Atrial Fibrillation – ABC CARDIOL

IJCS

Original Article

Long-Term Clinical Outcomes of Catheter Ablation in Hypertrophic Cardiomyopathy and Atrial Fibrillation: A Systematic Review and Meta-Analysis

Acácio Fernandes Cardoso et al. Fernanda Cristina Poscai Ribeiro Luiz Claudio Behrmann Martins Glaucylara Reis Geovanini … Cynthia Aparecida da Silva Rocha Nemer Luiz Pichara Áleff Mascarenhas da Silva

Abstract

Background:

Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of atrial fibrillation (AF). However, the benefits of catheter ablation (CA) for reducing adverse clinical outcomes in this population are not well established.

Objective:

To assess the long-term impact of CA on clinical outcomes in patients with HCM and AF through a systematic review and meta-analysis.

Methods:

Controlled studies of patients with HCM and AF undergoing CA were identified through PubMed/MEDLINE, Embase, LILACS, and Cochrane. Meta-analysis employed a random-effects model in R Studio, version 4.3.2, with p < 0.05 considered significant.

Results:

Four retrospective cohort studies met inclusion criteria, all with long follow-up period (5.52 ± 0.91 years). Arrhythmia-free survival after multiple CA ranged from 36.3% to 82%. Combined event analysis (mortality, stroke, and heart failure) yielded odds ratio 0.22 (95% confidence interval 0.08 to 0.60; p < 0.05; I² = 64%). In individual analysis, only heart failure hospitalizations were significantly lower in the CA group (odds ratio 0.32; 95% confidence interval 0.13 to 0.82; p = 0.01).

Conclusions:

This study suggests that CA may improve clinical outcomes in patients with HCM and AF, particularly by improving heart failure hospitalizations. Studies with greater methodological rigor are needed to prove this hypothesis, since only four studies were included in this systematic review.

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Original Article

The Association Between IL-4 Expression and Thrombus Events in Rheumatic Heart Disease Patients

Arini Rizky Wijayanti et al. Dyah Samti Mayasari Erika Maharani Hasanah Mumpuni … Sofia Pranacipta Emilia Theresia Nungki Anggorowati Ery Kus Dwianingsih

Abstract

Background:

Rheumatic heart disease (RHD) is the leading cause of valve disease in developing countries, with intracardiac thrombus events as one of the frequent manifestations. Based on Trias Virchow, a thrombus occurs because of endothelial injury, blood flow abnormality, and hypercoagulability. In RHD, this condition is caused by inflammation, mitral stenosis (MS), and atrial fibrillation (AF). Pro-inflammatory cytokines promote thrombus formation, and anti-inflammatory cytokines inhibit it. IL-4 is an anti-inflammatory cytokine that can potentially inhibit thrombus formation because it can inhibit other pro-inflammatory cytokines and polarize M2 macrophages.

Objectives:

This study aims to know the association of IL-4 expression with thrombus events in RHD patients.

Methods:

Twenty-five (25) patients enrolled in this study were diagnosed with RHD and underwent mitral valve replacement surgery. Valve tissues were collected for histopathological and immunohistochemical examination using IL-4. Thrombus event obtained from echocardiography result. The Mann-Whitney test was used to compare IL-4 expression in thrombus and non-thrombus patients. A p-value of less than 0.05 (p<0.05) was considered the significance level.

Results:

Of the 25 patients, 88% were older than 30 years. Thrombus occurs in 28% of RHD patients and is associated with AF (p 0.001). Patients with moderate and high IL-4 expression did not have less thrombus than patients with low IL-4 expression.

Conclusions:

Intracardiac thrombus formation in RHD patients is not associated with IL-4 expression but is strongly associated with AF. Further research that identifies other cytokines coexisting with IL-4 at the site of injury may reveal better insight into the event.

