The Role of Cardiac Macrophage and Cytokines on Ventricular Arrhythmias
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ABSTRACT:
SUBMITTER: Chen M
PROVIDER: S-EPMC7540080 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Cardiac sympathetic denervation (CSD) has been shown to reduce the burden of implantable cardioverter-defibrillator (ICD) shocks in small series of patients with structural heart disease (SHD) and recurrent ventricular tachyarrhythmias (VT). OBJECTIVES:This study assessed the value of CSD and the characteristics associated with outcomes in this population. METHODS:Patients with SHD who underwent CSD for refractory VT or VT storm at 5 international centers were analyzed by the International Cardiac Sympathetic Denervation Collaborative Group. Kaplan-Meier analysis was used to estimate freedom from ICD shock, heart transplantation, and death. Cox proportional hazards models were used to analyze variables associated with ICD shock recurrence and mortality after CSD. RESULTS:Between 2009 and 2016, 121 patients (age 55 ± 13 years, 26% female, mean ejection fraction of 30 ± 13%) underwent left or bilateral CSD. One-year freedom from sustained VT/ICD shock and ICD shock, transplant, and death were 58% and 50%, respectively. CSD reduced the burden of ICD shocks from a mean of 18 ± 30 (median 10) in the year before study entry to 2.0 ± 4.3 (median 0) at a median follow-up of 1.1 years (p < 0.01). On multivariable analysis, pre-procedure New York Heart Association functional class III and IV heart failure and longer VT cycle lengths were associated with recurrent ICD shocks, whereas advanced New York Heart Association functional class, longer VT cycle lengths, and a left-sided-only procedure predicted the combined endpoint of sustained VT/ICD shock recurrence, death, and transplantation. Of the 120 patients taking antiarrhythmic medications before CSD, 39 (32%) no longer required them at follow-up. CONCLUSIONS:CSD decreased sustained VT and ICD shock recurrence in patients with refractory VT. Characteristics independently associated with recurrence and mortality were advanced heart failure, VT cycle length, and a left-sided-only procedure.
| S-EPMC6330109 | biostudies-literature
Project description:Inflammatory activation is increasingly recognized as a nonconventional risk factor for arrhythmias, and experimental studies provided robust evidence that this association is mediated by direct arrhythmogenic effects of proinflammatory cytokines on cardiac cells. Additionally, inflammatory cytokines can favor arrhythmias indirectly through multiple systemic effects. Accumulating data confirm the clinical relevance of these mechanisms; the largest evidence being available for atrial fibrillation, acquired long-QT syndrome, and ventricular arrhythmias. However, clinical management of arrhythmias largely neglects inflammatory cytokines. This review integrates basic science and clinical research to present an updated overview of the topic and provides future directions for patient's management.
| S-EPMC10322731 | biostudies-literature
Project description:The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. Catheter ablation, a minimally invasive procedure deactivating abnormal firing cardiac tissue, is increasingly becoming the therapy of choice for atrial fibrillation. This is inevitably associated with the obliteration of cardiac cholinergic neurons. However, the impact on ventricular electrophysiology is unclear. Here we show that cardiac cholinergic neurons modulate ventricular electrophysiology. Mechanical disruption or pharmacological blockade of parasympathetic innervation shortens ventricular refractory periods, increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in murine hearts. Immunohistochemistry confirmed ventricular cholinergic innervation, revealing parasympathetic fibres running from the atria to the ventricles parallel to sympathetic fibres. In humans, catheter ablation of atrial fibrillation, which is accompanied by accidental parasympathetic and concomitant sympathetic denervation, raises the burden of premature ventricular complexes. In summary, our results demonstrate an influence of cardiac cholinergic neurons on the regulation of ventricular function and arrhythmogenesis.
