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Patients with acute MI and an ejection fraction of 35% or less were randomly assigned to receive a wearable cardioverter–defibrillator plus medical therapy or medical therapy alone. At 90 days, there was no significant between-group difference in the rate of arrhythmic death.

Cardiac sympathetic overactivation is involved in arrhythmogenesis in patients with chronic heart failure (CHF). Inflammatory infiltration in the stellate ganglion (SG) is a critical factor for cardiac sympathoexcitation in patients with ventricular arrhythmias. This study aims to investigate if macrophage depletion in SGs decreases cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. Surgical ligation of the coronary artery was used for induction of CHF. Clodronate liposomes were microinjected into bilateral SGs of CHF rats for macrophage depletion. Using cytokine array, immunofluorescence staining, and Western blot analysis, we found that macrophage expansion and expression of TNFα and IL-1β in SGs were markedly increased in CHF rats. Flow cytometry data confirmed that the percentage of macrophages in SGs was higher in CHF rats than that in sham rats. Clodronate liposomes significantly reduced CHF-elevated proinflammatory cytokine levels and macrophage expansion in SGs. Clodronate liposomes also reduced CHF-increased N-type Ca2+ currents and excitability of cardiac sympathetic postganglionic neurons and inhibited CHF-enhanced cardiac sympathetic nerve activity. ECG data from 24-h, continuous telemetry recording in conscious rats demonstrated that clodronate liposomes not only restored CHF-induced heterogeneity of ventricular electrical activities, but also decreased the incidence and duration of ventricular tachycardia/fibrillation in CHF. Macrophage depletion with clodronate liposomes attenuated CHF-induced cardiac sympathetic overactivation and ventricular arrhythmias through reduction of macrophage expansion and neuroinflammation in SGs.

Ventricular tachycardia (VT) is a potentially fatal tachyarrhythmia, which causes a rapid heartbeat as a result of improper electrical activity of the heart. This is a potentially life-threatening arrhythmia because it can cause low blood pressure and may lead to ventricular fibrillation, asystole, and sudden cardiac death. To prevent VT, we developed an early prediction model that can predict this event one hour before its onset using an artificial neural network (ANN) generated using 14 parameters obtained from heart rate variability (HRV) and respiratory rate variability (RRV) analysis. De-identified raw data from the monitors of patients admitted to the cardiovascular intensive care unit at Asan Medical Center between September 2013 and April 2015 were collected. The dataset consisted of 52 recordings obtained one hour prior to VT events and 52 control recordings. Two-thirds of the extracted parameters were used to train the ANN, and the remaining third was used to evaluate performance of the learned ANN. The developed VT prediction model proved its performance by achieving a sensitivity of 0.88, specificity of 0.82, and AUC of 0.93.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome that is often difficult to treat. Hiroshi Watanabe and coworkers now show that flecainide, an approved drug known to inhibit sodium channels, is able to target the underlying cause of CPVT by inhibiting calcium release through the ryanodine receptor. Flecainide prevented arrhythmia in a mouse model of CPVT and was also effective when tested in two individuals with CPVT. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited arrhythmia syndrome in which drug therapy is often ineffective. We discovered that flecainide prevents arrhythmias in a mouse model of CPVT by inhibiting cardiac ryanodine receptor–mediated Ca 2+ release and thereby directly targeting the underlying molecular defect. Flecainide completely prevented CPVT in two human subjects who had remained highly symptomatic on conventional drug therapy, indicating that this currently available drug is a promising mechanism-based therapy for CPVT.

