Short-term exposure to ambient ozone associated with cardiac arrhythmias in healthy adults

Objective The exact biological mechanism whereby exposure to ambient ozone(O3)may contribute to clinical onset of cardiovascular events remains unclear.In this study,we aim to examine the impacts of O3 exposure on cardiac arrhythmias and potential pathways involved through autonomic dysfunction and myocardial injury.Methods Seventy-three non-smoking healthy adults were followed with 4 repeated measurements of 24-hour ambulatory arrhythmias,heart rate variability,ST-segment deviation,and blood pressure(BP)in Beijing,China,2014‒2016.Generalized additive mixed models coupled with distributed lag nonlinear models were constructed to evaluate the associations and potential interlinks between O3 exposure and outcome measurements.Results During the study period,24-hour average concentrations of ambient O3 were 47.4µg/m3(ranging from 1.0 to 165.9µg/m3).Increased risks of premature ventricular contraction and ventricular tachycardia were associated with interquartile range increases in O3 exposure during the last 5 days before each participant's clinic visit,with relative risks of 2.14(95%confidence interval[CI]:1.95 to 2.32)and 5.47(95%CI:3.51 to 7.43),respectively.Mediation analyses further showed that sympathetic activation,parasympathetic inhibition,and elevated BP levels,as well as heightened risks of ST-segment depression could mediate up to 47.74%of the risks of arrhythmias attributable to O3 exposure.Conclusion Our results suggest that short-term exposure to ambient O3 could prompt the genesis of arrhythmias partially through worsening autonomic function and myocardial burden.

Nonalcoholic Fatty Liver Disease (NAFLD) and Risk of Cardiac Arrhythmias: A New Aspect of the Liver-heart Axis

Nonalcoholic fatty liver disease (NAFLD) is a pathologic condition frequently observed in clinical practice.To date,the prevalence of NAFLD is approximately 25-30% among adults of the general population in Western countries but increases to approximately 70-75% among patients with type 2 diabetes mellitus.In the last decade,accumulating evidence has clearly demonstrated that patients with NAFLD have not only an increased liver-related morbidity and mortality but also an increased risk of fatal and non-fatal cardiovascular events.In particular,several studies have documented the existence of an independent association among NAFLD and cardiac changes in structure and function in both non-diabetic and diabetic patients.In addition,mounting evidence also suggests that there is a strong relationship between NAFLD and cardiac arrhythmias,such as atrial fibrillation,QTc prolongation and ventricular arrhythmias.This is of clinical interest,as it could explain,at least in part,the increased risk of death for cardiovascular disease in patients with NAFLD.Therefore,seeing that cardiovascular disease complications are the leading cause of disability and death in NAFLD patients,the recent European clinical practice guidelines advised to check the cardiovascular system in all patients with NAFLD.This clinical mini review will briefly describe the increasing body of evidence regarding the association between NAFLD and cardiac arrhythmias,and discuss the potential biological mechanisms underlying this association.

Expert Consensus on Wenxin Granule for Treatment of Cardiac Arrhythmias

INTRODUCTIONAntiarrhythmic drugs remain a critically important component of the approach to therapy of cardiac arrhythmias. Over the past 20 years, despite their antiarrhythmic efficacy in many pathological settings, Class Ⅰ and Ⅲ antiarrhythmic drugs have been shown to be associated with the development of proarrhythmias and an increase in the likelihood of causing higher mortality by inducing torsade de pointes ventricular tachycardia and other serious adverse reactions. Consequently, the development of safe and effective antiarrhythmic regimens remains a primary focus of contemporary cardiovascular research.

