Prevention Of Arrhythmias Research Articles

Alpha-lipoic acid potentiates the anti-arrhythmic effects of ischemic postconditioning in the setting of cardiac ischemia/reperfusion injury in diabetic rats.

Prevention of lethal ventricular arrhythmias induced by myocardial ischemia/reperfusion (I/R) in diabetic patients is the major goal of cardioprotective strategies. Here, we aimed to examine the anti-arrhythmic effect of ischemic postconditioning (IPostC) and alpha-lipoic acid (ALA) in myocardial I/R injury of type-II diabetic rats, focusing on the involvement of connexin-43 and nitric oxide (NO) in this context. Diabetes (duration of 12weeks) was induced by high-fat diet and low dose of streptozotocin in thirty male Wistar rats (12weeks old, 200-250g). After mounting the hearts on the Langendorff apparatus, I/R was induced by the ligation of left anterior descending coronary artery for 35min, and reperfusion for 60min. ALA (100mg/kg/day) was administered orally in diabetic rats for five weeks before I/R. IPostC was applied immediately at early reperfusion. The arrhythmias were evaluated according to the Lambeth convention. Connexin-43 expression and NO levels were assessed by western blotting and Griess calorimetric method, respectively. IPostC could not significantly decrease the number, duration, and incidence of premature ventricular contraction, ventricular tachycardia, and ventricular fibrillation, also the severity of arrhythmias in diabetic hearts. However, IPostC in combination with ALA-preconditioning significantly decreased the above mentioned parameters compared with untreated or monotherapies-received diabetic rats (P < 0.05 to P < 0.001). Furthermore, this combination therapy significantly increased connexin-43 expression and NO levels, compared with untreated diabetic rats (P < 0.01). Preconditioning with ALA restored anti-arrhythmic effect of IPostC in diabetic hearts. Increased connexin-43 expression and NO levels may be the key players in this cardioprotection.

Differential effects of EPA and DHA on PPARγ-mediated sympathetic innervation in infarcted rat hearts by GPR120-dependent and -independent mechanisms

The ω-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to attenuate inflammation processes, whereas the molecular mechanisms remain unclear. This study was aimed at figuring out the differential effects of EPA and DHA on fatal arrhythmias and whether the signaling pathway could be a target after myocardial infarction, an inflammatory status. Male Wistar rats after ligating coronary artery were randomized to either vehicle, EPA, or DHA for 4 weeks. Postinfarction was associated with increased myocardial norepinephrine levels and sympathetic innervation. Furthermore, infarction was associated with the activation of NLRP3 inflammasomes and increased the protein and expression of IL-1β and nerve growth factor (NGF). These changes were blunted after adding either EPA or DHA with a greater extent of EPA than DHA. Immunoblotting and immunohistochemical analysis showed that EPA had significantly lower phosphorylation of PPARγ at Ser 112 compared with DHA. Arrhythmic severity during programmed stimulation in the infarcted rats treated with EPA was significantly lower than those treated with DHA. Specific inhibition of GPR120 by AH-7614 and PPARγ by T0070907 reduced the EPA-or DHA-related attenuation of IL-1β and NGF release. Besides, AH-7614 treatment partially reduced the PPARγ levels, whereas T0070907 administration did not affect the GPR120 levels. These results suggest that EPA was more effective than DHA in prevention of fatal arrhythmias by inhibiting NLRP3 inflammasome and sympathetic innervation through activation of PPARγ-mediated GPR120-dependent and -independent signaling pathways in infarcted hearts.

Advances in Cardiac Pacing: Arrhythmia Prediction, Prevention and Control Strategies.

