Since then, she experienced symptomatic VT, terminated by ATP. Her VT was unresponsive to sotalol and mexiletine. Two EPS in early 2010 failed to induce VT despite intravenous isoproterenol and triple extrastimuli at 2 right ventricular (RV) sites; therefore, no ablations were performed.

Atrial fibrillation (AF) and atrial flutter (AFL) are common cardiac arrhythmias in older adults. Medical management focuses on rate and rhythm control of AF and AFL to promote symptomatic relief and avoid tachycardia-mediated cardiomyopathy. Pharnnacologic treatment of AF and AFL is especially challenging in the elderly because of the presence of comorbidities that may affect drug kinetics, and polypharmacy, which may lead to drug interactions. The potential for complications from medications and procedures required to achieve and maintain sinus rhythm must be carefully balanced against the benefits of therapy. This article reviews medical management of AF and AFL specifically relating to rate and rhythm control. The controversy of rate versus rhythm control is also discussed.

The rapid heartbeat of ventricular tachycardia (VT) can lead to sudden cardiac death and is a major health issue worldwide. Efforts to identify patients at risk, determine mechanisms of VT, and effectively prevent and treat VT through a mechanism-based approach would all be facilitated by continuous, noninvasive imaging of the arrhythmia over the entire heart. Here, we present noninvasive real-time images of human ventricular arrhythmias using electrocardiographic imaging (ECGI). Our results reveal diverse activation patterns, mechanisms, and sites of initiation of human VT. The spatial resolution of ECGI is superior to that of the routinely used 12-lead electrocardiogram, which provides only global information, and ECGI has distinct advantages over the currently used method of mapping with invasive catheter-applied electrodes. The spatial resolution of this method and its ability to image electrical activation sequences over the entire ventricular surfaces in a single heartbeat allowed us to determine VT initiation sites and continuation pathways, as well as VT relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. Thus, ECGI can map the VT activation sequence and identify the location and depth of VT origin in individual patients, allowing personalized treatment of patients with ventricular arrhythmias.

Heart failure is a systemic disease in which both myocardium and skeletal muscle exhibit alterations of energy metabolism. Failing myocardium exhibits impaired utilization of free fatty acids and glucose, which are major substrates for myocardial energy production. Ketone bodies normally provide a modest contribution to energy balance, but serum concentrations of ketone bodies are elevated in heart failure. To profile ketone body metabolism in advanced heart failure, we directly measured ketone body utilization by heart and skeletal muscle.Metabolite concentrations in arterial, coronary sinus, and central venous beds were measured to derive myocardial and skeletal-muscle ketone body utilization in 11 patients with advanced heart failure and 10 healthy control subjects who were undergoing electrophysiologic procedures. As expected, the mean myocardial arteriovenous oxygen difference was significantly increased in the heart-failure patients (8.3 ± 0.4 mL/dL, vs 7 ± 0.5 mL/dL in the control subjects; P = 0.05). Although the mean myocardial ketone body extraction ratio was relatively unchanged (0.49 ± 0.05 in heart-failure patients vs 0.54 ± 0.06 in control subjects, P = 0.53), skeletal-muscle ketone body utilization was markedly lower in the heart-failure patients (0.18 ± 0.06, vs 0.4 ± 0.04 in control subjects; P = 0.01).In this preliminary study, heart failure was associated with tissue-specific alteration of ketone body metabolism. In advanced heart failure, skeletal-muscle ketone body utilization was impaired, whereas myocardial ketone body utilization was preserved. Future studies are needed to determine whether ketone body metabolism serves as a dynamic quantitative biomarker of skeletal myopathy and fatigue in heart failure.