Background Ventricular tachyarrhythmia (VTA) in ischemic cardiomyopathy (ICM) is a life‐threatening condition influenced by genetic factors and electrical remodeling. This study investigated the association between KCNQ1 gene polymorphisms (rs2237892 and rs2237895) and the development of VTA in ICM patients to improve risk stratification and guide device implantation decisions. Methods This single‐center study included 213 ICM patients with implantable cardioverter‐defibrillators (ICD) for primary prevention of VTA. Patients were divided into arrhythmia and control groups based on device interrogation findings. Genetic analysis for rs2237892 and rs2237895 polymorphisms was performed using real‐time polymerase chain reaction (PCR). Clinical, electrocardiographic, and laboratory parameters were analyzed. Correlation and logistic regression analyses evaluated the association between KCNQ1 polymorphisms and VTA risk. Results The arrhythmia group demonstrated significantly higher QT dispersion, frontal QRS‐T angle, and T‐wave peak‐to‐end interval compared to the control group. The TT genotype of rs2237892 and the AC genotype of rs2237895 were significantly associated with increased VTA risk (p < 0.001). Multivariate analysis confirmed these genotypes as independent predictors of VTA. No significant differences in other clinical or laboratory risk factors were observed. Conclusions KCNQ1 gene polymorphisms (rs2237892 and rs2237895) are strongly associated with VTA in ICM patients, suggesting a potential role as biomarkers for risk stratification. These findings may assist in tailoring ICD implantation decisions and improving patient outcomes. Potassium Channels and Ventricular Arrhythmia Risk. Altered potassium channel function modifies cardiac repolarization: gain‐of‐function shortens, loss‐of‐function prolongs the QT interval. Both increase susceptibility to ventricular tachyarrhythmias, especially with myocardial scarring. Shown: action potential phases, ionic currents, and key channel contributions.

In the Sudden Cardiac Death in Heart Failure Trial, 811 patients were randomly assigned to receive implantable cardioverter–defibrillators (ICDs). Of these patients, 269 (33.2%) received at least one ICD shock over a median follow-up period of 45.5 months. The occurrence of ICD shocks, whether appropriate or inappropriate, was associated with a significant increase in the subsequent risk of death from all causes. The occurrence of ICD shocks, whether appropriate or inappropriate, was associated with a significant increase in the subsequent risk of death from all causes. The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) (ClinicalTrials.gov number, NCT00000609) and the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) both showed that therapy with implantable cardioverter–defibrillators (ICDs) improves survival among patients who are at risk for sudden cardiac death but who have not previously had a sustained ventricular arrhythmia. 1 – 3 On the basis of these data, recent clinical guidelines consider the implantation of an ICD for “primary prevention” (i.e., prevention of a first life-threatening arrhythmic event) to be standard high-quality care for patients who meet the entry criteria for these trials. 4 One result of this broader use . . .

Purpose of ReviewThe purpose of this review is to summarize the epidemiology, mechanisms, and management of cardiovascular complications of Bruton’s Tyrosine Kinase inhibitors (BTKIs).Recent FindingsIbrutinib increases the risk of atrial fibrillation, bleeding, and hypertension compared with non-BTKI therapies. The evidence to support an association between ibrutinib and other cardiovascular complications including ventricular tachyarrhythmias or cardiomyopathy is limited. Ibrutinib metabolism can be inhibited by some medications used to treat cardiovascular complications. The cardiovascular effects of more selective BTKIs, such as acalabrutinib, remain to be determined.SummaryFuture research should address the mechanisms underlying the cardiovascular complications of BTKIs and how best to manage them. The risks and benefits of more selective BTKIs as compared with ibrutinib require further evaluation.

The arrhythmogenic effects of endothelin-1 (ET-1) are mediated via ETA-receptors, but the role of ETB-receptors is unclear. We examined the pathophysiologic role of ETB-receptors on ventricular tachyarrhythmias (VT/VF) during myocardial infarction (MI). MI was induced by coronary ligation in two animal groups, namely in wild-type ( n  = 63) and in ETB-receptor-deficient ( n  = 61) rats. Using a telemetry recorder, VT/VF episodes were evaluated during phase I (the 1st hour) and phase II (2–24 h) post-MI, with and without prior β-blockade. Action potential duration at 90% repolarization (APD90) was measured from monophasic epicardial recordings and indices of sympathetic activation were assessed using fast-Fourier analysis of heart rate variability. Serum epinephrine and norepinephrine were measured with radioimmunoassay. MI size was similar in the two groups. There was a marked temporal variation in VT/VF duration; during phase I, it was higher ( p  = 0.0087) in ETB-deficient (1,519 ± 421 s) than in wild-type (190 ± 34 s) rats, but tended ( p  = 0.086) to be lower in ETB-deficient (4.2 ± 2.0 s) than in wild-type (27.7 ± 8.0 s) rats during phase II. Overall, the severity of VT/VF was greater in ETB-deficient rats, evidenced by higher ( p  = 0.0058) mortality (72.0% vs. 32.1%). There was a temporal variation in heart rate and in the ratio of low- to high-frequency spectra, being higher (<0.001) during phase I, but lower ( p  < 0.05) during phase II in ETB-deficient rats. Likewise, 1 h post-MI, serum epinephrine ( p  = 0.025) and norepinephrine ( p  < 0.0001) were higher in ETB-deficient (4.20 ± 0.54, 14.24 ± 1.39 ng/ml) than in wild-type (2.30 ± 0.59, 5.26 ± 0.67 ng/ml) rats, respectively. After β-blockade, VT/VF episodes and mortality were similar in the two groups. The ETB-receptor decreases sympathetic activation and arrhythmogenesis during the early phase of MI, but these effects diminish during evolving MI.