Automatic Classification of Cardiac Arrhythmias Based on Hybrid Features and Decision Tree Algorithm

Accurate classification of cardiac arrhythmias is a crucial task because of the non-stationary nature of electrocardiogram(ECG)signals.In a life-threatening situation,an automated system is necessary for early detection of beat abnormalities in order to reduce the mortality rate.In this paper,we propose an automatic classification system of ECG beats based on the multi-domain features derived from the ECG signals.The experimental study was evaluated on ECG signals obtained from the MIT-BIH Arrhythmia Database.The feature set comprises eight empirical mode decomposition(EMD)based features,three features from variational mode decomposition(VMD)and four features from RR intervals.In total,15 features are ranked according to a ranker search approach and then used as input to the support vector machine(SVM)and C4.5 decision tree classifiers for classifying six types of arrhythmia beats.The proposed method achieved best result in C4.5 decision tree classifier with an accuracy of 98.89%compared to cubic-SVM classifier which achieved an accuracy of 95.35%only.Besides accuracy measures,all other parameters such as sensitivity(Se),specificity(Sp)and precision rates of 95.68%,99.28%and 95.8%was achieved better in C4.5 classifier.Also the computational time of 0.65 s with an error rate of 0.11 was achieved which is very less compared to SVM.The multi-domain based features with decision tree classifier obtained the best results in classifying cardiac arrhythmias hence the system could be used efficiently in clinical practices.

Dysglycemia and arrhythmias

Disorders in glucose metabolism can be divided into three separate but interrelated domains,namely hyperglycemia,hypoglycemia,and glycemic variability.Intensive glycemic control in patients with diabetes might increase the risk of hypoglycemic incidents and glucose fluctuations.These three dysglycemic states occur not only amongst patients with diabetes,but are frequently present in other clinical settings,such as during critically ill.A growing body of evidence has focused on the relationships between these dysglycemic domains with cardiac arrhythmias,including supraventricular arrhythmias(primarily atrial fibrillation),ventricular arrhythmias(malignant ventricular arrhythmias and QT interval prolongation),and bradyarrhythmias(bradycardia and heart block).Different mechanisms by which these dysglycemic states might provoke cardiac arrhythmias have been identified in experimental studies.A customized glycemic control strategy to minimize the risk of hyperglycemia,hypoglycemia and glucose variability is of the utmost importance in order to mitigate the risk of cardiac arrhythmias.

Control of cardiac excitability and arrhythmias by microRNAs

Recent studies revealing the important roles of microRNAs（miRNAs） in regulating expression of ion channel genes have opened up a research field for extending and deepening our investi- gation into the cardiac excitability and the associated arrhythmogenesis.Cardiac excitability,the fundamental property of the cardiac myocytes,defines the cardiac conduction,repolarization,automaticity,intracellular calcium handling,and their regional heterogeneity. Our previous and ongoing studies and the work from other laboratories have demonstrated the significant involvement of miRNAs in regulating every aspects of cardiac excitability.We have found earlier that the muscle-specific miRNA miR-1 boosts up the arrhythmogenic potential through targeting gap junction channel connexin 43 in myocardial infarction.A subsequent study revealed that miR-1 can also cause arrhythmias by impairing Ca2+ handling by targeting phosphatase.We then identified another muscle-specific miRNA miR-133 promotes abnormal QT prolongation by repressing HERG K+ channel expression in diabetic cardiomyopathy. Subsequently,we discovered that both miR- 1 and miR-133 are involved in the reexpression of pacemaker channels HCN2/HCN4 to enhance abnormal automaticity in cardiac hypertrophy.Recently, we further identified miR-328 as an important determinant for atrial fibrillation（AF） and the associated adverse atrial electrical remodeling via targeting L-type Ca2+ channels.While all the above-mentioned miRNAs are proarrhythmic,we have newly identified for the first time a natural antiarrhythmic miRNA miR-26.We found that all three members of the miR-26 family is downregulated in their expression in AF tissues and this downregulation increases AF vulnerability as a result of removal of an endogenous antiarrhythmic factor.miR-26 downregulation shortens atrial action potential favoring AF by increasing inward rectifier K+ current（IK1） density. This is caused by an upregulation of Kir2.1 K+ channel subunit due to derepression of its encoding gene KCNJ2 as we have validated KCNJ2 as a target gene for miR-26.Administration of a LNA-modified antimiR-26 antisense through tail vein injection increases AF vulnerability as indicated by increased number of mice with AF induction by intracardiac pacing.And this effect is blunted by co-injection of either an adenovirus vector carrying miR-26 precursor sequence or a LNA-modified miR-26 mimic to specifically target KCNJ2.We further discovered that the activity of NFAT transcription factor is enhanced in AF which represses the transcription of miR-26. We characterized the promoter region of the host genes of all three members of the miR-26 miRNA family and identified a common cis-acting element for NFAT binding.Thus,our study unraveled a novel miRNA signaling pathway AF NFAT miR-26 KC-NJ2 /Kir2.1/IK1 AF as a positive feedback loop favoring AF and the remodeling process.

