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OBJECTIVE To describe associations between cardiac abnormalities and Trypanosoma cruzi serostatus by use of a simplified diagnostic evaluation in dogs at risk for Tcruzi infection. METHODS A prospective, cross-sectional study was performed using a simplified diagnostic evaluation including high-sensitivity cardiac troponin I, 30-second ECG, and echocardiogram with 7 variables in 46 client-owned dogs from high-risk environments. Dogs were categorized as serologically positive (SP), negative (SN), or discordant (SD) by use of 2 antibody tests. Functional evaluation of cardiac health scores and blood PCR were obtained. RESULTS Dogs were SP (n = 19), SN (17), and SD (10), with 9 PCR positive (7 SP, 1 SN, 1 SD). Troponin was above reference range in 6 of 46 (4 SP, 1 SN, 1 SD), and functional evaluation of cardiac health scores were 0 in all dogs. Conduction system abnormalities (prolonged interval durations, second-degree atrioventricular block, splintered QRS complex) and ventricular arrhythmias were documented in 8 (7 SP, 0 SN, 1 SD). Twenty-six (12 SP, 8 SN, 6 SD) had echocardiographic abnormalities, most often myxomatous mitral valve disease (MMVD) and left ventricular enlargement. Seropositive dogs were significantly older and had a higher likelihood of MMVD. Conduction system abnormalities were associated with positive serostatus. CONCLUSIONS Echocardiographic abnormalities were complicated by MMVD and did not distinguish between serostatus. An ECG with assessment and detailed measurement of complexes and cardiac troponin I are simple tests to perform with abnormalities detected in seroreactive dogs. CLINICAL RELEVANCE Electrocardiographic abnormalities in high-risk or seroreactive dogs should prompt further evaluation and monitoring of T cruzi infection. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to lower the risk of re-hospitalization and cardiovascular mortality among heart failure (HF) patients. Nevertheless, the impact of these agents on ventricular arrhythmias (VAs) has not been thoroughly investigated. To assess the beneficial impact of SGLT2 inhibitors on VAs in patients at various stages of HF, a systematic review and meta-analysis of randomized controlled trials involving SGLT2 inhibitors in this patient population was performed. Methods: A comprehensive search of the PubMed, Embase, Ovid, ProQuest, Scopus, and Cochrane databases was performed for clinical trials published up to November 21, 2024. The primary outcomes of interest were incidences of VAs and sudden cardiac death (SCD) between the groups receiving SGLT2 inhibitors and the control drugs. For the outcomes observed in the populations of the included trials and in specific subgroups, hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled and meta-analysed across the analyses. Results: A total of 23 randomized trials (22 placebo-controlled trials and 1 active-controlled trial) involving 74,380 patients (37,372 receiving SGLT2 inhibitors and 37,008 in the control group) were included. The analysed SGLT2 inhibitors included canagliflozin, dapagliflozin, empagliflozin, bexagliflozin, sotagliflozin, and ertugliflozin. The participants were non-advanced HF patients, including at-risk for HF, pre-HF, and symptomatic HF, with follow-up duration ranging from 12 to 296 weeks. Compared with the control, treatment with SGLT2 inhibitors was associated with significantly reduced risk of VAs (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.74–0.98; P = 0.02) and SCD (RR 0.79, 95% CI 0.64–0.98; P = 0.03). Subgroup analyses indicated that longer follow-up (≥ 1 year) taking SGLT2 inhibitors can still reduce the risk of VAs (RR 0.79, 95% CI 0.65–0.96; P = 0.02) and SCD (RR 0.80, 95% CI 0.65–0.99; P = 0.04). Conclusion: SGLT2 inhibitors have beneficial effects on lowering risks of VAs and SCD in patients with type 2 diabetes, cardiovascular diseases, heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and heart failure with mildly reduced ejection fraction (HFmrEF), with longer follow-up duration reinforcing these findings. However, future prospective trials are needed to verify the effects of SGLT2 inhibitors on VAs and SCD. Systematic review registration: PROSPERO (CRD42024601914) Highlights: 1. Redefine outcomes of ventricular arrhythmias (VAs) and sudden cardiac death (SCD) for SGLT2 inhibitor medication in heart failure patients. 2. SGLT2 inhibitors lower the risks of VAs and SCD in patients at various stages of HF, excluding advanced HF. 3. Longer therapeutic effects were associated with a significant reduction in the incidence of VAs and SCD. [ABSTRACT FROM AUTHOR]

Obesity is a significant risk factor for cardiac arrhythmias, and the ferroptosis is closely related to cardiac arrhythmias. This study aimed to investigate whether puerarin (Pue), a natural isoflavone, could reduce the susceptibility to ventricular arrhythmias (VAs) associated with obesity and inhibit ferroptosis, with a particular focus on the Sirt1/Nrf2 signaling pathway. Male rats were randomly divided into three groups: normal chow diet (NC), high-fat diet (HFD), and HFD with Pue treatment (100mg/kg, HFD + Pue). After 16 weeks, electrophysiological, structural, and molecular analysis were performed. Compared to the NC group, HFD rats exhibited prolonged QT interval and Tpeak-Tend interval, amplified transmural dispersion of ventricular repolarization, and increased susceptibility to VAs. Pue treatment significantly ameliorated these electrophysiological abnormalities and reduced VAs susceptibility. HFD rats showed cardiac hypertrophy, fibrosis, and inflammation, which were alleviated by Pue application. Cardiac lipid peroxidation, iron deposition, mitochondrial abnormality, and ferroptosis marker induction were observed in HFD rats. Further, treatment with Pue improved these alterations. Additionally, molecular docking analysis confirmed the interaction of Pue with Sirt1 and Nrf2. Furthermore, Pue treatment upregulated Sirt1 and Nrf2 expression in HFD rats, thereby reducing reactive oxygen species (ROS) generation and ferroptosis. Moreover, Pue protected cardiomyocytes against palmitic acid (PA)-induced injury by inhibiting ferroptosis via the Sirt1/Nrf2 pathway in H9c2 cells. Overall, our study shows for the first time that Pue reduces susceptibility to VAs and inhibits ferroptosis in HFD rats by modulating the Sirt1/Nrf2 signaling pathway, offering a potential therapeutic strategy for obesity-related cardiac arrhythmias. [Display omitted] • Pue reduces the susceptibility to ventricular arrhythmias in HFD rats. • To emphasize the role of ferroptosis in obesity-associated cardiac arrhythmias. • Pue inhibits ferroptosis by targeting Sirt1/Nrf2 signaling in the hearts of HFD rats. [ABSTRACT FROM AUTHOR]

Objectives: Hemodynamic gain index (HGI), a novel hemodynamic index obtained from cardiopulmonary exercise testing (CPX), is associated with adverse cardiovascular outcomes. However, its specific relationship with ventricular arrhythmias (VAs) is unknown. We aimed to assess the association of HGI with risk of VAs in a prospective study. Design: Hemodynamic gain index was estimated using heart rate and systolic blood pressure (SBP) responses ascertained in 1945 men aged 42–61 years during CPX from rest to maximum exercise, using the formula: [(Heart ratemax x SBPmax) – (Heart raterest x SBPrest)]/(Heart raterest x SBPrest). Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for VAs. Results: Over a median follow-up duration of 28.2 years, 75 cases of VA were recorded. In analysis adjusted for established risk factors, a unit (bpm/mmHg) higher HGI was associated with a decreased risk of VA (HR 0.72, 95% CI: 0.55–0.95). The results remained consistent on adjustment for lifestyle factors and comorbidities (HR 0.72, 95% CI: 0.55–0.93). Comparing the top versus bottom tertiles of HGI, the corresponding adjusted HRs (95% CIs) were 0.51 (0.27–0.96) and 0.52 (0.28–0.94), respectively. The associations were attenuated on addition of CRF to the model. HGI improved risk discrimination beyond established risk factors but not CRF. Conclusions: Higher HGI is associated with a reduced risk of VAs in middle-aged and older Caucasian men, but dependent on CRF levels. Furthermore, HGI improves the prediction of the long-term risk for VAs beyond established risk factors but not CRF. [ABSTRACT FROM AUTHOR]

Ventricular arrhythmias (VA) can be life‐threatening arrhythmias that result in significant morbidity and mortality. Catheter ablation (CA) is an invasive treatment modality that can be effective in the treatment of VA where medications fail. Recurrence occurs commonly following CA due to an inability to deliver lesions of adequate depth to cauterise the electrical circuits that drive VA or reach areas of scar responsible for VA. Stereotactic body radiotherapy is a non‐invasive treatment modality that allows volumetric delivery of energy to treat circuits that cannot be reached by CA. It overcomes the weaknesses of CA and has been successfully utilised in small clinical trials to treat refractory VA. This article summarises the current evidence for this novel treatment modality and the steps that will be required to bring it to the forefront of VA treatment. [ABSTRACT FROM AUTHOR]

