Genetics Bases of Cardiac Sodium Channel Mutations linked to Inherited Cardiac Arrhythmias

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Traditional Chinese Medicine Is Widely Used for Cardiovascular Disease

A review article by Hao et al. ( J Am Coll Cardiol 2017;69(24):2952–66) has had huge repercussions among those familiar with traditional Chinese medicine (TCM) in the international academic community. It evaluated the efficacy and safety of TCM for cardiovascular disease and the pharmacological effect of active TCM ingredients on the cardiovascular system and potential mechanisms. We have several comments: Firstly, we give a brief summary addressing nonpharmacotherapy in TCM, including acupuncture, moxibustion, Qigong, and Tai Chi. Secondly, we have added traditional antiarrhythmic drug–related randomized controlled trials to make the coverage more comprehensive. Lastly, we support the concept that research into, development of, and application of active ingredients is part of modern TCM

Hypertension as a sequela in patients of SARS-CoV-2 infection.

BACKGROUND: COVID-19 is a respiratory infectious disease caused by SARS-CoV-2, and cardiovascular damage is commonly observed in affected patients. We sought to investigate the effect of SARS-CoV-2 infection on cardiac injury and hypertension during the current coronavirus pandemic. STUDY DESIGN AND METHODS: The clinical data of 366 hospitalized COVID-19-confirmed patients were analyzed. The clinical signs and laboratory findings were extracted from electronic medical records. Two independent, experienced clinicians reviewed and analyzed the data. RESULTS: Cardiac injury was found in 11.19% (30/268) of enrolled patients. 93.33% (28/30) of cardiac injury cases were in the severe group. The laboratory findings indicated that white blood cells, neutrophils, procalcitonin, C-reactive protein, lactate, and lactic dehydrogenase were positively associated with cardiac injury marker. Compared with healthy controls, the 190 patients without prior hypertension have higher AngⅡ level, of which 16 (8.42%) patients had a rise in blood pressure to the diagnostic criteria of hypertension during hospitalization, with a significantly increased level of the cTnI, procalcitonin, angiotensin-II (AngⅡ) than those normal blood pressure ones. Multivariate analysis indicated that elevated age, cTnI, the history of hypertension, and diabetes were independent predictors for illness severity. The predictive model, based on the four parameters and gender, has a good ability to identify the clinical severity of COVID-19 in hospitalized patients (area under the curve: 0.932, sensitivity: 98.67%, specificity: 75.68%). CONCLUSION: Hypertension, sometimes accompanied by elevated cTnI, may occur in COVID-19 patients and become a sequela. Enhancing Ang II signaling, driven by SARS-CoV-2 infection, might play an important role in the renin-angiotensin system, and consequently lead to the development of hypertension in COVID-19

Mechanisms Underlying the Antiarrhythmic Effect of ARumenamide-787 in Experimental Models of the J Wave Syndromes and Hypothermia

BACKGROUND: Brugada (BrS) and early repolarization syndromes (ERS), the so-called J wave syndromes (JWS), are associated with life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently limited. In this study, we examine the effects of ARumenamide-787 (AR-787) to suppress the electrocardiographic and arrhythmic manifestations of JWS and hypothermia. METHODS: We studied the effects of AR-787 on INa and IKr in HEK-293 cells stably expressing the α- and β1-subunits of the cardiac (NaV1.5) sodium channel and hERG channel, respectively. In addition, we studied its effect on Ito, INa and ICa in dissociated canine ventricular myocytes along with action potentials and ECG from coronary-perfused right (RV) and left (LV) ventricular wedge preparations. The Ito agonist, NS5806 (5-10 μM), ICa blocker, verapamil (2.5 μM), and INa blocker, ajmaline (2.5 μM), were used to mimic the genetic defects associated with JWS and to induce the electrocardiographic and arrhythmic manifestations of JWS (prominent J waves/ST segment elevation, phase 2 reentry and polymorphic VT/VF) in canine ventricular wedge preparations. RESULTS: AR-787 (1, 10 and 50 μM) exerted pleiotropic effects on cardiac ion channels. The predominant effect was inhibition of the transient outward current (Ito) and enhancement of the sodium channel current (INa), with lesser effects to inhibit IKr and augment calcium channel current (ICa). AR-787 diminished the electrocardiographic J wave and prevented and/or suppressed all arrhythmic activity in canine RV and LV experimental models of BrS, ERS and hypothermia. CONCLUSIONS: Our findings point to AR-787 as promising candidate for the pharmacologic treatment of JWS and hypothermia

Meta-Analysis of Risk Stratification of SCN5A With Brugada Syndrome: Is SCN5A Always a Marker of Low Risk?