Cardiac arrhythmia and heart failure： From bench to bedside

Cardiac arrhythmia is an abnormal rate and/or rhythm of a heart due to its abnormal electrical impulse origination and/or propagation. Various etiologies can cause arrhythmias. Heart failure （HF） is a clinical syndrome due to an impaired heart that can not pump sufficient blood to meet the systemic metabolic needs.

CARDIAC ARRHYTHMIA AFTER LUNG CANCER SURGERY －－ANALYSIS OF 140 PNEUMONECTTOMY CASES

Among 808 surgically resected lung cancer cases at Shanghai Chest Hospital during 1991 to 1992, 140 of them (17.3%) underwent Pneumonectomy. Of the 140 cases:124 male, 16 female; aged 27-74 yrs, 35.7% elder (60 and over), preoperative abnormal EKG was found in 38 cases, operative mortality was 4.3%. The histopathological diagnosis were: squamous 43.6%, adeno. 36.4%, small cell 8.6%, mixed type 11.4%. The pTNM stages: stage I 2.9%, II 17.1%, IIIa 55.0%, IIIb 21.4%, IV 3.6%.Postoperatively, arrhythmia occuried in 76 cases, with an incidence of 54.3%. Of the 76 arrhythmias, atrial fibrillation was seen in 7 patients, atrial premature beats in 2, supraventricular tachycardia in 1, and sinus tachycardia in 66. The incidences of cadiac arrhythmia during the postoperative day (DO), first day (D1), D2, D3,and D4 were 48.7%, 35.5%, 7.9%, 4.0%and 2.6%respectively. Conclusion: the cardiac arrhythmia is the most common complication after pneumonectomy for lung cancer surgery. The major causes were incisional pain, hypovolemia due to blood loss and respirative insufficiency due to anomia. The perioperative prevention and treatment for arrhythmia were also discussed.

Wenxin granule for cardiac arrhythmia: an overview of systematic reviews

Objectives: Evaluating the quality of systematic reviews/meta-analysis of Wenxin granule in treating cardiac arrhythmia to provide evidence for clinical practice, and analyzing the problems in the research to identify potential research priorities for researchers. Method: The systematic reviews of Wenxin granule in treating cardiac arrhythmia were searched from 8 databases. The methodological quality and evidence quality were assessed by AMSTAR and GRADE respectively. Results: Nineteen eligible systematic reviews with 52,905 participants were included. The overall scores of AMSTAR ranged from 3 to 10 with a mean score of 6.5, the median score was 6. There were 9 (9/19, 47.37%) systematic reviews had the score of 7 or more. 6 of them with appropriate information were assessed the quality of evidence by GRADE. The results showed that the overall quality of evidence was limited (range from “very low” to “low”), no “moderate” or “high” quality of evidence existed. For the outcome reporting, no systematic reviews reported endpoints and limited evidence showed that there is causality between Wenxin granule and adverse effects/events. The outcome matrix showed that there are obvious heterogeneity and incompleteness for the outcome reporting in included systematic reviews, so that some included studies cannot be conducted meta-analysis. Meanwhile, there were studies excluded because of inappropriate outcome measures, such as outcome measures did not meet inclusion criteria, treatment time did not meet inclusion criteria, treatment time was unclear, incomplete data or the data cannot be extracted. Conclusions: Wenxin granule have limited efficacy and safety for treating arrhythmia. In the future, high quality of RCTs and systematic reviews should be conducted. Core outcome set for cardiac arrhythmia is needed to improve outcome reporting and decrease waste.