Aims Methods Conclusion Timely referrals for transplantation and left ventricular assist device (LVAD) play a key role in favourable outcomes in patients with advanced heart failure (HF). Cardiovascular mortality, driven by sudden cardiac death, is the main reason for dying while waiting for heart transplantation (HTx). The purpose of the Preventive Catheter Ablation for ventricular arrhythmiaS in patients with end‐sTage heart faiLure rEferred for heart transplantation eValuaTion (CASTLE‐VT) trial is to test the hypothesis that prophylactic catheter ablation of arrhythmogenic ventricular scar tissue will reduce mortality, need for LVAD implantation, and urgent HTx in patients with end‐stage HF related to ischaemic cardiomyopathy (ICM).CASTLE‐VT is a randomized evaluation of prophylactic ablative treatment of arrhythmogenic ventricular scar in patients referred for HTx evaluation and diagnosed with ICM. Ablation will be performed with the use of a substrate‐based approach in which the myocardial scar is mapped and ablated while the heart remains predominantly in sinus rhythm. The primary endpoint is the composite of all‐cause mortality, worsening of HF requiring prioritized transplantation or LVAD implantation. The main secondary study endpoints are all‐cause mortality, cardiovascular mortality, incidence of implantable cardioverter‐defibrillator (ICD) therapy, hospitalizations, quality of life, time to first ICD therapy, number of device‐detected ventricular tachycardia/ventricular fibrillation episodes, left ventricular function, and exercise tolerance. CASTLE‐VT will randomize 160 patients with a follow‐up period of 2 years.CASTLE‐VT will determine whether prophylactic catheter ablation of arrhythmogenic ventricular scar tissue reduces mortality in patients with end‐stage HF who are referred for HTx evaluation. [ABSTRACT FROM AUTHOR]

Objectives: To perform a systematic review and meta-analysis of studies investigating the diagnostic value of cardiac magnetic resonance (CMR) features for arrhythmic risk stratification in mitral valve prolapse (MVP) patients. Materials and methods: EMBASE, PubMed/MEDLINE, and CENTRAL were searched for studies reporting MVP patients who underwent CMR with assessment of: left ventricular (LV) size and function, mitral regurgitation (MR), prolapse distance, mitral annular disjunction (MAD), curling, late gadolinium enhancement (LGE), and T1 mapping, and reported the association with arrhythmia. The primary endpoint was complex ventricular arrhythmias (co-VAs) as defined by any non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation, or aborted sudden cardiac death. Meta-analysis was performed when at least three studies investigated a CMR feature. PROSPERO registration number: CRD42023374185. Results: The meta-analysis included 11 studies with 1278 patients. MR severity, leaflet length/thickness, curling, MAD distance, and mapping techniques were not meta-analyzed as reported in < 3 studies. LV end-diastolic volume index, LV ejection fraction, and prolapse distance showed small non-significant effect sizes. LGE showed a strong and significant association with co-VA with a LogORs of 2.12 (95% confidence interval (CI): [1.00, 3.23]), for MAD the log odds-ratio was 0.95 (95% CI: [0.30, 1.60]). The predictive accuracy of LGE was substantial, with a hierarchical summary ROC AUC of 0.83 (95% CI: [0.69, 0.91]) and sensitivity and specificity rates of 0.70 (95% CI: [0.41, 0.89]) and 0.80 (95% CI: [0.67, 0.89]), respectively. Conclusions: Our study highlights the role of LGE as the key CMR feature for arrhythmia risk stratification in MVP patients. MAD might complement arrhythmic risk stratification. Clinical relevance statement: LGE is a key factor for arrhythmogenic risk in MVP patients, with additional contribution from MAD. Combining MRI findings with clinical characteristics is critical for evaluating and accurately stratifying arrhythmogenic risk in MVP patients. Key Points: MVP affects 2–3% of the population, with some facing increased risk for arrhythmia. LGE can assess arrhythmia risk, and MAD may further stratify patients. CMR is critical for MVP arrhythmia risk stratification, making it essential in a comprehensive evaluation. [ABSTRACT FROM AUTHOR]

Background: The association between the triglyceride-glucose (TyG) index and ventricular arrhythmias (VAs) is unclear. This study aimed to investigate the relationship between the TyG index, VAs, and major cardiovascular events in patients at high risk of sudden cardiac death (SCD). Methods: We enrolled 1046 patients at high risk of SCD with an indication for implantable cardioverter-defibrillator (ICD) implantation at the Chinese National Center for Cardiovascular Diseases. The primary outcome was VAs, defined as sustained ventricular tachycardia and ventricular fibrillation documented by the ICD. The secondary outcomes were cardiac mortality, heart transplantation, and rehospitalization for heart failure. Results: The mean (± SD) age was 59.6 ± 14.0 years old, and 25.7% were female. During the mean follow-up of 36.1 months, 342 (32.7%) patients had VAs, and 185 (17.7%) patients had major cardiovascular events. The mean fasting glucose and triglyceride levels were 111.9 ± 42.7 mg/dL and 140.0 ± 95.4 mg/L, respectively, with a TyG index range of 6.96–11.8. In the Fine-Gray subdistribution hazard model analysis, an increase in the TyG index was associated with a significant increase in the VAs (per 1 TyG index, hazard ratio [HR] 2.95; 95% confidence interval [CI], 2.29–3.80) and secondary outcome (HR 2.84; 95% CI 1.86–4.34). When stratified into tertiles, the risk of VAs was significantly higher in the highest tertile (HR 4.08; 95% CI, 2.81–5.92) than in the lowest tertile. Analysis of the secondary outcome revealed similar findings (HR 3.18; 95% CI, 1.73–5.85). Conclusions: In our cohort, the pre-operational TyG index is significantly associated with VAs and major cardiovascular events for patients with high risk of SCD. [ABSTRACT FROM AUTHOR]

Background: Antiarrhythmic therapy for recurrent ventricular arrhythmias (VAs) in patients having undergone catheter ablation and in whom amiodarone and/or beta-blockers were ineffective or contraindicated is a controversial issue. Purpose: The present study sought to compare the efficacy and tolerability of oral procainamide and mexiletine in patients with recurrent ventricular arrhythmias when the standard therapy strategy failed. Methods: All patients with an implantable cardioverter defibrillator (ICD) treated with oral procainamide or mexiletine for recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) in two cardiology divisions between January 2010 and January 2020 were enrolled. Patients were divided into group A (oral procainamide) and group B (mexiletine) and the two groups were compared to each other. The primary endpoint was the efficacy of therapy; the secondary endpoint was the discontinuation of therapy. All events that occurred during procainamide or mexiletine treatment were compared with a matched duration period before the initiation of the therapy. Antiarrhythmic therapy was considered effective when a ≥80% reduction of the sustained ventricular arrhythmias burden recorded by the ICD was achieved. Results: A total of 68 consecutive patients (61 males, 89.7%; mean age 74 ± 10 years) were included in this retrospective analysis. After a median follow-up of 19 months, 38 (56%) patients had a significant reduction in the VA burden. After multivariable adjustment, therapy with procainamide was independently associated with an almost 3-fold higher efficacy on VA suppression compared to mexiletine (HR 2.54, 95% CI 1.06–6.14, p = 0.03). Only three patients (9%) treated with procainamide presented severe side effects (dyspnea or hypotension) requiring discontinuation of therapy compared with six patients (18%) treated with mexiletine who interrupted therapy because of severe side effects (p = 0.47). Conclusions: Compared to mexiletine, oral procainamide had a higher efficacy for the treatment of recurrent and refractory VAs, and showed a good profile of tolerability. [ABSTRACT FROM AUTHOR]

Young (<18 years of age) patients with Brugada syndrome (BrS) are often under-represented in BrS studies and their management, especially related to syncopal episodes, remains unclear. This study sought to describe the arrhythmia prevalence among young patients with BrS undergoing continuous rhythm monitoring by implantable loop recorder (ILR) and to assess the etiology behind syncope of undetermined origin. A total of 147 patients with BrS with ILR were enrolled in 12 international centers and divided into pediatric (age <12 years; n = 77, 52%) and adolescents (age 13-18 years; n = 70, 48%). Mean age was 11.3 years, 53 patients (36.1%) were female, and 31 (21.1%) had spontaneous type 1 electrocardiograms. Over a median follow-up of 3.6 years (Q1-Q3: 1.6-4.8 years), an arrhythmic event was recorded in 33 patients (22.4%), mainly of nonventricular origin: 15 atrial (10.2%) and 16 bradyarrhythmic events (10.9%). Ventricular arrhythmias occurred in 4 patients, all with spontaneous BrS, and were fever-related in one-half. Among all patients with recurrence of syncope during follow-up, true arrhythmic syncope was documented in 5 (17.8%), and it was due to bradyarrhythmias or atrial arrhythmias in 3 cases (60%). Continuous rhythm monitoring with ILRs in young patients with BrS detects a broad range of arrhythmias. Ventricular arrhythmias occur predominantly in patients with spontaneous type 1 electrocardiograms and during fever. Despite the young age, bradyarrhythmias and atrial arrhythmias are frequent and represent the cause of arrhythmic syncope in 60% of patients. Young patients with BrS with syncope of undetermined origin may benefit from ILR implant. [ABSTRACT FROM AUTHOR]