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Original Article

Epidemiological Profile and Comparison of Mortality Due to Stroke and Atrial Fibrillation in Brazil Over the Past 26 Years

Leticia Da Costa Santana Silva et al. Luana Yasmim Fernández Avelaneda Castanheira Maria Dalila Santos Salim Ohara Rumayane Paiva Santos Rebouças Ruy Felipe Melo Viegas

Abstract

Background:

Atrial fibrillation (AF) stands out as the most prevalent arrhythmia, and its incidence increases with age. Stroke ranks as the second leading cause of mortality in Brazil and represents the primary contributor to global disability.

Objective:

Considering the severity of these conditions, this study seeks to elucidate the epidemiological landscape of AF and stroke-related deaths in Brazil from 1996 to 2022.

Methods:

The following variable were analyzed in the study – geographic region, federative state, age demographics, gender distribution, year of mortality, race/ethnicity, educational attainment, and place of death. This research adopted a descriptive approach through a retrospective, exploratory, epidemiological analysis of data sourced from the Mortality Information System (SIM) accessible through the Department of Health Informatics of the Brazilian Unified Health System (DATASUS) website.

Results:

Over the 26-year period, 1,201,327 deaths from AF and stroke were registered in Brazil. These deaths were mostly caused by stroke (94.5%) and were more concentrated in the southeast region, where the highest number of doctors capable of identifying and notifying these deaths are also concentrated.

Conclusion:

This study claims for a paradigm shift in disease control strategies and underscores the imperative of bolstering the efficacy of public health policies to address the huge impact of stroke and AF-related mortality on population health.

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Editorial

Factors Associated with Variation in Time in Therapeutic Range (TTR)

Felipe Costa de Souza

Anticoagulant therapy is recommended for several conditions, including atrial fibrillation (AF), venous thromboembolism, and after heart valve replacement. While warfarin is commonly used to prevent ischemic stroke in patients with AF, direct oral anticoagulants (DOACs) and nonpharmacologic therapies may be equally or more effective than traditional warfarin.^, In addition, warfarin has a narrow therapeutic index and can interact with many drugs and foods, which poses a challenge to using it.

A key strategy for reducing the risk of stroke or bleeding associated with warfarin is to maintain an optimal time in therapeutic range (TTR). TTR refers to the length of time a patient’s international normalized ratio (INR) remains between 2 and 3, which is a widely accepted measure of effective warfarin management. While there is no universally accepted safe range for TTR, patients whose INR is in the therapeutic range more than 70% of the time have better outcomes in terms of stroke prevention. In addition, those with INR control greater than 40% of the time have improved survival.

[…]

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Original Article

Evolution of Patients With Atrial Fibrillation According to the EHRA Categorization

Rose Mary Ferreira Lisboa da Silva et al. Letícia Tanure Diniz Laura Selga da Silva Gomes Lucas Espíndola Borges

Abstract

Background

The lifetime risk of developing Atrial Fibrillation (AF) is one in three adults, with a prevalence ranging from 2% to 4%. In 2017, the Evaluated Heart valves, Rheumatic or Artificial (EHRA) classification was introduced to guide oral anticoagulation (OAC) for patients with AF and valvular heart disease.

Objective

To analyze the evolution of patients with AF according to the EHRA categorization type 1, type 2, and those without valvular heart disease (group 3).

Method

Prospective, observational, and longitudinal study with 421 patients with AF, divided into three groups. Baseline risk scores for embolism, bleeding, and OAC quality were calculated. Events were verified during the 12-month clinical follow-up. Chi-square, parametric, and non-parametric tests were used for statistical analysis, in addition to the Kaplan-Meier curve. P-value < 0.05 was the statistical significance criterion.

Results

The average age was 58.6 years; 227 patients were women and 269 had OAC. There were 113 OAC EHRA type 1 patients, 53 type 2, and 255 patients from group 3. Age was lower, the proportion of women and OAC usage was higher in group 1 and there was a lower ejection fraction in group 3. During follow-up, the OAC percentage was 87.6% in type 1; 62.2% in type 2; and 56.0% in group 3 (p < 0.0001), with no difference regarding OAC quality, bleeding rate, embolism, or combined events. A higher total mortality rate was observed in group 3 (p = 0.02).

