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Concept: Cardiac dysrhythmia


The Brugada syndrome (BrS) is a malignant, genetically-determined, arrhythmic syndrome manifesting as syncope or sudden cardiac death (SCD) in individuals with structurally normal hearts. The diagnosis of the BrS is mainly based on the presence of a spontaneous or Na + channel blocker induced characteristic, electrocardiographic (ECG) pattern (type 1 or coved Brugada ECG pattern) typically seen in leads V1 and V2 recorded from the 4th to 2nd intercostal (i.c.) spaces. This pattern needs to be distinguished from similar ECG changes due to other causes (Brugada ECG phenocopies). This review focuses mainly on the ECG-based methods for diagnosis and arrhythmia risk assessment in the BrS. Presently, the main unresolved clinical problem is the identification of those patients at high risk of SCD who need implantable cardioverter-defibrillator (ICD), which is the only therapy with proven efficacy. Current guidelines recommend ICD implantation only in patients with spontaneous type 1 ECG pattern, and either history of aborted cardiac arrest or documented sustained VT (class I), or syncope of arrhythmic origin (class IIa) because they are at high risk of recurrent arrhythmic events (up to 10% or more annually for those with aborted cardiac arrest). The majority of BrS patients are asymptomatic when diagnosed and considered to have low risk (around 0.5% annually) and therefore not indicated for ICD. The majority of SCD victims in the BrS, however, had no symptoms prior to the fatal event and therefore were not protected with an ICD. While some ECG markers such as QRS fragmentation, infero-lateral early repolarisation, and abnormal late potentials on signal-averaged ECG are known to be linked to increased arrhythmic risk, they are not sufficiently sensitive or specific. Potential novel ECG-based strategies for risk stratification are discussed based on computerised methods for depolarisation and repolarisation analysis, a composite approach targeting several major components of ventricular arrhythmogenesis, and the collection of large digital ECG databases in genotyped BrS patients and their relatives.

Concepts: Cardiology, Implantable cardioverter-defibrillator, Cardiac arrest, Cardiac electrophysiology, Ventricular fibrillation, Sudden cardiac death, Brugada syndrome, Cardiac dysrhythmia


Background Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT). We combined these techniques to perform catheter-free, electrophysiology-guided, noninvasive cardiac radioablation for ventricular tachycardia. Methods We targeted arrhythmogenic scar regions by combining anatomical imaging with noninvasive electrocardiographic imaging during ventricular tachycardia that was induced by means of an implantable cardioverter-defibrillator (ICD). SBRT simulation, planning, and treatments were performed with the use of standard techniques. Patients were treated with a single fraction of 25 Gy while awake. Efficacy was assessed by counting episodes of ventricular tachycardia, as recorded by ICDs. Safety was assessed by means of serial cardiac and thoracic imaging. Results From April through November 2015, five patients with high-risk, refractory ventricular tachycardia underwent treatment. The mean noninvasive ablation time was 14 minutes (range, 11 to 18). During the 3 months before treatment, the patients had a combined history of 6577 episodes of ventricular tachycardia. During a 6-week postablation “blanking period” (when arrhythmias may occur owing to postablation inflammation), there were 680 episodes of ventricular tachycardia. After the 6-week blanking period, there were 4 episodes of ventricular tachycardia over the next 46 patient-months, for a reduction from baseline of 99.9%. A reduction in episodes of ventricular tachycardia occurred in all five patients. The mean left ventricular ejection fraction did not decrease with treatment. At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year. Conclusions In five patients with refractory ventricular tachycardia, noninvasive treatment with electrophysiology-guided cardiac radioablation markedly reduced the burden of ventricular tachycardia. (Funded by Barnes-Jewish Hospital Foundation and others.).

Concepts: Myocardial infarction, Cardiology, Ejection fraction, Implantable cardioverter-defibrillator, Cardiac arrest, Cardiac electrophysiology, Ventricular fibrillation, Cardiac dysrhythmia