Cardiac arrhythmias constitute a tremendous burden on healthcare and are the leading cause of mortality worldwide. An alarming number of people have been reported to manifest sudden cardiac death as the first symptom of cardiac arrhythmias, accounting for about 20% of all deaths annually. Furthermore, patients prone to atrial tachyarrhythmias such as atrial flutter and fibrillation often have associated comorbidities including hypertension, ischemic heart disease, valvular cardiomyopathy and increased risk of stroke. Technological advances in electrical stimulation and sensing modalities have led to the proliferation of medical devices including pacemakers and implantable defibrillators, aiming to restore normal cardiac rhythm. However, given the complex spatiotemporal dynamics and non-linearity of the human heart, predicting the onset of arrhythmias and preventing the transition from steady state to unstable rhythms has been an extremely challenging task. Defibrillatory shocks still remain the primary clinical intervention for lethal ventricular arrhythmias, yet patients with implantable cardioverter defibrillators often suffer from inappropriate shocks due to false positives and reduced quality of life. Here, we aim to present a comprehensive review of the current advances in cardiac arrhythmia prediction, prevention and control strategies. We provide an overview of traditional clinical arrhythmia management methods and describe promising potential pacing techniques for predicting the onset of abnormal rhythms and effectively suppressing cardiac arrhythmias. We also offer a clinical perspective on bridging the gap between basic and clinical science that would aid in the assimilation of promising anti-arrhythmic pacing strategies.

Selección de lo mejor del año 2021 en cardiopatías congénitas

This article shows the publications that we consider the most relevant on congenital heart disease in the last year. The COVID-19 pandemic has continued to mark scientific activity in this period. There has been concerns about the risk of complications from COVID-19 among adults with congenital heart disease (CHD). Likewise, the involvement of children with CHD has been studied. This year, the European guidelines for the treatment of CHD have been published, the second edition after 10years, that will be very useful in the treatment of these complex patients. Among the original publications, we highlight the contributions related to risk stratification in the primary prevention of ventricular arrhythmias, Fontan and liver disease, and the progress in percutaneous pulmonary valve implant techniques, the application of new drugs for advanced heart failure in complex CHD and in systemic right ventricle and long-term complications of young adults with transposition of the great arteries undergoing arterial switch surgery.

Abstract 14170: Incremental Value of Magnetic Resonance-Based Ventricular and Atrial Strain in Predicting Ventricular Arrhythmia

Introduction: Only a small subset of patients with primary prevention ICDs, for whom left ventricular ejection fraction (LVEF) is emphasized in current guidelines, receive appropriate ICD therapy. Objectives: To study the incremental value of cardiovascular MR (CMR)-derived right and left ventricular and left atrial strain measured using feature tracking in predicting ventricular arrhythmia in patients eligible for implantable cardioverter-defibrillator (ICD) primary prevention of ventricular arrhythmia. Methods: The study included patients who met the current clinical guideline to receive an ICD for primary prevention of SCD. CMR imaging was performed on either a 1.5 or a 3T scanner, including standard evaluation of LV function and structure, LV/RV/LA strains, LGE. Outcomes were comprised of 1) unstable VT/VF &gt;30sesonds, 2) appropriate ICD therapy; shock or anti-tachycardia pacing for VT/VF, or 3) SCD. The primary outcome was a composite endpoint of any of the above three outcomes. Results: A total of 239 patients were included and the average age was 57±14 years old. Patients with outcomes had slightly lower RV global longitudinal strain (GLS). Univariate Cox proportional hazards regression showed that every standard deviation increase in RV GLS was associated with a 73% increase in risk (p&lt; 0.01). The baseline multivariable Cox’s proportional hazards regression model with a standardized clinical risk score, standardized LVEF, LGE had an AUC of 0.64. The best performing model, which included standardized LV and RV GLS, significantly improved prognosis compared with the baseline model, with an AUC of 0.72 and a categorical free NRI of 0.88 (p=0.04). Model 1 indicated an increased risk of 77% for every standard deviation increase in RV GLS (p&lt; 0.01) and a decreased risk of 49% for every standard deviation increase in LV GLS (p= 0.02). Kaplan-Meier curves could be stratified using the selected thresholds; LV GCS ≥ 5.3 and RV GLS ≥ -10.8, respectively (p=0.02, p&lt;0.01).