Background:SCN5A with Brugada syndrome (BrS) is not commonly considered as an independent risk marker for subsequent cardiac events. However, the risk of SCN5A combined with other clinical characteristics has not been fully investigated.Objectives: The aim of this study is to investigate and evaluate risk stratification and related risk factors of SCN5A in BrS.Methods: The databases of PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI) and Wanfang Data were searched for related studies published from January 2002 to May 2018 followed by meta-analysis. The BrS patients who underwent SCN5A gene tests were included. The prognosis and risk stratification of SCN5A combined with symptoms and asymptoms diagnosis in BrS, electrophysiology study (EPS) were then investigated and evaluated. Outcomes were defined as ventricular tachycardia/fibrillation (VT/VF), sudden cardiac death (SCD).Results: Eleven suitable studies involving 1892 BrS patients who underwent SCN5A gene tests were identified. SCN5A (+) was not considered to be a significant predictor of future cardiac events (95% CI: 0.89–2.11; P = 0.15; I2 = 0%). However, SCN5A (+) patients with symptoms at diagnosis revealed a higher prevalence of future VT/VF, SCD compared to SCN5A (–) patients with symptoms at diagnosis. (95% CI: 1.06–3.70; P = 0.03 I2 = 0%) Among asymptomatic patients, the risk did not significantly differ between SCN5A (+) patients and SCN5A (–) patients. (95% CI: 0.51–4.72; P = 0.45 I2 = 0 %). In an investigation involving patients in EPS (–) BrS electrocardiogram (ECG), the risk of SCN5A (+) is higher than that of SCN5A (–) (P < 0.001).Conclusions: In BrS patients with symptoms at diagnosis or EPS (–), the meta-analysis suggests that SCN5A (+) are at a higher risk of arrhythmic events than SCN5A (–)

Clinical Characteristics and Electrophysiologic Properties of SCN5A Variants in Fever-Induced Brugada Syndrome

Background: Brugada syndrome (BrS) is a severe inherited arrhythmia syndrome that can be unmasked by fever. Methods: A multicentre clinical analysis was performed in 261 patients diagnosed with fever-induced BrS, including 198 (75.9%) and 27 (10.3%) patients who received next-generation genetic sequencing and epicardial arrhythmogenic substrate (AS) mapping, respectively. Findings: In fever-induced BrS patients, pathogenic or likely pathogenic (P/LP) SCN5A variant carriers developed fever-induced BrS at a younger age, and more often in females and those of Caucasian descent. They exhibited significant electrophysical abnormalities, including a larger epicardial AS area, and more prolonged abnormal epicardial electrograms. During a median follow-up of 50.5 months (quartiles 32.5-81.5 months) after the diagnosis, major cardiac events (MCE) occurred in 27 (14.4%) patients. Patients with P/LP SCN5A variants had a higher ratio of MCE compared with the rest. Additionally, history of syncope, QRS duration, and Tpe interval could also predict an increased risk for future MCE according to univariate analysis. Multivariate analysis indicated that only P/LP SCN5A variants were independent significant predictors of MCE. Computational structural modelling showed that most variants are destabilizing, suggesting that Nav1.5 structure destabilization caused by SCN5A missense variants may contribute to fever-induced BrS. Interpretation: In our cohort, P/LP SCN5A variant carriers with fever-induced BrS are more prevalent among patients of Caucasian descent, females, and younger patients. These patients exhibit aggressive electrophysiological abnormalities and worse outcome, which warrants closer monitoring and more urgent management of fever. Funding: None

Zoonosis, cambio climático y sociedad

La sociedad contemporánea se enfrenta a uno de los retos más grandes de la historia humana, el calentamiento global, mismo que acarrea enormes consecuencias, tales como los disturbios climáticos, así como los patrones de las enfermedades de origen animal transmisibles al hombre. Precisamente ante este escenario las instituciones educativas de nivel superior deben dar cumplimiento a su responsabilidad y ser las generadoras de alternativas de solución mediante el trabajo especializado de investigación; y para ello, la pesquisa científica es la mejor de las alternativas a nuestro alcance para comprender y encarar estos desafíos.Universidad Autónoma del Estado de México y Ediciones y Gráficos Eón, S.A. de C.V

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements