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1.
Contemporary Management of Electrical Storm.
Geraghty, L, Santangeli, P, Tedrow, UB, Shivkumar, K, Kumar, S
Heart, lung & circulation. 2019;(1):123-133
Abstract
Cardiac electrical storm (ES) is characterised by three or more discrete episodes of ventricular arrhythmia within 24hours, or incessant ventricular arrhythmia for more than 12hours. ES is a distinct medical emergency that portends a significant increase in mortality risk and often presages progressive heart failure. ES is also associated with psychological morbidity from multiple implanted cardioverter defibrillator (ICD) shocks and exponential health resource utilisation. Up to 30% of ICD recipients may experience storm in follow-up, with the risk higher in patients with a secondary prevention ICD indication. Storm recurs in a high proportion of patients after an initial episode, and multiple storm clusters may occur in follow-up. The mechanism of storm remains elusive but is likely influenced by a complex interplay of inciting triggers (e.g., ischaemia, electrolyte disturbances), with autonomic perturbations acting on a vulnerable structural and electrophysiologic substrate. Triggers can be identified only in a minority of patients. An emergent treatment approach is warranted, if possible with emergent transfer to a high-volume centre for ventricular arrhythmia management with a multi-modality approach including ICD reprogramming, sympathetic blockade (sedation, intubation, ventilation, beta blockers), and anti-arrhythmic drugs, and adjunctive intervention techniques, such as catheter ablation and neuraxial modulation (e.g., thoracic epidural anaesthesia, stellate ganglion block). Outcomes of catheter ablation of ES are excellent with resolution of storm in over 90% of patients at 1year with a low complication rate (∼2%). ES may occur in the absence of structural heart disease in the context of channelopathies, Brugada syndrome, early repolarisation and premature ventricular contraction-induced ventricular fibrillation. There are unique treatment approaches to these conditions that must be recognised. This state-of-the-art review will summarise the incidence, mechanism, and multi-modality treatment of ES in the contemporary era.
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2.
Classification and Reporting of Potentially Proarrhythmic Common Genetic Variation in Long QT Syndrome Genetic Testing.
Giudicessi, JR, Roden, DM, Wilde, AAM, Ackerman, MJ
Circulation. 2018;(6):619-630
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Abstract
The acquired and congenital forms of long QT syndrome represent 2 distinct but clinically and genetically intertwined disorders of cardiac repolarization characterized by the shared final common pathway of QT interval prolongation and risk of potentially life-threatening arrhythmias. Over the past 2 decades, our understanding of the spectrum of genetic variation that (1) perturbs the function of cardiac ion channel macromolecular complexes and intracellular calcium-handling proteins, (2) underlies acquired/congenital long QT syndrome susceptibility, and (3) serves as a determinant of QT interval duration in the general population has grown exponentially. In turn, these molecular insights led to the development and increased utilization of clinically impactful genetic testing for congenital long QT syndrome. However, the widespread adoption and potential misinterpretation of the 2015 American College of Medical Genetics and Genomics variant classification and reporting guidelines may have contributed unintentionally to the reduced reporting of common genetic variants, with compelling epidemiological and functional evidence to support a potentially proarrhythmic role in patients with congenital and acquired long QT syndrome. As a result, some genetic testing reports may fail to convey the full extent of a patient's genetic susceptibility for a potentially life-threatening arrhythmia to the ordering healthcare professional. In this white paper, we examine the current classification and reporting (or lack thereof) of potentially proarrhythmic common genetic variants and investigate potential mechanisms to facilitate the reporting of these genetic variants without increasing the risk of diagnostic miscues.
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3.
Atrial Fibrillation: Epidemiology, Pathophysiology, and Clinical Outcomes.
Staerk, L, Sherer, JA, Ko, D, Benjamin, EJ, Helm, RH
Circulation research. 2017;(9):1501-1517
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Abstract
The past 3 decades have been characterized by an exponential growth in knowledge and advances in the clinical treatment of atrial fibrillation (AF). It is now known that AF genesis requires a vulnerable atrial substrate and that the formation and composition of this substrate may vary depending on comorbid conditions, genetics, sex, and other factors. Population-based studies have identified numerous factors that modify the atrial substrate and increase AF susceptibility. To date, genetic studies have reported 17 independent signals for AF at 14 genomic regions. Studies have established that advanced age, male sex, and European ancestry are prominent AF risk factors. Other modifiable risk factors include sedentary lifestyle, smoking, obesity, diabetes mellitus, obstructive sleep apnea, and elevated blood pressure predispose to AF, and each factor has been shown to induce structural and electric remodeling of the atria. Both heart failure and myocardial infarction increase risk of AF and vice versa creating a feed-forward loop that increases mortality. Other cardiovascular outcomes attributed to AF, including stroke and thromboembolism, are well established, and epidemiology studies have championed therapeutics that mitigate these adverse outcomes. However, the role of anticoagulation for preventing dementia attributed to AF is less established. Our review is a comprehensive examination of the epidemiological data associating unmodifiable and modifiable risk factors for AF and of the pathophysiological evidence supporting the mechanistic link between each risk factor and AF genesis. Our review also critically examines the epidemiological data on clinical outcomes attributed to AF and summarizes current evidence linking each outcome with AF.
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Normal Ventricular Repolarization and QT Interval: Ionic Background, Modifiers, and Measurements.
Locati, ET, Bagliani, G, Padeletti, L
Cardiac electrophysiology clinics. 2017;(3):487-513
Abstract
The QT interval on surface electrocardiogram represents the sum of depolarization and repolarization process of the ventricles. The ventricular recovery process, reflected by ST segment and T wave, mainly depends on the transmembrane outward transport of potassium ions to reestablish the endocellular electronegativity. Outward potassium channels represent a heterogeneous family of ionic carriers, whose global kinetics is modulated by heart rate and autonomic nervous activity. Several cardiac and noncardiac drugs and disease conditions, and several mutations of genes encoding ionic channels, generating distinct genetic channellopathies, may affect the ventricular repolarization, provoke QT interval prolongation and shortening, and increase the susceptibility to ventricular arrhythmias.
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Dynamics and Molecular Mechanisms of Ventricular Fibrillation in Structurally Normal Hearts.
Jalife, J
Cardiac electrophysiology clinics. 2016;(3):601-12
Abstract
Ventricular fibrillation (VF) is the most severe cardiac rhythm disturbance and one of the most important immediate causes of sudden cardiac death. In the structurally normal heart, a small number of stable reentrant sources, perhaps 1 or 2, underlie the mechanism of VF, and the stabilization of the sources, their frequency, and the complexity of the turbulent waves they generate depend on the expression, spatial distribution, and intermolecular interactions of the 2 most important ion channels that control cardiac excitability: the inward rectifier potassium channel, Kir2.1, and the alpha subunit of the main cardiac sodium channel, NaV1.5.
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[Mechano-electric Feedback and Atrial Fibrillation].
Guo, Q, Liu, X, Shi, Y
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi. 2016;(4):801-5
Abstract
Atrial fibrillation is a common and refractory atrial arrhythmia.Changes of atrial mechanical circumstances are closely related to the occurrence and maintenance of atrial fibrillation.Mechanical factors can increase the automaticity,slow conduction velocity and shorten the effective refractory period of the atrium by causing electrical and structural remodeling,and eventually increase the inducibility of atrial fibrillation.The intracellular calcium level,function and structure of cytoskeleton,local renin-angiotensin system,integrin and mitogen-activated protein kinases(MAPKs)pathway might take part in the process.Here we analyze and review the underlining mechano-electric feedback process of atrial fibrillation and its related research in order to provide a theoretical basis for further research and elucidating of the mechanical mechanism of atrial fibrillation.
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Differential Association of Exercise Intensity With Risk of Atrial Fibrillation in Men and Women: Evidence from a Meta-Analysis.
Mohanty, S, Mohanty, P, Tamaki, M, Natale, V, Gianni, C, Trivedi, C, Gokoglan, Y, DI Biase, L, Natale, A
Journal of cardiovascular electrophysiology. 2016;(9):1021-9
Abstract
BACKGROUND Despite widespread interest and extensive research, the association between different levels of physical activity (PA) and risk of atrial fibrillation (AF) is still not clearly defined. Therefore, we systematically evaluated and summarized the evidences regarding association of different intensity of PA with the risk of AF in this meta-analysis. METHODS AND RESULTS An extensive literature search was performed on databases for studies showing association of exercise with AF risk. Twenty-two studies were identified that included 656,750 subjects. Meta-analytic estimates were derived using random-effects models and pooled odds ratio estimates were obtained. Potential sources of heterogeneity were examined in sensitivity analyses, and publication biases were estimated. Pooled analysis of 7 studies with 93,995 participants reported high risk of incident AF with sedentary lifestyle (pooled OR 2.47 [95% CI 1.25-3.7], P = 0.005). In 3 trials, 149,048 women involved in moderate PA were 8.6% less likely to develop AF compared to women with sedentary life (OR 0.91 [95% CI 0.78-0.97], P = 0.002). Women performing intense exercise were found to have 28% lower risk of AF (OR 0.72 [95% CI 0.57-0.88], P < 0.001). The overall pooled estimate indicated a protective impact of moderate PA in men (pooled OR 0.8133 [95% CI 0.26-1.004], P = 0.06) whereas vigorous PA was associated with a significantly increased AF risk (pooled OR 3.30 [1.97-4.63], P = 0.0002). CONCLUSION Sedentary lifestyle significantly increases and moderate amount of physical activity reduces the risk of AF in both men and women. However, intense exercise has a gender-specific association with AF risk.
