External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronised electric shock (electrical cardioversion). OBJECTIVES: To assess the efficacy and safety of pharmacological and electrical cardioversion for atrial fibrillation (AF), atrial flutter and atrial tachycardias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) and three trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) at the individual patient level. Patient populations were aged ≥ 18 years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring as a result of reversible causes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to collect data and performed a network meta-analysis using the standard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess the quality of the evidence which we presented in our summary of findings with a judgement on certainty. We calculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatments using a P value. We assessed clinical and statistical heterogeneity and split the networks for the primary outcome and acute procedural success, due to concerns about violating the transitivity assumption. MAIN RESULTS: We included 112 RCTs (139 records), from which we pooled data from 15,968 patients. The average age ranged from 47 to 72 years and the proportion of male patients ranged from 38% to 92%. Seventy-nine trials were considered to be at high risk of bias for at least one domain, 32 had no high risk of bias domains, but had at least one domain classified as uncertain risk, and one study was considered at low risk for all domains. For paroxysmal AF (35 trials), when compared to placebo, anteroapical (AA)/anteroposterior (AP) biphasic truncated exponential waveform (BTE) cardioversion (RR: 2.42; 95% CI 1.65 to 3.56), quinidine (RR: 2.23; 95% CI 1.49 to 3.34), ibutilide (RR: 2.00; 95% CI 1.28 to 3.12), propafenone (RR: 1.98; 95% CI 1.67 to 2.34), amiodarone (RR: 1.69; 95% CI 1.42 to 2.02), sotalol (RR: 1.58; 95% CI 1.08 to 2.31) and procainamide (RR: 1.49; 95% CI 1.13 to 1.97) likely result in a large increase in maintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate). The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions. Despite low certainty of evidence, antazoline may result in a large increase (RR: 28.60; 95% CI 1.77 to 461.30) in this outcome. Similarly, low-certainty evidence suggests a large increase in this outcome for flecainide (RR: 2.17; 95% CI 1.68 to 2.79), vernakalant (RR: 2.13; 95% CI 1.52 to 2.99), and magnesium (RR: 1.73; 95% CI 0.79 to 3.79). For persistent AF (26 trials), one network was created for electrical cardioversion and showed that, when compared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95% CI 1.17 to 1.55) likely results in a large increase, and active compression AP BTE incremental energy with patches (RR: 1.14, 95% CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95% CI 0.98 to 1.09; certainty of evidence: low) may lead to a slight increase, and AP MDS Incremental paddles (RR: 0.95, 95% CI 0.86 to 1.05; certainty of evidence: low) may lead to a slight decrease in efficacy. On the other hand, AP MDS incremental energy using patches (RR: 0.78, 95% CI 0.70 to 0.87), AA RBW incremental energy with patches (RR: 0.76, 95% CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95% CI 0.68 to 0.86), AA MDS incremental energy with patches (RR: 0.76, 95% CI 0.67 to 0.86) and AA MDS incremental energy with paddles (RR: 0.68, 95% CI 0.53 to 0.83) probably result in a decrease in this outcome when compared to AP BTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacological cardioversion showed that bepridil (RR: 2.29, 95% CI 1.26 to 4.17) and quindine (RR: 1.53, (95% CI 1.01 to 2.32) probably result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up when compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95% CI 0.56 to 1.44), sotalol (RR: 0.89, 95% CI 0.67 to 1.18), propafenone (RR: 0.79, 95% CI 0.50 to 1.25) and pilsicainide (RR: 0.39, 95% CI 0.02 to 7.01) may result in a reduction in this outcome when compared to amiodarone, but the certainty of evidence is low. For atrial flutter (14 trials), a network could be created only for antiarrhythmic drugs. Using placebo as the common comparator, ibutilide (RR: 21.45, 95% CI 4.41 to 104.37), propafenone (RR: 7.15, 95% CI 1.27 to 40.10), dofetilide (RR: 6.43, 95% CI 1.38 to 29.91), and sotalol (RR: 6.39, 95% CI 1.03 to 39.78) probably result in a large increase in the maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: moderate), and procainamide (RR: 4.29, 95% CI 0.63 to 29.03), flecainide (RR 3.57, 95% CI 0.24 to 52.30) and vernakalant (RR: 1.18, 95% CI 0.05 to 27.37) may result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: low). All tested electrical cardioversion strategies for atrial flutter had very high efficacy (97.9% to 100%). The rate of mortality (14 deaths) and stroke or systemic embolism (3 events) at 30 days was extremely low. Data on quality of life were scarce and of uncertain clinical significance. No information was available regarding heart failure readmissions. Data on duration of hospitalisation was scarce, of low quality, and could not be pooled. AUTHORS' CONCLUSIONS: Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter. In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method.

Defining electrocardiographic criteria to differentiate non-type 1 Brugada ECG variants from normal incomplete RBBB patterns in the young SCD-SOS cohort.

INTRODUCTION: We assessed the prevalence of non-type 1 Brugada pattern (T1BrP) in children and young adults from the Sudden Cardiac Death-Screening Of risk factorS cohort and the diagnostic yield of nonexpert manual and automatic algorithm electrocardiogram (ECG) measurements. METHODS: Cross-sectional study. We reviewed 14 662 ECGs and identified 2226 with a rSr'-pattern in V1-V2. Among these, 115 were classified by experts in hereditary arrhythmic-syndromes as having or not non-T1BrP, and were compared with measurements of 5 ECG-derived parameters based on a triangle formed by r' -wave (d(A), d(B), d(B)/h, ß-angle) and ST-ascent, assessed both automatically and manually by nonexperts. We estimated intra- and interobserver concordance for each criterion, calculated diagnostic accuracy and defined the most appropriate cut-off values. RESULTS: A rSr'-pattern in V1-V2 was associated with higher PQ interval and QRS duration, male gender, and lower body mass index (BMI). The manual measurements of non-T1BrP criteria were moderately reproducible with high intraobserver and moderate interobserver concordance coefficients (ICC: 0.72-0.98, and 0.63-0.76). Criteria with higher discriminatory capacity were: distance d(B) (0.72; 95% confidence interval [CI]: 0.65-0.80) and ST-ascent (0.87; 95% CI: 0.82-0.92), which was superior to the 4 r'-wave criteria together (area under curve [AUC: 0.74]). We suggest new cut-offs with improved combination of sensitivity and specificity: d(B) ≥ 1.4 mm and ST-ascent ≥ 0.7 mm (sensitivity: 1%-82%; specificity: 71%-84%), that can be automatically measured to allow classification in four morphologies with increasing non-T1BrP probability. CONCLUSION: rSr'-pattern in precordial leads V1-V2 is a frequent finding and the detection of non-T1BrP by using the aforementioned five measurements is reproducible and accurate. In this study, we describe new cut-off values that may help untrained clinicians to identify young individuals who may require further work-up for a potential Brugada Syndrome diagnosis.

Clinical applications of heart rhythm monitoring tools in symptomatic patients and for screening in high-risk groups.

Recent technological advances have facilitated and diversified the options available for the diagnosis of cardiac arrhythmias. Ranging from simple resting or exercise electrocardiograms to more sophisticated and expensive smartphones and implantable cardiac monitors. These tests and devices may be used for varying periods of time depending on symptom frequency. The choice of the most appropriate heart rhythm test should be guided by clinical evaluation and optimized following accurate characterization of underlying symptoms, 'red flags', risk factors, and consideration of cost-effectiveness of the different tests. This review provides evidence-based guidance for assessing suspected arrhythmia in patients who present with symptoms or in the context of screening, such as atrial fibrillation or advanced conduction disturbances following transcatheter aortic valve implantation in high-risk groups. This is intended to help clinicians choose the most appropriate diagnostic tool to facilitate the management of patients with suspected arrhythmias.

High-risk features and predictors of unexplained syncope in the young SCD-SOS cohort.

INTRODUCTION: The Sudden Cardiac Death-Screening of Risk FactOrS survey included a 12-lead electrocardiogram (ECG) plus a digital-based questionnaire and aimed to screen for warning signs of diseases that may course with sudden cardiac death in children and young adults. We aimed to estimate the prevalence of unexplained syncope (US) and characterize its high-risk features and predictors in this cohort. METHODS AND RESULTS: We determined the most probable etiology of transient loss of consciousness (TLOC) episodes based on clinical criteria. US was an exclusion diagnosis and we analyzed its potential clinical and ECG predictors. Among 11 878 individuals, with a mean age of 21 ± 6 (range 6-40) years old, the cumulative incidence of TLOC was 26.5%, 76.2% corresponding to females. Reflex syncope was present in 66.4%, orthostatic hypotension in 8.2%, and 14.8% of the individuals had US. Unexplained syncope was independently associated with age < 18 years old (odds ratio [OR] 1.695; 95% confidence interval [CI] 1.26-2.29, p = .001), male gender (OR 1.642; 95% CI 1.22-2.22, p = .001), participation in competitive sports (OR 1.644; 95% CI 1.01-2.66, p = .043), syncope during exertion and/or palpitations preceding syncope (OR 2.556; 95% CI 1.92-3.40, p < .001), syncope after exertion (OR 2.662; 95% CI 1.73-4.10, p < .001), fever context (OR 9.606; 95% CI 4.13-22.34, p < .001), isolated previous syncopal episode (OR 2.780; 95% CI 0.2.06-3.75, p < .001), and history of palpitations requiring medical care (OR 1.945; 95% CI 1.14-3.31, p = .014). We found no ECG predictors of US in this population. CONCLUSIONS: The cumulative incidence of TLOC in children and young adults is high and remains unexplained in an important proportion of individuals. We identified eight clinical characteristics that may be useful for the risk stratification of individuals evaluated in a nonacute setting.