Computer Simulation Methods of Cardiac Electrophysiology

The Luo Rudy models of mammalian ventricular cell were chosen in studying cardiac electrophysiology. Rush and Larsen’s algorithm and adaptive time step methods were used to solve the ordinary differential equations (ODE’s). The operator splitting (or time splitting) and adaptive time step methods were used to solve the partial differential equations (PDE’s) in cardiac tissue conduction models. The alternating direction implicit (ADI) method was used to integrate the PDE. Using these methods we accomplished the simulation programs of single cardiomyocyte model, one dimensional cable model(1 D) and two dimensional(2 D) tissue model. The methods of initiating spiral waves were studied with these software. The data getting from 2 D simulation can be used for further study on isopotential contour lines, spiral wave tip trajectories, and pseudo ECG. The software for computer simulation have been successfully used in simulation studying of electrophysiology properties of single cardiomyocyte, conduction in one dimensional cable model(1 D) and two dimensional(2 D) tissue model.

Repeated atrial arrhythmia induced by cochineal red poisoning:A case report

BACKGROUND Cochineal red is an organic compound widely used in food,cosmetics,pharmaceuticals,textiles,and other fields due to its excellent safety profile.Poisoning caused by eating foods containing cochineal red is rare,and repeated atrial arrhythmia due to cochineal red poisoning is even rarer.CASE SUMMARY An 88-year-old Asian female patient was admitted to hospital due to a disturbance of consciousness.Twelve hours prior to presentation,the patient consumed 12 eggs containing cochineal red over a period of 2 h.At presentation,the patient was in a coma and had a score of 6 on the Glasgow Coma Scale(E2+VT+M4).The patient’s skin and mucous membranes were pink.Electrocardiography(ECG)revealed rapid atrial fibrillation without any signs of ischemia.We prescribed cedilan and fluid replacement for arrhythmia correction.Shortly after admission,the atrial fibrillation corrected to a normal sinus rhythm.On the day 2 of admission,the patient had a sudden atrial flutter accompanied by hemodynamic instability and rapidly declining arterial oxygen saturation between 85%and 90%.The sinus rhythm returned to normal after two electrical cardioversions.Six days after admission,the skin color of the patient returned to normal,and the ECG results were normal.The patient was transferred out of the intensive care unit and eventually discharged after 12 d in hospital.At the 2-mo follow-up visit,the patient was in good health with no recurrence of arrhythmia.CONCLUSION Although cochineal red is a safe,natural food additive,excessive consumption or occupational exposure can induce cardiac arrhythmias.

Functional remodeling of Ca^(2+)-activated Cl^-channel in pacing induced canine failing heart

Objective To determine whether Ca2+ activated Cl- current(Icl(Ca)) contributes to the functional remodeling of the failing heart.Methods Whole cell patch-clamp recording technique was employed to record the Icl(Ca) in cardiac myocytes enzymatically isolatedfrom rapidly pacing induced canine failing hearts at room temperature and compared that of the normal hearts (Nor).Results Thecurrent density of DIDS(200M)sensitive Icl(Ca) induced by intracellular Ca2+ release trigged by L-type Ca2+ current(Ica,L)wassignificantly decreased in heart failare(HE)cells compared to Nor cells.At membrane voltage of 20mV,the Icl(Ca) density was 3.02±0.54 pA/pF in Nor(n=6)vs.1.31±0.25 pA/pF in HF(n=8)cells,(P＜0.01),while the averaged Ica,L density did not show differencebetween two groups.The time constant of current decay of Icl(Ca) was similar in both types of cells.On the other hand,in intra cellularCa2+ clamped mode,where the[Ca2+];was maintained at 100nmol/L,Icl(Ca) density be increased significantly in HF cells when themembrane voltage at+30mV or higher.Conclusions Our results suggest that Icl(Ca) density was decreased in pacing induced failingheart but the channel function be enhanced.Impaired Ca2+ handing in HF cells rather than reduced,Icl(Ca) channel function itself may havecaused this abnormality.The Icl(Ca) density reduction might contribute to the prolongation of action potential in failing heart.The Icl(Ca)channel function up-rugulation is likely to cause cardiac arrhythmia by inducing a delayed after depolarization,when Ca2+ overloadoccurred in diastolic failing heart cells.