Abstract 12552: Juxta-Purkinje Ventricular Myocytes Are the Cellular Trigger of Catecholaminergic Polymorphic Ventricular Tachycardia

Introduction: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic arrhythmia syndrome caused by mutations that render intracellular calcium release channels hyperactive during adrenergic stress. Hyperactive calcium release has also been identified as a cause of ventricular arrhythmia in acquired heart diseases such as heart failure. What remains unknown is the cellular source of ventricular arrhythmia triggered by inappropriate calcium release – Purkinje cells in the cardiac conduction system or ventricular cardiomyocytes in the working myocardium. Methods: To investigate the cellular origin, we used a genetic approach in mice to knock out cardiac calsequestrin (Casq2) either in Purkinje cells or in ventricular cardiomyocytes (Panel A). Total loss of calsequestrin in the heart causes a severe CPVT phenotype in mice and humans. Immunostaining and western blotting were used to examine protein expression and arrhythmias were induced by administration of isoprenaline. Results: Loss of Casq2 only in ventricular myocytes produced a full-blown CPVT phenotype, whereas mice with loss of Casq2 only in Purkinje cells were comparable to wild-type mice (Panel B). Subendocardial chemical ablation or restoration of Casq2 expression in subendocardial cardiomyocytes neighboring Purkinje cells was sufficient to protect against catecholamine-induced arrhythmias (Panels C, D). Conclusion: Our data indicate that subendocardial ventricular myocytes juxtaposed to Purkinje fibers are the source of ventricular arrhythmias triggered by intracellular calcium release and hence identify a novel cellular target for arrhythmia prevention.

Two-stage ECG signal denoising based on deep convolutional network

Background. An electrocardiogram (ECG) is an effective and non-invasive indicator for the detection and prevention of arrhythmia. ECG signals are susceptible to noise contamination, which can lead to errors in ECG interpretation. Therefore, ECG pretreatment is important for accurate analysis. Methods. The ECG data used are from CPSC2018, and the noise signal is from MIT-BIH Noise Stress Test Database. In the experiment, the signal-to-noise ratio (SNR), the root mean square error (RMSE), and the correlation coefficient P are used to evaluate the performance of the network. The method proposed is divided into two stages. In the first stage, a U de -net model is designed for ECG signal denoising to eliminate noise. The DR-net model in the second stage is used to reconstruct the ECG signal and to correct the waveform distortion caused by noise removal in the first stage. In this paper, the U de -net and the DR-net are constructed by the convolution method to achieve end-to-end mapping from noisy ECG signals to clean ECG signals. Result. In SNR, RMSE and P indicators, U de -net + DR-net proposed in this paper can achieve the best performance compared with the other five schemes (FCN, U-net etc). In the three data sets, SNR can be increased by 11.61 dB, 13.71 dB and 14.40 dB and RMSE can be reduced by 10.46 × 10−2, 21.55 × 10−2 and 15.98 × 10−2. Conclusions. Despite the contradictory results, the proposed two-stages method can achieve both the elimination of noise and the preservation of effective details to a large extent of the signals. The proposed method has good application prospects in clinical practice.

Carbon monoxide: modern concepts to the treatment of acute poisonings (literature review)

Introduction. Carbon monoxide (CO) is one of the most common causes of chemical injuries and the main toxic factor in the people death in fires. The mechanism of the toxic effect of CO, associated with the formation of carboxyhemoglobin and the development of hypoxia, determines the rapid development of the clinical picture of acute intoxication and the need for emergency first aid and medical care to the poisoned. Material and methods. Literature sources, summarized in the bibliographic databases eLIBRARY.RU, PubMed and Scopus, were the material for analysis. Results. First aid is based on quickly removing the victim from the fire zone or other area with a high concentration of CO and providing him with oxygen as soon as possible. During medical evacuation, it is necessary to carry out continuous inhalation of 80-100% oxygen, to ensure rest and warmth of the victim. In the emergency department of the hospital, oxygen inhalation and maintenance therapy should be continued, clinical and laboratory diagnostic measures aimed at assessing the severity of intoxication, identifying complications and concomitant pathology should be performed. In the case of severe CO poisoning, medical care continues to be provided to the victims in the intensive care unit or in the oxygen-barotherapy unit. The main antidote for CO poisoning is oxygen, which can be used in two versions - normobaric or hyperbaric oxygenation. As a pharmacological antidote to CO, zinc bisvinylimidazole diacetate (acizol) which can accelerate the breakdown of carboxyhemoglobin, improve the oxygen-binding and gas-transport properties of blood, as well as the dissociation of oxyhemoglobin in tissues is used. Along with antidotes, an important role in the treatment of CO poisoning is played by pathogenetic and symptomatic therapy aimed at the prevention and treatment of toxic encephalopathy, brain edema, cognitive dysfunction, toxic myocardiodystrophy and arrhythmia, prevention of pneumonia, correction of the acid-base state, compensation of the energy needs of the body, etc. Conclusion. Further improvement of existing means and methods for the treatment of intoxication, the development and introduction of new antidots into medical practice will increase the effectiveness of therapeutic measures, reduce the number of deaths and disabilities after acute poisoning with carbon monoxide.