Ectopic heartbeats can trigger reentrant arrhythmias, leading to ventricular fibrillation and sudden cardiac death. Such events have been attributed to perturbed Ca2+ handling in cardiac myocytes leading to spontaneous Ca2+ release and delayed afterdepolarizations (DADs). However, the ways in which perturbation of specific molecular mechanisms alters the probability of ectopic beats is not understood. We present a multiscale model of cardiac tissue incorporating a biophysically detailed three-dimensional model of the ventricular myocyte. This model reproduces realistic Ca2+ waves and DADs driven by stochastic Ca2+ release channel (RyR) gating and is used to study mechanisms of DAD variability. In agreement with previous experimental and modeling studies, key factors influencing the distribution of DAD amplitude and timing include cytosolic and sarcoplasmic reticulum Ca2+ concentrations, inwardly rectifying potassium current (IK1) density, and gap junction conductance. The cardiac tissue model is used to investigate how random RyR gating gives rise to probabilistic triggered activity in a one-dimensional myocyte tissue model. A novel spatial-average filtering method for estimating the probability of extreme (i.e. rare, high-amplitude) stochastic events from a limited set of spontaneous Ca2+ release profiles is presented. These events occur when randomly organized clusters of cells exhibit synchronized, high amplitude Ca2+ release flux. It is shown how reduced IK1 density and gap junction coupling, as observed in heart failure, increase the probability of extreme DADs by multiple orders of magnitude. This method enables prediction of arrhythmia likelihood and its modulation by alterations of other cellular mechanisms.

Concepts: Myocardial infarction, Heart, Cardiac muscle, Cardiac arrest, Cardiac electrophysiology, Probability, Sudden cardiac death, Cardiac dysrhythmia


Studies suggest that people who work long hours are at increased risk of stroke, but the association of long working hours with atrial fibrillation, the most common cardiac arrhythmia and a risk factor for stroke, is unknown. We examined the risk of atrial fibrillation in individuals working long hours (≥55 per week) and those working standard 35-40 h/week.

Concepts: Heart, Atrial fibrillation, Cardiac arrest, Cardiac electrophysiology, The Association, Atrial flutter, Working time, Cardiac dysrhythmia


Ventricular arrhythmias may be benign, requiring only evaluation for associated risks and then reassurance, or associated with a risk of sudden death or significant morbidity. Therapies for these arrhythmias have evolved considerably over the past twenty years. For some, a definitive, curative therapy is available in the form of catheter ablation. Others are best managed with an implantable defibrillator that provides effective arrhythmia termination and protection from sudden death, with antiarrhythmic drugs or ablation to control recurrent arrhythmias. Although progress has been substantial, many challenges remain.

Concepts: Medicine, Risk, Implantable cardioverter-defibrillator, Therapy, Cardiac electrophysiology, Antiarrhythmic agent, Therapy?, Cardiac dysrhythmia


AIM: This study was designed to evaluate the diagnostic value of B-type natriuretic peptide (BNP) in syncope in children and adolescents. METHODS: Serum BNP concentration was measured by electrochemiluminescence assay in 62 consecutive children and adolescents hospitalized for syncope. RESULTS: Of the 62 children and adolescents hospitalized for syncope, 39 had non-cardiac syncope, 37 (59.7%) of whom had autonomic-mediated reflex syncope, and two (3.2%) had syncope of unknown cause. Twenty-three patients (37.1%) had cardiac syncope; 11 of these had cardiac arrhythmias and 12 had structural cardiac/cardiopulmonary disease. Patients with cardiac syncope had significantly higher serum BNP than those with non-cardiac syncope (958.78 ± 2443.41 pg/ml vs. 31.05 ± 22.64 pg/ml, p < 0.05). Logistic multivariate regression analysis revealed that urinary incontinence during syncopal episodes, ECG abnormalities and increased serum BNP levels were independent predictors for cardiac syncope. At a cut-off value of 40.65 pg/ml, serum BNP was associated with significant risk for a cardiac cause of syncope, with sensitivity 73.9% and specificity 70.0% for distinguishing cardiac syncope from non-cardiac syncope. CONCLUSION: Serum BNP was helpful in differentiating cardiac syncope from non-cardiac syncope in children and adolescents ©2013 The Author(s)/Acta Paediatrica ©2013 Foundation Acta Paediatrica.

