Sodium overload during postnatal phases impairs diastolic function and exacerbates reperfusion arrhythmias in adult rats.

Sodium overload during childhood impairs baroreflex sensitivity and increases arterial blood pressure and heart rate in adulthood; these effects persist even after high-salt diet (HSD) withdrawal. However, the literature lacks details on the effects of HSD during postnatal phases on cardiac ischemia/reperfusion responses in adulthood. The current study aimed to elucidate the impact of HSD during infancy adolescence on isolated heart function and cardiac ischemia/reperfusion responses in adulthood. Male 21-day-old Wistar rats were treated for 60 days with hypertonic saline solution (NaCl; 0.3M; experimental group) or tap water (control group). Subsequently, both groups were maintained on a normal sodium diet for 30 days. Subsequently, the rats were euthanized, and their hearts were isolated and perfused according to the Langendorff technique. After 30 min of the basal period, the hearts were subjected to 20 min of anoxia, followed by 20 min of reperfusion. The basal contractile function was unaffected by HSD. However, HSD elevated the left ventricular end-diastolic pressure during reperfusion (23.1 ± 5.2 mmHg vs. 11.6 ± 1.4 mmHg; p < 0.05) and increased ectopic incidence period during reperfusion (208.8 ± 32.9s vs. 75.0 ± 7.8s; p < 0.05). In conclusion, sodium overload compromises cardiac function after reperfusion events, diminishes ventricular relaxation, and increases the severity of arrhythmias, suggesting a possible arrhythmogenic effect of HSD in the postnatal phases.

Electrocardiographic abnormalities in patients with microtia.

The main objective of this study was to investigate the incidence and characteristics of electrocardiographic abnormalities in patients with microtia, and to explore cardiac maldevelopment associated with microtia. This retrospective study analyzed a large cohort of microtia patients admitted to Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from September 2017 to August 2022. The routine electrocardiographic reports of these patients were reviewed to assess the incidence and characteristics of abnormalities. The study included a total of 10,151 patients (5598 in the microtia group and 4553 in the control group) who were admitted to the Plastic Surgery Hospital of Peking Union Medical College. The microtia group had a significantly higher incidence of abnormal electrocardiographies compared to the control group (18.3% vs. 13.6%, P < 0.01), even when excluding sinus irregularity (6.1% vs. 4.4%, P < 0.01). Among the 1025 cases of abnormal electrocardiographies in the microtia group, 686 cases were reported with simple sinus irregularity. After excluding sinus irregularity as abnormal, the most prevalent abnormalities was right bundle branch block (37.5%), followed by sinus bradycardia (17.4%), ST-T wave abnormalities (13.3%), atrial rhythm (9.1%), sinus tachycardia (8.3%), and ventricular high voltage (4.7%). Less common ECG abnormalities included atrial tachycardia (2.1%), ventricular premature contraction (2.4%), and ectopic atrial rhythm (1.8%). atrioventricular block and junctional rhythm were present in 1.2% and 0.9% of the cases, respectively. Wolff Parkinson White syndrome and dextrocardia had a lower prevalence, at 0.6% and 0.9%, respectively. The occurrence of electrocardiographic abnormalities in microtia patients was found to be higher compared to the control group. These findings highlight the potential congenital defect in cardiac electrophysiology beyond the presence of congenital heart defect that coincide with microtia.

Pediatric and Familial Genetic Arrhythmia Syndromes: SCN5A-Related Disorders When It Is Not Long QT Type 3: Clinical Signs and Symptoms.

The following case series presents three different pediatric patients with SCN5A-related disease. In addition, family members are presented to demonstrate the variable penetrance that is commonly seen. Identifying features of this disease is important, because even in the very young, SCN5A disorders can cause lethal arrhythmias and sudden death.

Pediatric and Familial Genetic Arrhythmia Syndromes-Evaluation of Prolonged QTc-Differential Diagnosis and what You Need to Know.