| S-EPMC5290156 | biostudies-literature
Project description:Background: Current stress cardiomyopathy (SCM) has a high incidence in older adults, and the theories revolve mostly around "catecholamine myocardial toxicity" and "sympathetic hyperactivation". However, the role of the central nervous system (CNS) in the pathogenesis of stress cardiomyopathy remains unknown. Methods: We investigated the role of microglia activation in the paraventricular hypothalamic nucleus (PVN) in the development of SCM. To create a SCM model, male Sprague-Dawley (SD) rats were immobilized for 6 hours every day for a week. Electrocardiogram, cardiac electrophysiology, and echocardiography were measured to verify the changes in cardiac structure and function in rats with stress cardiomyopathy. RNA sequencing was measured to explore the changes in the hypothalamus of stress cardiomyopathy. In addition, brain and heart tissues were extracted to detect microglial activation and sympathetic activity. Results: (1) Immobilization stress successfully induced SCM in SD rats. (2) Microglia were significantly activated in the hypothalamus, as evidenced by cytosol thickened and an increased in the number of branches and specifically enriched at PVN. (3) In SCM, microglia in the PVN increased central and peripheral cardiac sympathetic activity by increasing the expression of neuroinflammatory factors. (4) It is possible that inhibiting microglia activation could suppress central and heart sympathetic activity and increase the cardiac electrical stability in SCM rats. Conclusions: Immobilization stress induced SCM in SD rats can activate hypothalamic microglia, and the activated microglia are specifically enriched at PVN, which can increase the central and peripheral sympathetic nerve activity by regulating the expression of neuro-inflammatory factor, mediate left heart dysfunction and increase the susceptibility to ventricular fibrillation.
2024-04-01 | GSE261833 | GEO
Project description:Ventricular tachycardia (VT) and VF account for the majority of sudden cardiac deaths worldwide. Treatments for VT/VF include anti-arrhythmic drugs, ICDs and catheter ablation, but these treatments vary in effectiveness and carry substantial risks and/or expense. Current methods of selecting patients for ICD implantation are imprecise and fail to identify some at-risk patients, while leading to others being overtreated. In this article, the authors discuss the current role and future direction of cardiac MRI (CMRI) in refining diagnosis and personalising ventricular arrhythmia management. The capability of CMRI with gadolinium contrast delayed-enhancement patterns and, more recently, T1 mapping to determine the aetiology of patients presenting with heart failure is well established. Although CMRI imaging in patients with ICDs can be challenging, recent technical developments have started to overcome this. CMRI can contribute to risk stratification, with precise and reproducible assessment of ejection fraction, quantification of scar and 'border zone' volumes, and other indices. Detailed tissue characterisation has begun to enable creation of personalised computer models to predict an individual patient's arrhythmia risk. When patients require VT ablation, a substrate-based approach is frequently employed as haemodynamic instability may limit electrophysiological activation mapping. Beyond accurate localisation of substrate, CMRI could be used to predict the location of re-entrant circuits within the scar to guide ablation.
| S-EPMC6702467 | biostudies-literature
Project description:Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1β in DM mice. IL-1β causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity. IL-1β-induced spontaneous contractile events are associated with CaMKII oxidation and phosphorylation. We further show that DM-induced arrhythmias can be successfully treated by inhibiting the IL-1β axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1β as an inflammatory connection between metabolic dysfunction and arrhythmias in DM.
| S-EPMC5123037 | biostudies-literature
Project description:Purpose of reviewTo discuss the role of catheter ablation in treating life-threatening ventricular arrhythmias associated with Brugada syndrome (BrS), by presenting recent findings of BrS arrhythmogenic substrate, mechanisms underlying ventricular arrhythmias, and how they can be treated with catheter ablation.Recent findingsAlmost three decades ago when the clinical entity of Brugada syndrome (BrS) was described in patients who had abnormal coved-type ST elevation in the right precordial EKG leads in patients who had no apparent structural heart disease but died suddenly from ventricular fibrillation. Since its description, the syndrome has galvanized explosive research in this field over the past decades, driving major progress toward better understanding of BrS, gaining knowledge of the genetic pathophysiology and risk stratification of BrS, and creating significant advances in therapeutic modalities. One of such advances is the ability for electrophysiologists to map and identify the arrhythmogenic substrate sites of BrS, which serve as good target sites for catheter ablation. Subsequently, several studies have shown that catheter ablation of these substrates normalizes the Brugada ECG pattern and is very effective in eliminating these substrates and preventing recurrent VF episodes. Catheter ablation has become an important addition for treatment of symptomatic BrS patients with recurrent VT/VF episodes.