Concepts: Regression analysis, Cardiology, Urinary incontinence, Cardiac arrest, Multivariate statistics, Brain natriuretic peptide, Atrial natriuretic peptide, Cardiac dysrhythmia


It remains unclear if human atrial fibrillation (AF) is spatially non-hierarchical or exhibits a hierarchy of organization sustained by sources. We utilize activation times obtained at discrete locations during AF to compute the phase synchrony between tissue regions, in order to examine underlying spatial dynamics throughout both atria. We construct a binary synchronization network and show that this network can accurately define regions of coherence in coarse-grained in silico data. Specifically, domains controlled by spiral waves exhibit regions of high phase synchrony. We then apply this analysis to clinical data from patients experiencing cardiac arrhythmias using multielectrode catheters to simultaneously record from a majority of both atria. We show that pharmaceutical intervention with ibutilide organizes activation by increasing the size of the synchronized domain in AF, and quantify the increase in temporal organization when arrhythmia changes from fibrillation to tachycardia. Finally, in recordings from 24 patients in AF we show that the level of synchrony is spatially broad with some patients showing large spatially contiguous regions of synchronization, while in others synchrony is localized to small pockets. Using computer simulations, we show that this distribution is inconsistent with distributions obtained from simulations that mimic multi-wavelet reentry but is consistent with mechanisms in which one or more spatially conserved spiral waves are surrounded by tissue in which activation is disorganized.

Concepts: Blood, Heart, Atrial fibrillation, Cardiac arrest, Cardiac electrophysiology, Computer, Computer simulation, Cardiac dysrhythmia


Propranolol in slow-release form has been the first-line treatment in LQT until it was withdrawn from the market..We describe two cases where a switch to bisoprolol resulted in worsening of arrhythmia control: A man with LQT2, asymptomatic on propranolol, experienced syncope after switching to bisoprolol 5mg daily. He switched back to propranolol and has remained asymptomatic during subsequent 12 months. A man with classical Jervell Lange-Nielsen syndrome, previous gangliectomy and ICD-implantation, switched to bisoprolol 5mg daily. Four months later he experienced a tachycardia storm. He switched back to propranolol and has remained free from arrhythmias during subsequent 12 months. This article is protected by copyright. All rights reserved.

Concepts: Cardiac electrophysiology, Long QT syndrome, Syndromes, Supraventricular tachycardia, All rights reserved, All rights reversed, Copyright, Cardiac dysrhythmia


High-energy ion beams are successfully used in cancer therapy and precisely deliver high doses of ionizing radiation to small deep-seated target volumes. A similar noninvasive treatment modality for cardiac arrhythmias was tested here. This study used high-energy carbon ions for ablation of cardiac tissue in pigs. Doses of 25, 40, and 55 Gy were applied in forced-breath-hold to the atrioventricular junction, left atrial pulmonary vein junction, and freewall left ventricle of intact animals. Procedural success was tracked by (1.) in-beam positron-emission tomography (PET) imaging; (2.) intracardiac voltage mapping with visible lesion on ultrasound; (3.) lesion outcomes in pathohistolgy. High doses (40-55 Gy) caused slowing and interruption of cardiac impulse propagation. Target fibrosis was the main mediator of the ablation effect. In irradiated tissue, apoptosis was present after 3, but not 6 months. Our study shows feasibility to use high-energy ion beams for creation of cardiac lesions that chronically interrupt cardiac conduction.

Concepts: Ionizing radiation, Blood, Heart, Cardiac arrest, Ventricle, Ions, Cardiac dysrhythmia


Cardiac arrhythmias are often associated with mutations in ion channels or other proteins. To enable drug development for distinct arrhythmias, model systems are required that allow implementing patient-specific mutations. We assessed a muscular pump in Caenorhabditis elegans. The pharynx utilizes homologues of most of the ion channels, pumps and transporters defining human cardiac physiology. To yield precise rhythmicity, we optically paced the pharynx using channelrhodopsin-2. We assessed pharynx pumping by extracellular recordings (electropharyngeograms-EPGs), and by a novel video-microscopy based method we developed, which allows analyzing multiple animals simultaneously. Mutations in the L-type VGCC (voltage-gated Ca(2+)-channel) EGL-19 caused prolonged pump duration, as found for analogous mutations in the Cav1.2 channel, associated with long QT syndrome. egl-19 mutations affected ability to pump at high frequency and induced arrhythmicity. The pharyngeal neurons did not influence these effects. We tested whether drugs could ameliorate arrhythmia in the optogenetically paced pharynx. The dihydropyridine analog Nemadipine A prolonged pump duration in wild type, and reduced or prolonged pump duration of distinct egl-19 alleles, thus indicating allele-specific effects. In sum, our model may allow screening of drug candidates affecting specific VGCCs mutations, and permit to better understand the effects of distinct mutations on a macroscopic level.

Concepts: Neuron, Medical emergencies, Caenorhabditis elegans, Model organism, Cardiac arrest, Cardiac electrophysiology, Long QT syndrome, Cardiac dysrhythmia