The case series reviews differential diagnosis of a genetic arrhythmia syndrome when evaluating a patient with prolonged QTc. Making the correct diagnosis requires: detailed patient history, family history, and careful review of the electrocardiogram (ECG). Signs and symptoms and ECG characteristics can often help clinicians make the diagnosis before genetic testing results return. These skills can help clinicians make an accurate and timely diagnosis and prevent life-threatening events.

Pediatric and Familial Genetic Arrhythmia Syndromes: Evaluation of Bidirectional Ventricular Tachycardia-Differential Diagnosis.

Bidirectional ventricular tachycardia is a unique arrhythmia that can herald lethal arrhythmia syndromes. Using cases based on real patient stories, this article examines 3 different presentations to help clinicians learn the differential diagnosis associated with this condition. Each associated genetic disorder will be briefly discussed, and valuable tips for distinguishing them from each other will be provided.

Reduction of Filamin C Results in Altered Proteostasis, Cardiomyopathy, and Arrhythmias.

BACKGROUND: Many cardiomyopathy-associated FLNC pathogenic variants are heterozygous truncations, and FLNC pathogenic variants are associated with arrhythmias. Arrhythmia triggers in filaminopathy are incompletely understood. METHODS AND RESULTS: We describe an individual with biallelic FLNC pathogenic variants, p.Arg650X and c.970-4A>G, with peripartum cardiomyopathy and ventricular arrhythmias. We also describe clinical findings in probands with FLNC variants including Val2715fs87X, Glu2458Serfs71X, Phe106Leu, and c.970-4A>G with hypertrophic and dilated cardiomyopathy, atrial fibrillation, and ventricular tachycardia. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated. The FLNC truncation, Arg650X/c.970-4A>G, showed a marked reduction in filamin C protein consistent with biallelic loss of function mutations. To assess loss of filamin C, gene editing of a healthy control iPSC line was used to generate a homozygous FLNC disruption in the actin binding domain. Because filamin C has been linked to protein quality control, we assessed the necessity of filamin C in iPSC-CMs for response to the proteasome inhibitor bortezomib. After exposure to low-dose bortezomib, FLNC-null iPSC-CMs showed an increase in the chaperone proteins BAG3, HSP70 (heat shock protein 70), and HSPB8 (small heat shock protein B8) and in the autophagy marker LC3I/II. FLNC null iPSC-CMs had prolonged electric field potential, which was further prolonged in the presence of low-dose bortezomib. FLNC null engineered heart tissues had impaired function after low-dose bortezomib. CONCLUSIONS: FLNC pathogenic variants associate with a predisposition to arrhythmias, which can be modeled in iPSC-CMs. Reduction of filamin C prolonged field potential, a surrogate for action potential, and with bortezomib-induced proteasome inhibition, reduced filamin C led to greater arrhythmia potential and impaired function.

A review regarding the article 'Electrocardiographic abnormalities in patients with metabolic dysfunction-associated Steatotic liver disease: A systematic review and meta-analysis.'

Metabolic-dysfunction-associated Steatotic liver disease (MASLD) is a high-risk condition for both liver fibrosis and cardiovascular disease (CVD). Therefore, therapeutic strategies to prevent both liver fibrosis and atherosclerotic CVD are required for the treatment of MASLD. Metabolic dysfunction-associated steatohepatitis (MASH) is the more severe form of MASLD, is defined histologically by the presence of lobular inflammation and hepatocyte ballooning and is associated with a greater risk of fibrosis progression. While CVD is the leading cause of mortality in patients with MASLD, those with more severe liver fibrosis are at increased risk of liver-related mortality, with the risk increasing exponentially with fibrosis stage. MASH has been found in 63% of patients with MASLD undergoing liver biopsy in an Asian multi-center cohort. Multiple complex pathways are involved in the association between MASLD and CVD. The visceral accumulation of fat around the liver and other organs, including the pericardium, leads to the release of fat-derived metabolites with the activation of several inflammatory pathways Cardiac rhythm abnormalities are prevalent in MASLD, such as prolongation of the QT interval, ventricular arrhythmias, and atrial fibrillation. Therapeutic interventions that improve cardiometabolic risk factors may be beneficial for an improvement in MASLD. The effects of such therapeutic interventions on lipid, lipoprotein and apoprotein accumulation in the liver and on hepatic steatosis and fibrosis still remain unelucidated. Which lipid factor is crucial for developing MASLD also remains largely unknown.