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The classical "R-on-T" phenomenon.
Oksuz, F, Sensoy, B, Sahan, E, Sen, F, Baser, K, Cetin, H, Unal, S, Ozeke, O, Topaloglu, S, Aras, D
Indian heart journal. 2015;(4):392-4
Abstract
The polymorphic ventricular tachycardia (PVT) is uncommon arrhythmia with multiple causes and has been classified according to whether they are associated with long QT interval or normal QT. Whereas "Torsade de pointes (TdP)" is an uncommon and distinctive form of PVT occurring in a setting of prolonged QT interval, which may be congenital or acquired (congenital or acquired), "PVT with normal QT" is associated with myocardial ischemia, electrolyte abnormalities (hypokalemia), mutations of the cardiac sodium channel (Brugada syndrome), and the ryanodine receptor (catecholaminergic PVT). This distinction is crucial because of the differing etiologies and management of these arrhythmias. Moreover, the PVT in the setting of acute MI generally occurs during the hyperacute phase, is related to ischemia ("ischemic PVT") and is not associated with QT prolongation. It is triggered by ventricular extrasystoles with very short coupling interval (the "R-on-T" phenomenon) and is not pause-dependent. However, recently there has been described a new PVT during the "healing phase" of MI in patients with no evidence of ongoing ischemia and following excessive QT prolongation, the electrophysiologic abnormality being a "pause-dependent infarct-related TdP" due to a LQTS in healing MI patients. Therefore, "ischemic PVT" differs from "infarct-related TdP" in terms of pathophysiology and ECG manifestations.
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Considerations for assessing the potential effects of antidiabetes drugs on cardiac ventricular repolarization: A report from the Cardiac Safety Research Consortium.
Heller, S, Darpö, B, Mitchell, MI, Linnebjerg, H, Leishman, DJ, Mehrotra, N, Zhu, H, Koerner, J, Fiszman, ML, Balakrishnan, S, et al
American heart journal. 2015;(1):23-35
Abstract
Thorough QT studies conducted according to the International Council on Harmonisation E14 guideline are required for new nonantiarrhythmic drugs to assess the potential to prolong ventricular repolarization. Special considerations may be needed for conducting such studies with antidiabetes drugs as changes in blood glucose and other physiologic parameters affected by antidiabetes drugs may prolong the QT interval and thus confound QT/corrected QT assessments. This review discusses potential mechanisms for QT/corrected QT interval prolongation with antidiabetes drugs and offers practical considerations for assessing antidiabetes drugs in thorough QT studies. This article represents collaborative discussions among key stakeholders from academia, industry, and regulatory agencies participating in the Cardiac Safety Research Consortium. It does not represent regulatory policy.
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10.
Noninvasive characterization of atrioventricular conduction in patients with atrial fibrillation.
Corino, VD, Sandberg, F, Mainardi, LT, Platonov, PG, Sörnmo, L
Journal of electrocardiology. 2015;(6):938-42
Abstract
The atrioventricular (AV) node plays a fundamental role in patients with atrial fibrillation (AF), acting as a filter to the numerous irregular atrial impulses which bombard the node. A phenomenological approach to better understand AV nodal electrophysiology is to analyze the ventricular response with respect to irregularity. In different cohorts of AF patients, such analysis has been performed with the aim to evaluate the association between ventricular response characteristics and long-term clinical outcome and to determine whether irregularity is affected by rate-control drugs. Another approach to studying AV nodal characteristics is to employ a mathematical model which accounts for the refractory periods of the two AV nodal pathways. With atrial fibrillatory rate and RR intervals as input, the model has been considered for analyzing data during (i) rest and head-up tilt test, (ii) tecadenoson and esmolol, and (iii) rate-control drugs. The present paper provides an overview of our recent work on the characterization and assessment of AV nodal conduction using these two approaches.