Objectives The purpose of this study was to evaluate remote pacemaker interrogation for the earlier diagnosis of clinically actionable events compared with traditional transtelephonic monitoring and routine in-person evaluation.Background Pacemaker patient follow-up procedures have evolved from evaluating devices with little programmability and diagnostic information solely in person to transtelephonic rhythm strip recordings that allow monitoring of basic device function. More recently developed remote monitoring technology leverages expanded device capabilities, augmenting traditional transtelephonic monitoring to evaluate patients via full device interrogation.Methods The time to first diagnosis of a clinically actionable event was compared in patients who were followed by remote interrogation (Remote) and those who were followed per standard of care with office visits augmented by transtelephonic monitoring (Control). Patients were randomized 2:1. Remote arm patients transmitted pacemaker information at 3-month intervals. Control arm patients with a single-chamber pacemaker transmitted at 2-month intervals. Control arm patients with dual-chamber devices transmitted at 2-month intervals with an office visit at 6 months. All patients were seen in office at 12 months.Results The mean time to first diagnosis of clinically actionable events was earlier in the Remote arm (5.7 months) than in the Control arm (7.7 months). Three (2%) of the 190 events in the Control arm and 446 (66%) of 676 events in the Remote arm were identified remotely.Conclusions The strategic use of remote pacemaker interrogation follow-up detects actionable events that are potentially important more quickly and more frequently than transtelephonic rhythm strip recordings. The use of transtelephonic rhythm strips for pacemaker follow-up is of little value except for battery status determinations. (PREFER [ Pacemaker Remote Follow-up Evaluation and Review]; NCT00294645) (J Am Coll Cardiol 2009; 54: 2012-9) (C) 2009 by the American College of Cardiology Foundation

Background: Conventional insertion of implantable cardioverter‐defibrillator (ICD) includes an evaluation of the defibrillation threshold (DFT). Implanting an ancillary defibrillation lead in the azygos vein has been introduced as a therapeutic option in patients with “high” DFT. This study reports the efficacy and stability of azygos defibrillation coils implanted for elevated DFTs. Methods: This is a retrospective review of seven consecutive patients with right and left pectoral, single‐ and dual‐chamber, and biventricular ICDs and elevated DFTs, in whom an azygos defibrillation coil was introduced. Results: Addition of an azygos defibrillator lead achieved a satisfactory safety margin during single energy defibrillation efficacy testing in four out of seven patients, with success at maximum device output in two patients. No satisfactory safety margin was achieved in the remaining patient, despite the further addition of a subcutaneous defibrillation coil. No change in lead position was observed over a mean radiographic follow‐up of 8 months. No complications were noted during a mean follow‐up of 14 months, including no deaths, and no ICD shocks. Conclusion: Implanting a defibrillation coil into the azygos vein is feasible and safe. In a majority of patients with failed defibrillation efficacy testing, adding an azygos coil achieves success on repeat testing. Therefore, this technique is one option for lowering the defibrillation threshold in patients who fail DFT testing of their ICD.

The development of the implantable cardioverter-defibrillator (ICD) is primarily the result of pioneering work by Michel Mirowski. First-generation devices consisted of a large generator placed in an abdominal pocket capable only of high-energy shocks. In the 25 years since the first implantation in humans (1), advances in technology have resulted in significantly smaller devices, with sophisticated detection algorithms and tiered therapies. Despite these advances, the primary goal of the ICD continues to be the rapid and effective treatment of ventricular arrhythmias.

Background Although pacemakers are primarily used for the treatment of bradycardia, diagnostic data available in current pacemakers allow them to be also used as sophisticated, continuous monitoring devices. Easy access to these stored data may assist clinicians in making diagnostic and therapeutic decisions sooner, thus avoiding potential long-term sequelae due to untreated clinical disorders. Internet-based remote device interrogation systems provide clinicians with frequent and complete access to stored data in pacemakers. In addition to monitoring device function, remote monitors may be a helpful tool in assisting physicians in the management of common arrhythmia disorders. Methods The Pacemaker Remote Follow-up Evaluation and Review (PREFER) trial is a prospective, randomized, parallel, unblinded, multicenter, open label clinical trial to determine the utility of remote pacemaker interrogation in the earlier diagnosis of clinically actionable events compared to the existing practice of transtelephonic monitoring. There have been 980 patients enrolled and randomized to receive pacemaker follow up with either remote interrogation using the Medtronic CareLink ® Network (CareLink) versus the conventional method of transtelephonic monitoring (TTM) in addition to periodic in-person interrogation and programming evaluations. The purpose of this manuscript is to describe the design of the PREFER trial. The results, to be presented separately, will characterize the number of clinically actionable events as a result of pacemaker follow-up using remote interrogation instead of TTM. Trial registration ClinicalTrials.gov: NCT00294645.