AIM: To examine how the variation of the β1-adrenergic receptor gene affects the occurrence of ventricular arrhythmias and the prognosis over a 6-month period in individuals suffering from acute ST-segment elevation myocardial infarction (STEMI). METHODS: A study was conducted retrospectively, where patients diagnosed STEMI and treated at Yunfu City People's Hospital between January 2021 and February 2023 were included based on predefined criteria. The patients were then divided into three groups according to their genotypes of the β1-adrenergic receptor Arg389Gly gene polymorphism: CC group (Arg389Arg), CG group (Arg389Gly), and GG group (Gly389Gly). Discrepancies in initial clinical data upon admission [such as Killip classification, heart rate, systolic and diastolic blood pressure, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDD), and serum tumor necrosis factor alpha (TNF-α), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase MB (CK-MB) and high-sensitivity C-reactive protein (hs-CRP) ], and outcomes gathered during a 6-month follow-up via telephone after discharge (heart rate, NT-proBNP, CK-MB, LVEF, LVDD, and occurrences of major adverse cardiac events) were compared across the three groups. RESULTS: The study enrolled a total of 178 STEMI patients with ventricular arrhythmias, comprising 87 cases in CC group (48. 9%), 73 cases in CG group (41. 0%), and 18 cases in GG group (10. 1%). There were no notable variances in demographic characteristics such as age, sex, weight, BMI, smoking history, alcohol consumption history, comorbidities, blood pressure, heart rate, Killip classification (III amd IV), TNF-α, NT-proBNP, CK-MB, hs-CRP, LVEF and LVDD across the three groups (P>0. 05). Following a 6-month monitoring period, the cardiac function parameters in CG and GG groups exhibited significant improvement compared to those in CC group (P<0. 05), with noteworthy lower levels of NT-proBNP and CK-MB in GG group in contrast to CG group (P<0. 05). Notably, there were significant discrepancies in the incidence of major adverse cardiac events during the follow-up period among the study groups, with 17 cases in CC group (19. 5%), 5 cases in CG group (6. 9%), and 1 case in GG group (5. 6%) (χ²=6. 887, P<0. 05). CONCLUSION: There is no correlation between the severity of STEMI accompanied by ventricular arrhythmias and the β1-adrenergic receptor Arg389Gly gene polymorphism. However, this gene variant is connected with enhancements in cardiac function and short-term prognosis post-treatment. [ABSTRACT FROM AUTHOR]

Ranolazine is an anti-anginal medication that has demonstrated antiarrhythmic properties by inhibiting both late sodium and potassium currents. Studies have shown promising results for ranolazine in treating both atrial fibrillation and ventricular arrhythmias, particularly when used in combination with other medications. This review explores ranolazine's mechanisms of action and its potential role in cardiac arrhythmias treatment in light of previous clinical studies. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation (CA) is a well-established treatment in patients with ventricular tachycardia and appropriate implantable cardioverter defibrillator (ICD) therapies. Methods: We enrolled 57 consecutive carriers of ICD undergoing CA for electrical storm (ES). Our aim was to investigate differences in clinical, device-related, and electroanatomic features among patients who had history of appropriate ICD interventions before the ES compared to those who had not. The primary endpoint was a composite of death from any cause and recurrences of sustained VT, ventricular fibrillation, appropriate ICD therapy, or ES. Results: During a median follow up of 39 months, 28 patients (49%) met the primary endpoint. Those with previous ICD interventions had a higher prevalence of late potentials and a greater unipolar low-voltage area at electroanatomic mapping. Patients who met the primary endpoint had a higher prevalence of ATP/shock episodes preceding the ES event. At Cox regression analysis, non-ischemic dilated cardiomyopathy (NIDCM), QRS duration, and previous ATP and/or shock before the ES were associated with arrhythmic recurrences and/or death. At multivariate analysis, NIDCM and previous shock were associated with arrhythmic recurrences and/or death. Conclusions: A history of recurrent ICD therapies predicts worse outcomes when CA is needed because of ES. Although more studies are needed to definitively address this question, our data speak in support of an early referral for CA of ES. [ABSTRACT FROM AUTHOR]

Aim: Arrhythmic complications in patients with acute coronary syndromes during hospitalization are not uncommon in cardiology practice. In our retrospective study, we investigated the effect of primary ventricular arrhythmias occurring within the first 48 hours from the time of hospitalization on cardiovascular mortality and resuscitated cardiopulmonary arrest in patients with ST-segment elevation myocardial infarction. Introduction: Although the rate of myocardial infarction has decreased over the years, it is responsible for hundreds of thousands of deaths worldwide. Arrhythmic complications take an essential place for morbidity and mortality in the course of myocardial infarction. Ventricular arrhythmias play a pivotal role in terms of mortality in acute terms of myocardial infarction. Material and Method: In our single center and retrospective study, 18-year-old and older patients who presented to Sağlik Bilimleri University Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital emergency department with ischemic symptoms and were admitted to hospital with the diagnose of ST-segment elevation myocardial infarction were enrolled. The primary endpoint was in-hospital mortality and resuscitated cardiopulmonary arrest. Results: 1,137 patients were included in the study. Primary VT/VF which occurred within the first 48 hours from the time of hospitalization was observed in 8.2% of patients (n: 93). Previous MI history (3.47 OR, 95% CI 1.41–8.55 p=0.0068, LASSO: 0.388), KILLIP class at the time of admission (1.52 OR, 95% CI 0.94–2.45 p=0.0813, LASSO: 0.627), Primary VT/VF (4.02 OR, 95% CI 1.44–11.21 p=0.0077, LASSO: 0.440), left ventricle ejection fraction calculated by transthoracic echocardiography (0.88 OR, 95% CI 0.78–0.99 p=0.0444, LASSO: -0.032) and serum CRP level (1.81 OR, 95% CI 0.22–14.53 p=0.57, LASSO: 0.036) were independent predictors of MACE including in-hospital mortality and resuscitated cardiopulmonary arrest. Conclusion: Primary VT and VF are independent predictors of in-hospital mortality and resuscitated cardiopulmonary arrest events in patients with ST-segment elevation acute MI. [ABSTRACT FROM AUTHOR]

Obesity is a chronic disease that is rapidly increasing in prevalence and affects more than 600 million adults worldwide, and this figure is estimated to increase by at least double by 2030. In the United States, more than one-third of the adult population is either overweight or obese. The global obesity epidemic is a major risk factor for the development of life-threatening arrhythmias occurring in patients with long QT, particularly in conditions where multiple heart-rate-corrected QT-interval-prolonging mechanisms are simultaneously present. In obesity, excess dietary fat in adipose tissue stimulates the release of immunomodulatory cytokines such as interleukin (IL)-6, leading to a state of chronic inflammation in patients. Over the last decade, increasing evidence has been found to support IL-6 signaling as a powerful predictor of the severity of heart diseases and increased risk for ventricular arrhythmias. IL-6′s pro-inflammatory effects are mediated via trans-signaling and may represent a novel arrhythmogenic risk factor in obese hearts. The first selective inhibitor of IL-6 trans-signaling, olamkicept, has shown encouraging results in phase II clinical studies for inflammatory bowel disease. Nevertheless, the connection between IL-6 trans-signaling and obesity-linked ventricular arrhythmias remains unexplored. Therefore, understanding how IL-6 trans-signaling elicits a cellular pro-arrhythmic phenotype and its use as an anti-arrhythmic target in a model of obesity remain unmet clinical needs. [ABSTRACT FROM AUTHOR]

Mitral valve prolapse is a common valve disorder that usually has a benign prognosis unless there is significant regurgitation or LV impairment. However, a subset of patients are at an increased risk of ventricular arrhythmias and sudden cardiac death, which has led to the recognition of "arrhythmic mitral valve prolapse" as a clinical entity. Emerging risk factors include mitral annular disjunction and myocardial fibrosis. While echocardiography remains the primary method of evaluation, cardiac magnetic resonance has become crucial in managing this condition. Cine magnetic resonance sequences provide accurate characterization of prolapse and annular disjunction, assessment of ventricular volumes and function, identification of early dysfunction and remodeling, and quantitative assessment of mitral regurgitation when integrated with flow imaging. However, the unique strength of magnetic resonance lies in its ability to identify tissue changes. T1 mapping sequences identify diffuse fibrosis, in turn related to early ventricular dysfunction and remodeling. Late gadolinium enhancement sequences detect replacement fibrosis, an independent risk factor for ventricular arrhythmias and sudden cardiac death. There are consensus documents and reviews on the use of cardiac magnetic resonance specifically in arrhythmic mitral valve prolapse. However, in this article, we propose an algorithm for the broader use of cardiac magnetic resonance in managing this condition in various scenarios. Future advancements may involve implementing techniques for tissue characterization and flow analysis, such as 4D flow imaging, to identify patients with ventricular dysfunction and remodeling, increased arrhythmic risk, and more accurate grading of mitral regurgitation, ultimately benefiting patient selection for surgical therapy. [ABSTRACT FROM AUTHOR]