Pharmacological optimization of premedication to reduce the risk of cardiovascular complications

In 46 patients with arterial hypertension, arrhythmias and amiodarone-associated type I thyrotoxicosis, it was confirmed that prolonged premedication with long-acting benzodiazepines and magnesium preparations reduces the risk of cardiovascular complications and instability of systemic hemodynamics, mitigates the adverse effects of amiodarone dysfunction of the thyroid gland on the cardiovascular system. Postoperatively, under prolonged premedication with long-acting benzodiazepines and magnesium preparations, postoperative cardiac arrhythmias were found to be less common. When the pre-operative period was significantly reduced, the appointment of long-acting benzodiazepines had advantages over short-acting benzadiazepines due to the prevention of cardiac arrhythmias and increased blood pressure in the early post-operative period.

Proteomic Analysis of the Functional Inward Rectifier Potassium Channel (Kir) 2.1 Reveals Several Novel Phosphorylation Sites.

Membrane proteins represent a large family of proteins that perform vital physiological roles and represent key drug targets. Despite their importance, bioanalytical methods aiming to comprehensively characterize the post-translational modification (PTM) of membrane proteins remain challenging compared to other classes of proteins in part because of their inherent low expression and hydrophobicity. The inward rectifier potassium channel (Kir) 2.1, an integral membrane protein, is critical for the maintenance of the resting membrane potential and phase-3 repolarization of the cardiac action potential in the heart. The importance of this channel to cardiac physiology is highlighted by the recognition of several sudden arrhythmic death syndromes, Andersen-Tawil and short QT syndromes, which are associated with loss or gain of function mutations in Kir2.1, often triggered by changes in the β-adrenergic tone. Therefore, understanding the PTMs of this channel (particularly β-adrenergic tone-driven phosphorylation) is important for arrhythmia prevention. Here, we developed a proteomic method, integrating both top-down (intact protein) and bottom-up (after enzymatic digestion) proteomic analyses, to characterize the PTMs of recombinant wild-type and mutant Kir2.1, successfully mapping five novel sites of phosphorylation and confirming a sixth site. Our study provides a framework for future work to assess the role of PTMs in regulating Kir2.1 functions.

Isolated superfused rats atrial model for the investigation of atrial fibrillation mechanisms and treatment

