AutoRhythmAI: A Hybrid Machine and Deep Learning Approach for Automated Diagnosis of Arrhythmias

In healthcare,the persistent challenge of arrhythmias,a leading cause of global mortality,has sparked extensive research into the automation of detection using machine learning(ML)algorithms.However,traditional ML and AutoML approaches have revealed their limitations,notably regarding feature generalization and automation efficiency.This glaring research gap has motivated the development of AutoRhythmAI,an innovative solution that integrates both machine and deep learning to revolutionize the diagnosis of arrhythmias.Our approach encompasses two distinct pipelines tailored for binary-class and multi-class arrhythmia detection,effectively bridging the gap between data preprocessing and model selection.To validate our system,we have rigorously tested AutoRhythmAI using a multimodal dataset,surpassing the accuracy achieved using a single dataset and underscoring the robustness of our methodology.In the first pipeline,we employ signal filtering and ML algorithms for preprocessing,followed by data balancing and split for training.The second pipeline is dedicated to feature extraction and classification,utilizing deep learning models.Notably,we introduce the‘RRI-convoluted trans-former model’as a novel addition for binary-class arrhythmias.An ensemble-based approach then amalgamates all models,considering their respective weights,resulting in an optimal model pipeline.In our study,the VGGRes Model achieved impressive results in multi-class arrhythmia detection,with an accuracy of 97.39%and firm performance in precision(82.13%),recall(31.91%),and F1-score(82.61%).In the binary-class task,the proposed model achieved an outstanding accuracy of 96.60%.These results highlight the effectiveness of our approach in improving arrhythmia detection,with notably high accuracy and well-balanced performance metrics.

Facing ethical concerns in the age of precise gene therapy:Outlook on inherited arrhythmias

This editorial,comments on the article by Spartalis et al published in the recent issue of the World Journal of Cardiology.We here provide an outlook on potential ethical concerns related to the future application of gene therapy in the field of inherited arrhythmias.As monogenic diseases with no or few therapeutic options available through standard care,inherited arrhythmias are ideal candidates to gene therapy in their treatment.Patients with inherited arrhythmias typically have a poor quality of life,especially young people engaged in agonistic sports.While genome editing for treatment of inherited arrhythmias still has theoretical application,advances in CRISPR/Cas9 technology now allows the generation of knock-in animal models of the disease.However,clinical translation is somehow expected soon and this make consistent discussing about ethical concerns related to gene editing in inherited arrhythmias.Genomic off-target activity is a known technical issue,but its relationship with ethnical and individual genetical diversity raises concerns about an equitable accessibility.Meanwhile,the costeffectiveness may further limit an equal distribution of gene therapies.The economic burden of gene therapies on healthcare systems is is increasingly recognized as a pressing concern.A growing body of studies are reporting uncertainty in payback periods with intuitive short-term effects for insurance-based healthcare systems,but potential concerns for universal healthcare systems in the long term as well.Altogether,those aspects strongly indicate a need of regulatory entities to manage those issues.

Characterizing the Impact of Caffeine on Heart Arrhythmias

Caffeine is one of the most commonly consumed stimulants and is found in many items like coffee and energy drinks. Heart arrhythmias are irregular heart rhythms, which can occur when the electrical signals that control the heart’s rhythm are not functioning properly. Due to the stimulant properties of caffeine, it is theorized that caffeine consumption may cause tachycardias-like ventricular arrhythmias. This review article describes the relationship between caffeine intake and heart arrhythmias using a comprehensive Pub-Med search. A comprehensive search was conducted using the search terms “caffeine arrhythmia” which was conducted and a total of 26 search results were obtained. The majority of clinical studies suggest that there are no strong associations between caffeine consumption and arrhythmias. There is little evidence suggesting a direct relationship between caffeine and ventricular arrhythmias (relative Risk 1.00, 95% CI 0.94 - 1.06;13.5%, p = 0.32). Conversely, caffeine consumption has an inverse relationship with the risk of atrial fibrillation (p for overall trend = 0.015;p for nonlinearity = 0.27). Caffeine related deaths are uncommon, but certain groups such as infants, psychiatric patients, and athletes may have an increased risk of arrhythmias following caffeine consumption. Overall, caffeine consumption is not strongly linked to heart arrhythmias and limited studies suggest it may reduce the risk of arrhythmias. Although there is not a strong relationship between caffeine intake and heart arrhythmias, it does cause other cardiovascular problems including high blood pressure and hence should be consumed responsibly (40 - 180 mg/day).