Reperfusion therapy in myocardial infarction patients with acute ST-segment elevation significantly reduced the frequency of ventricular tachycardia and ventricular fibrillation, however, such arrhythmias still occur in 6-8% of patients, posing a threat to their lives. The aim of the study was to determine the nature of ventricular arrhythmias occurring in myocardial infarction patients with acute ST-segment elevation within the first 24 hours after primary percutaneous coronary intervention, and their prognostic value regarding the development of complications during the inpatient treatment phase. The study involved 82 individuals (mean age: 62,4±10,2 years; male: 69,23 (58,6-78,92)%, female: 30,77 (21,08-41,4)%). Within 24 hours after the infarct-related artery stenting, all patients underwent a 24-hour Holter ECG monitoring. The course of the disease was analyzed based on the presence of risk factors such as hypertension, diabetes mellitus, past COVID-19, and obesity. Ventricular rhythm disturbances were represented mainly by premature contractions. They occurred significantly more frequently in patients with arterial hypertension (883,71 (96,0; 986.0); p=0,02; p=0,03; p=0,02, compared to patients with a history of COVID-19, diabetes, and obesity, respectively) and in those with past COVID-19 (711,3 (125,0; 846,5); p=0,01; p=0,04, compared to individuals with diabetes and obesity, respectively). Isolated premature ventricular complexes, pairs, triplets were recorded, and in individuals with arterial hypertension and past COVID-19 “runs” of ventricular extrasystoles and episodes of nonsustained monomorphic and even polymorphic ventricular tachycardia, such as Torsades de Pointes, (under the condition of combined risk factors) were noted; predominantly in these patients during the hospital phase such сomplications as ventricular fibrillation and asystole,with sudden cardiac arrest developed. The obtained results is an evidence of electrical myocardial instability and indicate that myocardial infarction patients with acute ST-segment elevation, in addition to myocardial revascularization, require optimization of pharmacological treatment. The use of intravenous beta-blockers as part of complex treatment prevented the occurrence of life-threatening ventricular arrhythmias during the inpatient treatment phase. [ABSTRACT FROM AUTHOR]

Background: Ubiquitin-specific protease 38 (USP38), belonging to the USP family, is recognized for its role in controlling protein degradation and diverse biological processes. Ventricular arrhythmias (VAs) following heart failure (HF) are closely linked to ventricular electrical remodeling, yet the specific mechanisms underlying VAs in HF remain inadequately explored. In this study, we examined the impact of USP38 on VAs in pressure overload-induced HF. Methods: Cardiac-specific USP38 knockout mice, cardiac-specific USP38 transgenic mice and their matched control littermates developed HF induced by aortic banding (AB) surgery. After subjecting the mice to AB surgery for a duration of four weeks, comprehensive investigations were conducted, including pathological analysis and electrophysiological assessments, along with molecular analyses. Results: We observed increased USP38 expression in the left ventricle of mice with HF. Electrocardiogram showed that the USP38 knockout shortened the QRS interval and QTc, while USP38 overexpression prolonged these parameters. USP38 knockout decreased the susceptibility of VAs by shortening action potential duration (APD) and prolonging effective refractory period (ERP). In addition, USP38 knockout increased ion channel and Cx43 expression in ventricle. On the contrary, the increased susceptibility of VAs and the decreased expression of ventricular ion channels and Cx43 were observed with USP38 overexpression. In both in vivo and in vitro experiments, USP38 knockout inhibited TBK1/AKT/CAMKII signaling, whereas USP38 overexpression activated this pathway. Conclusion: Our data indicates that USP38 increases susceptibility to VAs after HF through TBK1/AKT/CAMKII signaling pathway, Consequently, USP38 may emerge as a promising therapeutic target for managing VAs following HF. [ABSTRACT FROM AUTHOR]

Background: The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. Methods: Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration. Results: An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01). Conclusions: The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population. Trial registration: NCT: 04117763. [ABSTRACT FROM AUTHOR]

The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians. [ABSTRACT FROM AUTHOR]

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians. [ABSTRACT FROM AUTHOR]

Introduction: The left ventricular summit (LVS) is the highest point on the epicardial surface of the left ventricle. A part of the LVS that is located between the left coronary arteries (lateral‐LVS) is one of the major sites of idiopathic ventricular arrhythmia (VA) origins. Some idiopathic epicardial VAs can be ablated at endocardial sites adjacent to the epicardial area septal to the lateral‐LVS (septal‐LVS). This study examined the prevalence and electrocardiographic and electrophysiological characteristics of septal‐LVS VAs. Methods: We studied consecutive patients with idiopathic VAs originating from the LVS (67 patients) and aortic root (93 patients). Results: Based on the ablation results, among 67 LVS VAs, 54 were classified as lateral and 13 as septal‐LVS VAs. As compared with the lateral‐LVS VAs, the septal‐LVS VAs were characterized by a greater prevalence of left bundle branch block with left inferior‐axis QRS pattern, later precordial transition, lower R‐wave amplitude ratio in leads III to II, lower Q‐wave amplitude ratio in leads aVL to aVR, and later local ventricular activation time relative to the QRS onset during VAs (V‐QRS) in the great cardiac vein. The electrocardiographic and electrophysiological characteristics of the septal‐LVS VAs were similar to those of the aortic root VAs. However, the V‐QRS at the successful ablation site was significantly later during the septal‐LVS VAs than aortic root VAs (p <.0001). The precordial transition was significantly later during the septal‐LVS VAs than aortic root VAs (p <.05). Conclusions: Septal‐LVS VAs are considered a distinct subgroup of idiopathic VAs originating from the left ventricular outflow tract. [ABSTRACT FROM AUTHOR]

The sodium channel NaV1.8, encoded by the SCN10A gene, has recently emerged as a potential regulator of cardiac electrophysiology. We have previously shown that NaV1.8 contributes to arrhythmogenesis by inducing a persistent Na+ current (late Na+ current, INaL) in human atrial and ventricular cardiomyocytes (CM). We now aim to further investigate the contribution of NaV1.8 to human ventricular arrhythmogenesis at the CM-specific level using pharmacological inhibition as well as a genetic knockout (KO) of SCN10A in induced pluripotent stem cell CM (iPSC-CM). In functional voltage-clamp experiments, we demonstrate that INaL was significantly reduced in ventricular SCN10A-KO iPSC-CM and in control CM after a specific pharmacological inhibition of NaV1.8. In contrast, we did not find any effects on ventricular APD90. The frequency of spontaneous sarcoplasmic reticulum Ca2+ sparks and waves were reduced in SCN10A-KO iPSC-CM and control cells following the pharmacological inhibition of NaV1.8. We further analyzed potential triggers of arrhythmias and found reduced delayed afterdepolarizations (DAD) in SCN10A-KO iPSC-CM and after the specific inhibition of NaV1.8 in control cells. In conclusion, we show that NaV1.8-induced INaL primarily impacts arrhythmogenesis at a subcellular level, with minimal effects on systolic cellular Ca2+ release. The inhibition or knockout of NaV1.8 diminishes proarrhythmic triggers in ventricular CM. In conjunction with our previously published results, this work confirms NaV1.8 as a proarrhythmic target that may be useful in an anti-arrhythmic therapeutic strategy. [ABSTRACT FROM AUTHOR]

Ventricular aneurysm represents a rare complication of transmural acute myocardial infarction, although other cardiac, congenital, or metabolic diseases may also predispose to such condition. Ventricular expansion includes all the cardiac layers, usually with a large segment involved. Adverse events include recurrent angina, reduced ventricular stroke volume with congestive heart failure, mitral regurgitation, thromboembolism, and ventricular arrhythmias. Multimodality imaging is paramount to provide comprehensive assessment, allowing for appropriate therapeutic decision-making. When indicated, surgical intervention remains the gold standard, although additional therapy (heart failure, anticoagulation, and advanced antiarrhythmic treatment) might be required. However, the STICH (Surgical Treatment for Ischemic Heart Failure) trial did not show any advantage from adding surgical ventricular reconstruction to coronary artery bypass surgery in terms of survival, rehospitalization or symptoms, compared with revascularization alone. Finally, implantable cardiac defibrillator may reduce the risk of fatal arrhythmias. [Display omitted] • Acute myocardial infarction is the most frequent cause of left ventricular aneurysm formation, although genetic, metabolic, inflammatory, and traumatic conditions are additional etiologies. • Angina, heart failure, thromboembolism, and ventricular arrhythmias are potential complications requiring specific therapies, including surgical reconstruction, anticoagulation, ablation of arrhythmias, implantable devices, and pharmacological therapy. • In patients with ventricular aneurysm complicated by ventricular tachycardia, implanted cardioverter-defibrillators may reduce the risk of sudden death. Electrophysiological mapping is critical to determining whether to pursue surgical or percutaneous ablation. [ABSTRACT FROM AUTHOR]