| S-EPMC8068636 | biostudies-literature
Project description:BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe inherited cardiac disorder caused by mutations predominantly in the ryanodine receptor (RyR2) gene. We sought to identify mutations in genes affecting cardiac calcium cycling in patients with CPVT and in less typical familial exercise-related ventricular arrhythmias. METHODS AND RESULTS: We recruited 33 consecutive patients with frequent ventricular premature complexes (VPCs) without structural heart disease and often history of syncope or sudden death in family. Sixteen of the patients featured a phenotype typical of CPVT. In 17 patients, VPCs emerged also at rest. Exercise stress test and echocardiography were performed to each patient and 232 family members. Familial background was evident in 42% of cases (n = 14). We sequenced all the coding exons of the RyR2, FKBP1B, ATP2A2 and SLC8A1 genes from the index patients. Single channel recordings of a mutant RyR2 were performed in planar lipid bilayers. Two novel RyR2 missense mutations (R1051P and S616L) and two RyR2 exon 3 deletions were identified, explaining 25% of the CPVT phenotypes. A rare variant (N3308S) with open probabilities similar to the wild type channels in vitro, was evident in a patient with resting VPCs. No disease-causing variants were detectable in the FKBP1B, ATP2A2 or SLC8A1 genes. CONCLUSION: We report two novel CPVT-causing RyR2 mutations and a novel RyR2 variant of uncertain clinical significance in a patient with abundant resting VPCs. Our data also strengthen the previous assumption that exon 3 deletions of RyR2 should screened for in CPVT and related phenotypes.
| S-EPMC2667497 | biostudies-literature
Project description:BackgroundBilateral cardiac sympathetic denervation (BCSD) is an effective therapy for ventricular arrhythmias (VAs) in cardiomyopathies (CMPs). After BCSD, residual autonomic nervous system (ANS) function is unknown.ObjectiveThe purpose of this study was to assess ANS responses in patients with CMP before and after BCSD as compared with demographically matched healthy controls.MethodsPatients with CMP undergoing BCSD and matched healthy controls were recruited. Noninvasive measures-finger cuff beat-to-beat blood pressure (BP), electrocardiography, palmar electrodermal activity (EDA), and finger pulse volume (FPV)-were obtained at rest and during autonomic stressors-posture change, handgrip, and mental stress. Maximal as well as specific responses to stressors were compared.ResultsEighteen patients with CMP (mean age 54 ± 14 years; 16 men, 89%; left ventricular ejection fraction 36% ± 14%) with refractory VAs and 8 matched healthy controls were studied; 9 patients with CMP underwent testing before and after (median 28 days) BCSD, with comparable ongoing medication. Before BCSD, patients with CMP (n = 13) had lower resting systolic BP and FPV than did healthy controls (P < .01). Maximal FPV and systolic BP reflex responses, expressed as percent change were similar, while diastolic BP, mean BP, and EDA responses were blunted. After BCSD, resting measurements were unchanged relative to presurgical baseline (n = 9). EDA responses to stressors were abolished, confirming BCSD, while maximal FPV and BP responses were preserved. Diastolic BP, mean BP, and FPV responses to orthostatic challenge pointed toward a better tolerance of active standing after BCSD as compared with before. Responses to other stressors remained unchanged.ConclusionPatients with CMP and refractory VAs on optimal medical therapy have detectable but blunted adrenergic responses, which are not disrupted by BCSD.
| S-EPMC7395890 | biostudies-literature
Project description:We investigated the effects of intermittent hypoxia (IH), such as that encountered in severe obstructive sleep apnea (OSA) patients, on the development and severity of myocardial ischemia-related ventricular arrhythmias. Rats were exposed to 14 days of IH (30?s at 5%O2 and 30?s at 21%O2, 8?h·day-1) or normoxia (N, similar air-air cycles) and submitted to a 30-min coronary ligature. Arterial blood pressure (BP) and ECG were recorded for power spectral analysis, ECG interval measurement and arrhythmia quantification. Left ventricular monophasic action potential duration (APD) and expression of L-type calcium (LTCC) and transient receptor potential (TRPC) channels were assessed in adjacent epicardial and endocardial sites. Chronic IH enhanced the incidence of ischemic arrhythmias, in particular ventricular fibrillation (66.7% vs. 33.3% in N rats, p?<?0.05). IH also increased BP and plasma norepinephine levels along with increased low-frequency (LF), decreased high-frequency (HF) and increased LF/HF ratio of heart rate and BP variability. IH prolonged QTc and Tpeak-to-Tend intervals, increased the ventricular APD gradient and upregulated endocardial but not epicardial LTCC, TRPC1 and TRPC6 (p?<?0.05). Chronic IH, is a major risk factor for sudden cardiac death upon myocardial ischemia through sympathoactivation and alterations in ventricular repolarization, transmural APD gradient and endocardial calcium channel expression.
| S-EPMC5813022 | biostudies-literature