Interventricular septal thickness on cardiac computed tomography as a novel risk factor for conduction disturbances in patients undergoing transcatheter aortic valve replacement.

AIMS: We examined whether thickness of the basal muscular interventricular septum (IVS), as measured by pre-procedural computed tomography (CT), could be used to identify the risk of conduction disturbances following transcatheter aortic valve replacement (TAVR). The IVS is a pivotal region of the electrical conduction system of the heart where the atrioventricular conduction axis is located. METHODS AND RESULTS: Included were 78 patients with severe aortic stenosis who underwent CT imaging prior to TAVR. The thickness of muscular IVS was measured in the coronal view, in systolic phases, at 1, 2, 5, and 10 mm below the membranous septum (MS). The primary endpoint was a composite of conduction disturbance following TAVR. Conduction disturbances occurred in 24 out of 78 patients (30.8%). Those with conduction disturbances were significantly more likely to have a thinner IVS than those without conduction disturbances at every measured IVS level (2.98 ± 0.52 mm vs. 3.38 ± 0.52 mm, 4.10 ± 1.02 mm vs. 4.65 ± 0.78 mm, 6.11 ± 1.12 mm vs. 6.88 ± 1.03 mm, and 9.72 ± 1.95 mm vs. 10.70 ± 1.55 mm for 1, 2, 5 and 10 mm below MS, respectively, P < 0.05 for all). Multivariable logistic regression analysis showed that pre-procedural IVS thickness (<4 mm at 2 mm below the MS) was a significant independent predictor of post-procedural conduction disturbance (adjOR 7.387, 95% CI: 2.003-27.244, P = 0.003). CONCLUSION: Pre-procedural CT assessment of basal IVS thickness is a novel predictive marker for the risk of conduction disturbances following TAVR. The IVS thickness potentially acts as an anatomical barrier protecting the underlying conduction system from mechanical compression during TAVR.

Definition and management of arrhythmia-induced cardiomyopathy: findings from the European Heart Rhythm Association survey.

AIMS: Arrhythmia-induced cardiomyopathy (AiCM) represents a subtype of acute heart failure (HF) in the context of sustained arrhythmia. Clear definitions and management recommendations for AiCM are lacking. The European Heart Rhythm Association Scientific Initiatives Committee (EHRA SIC) conducted a survey to explore the current definitions and management of patients with AiCM among European and non-European electrophysiologists. METHODS AND RESULTS: A 25-item online questionnaire was developed and distributed among EP specialists on the EHRA SIC website and on social media between 4 September and 5 October 2023. Of the 206 respondents, 16% were female and 61% were between 30 and 49 years old. Most of the respondents were EP specialists (81%) working at university hospitals (47%). While most participants (67%) agreed that AiCM should be defined as a left ventricular ejection fraction (LVEF) impairment after new onset of an arrhythmia, only 35% identified a specific LVEF drop to diagnose AiCM with a wide range of values (5-20% LVEF drop). Most respondents considered all available therapies: catheter ablation (93%), electrical cardioversion (83%), antiarrhythmic drugs (76%), and adjuvant HF treatment (76%). A total of 83% of respondents indicated that adjuvant HF treatment should be started at first HF diagnosis prior to antiarrhythmic treatment, and 84% agreed it should be stopped within six months after LVEF normalization. Responses for the optimal time point for the first LVEF reassessment during follow-up varied markedly (1 day-6 months after antiarrhythmic treatment). CONCLUSION: This EHRA Survey reveals varying practices regarding AiCM among physicians, highlighting a lack of consensus and heterogenous care of these patients.