Background: Mitral valve prolapse (MVP) and mitral annular disjunction (MAD) are common valvular abnormalities that have been associated with ventricular arrhythmias (VA). Cardiac magnetic resonance imaging (CMR) has a key role in risk stratification of VA, including assessment of late gadolinium enhancement (LGE). Methods: Single-center retrospective analysis of patients with MVP or MAD who had >1 CMR and >1 24 h Holter registration available. Data are presented in detail, including evolution of VA and presence of LGE over time. Results: A total of twelve patients had repeated CMR and Holter registrations available, of which in four (33%) patients, it was conducted before and after minimal invasive mitral valve repair (MVR). After a median of 4.7 years, four out of eight (50%) patients without surgical intervention had new areas of LGE. New LGE was observed in the papillary muscles and the mid to basal inferolateral wall. In four patients, presenting with syncope or high-risk non-sustained ventricular tachycardia (VT), programmed ventricular stimulation was performed and in two (50%), sustained monomorphic VT was easily inducible. In two patients who underwent MVR, new LGE was observed in the basal inferolateral wall of which one presented with an increased burden of VA. Conclusions: In patients with MVP and MAD, repeat CMR may show new LGE in a small subset of patients, even shortly after MVR. A subgroup of patients who presented with an increase in VA burden showed new LGE upon repeat CMR. VA in patients with MVP and MAD are part of a heterogeneous spectrum that requires further investigation to establish risk stratification strategies. [ABSTRACT FROM AUTHOR]

Introduction: Wearable cardioverter defibrillator (WCD) is utilized in patients with assumed but not yet confirmed risk for sudden cardiac death (SCD). Many of these patients also present with atrial fibrillation (AF). However, the rate of WCD‐detected ventricular or atrial arrhythmia events in this specific high‐risk cohort is not well understood. Methods: In WEARIT‐II, the cumulative probability of any sustained or nonsustained VT/VF (WCD‐treated and nontreated), and atrial/supraventricular arrhythmias during WCD use was assessed using the Kaplan–Meier method by prior AF, with comparisons by the log‐rank test. The incidence of ventricular and atrial arrhythmia events were expressed as events per 100 patient‐years, and were analyzed by prior AF using negative binomial regression. Results: WEARIT‐II enrolled 2000 patients, 557 (28%) of whom had AF before enrollment. Cumulative probability of any sustained or nonsustained WCD‐detected VT/VF during WCD use was significantly higher among patients with a history of AF than without AF (6% vs. 3%, p =.001). Similarly, the recurrent rate of any sustained or nonsustained VT/VF was significantly higher in patients with prior AF versus no prior AF (131.5 events per 100 patient‐years vs. 22.7 events per 100 patient‐years, p =.001). Patients with prior AF also had a significantly higher burden of any WCD‐detected atrial arrhythmias/SVT/inappropriate arrhythmias therapy (183.2 events per 100 patient‐years vs. 74.8 events per 100 patient‐years, p <.001). Conclusion: Our results demonstrate that patients with a history of AF wearing the WCD for risk assessment have a higher incidence of ventricular arrhythmias that may facilitate the decision making for ICD implantation. [ABSTRACT FROM AUTHOR]

Introduction: Despite rapid technological progress, some arrhythmias are still resistant to standard unipolar ablation. These include arrhythmias arising from the base of the heart, cardiac crux, or epicardium. Bipolar radiofrequency ablation (B‐RFA) may be useful in some cases, however, data on the efficacy of this approach in various arrhythmia localizations are scarce. The aim of this study was to assess the efficacy of B‐RFA in patients with ventricular arrhythmias originating from various locations, occurring refractory to standard unipolar ablation approaches. Methods: An observational, single center study was conducted over a 30‐month period. B‐RFA were performed using dedicated radio frequency (RF) generator and electroanatomic mapping system. Results: Twenty‐four procedures, in 23 patients with a median (range) of 1 (1–2) previously failed unipolar ablation procedures, were included in the final analysis. There were 12 ablations of ventricular arrhythmias originating from interventricular septum with an acute success rate of 75%, and 12 from left ventricular (LV) summit with an acute success rate of 58%. The midterm success rate (median interquartile range follow‐up of 205 days [188–338]) was 66% and 50%, respectively. Conclusions: B‐RFA is a promising method of catheter ablation for refractory cardiac arrhythmias. A higher success rate was observed in ablation for difficult ventricular arrhythmias originating from interventricular septal region than LV summit. [ABSTRACT FROM AUTHOR]

Ventricular arrhythmias are life-threatening cardiac events. Sympathetic nervous system blockade represents a crucial therapeutic method for refractory ventricular arrhythmias. Ultrasound (US) imaging for stellate ganglion block (SGB) suggests potential for its application to safer and more accurate methods. We had thirteen patients diagnosed with refractory ventricular arrhythmia and referred to the pain clinic for SGB. We visited the intensive care unit (ICU) and performed SGB with the lateral paracarotid approach technique in the ICU. Using a new approach, we easily performed SGB and felt the convenience of the procedure in the ICU. In eleven cases, we also confirmed that the effect of the block with the new technique was satisfactory. SGB, with the new technique, revealed efficiency in the recovery process of the patients. We recommended the lateral paracarotid approach technique for SGB when a patient in an ICU showed ventricular arrhythmias and should be treated with SGB. [ABSTRACT FROM AUTHOR]

Background: The implantation of left ventricular assist devices (LVADs) as a bridge to transplantation or as destination therapy in end-stage heart failure patients is frequently complicated by the emergence of ventricular arrhythmias (VAs). These arrhythmias have been implicated in precipitating deleterious clinical outcomes, increased mortality rates and augmented healthcare expenditures. Case Presentation: We present a challenging case of a 49-year-old male with a history of dilated cardiomyopathy who received an LVAD. Post-implantation, the patient suffered from intractable VAs, leading to multiple rehospitalizations and hemodynamic deterioration. Despite exhaustive medical management and electrical cardioversion attempts, the patient's VAs persisted, ultimately necessitating prioritization for cardiac transplantation. Discussion: This case highlights the challenges in managing VAs in LVAD patients and the importance of multidisciplinary collaboration. While pharmacological intervention is the initial strategy, catheter ablation may be considered in selected cases when medication is insufficient. In instances of intractable VAs, expeditious listing for heart transplantation as a high-priority candidate is advisable when feasible. [ABSTRACT FROM AUTHOR]

Background: Hypokalemia is common in hospitalized patients and associated with ECG abnormalities. The prevalence and prognostic value of ECG abnormalities in hypokalemic patients are, however, not well established. Methods: The study was a multicentered cohort study, including all ault patients with an ECG and potassium level <4.4 mmol/L recorded at arrival to four emergency departments in Denmark and Sweden. Using computerized measurements from ECGs, we investigated the relationship between potassium levels and heart rate, QRS duration, corrected QT (QTc) interval, ST‐segment depressions, T‐wave flattening, and T‐wave inversion using cubic splines. Within strata of potassium levels, we further estimated the hazard ratio (HR) for 7‐day mortality, admission to the intensive care unit (ICU), and diagnosis of ventricular arrhythmia or cardiac arrest, comparing patients with and without specific ECG abnormalities matched 1:2 on propensity scores. Results: Among 79,599 included patients, decreasing potassium levels were associated with a concentration‐dependent increase in all investigated ECG variables. ECG abnormalities were present in 40% of hypokalemic patients ([K+] <3.5 mmol/L), with T‐wave flattening, ST‐segment depression, and QTc prolongation occurring in 27%, 16%, and 14%. In patients with mild hypokalemia ([K+] 3.0–3.4 mmol/L), a heart rate >100 bpm, ST‐depressions, and T‐wave inversion were associated with increased HRs for 7‐day mortality and ICU admission, whereas only a heart rate >100 bpm predicted both mortality and ICU admission among patients with [K+] <3.0 mmol/L. HR estimates were, however, similar to those in eukalemic patients. The low number of events with ventricular arrhythmia limited evaluation for this outcome. Conclusions: ECG abnormalities were common in hypokalemic patients, but they are poor prognostic markers for short‐term adverse events under the current standard of care. [ABSTRACT FROM AUTHOR]