Abstract Background One of the major barriers to an improved mechanistic understanding of atrial fibrillation (AF), and thus in the pipeline of drug development, has been a lack of appropriate tissue models, especially in small animals. Aim We propose an advanced anatomical ex-vivo model based on rat atria for acute assessment of AF susceptibility. This novel model could yield a better understanding of arrhythmia mechanisms as well as the development of potential therapeutic strategies for the prevention or termination of atrial arrhythmias. Methods Wistar rats atria (N=25) were isolated, flattened and pinned to a custom-made silicon plate. Atria were superfused with an oxygenized Tyrode's solution. Tissues were then loaded with a voltage-sensitive dye and mapped using a high-resolution optical mapping system. AF was induced with 1uM carbamylcholine (N=23) coupled with pacing maneuvers and treated with 30uM Vernakalant (N=10) or 10uM Flecainide (N=10). Finally, the feasibility of a new ablation technique (electroporation) was evaluated. Results Optical mapping results suggested that the superfusion procedure led to a fast atrial recovery. Sinus activity was conserved for all atria for a long period. All the anatomical landmarks were clearly visualized. The acquired optical signals were analyzed during sinus rhythm and pacing, which allowed the creation of detailed activation maps and measurements of action potential duration (APD) and conduction velocity (CV) at different pacing rates. The resulting APD restitution curves revealed electrical excitation at high pacing rates (cycle length between 50ms and 300ms) with a relatively flattened curve. AF was successfully induced and optically mapping confirmed the presence of reentrant activity. AF was successfully treated using Vernacalant and Flecainide. Finally, we demonstrated the feasibility of a new ablation approach (electroporation) for creation of a continuous linear lesion serving as a functional block. Conclusion The isolated superfused atria model, coupled with voltage-sensitive dyes, can be utilized for long-term high-resolution functional imaging of the atria during sinus rhythm, pacing and arrhythmogenic activity. This allows the study of the atrial electrophysiological properties, the mechanisms involved in AF initiation, perpetuation, and termination as well as the study of drug and new ablation modalities. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council (ERC) Spontaneous activation of isolated atria

Arrhythmia in Cardiomyopathy: Sex and Gender Differences.

There is emerging evidence for important sex differences in cardiac arrhythmias. In this up-to-date review, we summarise the differences in incidence, aetiology, treatment and prevention of ventricular arrhythmias (VAs) and sudden cardiac death (SCD) in women versus men, in the context of ischaemic and nonischaemic cardiomyopathies. The incidence of ventricular tachyarrhythmia and SCD is significantly lower in women than in men with ischaemic cardiomyopathy, whereas sex differences in nonischaemic cardiomyopathy are less clear. Women who receive a primary prevention implantable cardioverter-defibrillator (ICD) are less likely to receive appropriate activations, compared to men; however, such findings are limited by under-representation of women. Women with ischaemic cardiomyopathy have significantly lower incidence of VA and SCD compared to men and may not derive the same benefit from a primary prevention ICD. However, further clinical ICD studies are needed that ensure adequate female participation, in order to examine sex differences in outcomes in both ischaemic and nonischaemic cardiomyopathies.

Calcineurin Aβ gene knockdown inhibits transient outward potassium current ion channel remodeling in hypertrophic ventricular myocyte.

It has been shown that the activation of calcineurin is involved in regulating ion channel remodeling in hypertrophic cardiomyocytes. But the precise role of calcineurin in the regulation of transient outward potassium current (I to), an ion channel associated with fatal arrhythmia, remains controversial. This study aimed to examine the effects of calcineurin Aβ (CnAβ) gene knockdown on I to channel remodeling and action potential duration (APD) in the hypertrophic ventricular myocytes of neonatal rats. Results showed that phenylephrine stimulation caused hypertrophy of ventricular myocytes, upregulation of CnAβ protein expression, downregulation of Kv4.2 mRNA and protein expression, a decrease in I to current density, and prolongation of APD. CnAβ gene knockdown significantly inhibited the effects of phenylephrine stimulation. Our data indicate that CnAβ gene knockdown can inhibit I to channel remodeling and APD prolongation in hypertrophic neonatal rat ventricular myocytes. This finding suggests that calcineurin may be a potential target for the prevention of malignant ventricular arrhythmia in a hypertrophic heart.

The Investigation of Combined Na+/Ca2+ Exchanger and the L-type Ca2+- Channel Inhibition in Langendorff-Perfused Isolated Guinea Pig Hearts