Inherited arrhythmias and gene therapy: Are there any ethical considerations to take into account?

Interventional electrophysiology represents a relatively recent subspecialty within the field of cardiology.In the past half-century,there has been significant advan-cement in the development and implementation of innovative ablation treatments and approaches.However,the treatment of arrhythmias continues to be inade-quate.Several arrhythmias,such as ventricular tachycardia and atrial fibrillation,pose significant challenges in terms of therapeutic efficacy,whether through interventional procedures or the administration of antiarrhythmic drugs.Cardio-logists are engaged in ongoing research to explore innovative methodologies,such as genome editing,with the purpose of effectively managing arrhythmias and meeting the growing needs of patients afflicted with rhythm disturbances.The field of genome editing has significant promise and has the potential to serve as a highly effective personalized therapy for rhythm disorders in patients.However,several ethical issues must be considered.

Cardiac-targeted PIASy gene silencing mediates deSUMOylation of caveolin-3 and prevents ischemia/reperfusion-induced Na_(v)1.5 downregulation and ventricular arrhythmias

Background:Abnormal myocardial voltage-gated sodium channel 1.5(Nav1.5)expression and function cause lethal ventricular arrhythmias during myocardial ischemia–reperfusion(I/R).Protein inhibitor of activated STAT Y(PIASy)-mediated caveolin-3(Cav-3)small ubiquitin-related modifier(SUMO)modification affects Cav-3 binding to the Nav1.5.PIASy activity is increased after myocardial I/R,but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias.Methods:Using recombinant adeno-associated virus subtype 9(AAV9),rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA(shRNA).After two weeks,rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias.Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements.Results:PIASy was upregulated by I/R(P<0.01),with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density(P<0.01).AAV9-PIASy shRNA intraventricular injection into the rat heart down-regulated PIASy after I/R,at both mRNA and protein levels(P<0.05 vs.Scramble-shRNA+I/R group),decreased SUMO-modified Cav-3 levels,enhanced Cav-3 binding to Nav1.5,and prevented I/R-induced decrease of Nav1.5 and Cav-3co-localization in the intercalated disc and lateral membrane.PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias,which was reflected by a modest decrease in the duration of ventricular fibrillation(VF;P<0.05 vs.Scramble-shRNA+I/R group)and a significantly reduced arrhythmia score(P<0.01 vs.Scramble-shRNA+I/R group).The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia(VT),sustained VT and VF,especially at the time 5–10 min after ischemia(P<0.05 vs.Scramble-shRNA+IR group).Using in vitro human embryonic kidney 293 T(HEK293T)cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation(H/R),we confirmed that increased PIASy promoted Cav-3 modification by SUMO2/3 and Nav1.5/Cav-3 dissociation after H/R.Mutation of SUMO consensus lysine sites in Cav-3(K38R or K144R)altered the membrane expression levels of Nav1.5 and Cav-3 before and after H/R in HEK293T cells.Conclusions:I/R-induced cardiac PIASy activation increased Cav-3 SUMOylation by SUMO2/3 and dysregulated Nav1.5-related ventricular arrhythmias.Cardiac-targeted PIASy silencing mediated Cav-3 deSUMOylation and partially prevented I/R-induced Nav1.5 downregulation in the plasma membrane of cardiomyocytes,and subsequent ventricular arrhythmias in rats.PIASy was identified as a potential therapeutic target for life-threatening arrhythmias in patients with ischemic heart diseases.

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.

Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43(cx43)

Objective: To explore the effect and mechanism of angiotensin Ⅱ receptor blockers-Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods: Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan+ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43(Cx43) mR NA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group(SO), myocardial infarction group(MI), Irbesartan group and MI+ Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mR NA and protein level. Results: The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia(P<0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group(P<0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arerythmia between MI group and SO group(P<0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group(P<0.05). There was the significant difference in the overall score between MI+Irbesartan group and MI group(P<0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased(P<0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan. Conclusions: Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.