Atrial Arrhythmias Following Pulmonary Thromboendarterectomy: A Comprehensive Review Of Current Literature.

Chronic thromboembolic pulmonary hypertension (CTEPH) presents as a progressive vascular condition arising from previous episodes of acute pulmonary embolism, contributing to the development of pulmonary hypertension (PH). Pulmonary thromboendarterectomy (PTE) is the gold-standard surgical treatment for CTEPH; however, it may be associated with postoperative sequelae, including atrial arrhythmias (AAs). This comprehensive literature review explores the potential mechanisms for PTE-induced AAs with emphasis on the role of PH-related atrial remodelling and the predisposing factors. The identified preoperative predictors for AAs include advanced age, male gender, elevated resting heart rate, previous AAs, and baseline elevated right atrial pressure. Furthermore, we explore the available data on the association between post-PTE pericardial effusions and the development of AAs. Lastly, we briefly discuss the emerging role of radiomic analysis of epicardial adipose tissue as an imaging biomarker for predicting AAs.

The Potential Mechanisms of Arrhythmia in Coronavirus disease-2019.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) leads to coronavirus disease-2019 (COVID-19) which can cause severe cardiovascular complications including myocardial injury, arrhythmias, acute coronary syndrome and others. Among these complications, arrhythmias are considered serious and life-threatening. Although arrhythmias have been associated with factors such as direct virus invasion leading to myocardial injury, myocarditis, immune response disorder, cytokine storms, myocardial ischemia/hypoxia, electrolyte abnormalities, intravascular volume imbalances, drug interactions, side effects of COVID-19 vaccines and autonomic nervous system dysfunction, the exact mechanisms of arrhythmic complications in patients with COVID-19 are complex and not well understood. In the present review, the literature was extensively searched to investigate the potential mechanisms of arrhythmias in patients with COVID-19. The aim of the current review is to provide clinicians with a comprehensive foundation for the prevention and treatment of arrhythmias associated with long COVID-19.

Arrhythmia-Induced Cardiomyopathy: JACC State-of-the-Art Review.

Arrhythmias frequently accompany heart failure and left ventricular dysfunction. Tachycardias, atrial fibrillation, and premature ventricular contractions can induce a reversible form of dilated cardiomyopathy (CM) known as arrhythmia-induced CM (AiCM). The intriguing question is why certain individuals are more susceptible to AiCM, despite similar arrhythmia burdens. The primary challenge is determining the extent of arrhythmias' contribution to left ventricular systolic dysfunction. AiCM should be considered in patients with a mean heart rate of >100 beats/min, atrial fibrillation, or a PVC burden of >10%. Confirmation of AiCM occurs when CM reverses upon eliminating the responsible arrhythmia. Therapy choice depends on the specific arrhythmia, patient comorbidities, and preferences. After left ventricular function is restored, ongoing follow-up is essential if an abnormal myocardial substrate persists. Accurate diagnosis and treatment of AiCM have the potential to enhance patients' quality of life, improve clinical outcomes, and reduce hospital admissions and overall health care costs.

Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside.

Chagas cardiomyopathy caused by infection with the intracellular parasite Trypanosoma cruzi is the most common and severe expression of human Chagas disease. Heart failure, systemic and pulmonary thromboembolism, arrhythmia, and sudden cardiac death are the principal clinical manifestations of Chagas cardiomyopathy. Ventricular arrhythmias contribute significantly to morbidity and mortality and are the major cause of sudden cardiac death. Significant gaps still exist in the understanding of the pathogenesis mechanisms underlying the arrhythmogenic manifestations of Chagas cardiomyopathy. This article will review the data from experimental studies and translate those findings to draw hypotheses about clinical observations. Human- and animal-based studies at molecular, cellular, tissue, and organ levels suggest 5 main pillars of remodeling caused by the interaction of host and parasite: immunologic, electrical, autonomic, microvascular, and contractile. Integrating these 5 remodeling processes will bring insights into the current knowledge in the field, highlighting some key features for future management of this arrhythmogenic disease.