Health inequalities in cardiopulmonary resuscitation and use of automated electrical defibrillators in out-of-hospital cardiac arrest.

Out of hospital cardiac arrest (OHCA) outcomes can be improved by strengthening the chain of survival, namely prompt cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED). However, provision of bystander CPR and AED use remains low due to individual patient factors ranging from lack of education to socioeconomic barriers and due to lack of resources such as limited availability of AEDs in the community. Although the impact of health inequalities on survival from OHCA is documented, it is imperative that we identify and implement strategies to improve public health and outcomes from OHCA overall but with a simultaneous emphasis on making care more equitable. Disparities in CPR delivery and AED use in OHCA exist based on factors including sex, education level, socioeconomic status, race and ethnicity, all of which we discuss in this review. Most importantly, we discuss the barriers to AED use, and strategies on how these may be overcome.

Sudden death in young South European population: a cross-sectional study of postmortem cases.

To describe the annual incidence and the leading causes of sudden non-cardiac and cardiac death (SCD) in children and young adult Portuguese population. We retrospectively reviewed autopsy of sudden unexpected deaths reports from the Portuguese National Institute of Legal Medicine and Forensic Sciences' database, between 2012 and 2016, for the central region of Portugal, Azores and Madeira (ages 1-40: 26% of the total population). During a 5-year period, 159 SD were identified, corresponding to an annual incidence of 2,4 (95%confidence interval, 1,5-3,6) per 100.000 people-years. Victims had a mean age of 32 ± 7 years-old, and 72,3% were male. There were 70,4% cardiac, 16,4% respiratory and 7,5% neurologic causes of SD. The most frequent cardiac anatomopathological diagnosis was atherosclerotic coronary artery disease (CAD) (33,0%). There were 15,2% victims with left ventricular hypertrophy, with a diagnosis of hypertrophic cardiomyopathy only possible in 2,7%. The prevalence of cardiac pathological findings of uncertain significance was 30,4%. In conclusion, the annual incidence of SD was low. Atherosclerotic CAD was diagnosed in 33,0% victims, suggesting the need to intensify primary prevention measures in the young. The high prevalence of pathological findings of uncertain significance emphasizes the importance of molecular autopsy and screening of first-degree relatives.

The importance of transesophageal echocardiography evaluation in a patient with acute limb ischaemia.

This a case of a patient with acute limb ischaemia in whom thorough transesophageal echocardiography (TEE) evaluation depicted a patent foramen ovale and allowed for the detection of a large thrombus arising from an atherosclerotic calcified plaque in the thoracic aorta. We aim to illustrate the importance of performing TEE when systemic emboli are suspected and to not neglect thoracic aorta evaluation when a potential intracardiac cause has been detected.

Intracardiac versus extracardiac shunt in a young man with ischaemic stroke.

A 24-year-old man with a history of recent ischaemic stroke was diagnosed with patent foramen ovale (PFO) and referred for closure at our hospital. At admission, besides low peripheral oxygen saturation (88%), physical examination was otherwise normal. We performed intraprocedural transoesophageal echocardiogram that revealed no PFO, although agitated saline injection demonstrated bubbles lately on the left atrium. The atrial septum could not be crossed. We suspected an extracardiac shunt, so pulmonary angiograms were performed that revealed the presence of a left pulmonary arteriovenous malformation (PAVM). A Konar-MF Occluder was used to occlude the PAVM, with a satisfactory result. At 6 months follow-up, the patient had normal peripheral oxygen saturation and a new pulmonary angiogram showed no residual shunt. Intrapulmonary shunts are a rare and under-recognised cause of paradoxical emboli in young patients; physicians should be aware of this diagnosis as percutaneous occlusion is indicated and critical to avoid recurrent ischaemic episodes.

Monitoring and diagnosis of intermittent arrhythmias: evidence-based guidance and role of novel monitoring strategies.