Continuous Positive Airway Pressure Effectively Alleviates Arrhythmias in Patients with Obstructive Sleep Apnea:Possible Relationship with Counteracting Oxidative Stress

This work is aimed at exploring the clinical efficacy of continuous positive airway pressuie(CPAP)in treatment of patients with arrhythmias combined with obstructive sleep apnea(OSA).Through evaluating serum native thiol,malonaldehyde(MDA)and nicotinamide adenine dinucleotide phosphate oxidase(NADPH oxidase)in these patients and describing the effects on oxidative parameters of CPAP therapy for 3 months,we confirmed the impact of oxidative stress on arrhythmias.A total of 64 patients with OSA combined with arrhythmias were collected from April 2014 to April 2017 with full clinical information.Patients were divided into two groups(paired experiment design):32 patients in group A(control group),who received unchanged anti-arrhythmia treatment and 32 patients in group B,who were subjected to unchanged pharmacological anti-arrhythmia therapy combined with CPAP.OSA related parameters were compared between the two groups after 3-month therapy.And the levels of parameters of oxidative stress in patients were measured before and after CPAP therapy.After 3 months of CPAP therapy,compared with the control group,the percentage of sage N3(NREM 3)and stage R(REM)in total sleep time was significantly increased,while apnea-hypopnea index(AHI)and the Epworth Sleepiness Scale(ESS)score were evidently decreased.Meanwhile,the lowest oxygen saturation(LSpCh)was also elevated after CPAP treatment for 3 months.The CPAP therapy significantly prevented the occurrence of arrhythmias(P<0.05).Both the MDA level and NADPH oxidase levels were significantly lower in the group B than in the group A(P<0.05).But serum native thiol was improved by CPAP treatment(P<0.05).In conclusion,proper use of CPAP therapy provides significant benefits for the treatment of arrhythmia in patients with OSA.

C-reactive protein as a predictor of malignant ventricular arrhythmias in non-ST elevation myocardial infarction

Objective To investigate whether C-reactive protein (CRP) is a biomarker of malignant ventricular arrhythmias (MVA) occurring in non-ST elevation myocardial infarction (NSTEMI) patients with Global Registry of Acute Coronary events (GRACE) scores < 140. Methods A total of 1450 NSTEMI patients were included in this study. Hs-CRP blood levels were measured via a turbidimetric immunoassay after confirming the diagnosis of NSTEMI with GRACE scores < 140. Results Consistent with prior studies, the MVA occurrence rate in our cohort was 6.7%, and patients with MVA exhibited a reduced left ventricular ejection fraction (46.1%± 6.9% vs. 61.5%± 8.7%, P = 0.032), a higher incidence of Killip classification > 1 (34.1% vs. 24.2%, P < 0.001), an increased surgical revascularization rate (34.1% vs. 9.7%, P < 0.001), and increased mortality (16.5% vs. 5.8%, P < 0.001). Serum hs-CRP levels were higher (P = 0.003) in NSTEMI patients with MVA, and this increase appeared unrelated to other clinical parameters. The C-statistic to discriminate MVA was 0.82 (95% CI: 0.74–0.89). Using receiver operating characteristics analysis, we optimized a cutoff point of 16 mL/L, and the sensitivity and specificity were 95% and 61%, respectively;the positive predictive value was 20% and the negative predictive value was 99%. Conclusions An hs-CRP assay is a potential MVA biomarker in low-risk NSTEMI patients with GRACE scores < 140. If validated in prospective studies, hs-CRP may offer a low-cost supplementary strategy for risk stratification for NSTEMI patients.

Heart rate-adjusted PR as a prognostic marker of long-term ventricular arrhythmias and cardiac death in ICD/CRT-D recipients

Objective To evaluate the PR to RR interval ratio (PR/RR,heart rate-adjusted PR) as a prognostic marker for long-term ventricular arrhythmias and cardiac death in patients with implantable cardioverter defibrillator (ICDs) and cardiac resynchronization therapy with defibrillators (CRT-D).Methods We retrospectively analyzed data from 428 patients who had an ICD/CRT-D equipped with home monitoring.Baseline PR and RR interval data prior to ICD/CRT-D implantation were collected from standard 12-lead electrocardiograph,and the PR/RR was calculated.The primary endpoint was appropriate ICD/CRT-D treatment of ventricular arrhythmias (VAs),and the secondary endpoint was cardiac death.Results During a mean follow-up period of 38.8 ± 10.6 months,197 patients (46%) experienced VAs,and 47 patients (11%) experienced cardiac death.The overall PR interval was 160 ± 40 ms,and the RR interval was 866 ± 124 ms.Based on the receiver operating characteristic curve,a cut-off value of 18.5% for the PR/RR was identified to predict VAs.A PR/RR ≥ 18.5% was associated with an increased risk of VAs [hazard ratio (HR)= 2.243,95% confidence interval (CI)= 1.665–3.022,P < 0.001) and cardiac death (HR = 2.358,95%CI = 1.240–4.483,P = 0.009) in an unadjusted analysis.After adjustment in a multivariate Cox model,the relationship remained significant among PR/RR ≥ 18.5%,VAs (HR = 2.230,95%CI = 1.555–2.825,P < 0.001) and cardiac death (HR = 2.105,95%CI = 1.101–4.025,P = 0.024.Conclusions A PR/RR ≥ 18.5% at baseline can serve as a predictor of future VAs and cardiac death in ICD/CRT-D recipients.