A novel splice mutation of HERG in a Chinese family with long QT syndrome

Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in which six ion-channel genes have been identified. The phenotype-genotype relationships of the HERG (human ether-a-go-go-related gene) mutations are not fully understood. The objective of this study is to identify the underlying genetic basis of a Chinese family with LQTS and to characterize the clinical manifestations properties of the mutation. Single strand conformation polymorphism (SSCP) analyses were conducted on DNA fragments amplified by polymerase chain reaction from five LQT-related genes. Aberrant conformers were analyzed by DNA sequencing. A novel splice mutation in C-terminus of HERG was identified in this Chinese LQTS family,leading to the deletion of 11-bp at the acceptor splice site of Exon9 [Exon9 IVS del (-12→-2)]. The mutation might affect,through deficient splicing, the putative cyclic nucleotide binding domain (CNBD) of the HERG K+ channel. This mutation resulted in a mildly affected phenotype. Only the proband had a history of syncopes, while the other three individuals with long QT interval had no symptoms. Two other mutation carriers displayed normal phenotype. No sudden death occurred in the family. The 4 affected individuals and the two silent mutation carriers were all heterozygous for the mutation. It is the first splice mutation of HERG reported in Chinese LQTS families. Clinical data suggest that the CNBD mutation may be less malignant than mutations occurring in the pore region and be partially dominant over wild-type function.

Electrophysiological Study of V535M hERG Mutation of LQT2

This study examined the current changes of human ether-a-go-go-related gene （hERG） mutation derived from a LQT2 Chinese family with a highly penetrating phenotype. Mutation was identi-fied and site-directed mutagenesis was performed to induce the mutation in wild-type （WT） hERG. WT hERG and mutated V535M were cloned and transiently expressed in HEK293 cells. At the 48th and 72nd h after transfection, membrane currents were recorded using whole cell patch-clamp procedures. An A〉G transition at 1605 resulting in replacement of V535M was identified. Compared to WT, V535M mutation significantly decreased tail currents of hERG. At test potential of-40 mV after depolarizing at ＋50 mV, tail current densities were 83.354-7.06 pA/pF in WT and 50.38-4-7.74 pA/pF in V535M respectively （n=20, P〈0.01）. Gating kinetics of bERG revealed that Vl/2 of steady-state inactivation shifted to negative potential in the mutant （V1/2,v535M： -61.814-1.7 mV vs. V1/2, wx： -43.1q-0.71 mV）. The time constant of recovery from inactivation was markedly prolonged in the mutant compared to WT among test potentials. V535M hERG mutation demonstrated markedly decreased tail current densities, which suggests that V535M is a new loss-of-function mutation of hERG channel responsible for LQT2.

Transient ventricular arrhythmia as a rare cause of dizziness during exercise:A case report

BACKGROUND Dizziness is a common symptom in adults and usually due to peripheral causes affecting semicircular canal function or central causes affecting the pons,medulla,or cerebellum.Arrhythmia is a recognized cause of dizziness in people with structural or ischemic heart disease.We report a case of exercise-induced transient ventricular tachycardia and dizziness in a man with no evidence of organic heart disease.CASE SUMMARY A 42-year-old man presented with a 6 mo history of transient exercise-induced dizziness and prodromal palpitations.The patient was otherwise asymptomatic.Physical examination,otoscopy,vestibular tests,cerebellar tests,laboratory investigations,and imaging investigations were all unremarkable.Twenty-four hour Holter monitoring revealed four episodes of transient ventricular tachycardia during exercise.The patient was started on metoprolol and subsequently underwent radiofrequency catheter ablation.The patient reported a full recovery and no dizziness during daily activities.These results were maintained at the 6 mo follow-up.CONCLUSION Ventricular tachycardia is an uncommon but potentially serious cause of dizziness.The outcome of this case illustrates the benefits of careful clinical examination and communication with specialized centers.High clinical suspicion of arrhythmia in a patient with dizziness merits consultation with a cardiologist and referral to a specialized center to ensure timely diagnosis and treatment.