Technological advances have made diagnosis of heart rhythm disturbances much easier, with a wide variety of options, including single-lead portable devices, smartphones/watches to sophisticated implantable cardiac monitors, allowing accurate data to be collected over different time periods depending on symptoms frequency. This review provides an overview of the novel and existing heart rhythm testing options, including a description of the supporting evidence for their use. A description of each of the tests is provided, along with discussion of their advantages and limitations. This is intended to help clinicians towards choosing the most appropriate test, thus improving diagnostic yield management of patients with suspected arrhythmias.

Cardiopulmonary Resuscitation and Defibrillator Use in Sports.

Sudden cardiac arrest (SCA) in young athletes is rare, with an estimated incidence ranging from 0.1 to 2 per 100,000 per athlete year. The creation of SCA registries can help provide accurate data regarding incidence, treatment, and outcomes and help implement primary or secondary prevention strategies that could change the course of these events. Early cardiopulmonary resuscitation (CPR) and defibrillation are the most important determinants of survival and neurological prognosis in individuals who suffer from SCA. Compared with the general population, individuals with clinically silent cardiac disease who practice regular physical exercise are at increased risk of SCA events. While the implementation of national preparticipation screening has been largely debated, with no current consensus, the number of athletes who will be diagnosed with cardiac disease and have an indication for implantable defibrillator cardioverter defibrillator (ICD) is unknown. Many victims of SCA do not have a previous cardiac diagnosis. Therefore, the appropriate use and availability of automated external defibrillators (AEDs) in public spaces is the crucial part of the integrated response to prevent these fatalities both for participating athletes and for spectators. Governments and sports institutions should invest and educate members of the public, security, and healthcare professionals in immediate initiation of CPR and early AED use. Smartphone apps could play an integral part to allow bystanders to alert the emergency services and CPR trained responders and locate and utilize the nearest AED to positively influence the outcomes by strengthening the chain of survival. This review aims to summarize the available evidence on sudden cardiac death prevention among young athletes and to provide some guidance on strategies that can be implemented by governments and on the novel tools that can help save these lives.

Creatinine variation improves Zwolle score in selecting low-risk patients after ST-segment elevation myocardial infarction.

BACKGROUND: The Zwolle score is recommended to identify ST-segment elevation myocardial infarction (STEMI) patients with low-risk eligible for early discharge. Our aim was to ascertain if creatinine variation (Δ-sCr) would improve Zwolle score in the decision-making of early discharge after primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 3296 patients with STEMI that underwent primary PCI were gathered from the Portuguese Registry on Acute Coronary Syndromes. A Modified-Zwolle score, including Δ-sCr, was created and compared with the original Zwolle score. Δ-sCr was also compared between low (Zwolle score ≤3) and non-low-risk patients (Zwolle score >3). The primary endpoint is 30-day mortality and the secondary endpoints are in-hospital mortality and complications. Thirty-day mortality was 1.5% in low-risk patients (35 patients) and 9.2% in non-low-risk patients (92 patients). The Modified-Zwolle score had a better performance than the original Zwolle score in all endpoints: 30-day mortality (area under curve 0.853 versus 0.810, P < 0.001), in-hospital mortality (0.889 versus 0.845, P < 0.001) and complications (0.728 versus 0.719, P = 0.037). Reclassification of patients lead to a net reclassification improvement of 6.8%. Additionally, both original Zwolle score low-risk patients and non-low-risk patients who had a Δ-sCr ≥0.3 mg/dl had higher 30-day mortality (low-risk: 1% versus 6.6%, P < 0.001; non-low-risk 4.4% versus 20.7%, P < 0.001), in-hospital mortality and complications. CONCLUSION: Δ-sCr enhanced the performance of Zwolle score and was associated with higher 30-day mortality, in-hospital mortality and complications in low and non-low-risk patients. This data may assist the selection of low-risk patients who will safely benefit from early discharge after STEMI.

New-Onset Atrial Fibrillation in St-Segment Elevation Myocardial Infarction: Predictors and Impact on Therapy And Mortality.