COVID-19 pandemic:usefulness of telemedicine in management of arrhythmias in elderly people

In March 2020,the WHO defined the diffusion of novel coronavirus,Severe Acute Respiratory Syndrome-Coronavirus-2(SARS-CoV-2)as pandemic.[1-3]As a consequence,the Italian Government among others has enforced quarantine on the population to contain the diffusion of the infection.Quarantine refers to the separation of communities who have been exposed to an infectious disease.[1-3]Elderly people's lives have been drastically affected by the lockdown and the fear related to the disease’s potential effects and transmission.Fear of contracting COVID-19 is on the rise due to the death toll and alarming news reports in the media.[2,3].

Cardiac arrhythmias detection in an ECG beat signal using fast fourier transform and artificial neural network

Cardiac Arrhythmias shows a condition of abnor-mal electrical activity in the heart which is a threat to humans. This paper presents a method to analyze electrocardiogram (ECG) signal, extract the fea-tures, for the classification of heart beats according to different arrhythmias. Data were obtained from 40 records of the MIT-BIH arrhythmia database (only one lead). Cardiac arrhythmias which are found are Tachycardia, Bradycardia, Supraventricular Tachycardia, Incomplete Bundle Branch Block, Bundle Branch Block, Ventricular Tachycardia. A learning dataset for the neural network was obtained from a twenty records set which were manually classified using MIT-BIH Arrhythmia Database Directory and docu- mentation, taking advantage of the professional experience of a cardiologist. Fast Fourier transforms are used to identify the peaks in the ECG signal and then Neural Networks are applied to identify the diseases. Levenberg Marquardt Back-Propagation algorithm is used to train the network. The results obtained have better efficiency then the previously proposed methods.

Amiodarone Therapy for Cardiac Arrhythmias: Is It Associated with the Development of Cancers?

Amiodarone is used worldwide to treat cardiac arrhythmias, as well as highly symptomatic cases of atrial fibrillation. With this expanded use, especially following its 1985 United States Food and Drug Administration approval, and its use as a long-term therapy in common practice, reports of cancers temporarily related to amiodarone have begun to increase. Animal studies, several clinical trials, numerous case reports, and a population-based cohort study have suggested that cancers may be associated with amiodarone use. This review focuses on the ever increasing evidence in the literature that suggests amiodarone therapy, especially with long-term use, may increase the potential risk of cancer development. It also expresses the need for more definitive studies to be conducted to provide clinicians with a clear answer to this important question.

Prophylactic effect of magnesium sulfate against reperfusion induced arrhythmias in the isolated rat hearts

Prophylactic effect of magnesium sulfate on reperfusion arrhythmias was studiedusing a left anterior descending coronary artery occlusion followed by reperfusion in theisolated rat heart.In the first studies,we have observed a bell-shaped relationship be-tween the incidence of reperfusion-induced ventricular fibrillation（VF）and the durationof preceding ischemia.With 5,10,15,20 and 25 min of ischemia,10,70,60,50 and 20per cent of the hearts exhibited irreversible VF,respectively.In the second studies（10 minischemia）,perfusate magnesium sulfate was increased to 3.6,4.8 and 6.0 mmol/L 1 min be-fore coronary ligation,VF fell in a dose-dependent manner from its control total inci-dence of 100%（1.2mmol/L MgSO4）to 82%,73% and 18%（P【0.01）,respectively.Heartrate was also reduced in a dose-dependent manner,falling from its control value of326±11 to 227±22 beats/min with the highest concentration of magnesium sulfate.Asperfusate magnesium sulfate was increased to 6.0 mmol/L just before reperfusion,no an-ti-arrhythmic effects were observed.With an anti-arrhythmic concentration of magnesiumsulfate（6.0 mmol/L,increased 1 min before ligation）,calcium concentration was increasedby 1.5 mmol/L at the same time,under these conditions the anti-arrhythmic effect of mag-nesium sulfate was lost and its negative chronotropic effect was also partially abolished.We conclude that magnesium sulfate has a certain prophylactic effect againstreperfusion induced arrhythmias and this could be due to a direct or indirect calci-um-antagonist action.