Brugada Syndrome: Anesthesia Management

Brugada’s Syndrome (BrS) is a rare but highly risky medical condition. It is a genetic disorder that may result in Ventricular Fibrillations (VF) that can lead to sudden cardiac arrest. The highest possible standards of safety in anesthetic medications must be followed and adequate measures must be taken with sufficient monitorization in patients with BrS. We wanted to mention the importance of monitorization in the early detection of possible complications and a careful follow-up even though no administration of anesthetic medication is present.

Self-Control of Heart Rhythmdisorders

The broken rhythm of the heart activity of a person can lead to fatal consequences if it is not detected at an early stage. The article described a device for counting and indicating the number of violations of rhythm of cardiac activity. The device is intended for home use and does not require medical knowledge. If the patient will notice a trend towards the increasing number of arrhythmias, he must seek for cardiology advice.

Conventional Acupuncture for Cardiac Arrhythmia：A Systematic Review of Randomized Controlled Trials

Objective：To exam the effect and safety of conventional acupuncture（CA） on cardiac arrhythmia.Methods：Nine medical databases were searched until February 2016 for randomized controlled trials.Heterogeneity was measured by Cochran Q test.Meta-analysis was conducted if I2 was less than 85% and the characteristics of included trials were similar.Results：Nine qualified studies involving 638 patients were included.Only 1 study had definitely low risk of bias,while 7 trials were rated as unclear and 1 as high.Meta-analysis of CA alone did not have a significant benefit on response rate compared to amiodarone in patients with atrial fibrillation（Af） and atrial flutter（AF） [relative risk（RR）：1.09;95% confidence interval（CI）：0.79–1.49;P=0.61;I2=61%,P=0.11].However,1 study with higher methodological quality detected a lower recurrence rate of Af in CA alone as compared with sham acupuncture plus no treatment,and benefits on ventricular rate and time of conversion to normal sinus rhythm were found in CA alone group by 1 study,as well as the response rate in CA plus deslanoside group by another study.Meta-analysis of CA plus anti-arrhythmia drug（AAD） was associated with a significant benefit on the response rate when compared with AAD alone in ventricular premature beat（VPB） patients（RR,1.19,95% CI：1.05–1.34;P=0.005;I2=13%,P=0.32）,and an improvement in quality-of-life score（QOLS） of VPB also showed in 1 individual study.Besides,a lower heart rate was detected in the CA alone group by 1 individual study when compared with no treatment in sinus tachycardia patients（MD –21.84 [–27.21,–16.47]） and lower adverse events of CA alone were reported than amiodarone.Conclusions：CA may be a useful and safe alternative or additive approach to AADs for cardiac arrhythmia,especially in VPB and Af patients,which mainly based on a pooled estimate and result from 1 study with higher methodological quality.However,we could not reach a robust conclusion due to low quality of overall evidence.

Cardiac arrhythmia with premature ventricular contractures induced by interferon beta in a patient with multiple sclerosis

Multiple sclerosis(MS)is an immune‑mediated inflammatory and neurodegenerative disease of the central nervous system.Interferon(IFN)beta is an active ingredient of five out of twelve disease modifying treatments approved for MS.We report a case of IFN‑beta‑induced cardiac arrhythmia with premature ventricular contractures in a patient recently diagnosed with MS.

Domain knowledge enhanced deep learning for electrocardiogram arrhythmia classification

Deep learning provides an effective way for automatic classification of cardiac arrhythmias,but in clinical decisionmaking,pure data-driven methods working as black-boxes may lead to unsatisfactory results.A promising solution is combining domain knowledge with deep learning.This paper develops a flexible and extensible framework for integrating domain knowledge with a deep neural network.The model consists of a deep neural network to capture the statistical pattern between input data and the ground-truth label,and a knowledge module to guarantee consistency with the domain knowledge.These two components are trained interactively to bring the best of both worlds.The experiments show that the domain knowledge is valuable in refining the neural network prediction and thus improves accuracy.