BACKGRUND: New-onset atrial fibrillation complicating acute myocardial infarction represents an important challenge, with prognostic significance. OBJECTIVE: To study the incidence, impact on therapy and mortality, and to identify predictors of development of new-onset atrial fibrillation during hospital stay for ST-segment elevation myocardial infarction. METHODS: We studied all patients with ST-elevation myocardial infarction included consecutively, between 2010 and 2017, in a Portuguese national registry and compared two groups: 1 - no atrial fibrillation and 2 - new-onset atrial fibrillation. We adjusted a logistic regression model data analysis to assess the impact of new-onset atrial fibrillation on in-hospital mortality and to identify independent predictors of its development. A p value < 0.05 was considered significant. RESULTS: We studied 6325 patients, and new-onset atrial fibrillation was found in 365 (5.8%). Reperfusion was successfully accomplished in both groups with no difference regarding type of reperfusion. In group 2, therapy with beta-blockers and angiotensin-conversion enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) was less frequent, 20.6% received anticoagulation at discharge and 16.1% were on triple therapy. New-onset atrial fibrillation was associated with more in-hospital complications and mortality. However, it was not found as an independent predictor of in-hospital mortality. We identified age, prior stroke, inferior myocardial infarction and complete atrioventricular block as independent predictors of new-onset atrial fibrillation. CONCLUSION: New-onset atrial fibrillation remains a frequent complication of myocardial infarction and is associated with higher rate of complications and in-hospital mortality. Age, prior stroke, inferior myocardial infarction and complete atrioventricular block were independent predictors of new onset atrial fibrillation. Only 36.7% of the patients received anticoagulation at discharge.

New-Onset Atrial Fibrillation in St-Segment Elevation Myocardial Infarction: Predictors and Impact on Therapy And Mortality / Fibrilação Auricular de Novo no Infarto Agudo do Miocárdio com Supradesnível do Segmento ST: Preditores e Impacto na Terapêutica e Mortalidade

Abstract Backgrund: New-onset atrial fibrillation complicating acute myocardial infarction represents an important challenge, with prognostic significance. Objective: To study the incidence, impact on therapy and mortality, and to identify predictors of development of new-onset atrial fibrillation during hospital stay for ST-segment elevation myocardial infarction. Methods: We studied all patients with ST-elevation myocardial infarction included consecutively, between 2010 and 2017, in a Portuguese national registry and compared two groups: 1 - no atrial fibrillation and 2 - new-onset atrial fibrillation. We adjusted a logistic regression model data analysis to assess the impact of new-onset atrial fibrillation on in-hospital mortality and to identify independent predictors of its development. A p value < 0.05 was considered significant. Results: We studied 6325 patients, and new-onset atrial fibrillation was found in 365 (5.8%). Reperfusion was successfully accomplished in both groups with no difference regarding type of reperfusion. In group 2, therapy with beta-blockers and angiotensin-conversion enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) was less frequent, 20.6% received anticoagulation at discharge and 16.1% were on triple therapy. New-onset atrial fibrillation was associated with more in-hospital complications and mortality. However, it was not found as an independent predictor of in-hospital mortality. We identified age, prior stroke, inferior myocardial infarction and complete atrioventricular block as independent predictors of new-onset atrial fibrillation. Conclusion: New-onset atrial fibrillation remains a frequent complication of myocardial infarction and is associated with higher rate of complications and in-hospital mortality. Age, prior stroke, inferior myocardial infarction and complete atrioventricular block were independent predictors of new onset atrial fibrillation. Only 36.7% of the patients received anticoagulation at discharge.

Resumo Fundamento: A fibrilação auricular de novo no contexto de infarto agudo do miocárdio representa um importante desafio com potencial impacto prognóstico. Objetivo: Determinar a incidência, impacto na terapêutica e mortalidade, e identificar possíveis preditores do aparecimento de fibrilação auricular de novo durante o internamento por infarto agudo do miocárdio com supradesnivelamento do segmento ST. Métodos: Estudamos todos os pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST inseridos consecutivamente de 2010 a 2017 num registro nacional português e comparamos dois grupos: 1 - sem fibrilação auricular; 2- com fibrilação auricular de novo. Efetuamos análise com modelo de regressão logística para avaliar o impacto de fibrilação auricular de novo na mortalidade intra-hospitalar e identificar preditores independentes para o seu aparecimento. Para teste de hipóteses, considerou-se significativo p < 0,05. Resultados: Estudamos 6325 pacientes, dos quais 365 (5.8%) apresentaram fibrilação auricular de novo. Não houve diferença no número de pacientes reperfundidos nem na estratégia de reperfusão. No grupo 2, terapêutica com betabloqueadores e IECA/ARA foi menos frequente, 20.6% tiveram alta sob anticoagulação oral e 16.1% sob terapêutica tripla. A fibrilação auricular de novo associou-se a maior incidência de complicações e mortalidade intra-hospitalar, mas não foi preditor independente de mortalidade intra-hospitalar. Identificamos idade, acidente vascular cerebral prévio, infarto inferior e bloqueio auriculoventricular completo como preditores independentes de fibrilação auricular de novo. Conclusões: A fibrilação auricular de novo continua sendo uma complicação frequente do infarto agudo do miocárdio, estando associada a aumento das complicações e mortalidade intra-hospitalar. Apenas 36.7% desses pacientes teve alta sob anticoagulação.