Ventricular arrhythmia is the most common cause of sudden cardiac death in patients with myocardial infarction (MI). Fibroblast growth factor 21 (FGF21) has been shown to play an important role in cardiovascular and metabolic diseases. However, the effects of FGF21 on ventricular arrhythmias following MI have not been addressed yet. The present study was conducted to investigate the pharmacological action of FGF21 on ventricular arrhythmias after MI. Adult male mice were administrated with or without recombinant human basic FGF21 (rhbFGF21), and the susceptibility to arrhythmias was assessed by programmed electrical stimulation and optical mapping techniques. Here, we found that rhbFGF21 administration reduced the occurrence of ventricular tachycardia (VT), improved epicardial conduction velocity and shorted action potential duration at 90% (APD90) in infarcted mouse hearts. Mechanistically, FGF21 may improve cardiac electrophysiological remodeling as characterized by the decrease of INa and IK1 current density in border zone of infarcted mouse hearts. Consistently, in vitro study also demonstrated that FGF21 may rescue oxidant stress-induced dysfunction of INa and IK1 currents in cultured ventricular myocytes. We further found that oxidant stress-induced down-regulation of early growth response protein 1 (EGR1) contributed to INa and IK1 reduction in post-infarcted hearts, and FGF21 may recruit EGR1 into the SCN5A and KCNJ2 promoter regions to up-regulate NaV1.5 and Kir2.1 expression at transcriptional level. Moreover, miR-143 was identified as upstream of EGR1 and mediated FGF21-induced EGR1 up-regulation in cardiomyocytes. Collectively, rhbFGF21 administration effectively suppressed ventricular arrhythmias in post-infarcted hearts by regulating miR-143-EGR1-NaV1.5/Kir2.1 axis, which provides novel therapeutic strategies for ischemic arrhythmias in clinics.

Dexmedetomidine (DEX) is commonly used in clinical practice because of its sedative, analgesic, antisympathetic, hemodynamic stabilization and antianxiety effects. Previous clinical studies have demonstrated that DEX plays a role in both the prevention and treatment of perioperative arrhythmias. However, the precise mechanisms underlying the effects of DEX remain unclear. Furthermore, few studies have examined the effect of DEX on cardiac electrophysiology. ECG recording was performed in vivo and ex vivo on C57 mice. Simultaneous recording of membrane voltage (Vm) and [Ca 2+ ]i changes was achieved with dual-dye optical mapping, in which voltage- and Ca 2+ -sensitive dyes are employed. Simultaneous programmed electrical stimulation was used to pacing and induce arrhythmias. Simulating catecholamine-induced arrhythmias with isoprotereno (ISO) and preconditioning with DEX to investigate the antiarrhythmic effects of DEX. Our findings demonstrated that ISO increased the incidence of ventricular tachycardia or ventricular fibrillation in mice during rapid pacing stimulation. DEX preconditioning reduced the incidence of ISO-induced ventricular arrhythmias. Optical mapping with simultaneous recordings of dual dyes ( Vm dye and intracellular Ca 2+ dye) revealed that DEX pretreatment attenuated the ISO-induced shortening of action potential duration (APD), calcium transient duration (CaTD), and time-to-peak (TTP) of calcium transients, as well as the ISO-induced increase in repolarization heterogeneity. DEX also slowed the conduction velocity. More importantly, DEX preconditioning significantly reduced the calcium transient alternans ratio at 80-ms, 70-ms, and 60-ms pacing cycles. These findings suggest that DEX preconditioning can reduce the incidence of ventricular arrhythmias induced by acute stress simulated by ISO. Prolongation of action potential duration and calcium transient duration and the maintenance of intracellular calcium homeostasis may be the electrophysiological mechanisms involved.