Abstract Objective The sodium/calcium exchanger (NCX) and the L-type Ca2+-channel (LTCC) are nowadays considered the major transmembrane transport mechanisms that control Ca2+ homeostasis. In pathophysiological conditions the altered function of these currents may influence the Ca2+ homeostasis and cardiac contractility and thereby, may enhance the development of severe tachyarrhythmias. The blockade of NCX current has been proposed as possible approach in the prevention and/or suppression of arrhythmias; however, this mechanism is not always favourable because the inhibition of both modes of NCX may induce Ca2+-overload. The decrease of the Ca2+ level by partial LTCC inhibition may be beneficial in increasing the antiarrhythmic efficacy. Therefore, the aim of our study was to investigate the antiarrhythmic effects of combined NCX and LTCC blockade in the ex vivo guinea pig arrhythmia model. Methods We have performed Langendorff experiments in isolated guinea pig hearts. We have recorded electrocardiograms (ECG) and left ventricle pressure. We have applied 1 μM ORM-10962 (ORM), a compound that block NCX current and 30 nM nisoldipine for the inhibition of LTCC. Arrhythmias have been provoked by decreasing the activity of the sodium/potassium pump with 5 μM ouabain. Results We found that neither LTCC nor NCX blockade alone increased, while the combined inhibition of the two currents significantly delayed (p&lt;0.05) the mean time of appearance of ouabain-induced ventricular fibrillation. The heart frequency was affected by none of the drugs, only the left ventricular pressure (end-systolic and diastolic difference) was significantly elevated by ORM (p&lt;0.001). Conclusion In the Langendorff-perfused guinea pig heart, specific, combined NCX and LTCC blockade may be favourable than the inhibition of NCX or LTCC alone. However, further investigations are necessary to identify the pathological settings in which this combined cardiac drug therapy may be a potential new approach.

Remote Monitoring of the QT Interval and Emerging Indications for Arrhythmia Prevention.

QT interval prolongation is a marker of increased risk for life-threatening arrhythmias, and needs to be promptly recognized. Many effective drugs, however, prolong QTc (QT interval corrected for heart rate) in genetically predisposed subjects. The possibility of remote monitoring and QTc measurement for up to 2 weeks, continuously providing physicians with real time data, allows life-saving interventions or changes in drug therapy. This applies especially to patients with the long QT syndrome and to those taking drugs blocking the IKr current and prolonging the QT interval. Patch monitors recording ECG traces continuously are available and contribute to effective arrhythmic prevention.

Comparative Characteristics of Beta-Blockers in Patients with Congenital Long QT Syndrome

Congenital long QT syndrome is a pathology that requires special attention and knowledge about the safety and effectiveness of various medications. Prolongation of the QT interval due to congenital or acquired causes is an important factor in the development of an unfavorable life forecast with the formation of an elongated QT syndrome. With an unfavorable course, patients suffer from loss of consciousness, episodes of tachycardia. Often, stable polymorphic ventricular tachycardia develops. The risk of sudden cardiac death in this pathology can vary from 0.33% to 5%. In people who have suffered an episode of cardiac arrest, and do not have a permanent prescribed antiarrhythmic therapy, the mortality rate reaches 50% within 15 years. Preventive administration of antiarrhythmic drugs is not always effective. A positive result of treatment depends on the severity of long QT syndrome and its genotype. Beta-blockers are often prescribed to patients of different ages with various cardiac pathologies, including for the prevention of arrhythmia in long QT syndrome. Beta-blockers differ in various pharmacokinetic and pharmacodynamic parameters (lipophilicity/hydrophilicity, selectivity, presence/absence of internal sympathomimetic activity), which, along with the variant of the disease genotype, can affect their effectiveness and safety in the considered pathology. This review article presents the results of major studies on the safety and effectiveness of different groups of beta blockers in various variants of long QT syndrome. The preferred beta-blockers for various genotypes of the syndrome were determined, and a comparative characteristic of beta-blockers for their safety and preventive effectiveness was given.

Molecular Profiling of the Cardiac Conduction System: the Dawn of a New Era.

Recent technological advances have led to an increased ability to define the gene expression profile of the cardiac conduction system (CCS). Here, we review the most salient studies to emerge in recent years and discuss existing gaps in our knowledge as well as future areas of investigation. Molecular profiling of the CCS spans several decades. However, the advent of high-throughput sequencing strategies has allowed for the discovery of unique transcriptional programs of the many diverse CCS cell types. The CCS, a diverse structure with significant inter- and intra-component cellular heterogeneity, is essential to the normal function of the heart. Progress in transcriptomic profiling has improved the resolution and depth of characterization of these unique and clinically relevant CCS cell types. Future studies leveraging this big data will play a crucial role in improving our understanding of CCS development and function as well as translating these findings into tangible translational tools for the improved detection, prevention, and treatment of cardiac arrhythmias.