FKBP12.6, a binding protein to the immunosuppressant FK506, which also binds the ryanodine receptor (RyR2) in the heart, has been proposed to regulate RyR2 function and to have antiarrhythmic properties. However, the level of FKBP12.6 expression in normal hearts remains elusive and some controversies still persist regarding its effects, both in basal conditions and during β-adrenergic stimulation. We quantified FKBP12.6 in the left ventricles (LV) of WT (wild-type) mice and in two novel transgenic models expressing distinct levels of FKBP12.6, using a custom-made specific anti-FKBP12.6 antibody and a recombinant protein. FKBP12.6 level in WT LV was very low (0.16 ± 0.02 nmol/g of LV), indicating that <15% RyR2 monomers are bound to the protein. Mice with 14.1 ± 0.2 nmol of FKBP12.6 per g of LV (TG1) had mild cardiac hypertrophy and normal function and were protected against epinephrine/caffeine-evoked arrhythmias. The ventricular myocytes showed higher [Ca2+] i transient amplitudes than WT myocytes and normal SR-Ca2+ load, while fewer myocytes showed Ca2+ sparks. TG1 cardiomyocytes responded to 50 nM Isoproterenol increasing these [Ca2+] i parameters and producing RyR2-Ser2808 phosphorylation. Mice with more than twice the TG1 FKBP12.6 value (TG2) showed marked cardiac hypertrophy with calcineurin activation and more arrhythmias than WT mice during β-adrenergic stimulation, challenging the protective potential of high FKBP12.6. RyR2R420Q CPVT mice overexpressing FKBP12.6 showed fewer proarrhythmic events and decreased incidence and duration of stress-induced bidirectional ventricular tachycardia. Our study, therefore, quantifies for the first time endogenous FKBP12.6 in the mouse heart, questioning its physiological relevance, at least at rest due its low level. By contrast, our work demonstrates that with caution FKBP12.6 remains an interesting target for the development of new antiarrhythmic therapies. [Display omitted] • FKBP12.6 expression in normal mouse heart is very low: 0.16 ± 0.02 nmol/g of left ventricle. • Moderate overexpression of FKBP12.6 has a protective role against arrhythmias. • High overexpression of FKPB12.6 activates calcineurin and provoke dilated hypertrophy. • High level of FKBP12.6 is arrhythmogenic. • The effects of FKBP12.6 are unrelated to RyR2 phosphorylation at Ser2808. [ABSTRACT FROM AUTHOR]

Although mitral valve prolapse (MVP) is the most prevalent valvular abnormality in Western countries and generally carries a good prognosis, a small subset of patients is exposed to a significant risk of malignant ventricular arrhythmias (VAs) and sudden cardiac death (SCD), the so-called arrhythmic MVP (AMVP) syndrome. Recent work has emphasized phenotypical risk features of severe AMVP and clarified its pathophysiology. However, the appropriate assessment and risk stratification of patients with suspected AMVP remains a clinical conundrum, with the possibility of both overestimating and underestimating the risk of malignant VAs, with the inappropriate use of advanced imaging and invasive electrophysiology study on one hand, and the catastrophic occurrence of SCD on the other. Furthermore, the sports eligibility assessment of athletes with AMVP remains ill defined, especially in the grey zone of intermediate arrhythmic risk. The definition, epidemiology, pathophysiology, risk stratification, and treatment of AMVP are covered in the present review. Considering recent guidelines and expert consensus statements, we propose a comprehensive pathway to facilitate appropriate counseling concerning the practice of competitive/leisure-time sports, envisioning shared decision making and the multidisciplinary "sports heart team" evaluation of borderline cases. Our final aim is to encourage an active lifestyle without compromising patients' safety. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) accounts for a substantial proportion of mortality in heart failure with reduced ejection fraction (HFrEF), frequently triggered by ventricular arrhythmias (VA). This review aims to analyze the pathophysiological mechanisms underlying VA and SCD in HFrEF and evaluate the effectiveness of guideline-directed medical therapy (GDMT) in reducing SCD. Beta-blockers, angiotensin receptor–neprilysin inhibitors, and mineralocorticoid receptor antagonists have shown significant efficacy in reducing SCD risk. While angiotensin-converting enzyme inhibitors and angiotensin receptor blockers exert beneficial impacts on the renin-angiotensin-aldosterone system, their direct role in SCD prevention remains less clear. Emerging treatments like sodium-glucose cotransporter 2 inhibitors show promise but necessitate further research for conclusive evidence. The favorable outcomes of those molecules on VA are notably attributable to sympathetic nervous system modulation, structural remodeling attenuation, and ion channel stabilization. A multidimensional pharmacological approach targeting those pathophysiological mechanisms offers a complete and synergy approach to reducing SCD risk, thereby highlighting the importance of optimizing GDMT for HFrEF. The current landscape of HFrEF pharmacotherapy is evolving, with ongoing research needed to clarify the full extent of the anti-arrhythmic benefits offered by both existing and new treatments. [ABSTRACT FROM AUTHOR]

Introduction: Mitral valve prolapse (MVP) is a common clinical condition in the general population. A subgroup of patients with MVP may experience ventricular arrhythmias and sudden cardiac death ("arrhythmic mitral valve prolapse" [AMVP]) but how to stratify arrhythmic risk is still unclear. Our meta‐analysis aims to identify predictive factors for arrhythmic risk in patients with MVP. Methods: We systematically searched Medline, Cochrane, Journals@Ovid, Scopus electronic databases for studies published up to December 28, 2022 and comparing AMVP and nonarrhythmic mitral valve prolapse (NAMVP) for what concerns history, electrocardiographic, echocardiographic and cardiac magnetic resonance features. The effect size was estimated using a random‐effect model as odds ratio (OR) and mean difference (MD). Results: A total of 10 studies enrolling 1715 patients were included. Late gadolinium enhancement (LGE) (OR: 16.67; p =.005), T‐wave inversion (TWI) (OR: 2.63; p <.0001), bileaflet MVP (OR: 1.92; p <.0001) and mitral anulus disjunction (MAD) (OR: 2.60; p <.0001) were more represented among patients with AMVP than in NAMVP. Patients with AMVP were shown to have longer anterior mitral leaflet (AML) (MD: 2.63 mm; p <.0001), posterior mitral leaflet (MD: 2.96 mm; p <.0001), thicker AML (MD: 0.49 mm; p <.0001), longer MAD length (MD: 1.24 mm; p <.0001) and higher amount of LGE (MD: 1.41%; p <.0001) than NAMVP. AMVP showed increased mechanical dispersion (MD: 8.04 ms; 95% confidence interval: 5.13–10.96; p <.0001) compared with NAMVP. Conclusions: Our meta‐analysis proved that LGE, TWI, bileaflet MVP, and MAD are predictive factors for arrhythmic risk in MVP patients. [ABSTRACT FROM AUTHOR]

Introduction: Standard unipolar catheter ablation with radiofrequency for ventricular arrhythmias has reportedly high recurrence rates, mostly due to a lack of efficient lesions in the deep myocardial substrates to disrupt the critical components of the arrhythmia circuit. First in-vivo bipolar catheter ablations show promising results to counter this issue. Precise handling of two catheters simultaneously during BPA is a challenge that the utilization of a robotic magnetic navigation system could make safer by robotically controlling one of the catheters. Methods: An remote magnetic technology (RMT) catheter, as an active catheter, as well as an indifferent manual catheter was connected to a bipolar ablation -- certified generator system. The RMT catheter was controlled by a RMN system. Three premature ventricular contractions (PVC) patients with prior unsuccessful unipolar catheter ablation received bipolar catheter ablation. The safety and feasibility of this combination were explored. Results: Two patients had PVCs of origin between the right ventricular outflow tract (RVOT)/left ventricular outflow tract (LVOT) and one patient mid-septal right ventricle (RV)/left ventricle (LV). A combination of bipolar catheter ablation at 30W and unipolar catheter ablation at 50W/70W was acutely successful. The follow-up duration was 3-months with one complex patient conservatively treated being PVC recurrent. No complications occurred. Conclusions: Bipolar catheter ablation with a robotic magnetic navigation system is feasible and safe. The robotic control of one of the two ablation catheters provides a precise and stable execution of the bipolar ablation since the operator only needs to control the second catheter manually while the magnetic field holds the first in place. It therefore also allows a single operator approach. [ABSTRACT FROM AUTHOR]