Athletes and Arrhythmias

Sudden cardiac death related to athletic competition is a rare but tragic event.The victims are typically young with no previous cardiovascular symptoms or limitations.The majority of sudden cardiac death events in athletes are due to ventricular arrhythmias as a result of underlying molecular and/or structural level pathologic substrate.In this article,we will review the physiologic cardiac adaptations to exercise along with arrhythmias seen in athletes with a focus on those commonly associated with sudden cardiac death.

Effect of berberine on reperfusion arrhythmias in the isolated rat heart

Effect of berberine on reperfusion arrhythmias was studied using a10min left anterior descending coronary artery occlusion followed by reperfusionin the isolated rat heart.Berberine when given 10min before coronary ligation re-duced the incidence of reperfusion arrhythmias in a dose-dependent manner.With10-5,3.16×10-5 and 10-4mol/L of berberine,ventricular fibrillation was reducedfrom its control incidence of 100% to 90%,70% and 40% （P【0.05） respectively.Heart rate was also reduced in a dose-dependent manner,falling from its controlvalue of 282±11 to 180±11 beats/min with the highest concentration of berberine.Coronary flow was increased in all berberine treated groups.With anantiarrhythmic dose of berberine (10-4mol/L),hearts were paced （5 Hz） duringischemia period;under these conditions the anti-arrhythmic effect of berberinewas lost.When berberine (3.16×10-5 and 10-4mol/L) was administered just beforereperfusion,no anti-arrhythmic effects were observed.The α-adrenoceptor antago-nist phentolamine (2.6×10-5mol/L) prevented reperfusion arrhythmias and ismuch more effective than berberine.These results suggest that the prophylatic ef-fects of berberine on reperfusion arrhythmias in the isolated rat heart are due toits negative chronotropic properties.

Fetal Bradyarrhythmias:Etiopathogenesis,Diagnosis and Treatment:Between Literature Review and Experience of a Tertiary Center

Fetal arrhythmias reach up around 10%of the total third-level perinatal cardiology references.Sustained bradycardia is defined as a baseline fetal heart rate(FHR)of less than 110 bpm sustained for at least 10 min.The overall incidence of malignant fetal bradyarrhythmias,such as complete atrioventricular block(AVB)and channellopathies,is relatively rare,1:5000 pregnancies,but represents a serious emergency for the gynecologist,neonatologists,and pediatric cardiologists.Fetal complete AVB is strongly associated with maternal connective tissue disease,but it can be also associated with congenital heart disease and usually with a poorer prognosis with high risk of fetal hydrops and abortion.Currently,the treatment of severe fetal bradyarrhythmias is principally pharmacological and aims to increase the FHR,besides an early resolution of underlying causes,when possible,and a promptly management of fetal heart failure.Intrauterine electrostimulation nowadays is an experimental pioneering method,reserved for limited selected cases.

Arrhythmias,chronic kidney disease and the elderly:a triple jeopardy

Crdiovascular diseases (CVD) incur a heavy burden of morbidity and mortality among patients with chronic kidney disease (CKD),particularly among the elderly.It is estimated that about 22-25% of all adults beyond the age of 65 years have moderate or severe renal dysfunction.1。

The Role of Sleep Deprivation in Arrhythmias

Sleep is essential to the normal psychological and physiological activities of the human body.Increasing evidence indicates that sleep deprivation is associated with the occurrence,development,and poor treatment effects of various arrhythmias.Sleep deprivation affects not only the peripheral nervous system but also the central nervous system,which regulates the occurrence of arrhythmias.In addition,sleep deprivation is associated with apoptotic pathways,mitochondrial energy metabolism disorders,and immune system dysfunction.Although studies increasingly suggest that pathological sleep patterns are associated with various atrial and ventricular arrhythmias,further research is needed to identify specific mechanisms and recommend therapeutic interventions.This review summarizes the findings of sleep deprivation in animal experiments and clinical studies,current challenges,and future research directions in the field of arrhythmias.

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.