Histone deacetylase 2-dependent ventricular electrical remodeling in a porcine model of early heart failure

AimsHeart failure (HF) is linked to electrical remodeling that promotes ventricular arrhythmias. Underlying molecular signaling is insufficiently understood, in particular concerning patients with early disease stages. Previous observations suggest a key role for epigenetic mechanisms in cardiac remodeling processes. We hypothesized that histone deacetylases (HDACs) 1 and 2 contribute to cellular electrophysiological dysregulation in ventricular cardiomyocytes during HF development. Materials and methodsHDAC and ion channel expression was quantified in a porcine model of early HF induced by short-term atrial tachypacing, resulting in atrial fibrillation with rapid ventricular rate response. Anti-Hdac1 and anti-Hdac2 siRNA treatment was employed in neonatal murine cardiomyocytes (NMCM) to study effects of HDACs on ion channel mRNA expression and action potential duration (APD). Key findingsEarly HF was characterized by mild reduction of left ventricular ejection fraction, prolonged QTc intervals, and increased ventricular effective refractory periods. Delayed repolarization was linked to significant downregulation of HDAC2 in left ventricular (LV) tissue. In addition, there was a tendency towards reduced transcript expression of KCNJ2/Kir2.1 K+ channels. In NMCM, knock-down of Hdac2 recapitulated AP prolongation. Finally, siRNA-mediated suppression of Hdac2 reduced Kcnh2/Kv11.1 K+ channel expression. SignificanceSuppression of HDAC2 is linked to ventricular electrical remodeling of APD and ion channel expression in early stages of heart failure. This previously unrecognized mechanism may serve as basis for future approaches to prevention and treatment of ventricular arrhythmias.

Coronary vasospasm as an etiology of recurrent ventricular fibrillation in the absence of coronary artery disease: a case report

ABSTRACT Background: Vasospastic angina (VA), or Prinzmetal’s angina, is characterized by symptoms of coronary angina caused by coronary vasospasm, usually in the absence of atherosclerotic changes. It typically presents with chest pain, which can be accompanied by transient electrocardiographic changes, if visualized during the attack. It can also rarely present with severe manifestations of acute myocardial angina, ventricular fibrillation, or cardiac arrest. Case presentation:We present a case of a 50-year-old Caucasian male who initially presented to the hospital with chest pain and was diagnosed with VA. Later, he was brought to the hospital by emergency medical services later with ventricular fibrillation, despite normal coronary anatomy on angiogram. He was managed with placement of an intra–cardiac defibrillator (ICD) for secondary prevention. The patient continued to have recurrent episodes of ventricular fibrillation with associated ICD shocks, and had multiple admissions to the hospital with similar presentations. Symptoms and arrhythmia improved after optimizing antianginal therapy. Conclusions:Ventricular fibrillation can be an uncommon but severe manifestation during VA crises. In cases with normal coronary vasculature, it is important to recognize VA as a cause of recurrent ventricular fibrillation in order to optimize medical management for prevention of fatal arrhythmias.

Recognition, Prevention, and Management of Arrhythmias and Autonomic Disorders in Cardio-Oncology: A Scientific Statement From the American Heart Association.

With the advent of novel cancer therapeutics and improved screening, more patients are surviving a cancer diagnosis or living longer with advanced disease. Many of these treatments have associated cardiovascular toxicities that can manifest in both an acute and a delayed fashion. Arrhythmias are an increasingly identified complication with unique management challenges in the cancer population. The purpose of this scientific statement is to summarize the current state of knowledge regarding arrhythmia identification and treatment in patients with cancer. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. Despite increased recognition, dedicated prospective studies evaluating true incidence are lacking. Moreover, few studies have addressed appropriate prevention and treatment strategies. As such, this scientific statement serves to mobilize the cardio-oncology, electrophysiology, and oncology communities to develop clinical and scientific collaborations that will improve the care of patients with cancer who have arrhythmias.