ForCEPSS-A framework for cardiac electrophysiology simulations standardization.

BACKGROUND AND OBJECTIVE: Simulation of cardiac electrophysiology (CEP) is an important research tool that is increasingly being adopted in industrial and clinical applications. Typical workflows for CEP simulation consist of a sequence of processing stages starting with building an anatomical model and then calibrating its electrophysiological properties to match observable data. While the calibration stages are common and generalizable, most CEP studies re-implement these steps in complex and highly variable workflows. This lack of standardization renders the execution of computational CEP studies in an efficient, robust, and reproducible manner a significant challenge. Here, we propose ForCEPSS as an efficient and robust, yet flexible, software framework for standardizing CEP simulation studies. METHODS AND RESULTS: Key processing stages of CEP simulation studies are identified and implemented in a standardized workflow that builds on openCARP1 Plank et al. (2021) and the Python-based carputils2 framework. Stages include (i) the definition and initialization of action potential phenotypes, (ii) the tissue scale calibration of conduction properties, (iii) the functional initialization to approximate a limit cycle corresponding to the dynamic reference state according to an experimental protocol, and, (iv) the execution of the CEP study where the electrophysiological response to a perturbation of the limit cycle is probed. As an exemplar application, we employ ForCEPSS to prepare a CEP study according to the Virtual Arrhythmia Risk Prediction protocol used for investigating the arrhythmogenic risk of developing infarct-related ventricular tachycardia (VT) in ischemic cardiomyopathy patients. We demonstrate that ForCEPSS enables a fully automated execution of all stages of this complex protocol. CONCLUSION: ForCEPSS offers a novel comprehensive, standardized, and automated CEP simulation workflow. The high degree of automation accelerates the execution of CEP simulation studies, reduces errors, improves robustness, and makes CEP studies reproducible. Verification of simulation studies within the CEP modeling community is thus possible. As such, ForCEPSS makes an important contribution towards increasing transparency, standardization, and reproducibility of in silico CEP experiments.

Lack of Prognostic Value of T-Wave Alternans for Implantable Cardioverter-Defibrillator Benefit in Primary Prevention.

BACKGROUND: New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention. METHODS AND RESULTS: In the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter-Defibrillators) study, we prospectively enrolled 2327 candidates for primary prophylactic ICD. A 24-hour Holter monitor reading was taken from all recruited patients at enrollment. TWA was assessed from Holter monitoring using the modified moving average method. Study outcomes were all-cause death, appropriate shock, and survival benefit. TWA was assessed both as a contiguous variable and as a dichotomized variable with cutoff points <47 µV and <60 µV. The final cohort included 1734 valid T-wave alternans samples, 1211 patients with ICD, and 523 control patients with conservative treatment, with a mean follow-up time of 2.3 years. TWA ≥60 µV was a predicter for a higher all-cause death in patients with an ICD on the basis of a univariate Cox regression model (hazard ratio, 1.484 [95% CI, 1.024-2.151]; P=0.0374; concordance statistic, 0.51). In multivariable models, TWA was not prognostic of death or appropriate shocks in patients with an ICD. In addition, TWA was not prognostic of death in control patients. In a propensity score-adjusted Cox regression model, TWA was not a predictor of ICD benefit. CONCLUSIONS: T-wave alternans is poorly prognostic in patients with a primary prophylactic ICD. Although it may be prognostic of life-threatening arrhythmias and sudden cardiac death in several patient populations, it does not seem to be useful in assessing benefit from ICD therapy in primary prevention among patients with an ejection fraction of ≤35%.