Ventricular arrhythmias in cardiac channelopathies are linked to autonomic triggers, which are sub-optimally targeted in current management strategies. Improved molecular understanding of cardiac channelopathies and cellular autonomic signalling could refine autonomic therapies to target the specific signalling pathways relevant to the specific aetiologies as well as the central nervous system centres involved in the cardiac autonomic regulation. This review summarizes key anatomical and physiological aspects of the cardiac autonomic nervous system and its impact on ventricular arrhythmias in primary inherited arrhythmia syndromes. Proarrhythmogenic autonomic effects and potential therapeutic targets in defined conditions including the Brugada syndrome, early repolarization syndrome, long QT syndrome, and catecholaminergic polymorphic ventricular tachycardia will be examined. Pharmacological and interventional neuromodulation options for these cardiac channelopathies are discussed. Promising new targets for cardiac neuromodulation include inhibitory and excitatory G-protein coupled receptors, neuropeptides, chemorepellents/attractants as well as the vagal and sympathetic nuclei in the central nervous system. Novel therapeutic strategies utilizing invasive and non-invasive deep brain/brain stem stimulation as well as the rapidly growing field of chemo-, opto-, or sonogenetics allowing cell-specific targeting to reduce ventricular arrhythmias are presented. [ABSTRACT FROM AUTHOR]

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14--29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7--3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4--7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0--6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38--0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31--0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14--0.45]; P<0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy. [ABSTRACT FROM AUTHOR]

Background: Programed ventricular stimulation (PVS) is a risk stratification tool in patients at risk for adverse arrhythmia outcomes. Patients with negative PVS may yet be at risk for adverse arrhythmia‐related events, particularly in the presence of symptomatic ventricular arrhythmias (VA). Objective: To investigate the long‐term outcomes of real‐world patients with symptomatic VA without indication for device therapy and negative PVS, and to examine the role of cardiac scaring on arrhythmia recurrence. Methods: Patients with symptomatic VA, and late gadolinium enhancement cardiac magnetic resonance imaging (LGE‐CMR), and negative PVS testing were included. All patients underwent placement of implantable cardiac monitors (ICM). Survival analysis was performed to investigate the impact of LGE‐CMR findings on survival free from adverse arrhythmic events. Results: Seventy‐eight patients were included (age 60 ± 14 years, women n = 36 (46%), ejection fraction 57 ± 9%, cardiomyopathy n = 26 (33%), mitral valve prolapse [MVP] n = 9 (12%), positive LGE‐CMR scar n = 49 (62%), history of syncope n = 23 (29%)) including patients with primarily premature ventricular contractions (n = 21) or nonsustained VA (n = 57). Patients were followed for 1.6 ± 1.5 years during which 14 patients (18%) experienced VA requiring treatment (n = 14) or syncope due to bradycardia (n = 2). Four/9 patients (44%) with MVP experienced VA (n = 3) or syncope (n = 1). Baseline characteristics between those with and without adverse events were similar (p > 0.05); however, the presence of cardiac scar on LGE‐CMR was independently associated with an increased risk of adverse events (hazard ratio: 5.6 95% confidence interval: [1.2–27], p = 0.03, log‐rank p = 0.03). Conclusions: In a real‐world cohort with long‐term follow‐up, adverse arrhythmic outcomes occurred in 18% of patients with symptomatic VA despite negative PVS, and this risk was significantly greater in patients with positive DE‐CMR scar. Long term‐monitoring, including the use of ICM, may be appropriate in these patients. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune connective tissue disease which affects various tissues and organs, including skin, lungs, kidneys, gastrointestinal tract and cardiovascular system. Cardiac involvement is the most commonly recognized problem and a significant cause of morbidity. Abnormal ECG is present in 25-75% of patients with SSc and is considered to be an independent redictor of mortality. It is known that the supraventricular arrhythmias are considered as more common in SSc patients, occurring in about two-thirds of the cases, and more often than ventricular tachyarrhythmias. It has been established that right bundle branch block is associated with an increased risk of mortality and that it is an independent predictor of mortality, and should be considered as a marker of the severity of the disease in SSc. The prolonged QTc interval is an independent risk factor for a sudden cardiac death reflecting the instability of repolarization and predisposing the onset of cardiac arrhythmias.The prognosis of the disease depends on the SSc subtype and the involvement of internal organs. SSc is a lifelong disease and cannot be cured, but knowing that cardiac dysfunction significantly worsens the prognosis, early detection of cardiac complications and appropriate therapy can influence its progress and improve the patients' quality of life. [ABSTRACT FROM AUTHOR]

The increasing number of patients with heart failure and implantable cardioverter-defibrillators (ICD) has led to a growing of the emergency presentations for ICD internal shocks. Appropriate shocks are sometimes caused by acute events in the course of disease and could be one of the earliest symptoms contributing to the diagnosis and timely treatment of these acute conditions. We present the case of a 64-year-old male patient with ischemic cardiomyopathy, ICD carrier, who presented to the emergency department for recurrent appropriate ICD shocks caused by episodes of polymorphic ventricular tachycardia and ventricular fibrillation. Even if he did not have chest pain, he was referred to cath lab, where the coronary angiography has shown a severe stenosis at the origin of the left anterior descending artery and a moderate stenosis at the proximal left circumflex artery. The percutaneous revascularization of both lesions resulted in the eradication of the sustained ventricular arrhythmias and the improvement of the clinical status. The case argues for the need for coronary vascularization assessment in ICD carrier patients with ischemic heart failure and adequate recurrent shocks, also emphasizing the importance of remote monitoring in early diagnosis of acute conditions in these patients. [ABSTRACT FROM AUTHOR]

Background: There is limited information on clinical outcomes of COVID-19 patients presenting with ventricular arrhythmias (VAs) during hospital admission. Methods: This multicenter retrospective study included hospitalized patients under Patients-Under-Investigation (PUI) status for suspected COVID-19 and compared clinical outcomes between those tested positive vs. negative for COVID-19, and those with and without VAs during hospital admission. Results: A total of 231 patients [COVID (+) = 174, COVID (-) = 57] were included. COVID-19 (+) patients with VAs were more likely to have hypertension (86% vs. 63%), chronic kidney disease (37% vs. 11%), and prior atrial fibrillation (40% vs. 14%), compared to patients without VAs. In comparison with w/COVID-19 (-) patients with VAs, COVID-19 (+) patients w/VAs were older (77 years vs. 60 years), and less likely to have prior congestive heart failure (34% vs. 70%) and cardiac implantable electronic device (11% vs. 77%). Monomorphic VT (11% vs. 60%) and ICD shocks (0% vs. 42%) were significantly lower, while premature ventricular contractions (57% vs. 9%) were significantly higher in the COVID-19 (+) patients with VAs compared with COVID-19 (-) patients with VAs. Despite no difference in cardiac injury (32% vs. 47%), COVID-19 (+) patients had higher mortality (30% vs. 4%) compared to COVID-19 (-) patients. There was no significant difference in cardiac injury or mortality in COVID-19 (+) patients presenting with and without VAs. Conclusions: Our results demonstrate that VAs in COVID-19 patients are a consequence of systemic illness and are not associated with an increased risk of in-hospital mortality. [ABSTRACT FROM AUTHOR]

Mitral valve prolapse (MVP) is a prevalent cardiac disorder that impacts approximately 2% to 3% of the overall population. While most patients experience a benign clinical course, there is evidence suggesting that a subgroup of MVP patients face an increased risk of sudden cardiac death (SCD). Although a conclusive causal link between MVP and SCD remains to be firmly established, various factors have been associated with arrhythmic mitral valve prolapse (AMVP). This study aims to provide a comprehensive review encompassing the historical background, epidemiology, pathology, clinical manifestations, electrocardiogram (ECG) findings, and treatment of AMVP patients. A key focus is on utilizing multimodal imaging techniques to accurately diagnose AMVP and to highlight the role of mitral annular disjunction (MAD) in AMVP. [ABSTRACT FROM AUTHOR]

Introduction: AVEIR‐VR leadless pacemaker (LP) was recently approved for clinical use. Although trial data were promising, post‐approval real world data with regard to its effectiveness and safety is lacking. To report our early experience with AVEIR‐VR LP with regard to its effectiveness and safety and compare it with MICRA‐VR. Methods: The first 25 patients to undergo AVEIR‐VR implant at our institution between June and November 2022, were compared to 25 age‐ and sex‐matched patients who received MICRA‐VR implants. Results: In both groups, mean age was 73 years and 48% were women. LP implant was successful in 100% of patients in both groups. Single attempt deployment was achieved in 80% of AVEIR‐VR and 60% of MICRA‐VR recipients (p = 0.07). Fluoroscopy, implant, and procedure times were numerically longer in the AVEIR‐VR group compared to MICRA‐VR group (p > 0.05). No significant periprocedural complications were noted in both groups. Incidence of ventricular arrhythmias were higher in the AVEIR‐VR group (20%) compared to the MICRA‐VR group (0%) (p = 0.043). At 2 and 8 weeks follow‐up, device parameters remained stable in both groups with no device dislodgements. The estimated battery life at 8 weeks was significantly longer in the AVEIR‐VR group (15 years) compared to the MICRA‐VR group (8 years) (p = 0.047). With 3−4 AVEIR‐VR implants, the learning curve for successful implantation reached a steady state. Conclusion: Our initial experience with AVEIR‐VR show that it has comparable effectiveness and safety to MICRA‐VR. Larger sample studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