Atrial fibrillation is increasingly prevalent among older adults. It causes approximately 24% of strokes in patients aged 80 to 89 years. The management of atrial fibrillation is directed at preventing thromboembolism and controlling the heart rate and rhythm. Stroke prevention is most effectively accomplished through administering anticoagulants such as warfarin, although older patients have higher hemorrhagic risk. Cognitive dysfunction, functional impairments, and increased fall risk further complicate warfarin management in elderly patients. The use of risk stratification schemes can help guide the anticoagulation decision, although the benefits of warfarin generally outweigh the risks in most older patients with atrial fibrillation. Pharmacologic rate control has been shown to result in similar outcomes compared with pharmacologic restoration of sinus rhythm and should be the initial therapy for elderly patients. Anti-arrhythmic medications should be selected based on an individual patient’s coexisting medical conditions. In symptomatic patients who fail pharmacologic therapy, invasive strategies such as AV nodal ablation may help improve quality of life and symptoms, although such strategies do not obviate the need for antithrombotic therapy.

trial fibrillation is increasingly prevalent among older adults. It causes approximately 24% of strokes in atients aged 80 to 89 years. The management of atrial fibrillation is directed at preventing thromboemolism and controlling the heart rate and rhythm. Stroke prevention is most effectively accomplished hrough administering anticoagulants such as warfarin, although older patients have higher hemorrhagic isk. Cognitive dysfunction, functional impairments, and increased fall risk further complicate warfarin anagement in elderly patients. The use of risk stratification schemes can help guide the anticoagulation ecision, although the benefits of warfarin generally outweigh the risks in most older patients with atrial brillation. Pharmacologic rate control has been shown to result in similar outcomes compared with harmacologic restoration of sinus rhythm and should be the initial therapy for elderly patients. Antirrhythmic medications should be selected based on an individual patient’s coexisting medical conditions. n symptomatic patients who fail pharmacologic therapy, invasive strategies such as AV nodal ablation ay help improve quality of life and symptoms, although such strategies do not obviate the need for ntithrombotic therapy. © 2007 Elsevier Inc. All rights reserved.

Introduction: Chronic kidney disease (CKD) has been independently associated with increased cardiovascular mortality. Little is known about the benefit of implantable cardioverter defibrillator (ICD) therapy for prevention of sudden death in this large, high‐risk population. We sought to evaluate the impact of CKD on survival in patients who received an ICD for primary prevention of sudden death. Methods and Results: In this retrospective study of patients who underwent ICD implantation for primary prevention of sudden death, patients were stratified by CKD, defined as serum creatinine ≥2 mg/dL or dialysis use. Primary endpoint was mortality. CKD was identified in 35 of 229 patients (15.3%). There were 33 deaths during a follow‐up period of 18.0 ± 15.2 months: 17 of 35 CKD patients and 16 of 194 patients without CKD (48.6% vs 8.2%, P < 0.00001 by log‐rank). One‐year survival for patients with and without CKD was 61.2% and 96.3%, respectively. Cox regression analysis controlling for age, sex, comorbidities, ejection fraction, and medications proved CKD to be the strongest independent predictor of death (hazard ratio 10.5; 95% confidence interval 4.8–23.1; P = 0.0001). This risk was dependant on severity of CKD; a 10 mL/min reduction in creatinine clearance was associated with a 55% increase in hazard of death (P < 0.0001). Conclusions: In patients receiving an ICD for primary prevention of sudden death, CKD significantly reduced long‐term survival. This poor prognosis may limit the impact of primary prevention ICD therapy in this patient population.