The definition of mitral annular disjunction (MAD) is still controversial. In the different areas of research, anatomical, clinical, and imaging studies, the separation of the junction points between the mitral valve annulus and the left ventricular wall (greater than 5 mm) has been proposed as a definition, which has been observed in patients with mitral valve prolapse, ventricular arrhythmias, and sudden death. Many of them presented myxomatous degeneration of the valve, a pathology that generates a weakening of the tissue and changes in its normal function. Changes in the geometry of the left ventricle are accompanied by changes in its function, modifying the valve apparatus and generating abnormal dynamics of the mitral annulus. Given the proximity to the anatomical structures of the conduction system, it is likely that these changes have an impact on the it, generating alterations such as arrhythmias, related to sudden death. Material and methods: 30 human hearts preserved with the Kaiserling technique were used. The dissections were performed with microsurgery and standard cardiovascular surgery forceps and scissors with the naked eye, with magnifying glasses and with an optical microscope. A cut was made at the level of the posterior leaflet of the mitral valve, between both papillary muscles, with part of the left atrium and ventricle, to assess whether there is disjunction or not. Results: We have managed to identify MAD in approximately 10% of cases. Conclusions: It is proposed to establish the measurement of MAD parameters in routine controls to perform cardiological follow-up of those patients who present them, their early detection may contribute to the prevention, monitoring and treatment of the aforementioned pathologies. [ABSTRACT FROM AUTHOR]

• Atrial fibrillation (AF) patients may have a higher risk of ventricular arrhythmias (VAs) and sudden death. • We evaluated this specifically in cardiac device patients with and without AF. • The risk of VAs and cardiac arrests was 24% higher in pacemaker patients with AF. • ICD patients with AF had a 17% higher risk of VAs and cardiac arrests. • Device patients with AF had a higher risk of VT/VF/CA, all-cause mortality and cardiovascular death. Atrial fibrillation (AF) has been linked to ventricular arrhythmias (VAs) and sudden death, but few studies have specifically explored this association. We investigated whether AF is associated with an increased risk of ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrests (CA) in patients with cardiac implantable electronic devices (CIEDs). All patients with pacemakers and implantable cardioverter-defibrillators (ICDs) hospitalised between 2010 and 2020 were identified from the French National database. Patients with a prior history of VT/VF/CA were excluded. 701,195 patients were identified initially. After excluding 55,688 patients, 581,781 (90.1%) and 63,726 (9.9%) remained in the pacemaker and ICD groups respectively. 248,046 (42.6%) pacemaker patients had AF and 333,735 (57.4%) had no AF, whereas in the ICD group 20,965 (32.9%) had AF and 42,761 (67.1%) had no AF. The incidence of VT/VF/CA was higher in AF patients compared to non-AF patients both in pacemaker (1.47%/year vs. 0.94%/year) and ICD (5.30%/year vs. 4.21%/year) groups. After multivariable analysis, AF was independently associated with an increased risk of VT/VF/CA in pacemaker (HR 1.236 [95% CI 1.198–1.276]) and ICD (HR 1.167 [95% CI 1.111–1.226]) patients. This risk was still significant in the 1:1 propensity score-matched analysis of the pacemaker (n = 200,977 per subgroup) and ICD cohorts (n = 18,349 per subgroup), HR 1.230 [95% CI 1.187–1.274] and HR 1.134 [95% CI 1.071–1.200] respectively and in the competing risk analysis (pacemaker: HR 1.195 (95% CI 1.154–1.238], ICD: HR 1.094 [95% CI 1.034–1.157]). CIED patients with AF have a higher risk of VT/VF/CA compared to CIED patients without AF. Abbreviations : AF - atrial fibrillation, CA - cardiac arrest, ICD - implantable cardioverter-defibrillator, HR - hazard ratio, PPM – pacemaker, SR - sinus rhythm, VT - ventricular tachycardia, VF - ventricular fibrillation Abbreviations: AF - atrial fibrillation, CA - cardiac arrest, ICD - implantable cardioverter-defibrillator, HR - hazard ratio, PPM – pacemaker, SR - sinus rhythm, VT - ventricular tachycardia, VF - ventricular fibrillation [Display omitted] [ABSTRACT FROM AUTHOR]

Nonischemic cardiomyopathy (NICM) is common and patients are at significant risk for early mortality secondary to ventricular arrhythmias. Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy to decrease sudden cardiac death (SCD) in patients with heart failure and reduced left ventricular ejection fraction. However, in randomized clinical trials comprised solely of patients with NICM, primary prevention ICDs did not confer significant mortality benefit. Moreover, left ventricular ejection fraction has limited sensitivity and specificity for predicting SCD. Therefore, precise risk stratification algorithms are needed to define those at the highest risk of SCD. This review examines mechanisms of sudden arrhythmic death in patients with NICM, discusses the role of ICD therapy and treatment of heart failure for prevention of SCD in patients with NICM, examines the role of cardiac magnetic resonance imaging and computational modeling for SCD risk stratification, and proposes new strategies to guide future clinical trials on SCD risk assessment in patients with NICM. [Display omitted] • NICM patients are at increased risk for SCD; however, current guidelines are insufficient in identifying those who may benefit from ICD therapy. • Identifying the underlying cause for the NICM is important in understanding the disease trajectory. CMR imaging adds additional information in understanding the risk for SCD. • Optimizing guideline-directed medical therapy for heart failure, incorporating clinical parameters, and detailed myocardial structural assessment will be critical to personalized decision-making in SCD risk stratification. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac involvement is common and may become clinically relevant in approximately 5%–10% of patients with systemic sarcoidosis. Although reduced left ventricular ejection fraction is a recognized predictor of mortality, recent studies have suggested an increased risk of ventricular arrhythmia (VAs) and sudden cardiac death (SCD) in patients with cardiac sarcoidosis (CS) and evidence of late gadolinium enhancement‐cardiac magnetic resonance (LGE‐CMR), irrespective of the underlying left ventricular systolic function. We performed a meta‐analysis to assess the correlation between VAs/SCD and presence of LGE‐CMR in CS patients. Methods: We systematically searched Medline, Embase, and Cochrane electronic databases up to January 2, 2023, for studies enrolling patients with suspected or confirmed CS undergoing LGE‐CMR. Clinical outcomes of interest included clinically relevant VAs, defined as sustained ventricular tachycardia, ventricular fibrillation, SCD, or aborted SCD during follow‐up. The effect size was estimated using a random‐effect model as risk ratio (RR) and relative 95% confidence interval (CI). Results: A total of 14 studies fulfilled the selection criteria and were included in the final analysis. Among 1273 patients, LGE was detected in 465 (36.5%; Group LGE+). Males accounted for 45.2% (95% CI: 40.5%–55.7%) of the total population and the average age was 56.8 (95% CI: 52.7%–60.9) years. A total of 104 (22.3%) of 465 LGE+ patients experienced a clinically relevant VA, compared to 6 (0.7%) of 808 LGE‐ ones. LGE+ was associated with a ninefold increased risk in life‐threatening VAs (22.3% vs. 0.7%; RR = 9.52; 95% CI [5.18–17.49]; p <.0001) compared to patients without LGE (heterogeneity I2 = 0%). Conclusion: In our meta‐analysis, LGE+ in patients with CS was associated with a ninefold increased risk in life‐threatening VAs compared to patients without LGE. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of the art on the pathological remodeling that occurs within the autonomic nervous system with cardiac injury and available neuromodulatory therapies for autonomic dysfunction in heart failure. Methods: Data from peer-reviewed publications on autonomic function in health and after cardiac injury are reviewed. The role of and evidence behind various neuromodulatory therapies both in preclinical investigation and in-use in clinical practice are summarized. Results: A harmonic interplay between the heart and the autonomic nervous system exists at multiple levels of the neuraxis. This interplay becomes disrupted in the setting of cardiovascular disease, resulting in pathological changes at multiple levels, from subcellular cardiac signaling of neurotransmitters to extra-cardiac, extra-thoracic remodeling. The subsequent detrimental cycle of sympathovagal imbalance, characterized by sympathoexcitation and parasympathetic withdrawal, predisposes to ventricular arrhythmias, progression of heart failure, and cardiac mortality. Knowledge on the etiology and pathophysiology of this condition has increased exponentially over the past few decades, resulting in a number of different neuromodulatory approaches. However, significant knowledge gaps in both sympathetic and parasympathetic interactions and causal factors that mediate progressive sympathoexcitation and parasympathetic dysfunction remain. Conclusions: Although our understanding of autonomic imbalance in cardiovascular diseases has significantly increased, specific, pivotal mediators of this imbalance and the recognition and implementation of available autonomic parameters and neuromodulatory therapies are still lagging. [ABSTRACT FROM AUTHOR]