Conclusion

Despite the higher use of OAC in EHRA type 1, there were no differences between the groups regarding bleeding, embolism, or combined events. Group 3, characterized by greater systolic dysfunction, exhibited higher total mortality rates.

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Viewpoint

Heart Rate Control or Rhythm Control in Patients With Atrial Fibrillation and Cardiac Amyloidosis

Lígia Lopes Balsalobre Trevizan et al. Sandrigo Mangini

Introduction

Cardiac amyloidosis (CA) manifests as a gradually progressive infiltrative condition characterized by the accumulation of insoluble protein aggregates within the myocardium and cardiac conduction system. The majority of CA cases are associated with precursor proteins, particularly immunoglobulin light chains (AL-CA) and transthyretin (ATTR-CA), which represent over 95% of cases. ATTR precursor substances may originate from a broad spectrum, encompassing both wild-type (ATTRwt) and variant (ATTRv) genes.

Arrhythmias in CA result from a combination of factors. The deposition of amyloid fibrils and infiltration into the myocardium cause thickening of the atrial and ventricular walls, leading to compromised relaxation. Consequently, this cascade results in increased filling pressures and atrial dilation, making individuals more susceptible to atrial fibrillation (AF) and other atrial arrhythmias. While left atrial (LA) enlargement has historically been linked with AF, new-onset AF can occur even without LA enlargement, suggesting a complex pathophysiology of AF in CA, where various processes affect LA structure, function, and mechanics in different ways, thereby heightening the AF risk. The usual manifestation of LA remodeling involves substantial infiltration of the atrial walls, leading to gradual impairment of atrial function and heightened stiffness, often observed without significant LA dilation.

[…]

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Original Article

Increased Circulating Fetuin-A Levels in Patients with Atrial Fibrillation

Gülaçan Tekin et al. Yusuf Kenan Tekin Hüseyin Aydın Naim Nur

Abstract

Background

Biomarkers related to the pathogenesis of atrial fibrillation (AF) have attracted the attention of experts. One of these recently studied biomarkers is Fetuin-A.

Objectives

This study aimed to evaluate the relationship between serum Fetuin-A levels and AF.

Methods

This study used the convenience sampling method, based on inclusion criteria and consent to participate in the study. The Shapiro-Wilk test was used to confirm the normal distribution of all continuous variables. Categorical variables were presented using absolute and relative frequencies. Both groups (48 patients with AF and 47 controls) were compared in terms of biochemical, hematological, and echocardiographic findings and Fetuin-A. the Chi-square or Fisher’s exact test were used to compare groups concerning categorical variables. Continuous variables were compared using the independent samples t-test. P<0.05 was considered statistically significant.

Results

Serum Fetuin-A values increased in AF patients when compared to the controls (544±49 μg/mL versus 484±46 μg/mL, p=0.001). Moreover, Fetuin-A level was independently associated with AF — AOR = 0.978, 95%; confidence interval (CI) 0.969-988, p 511.80 μg/mL with a sensitivity of 75% and a specificity of 73% — area under the curve (AUC) = 0.804, 95% CI = 0.715 – 0.892.

Conclusions

According to this study, there was a relationship between serum Fetuin-A levels and AF, regardless of conventional cardiovascular risk factors. Therefore, Fetuin-A may play a role in the pathophysiology of AF. Prospectively designed cohort studies are necessary to assess whether or not the results can be generalized for other populations.

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Editorial

Increased Circulating Fetuin-A Levels in Patients With Atrial Fibrillation: Are We Really There?

Claudia da Silva Fragata

Fetuin-A is a protein almost exclusively secreted by the liver. Circulating fetuin-A levels are elevated in humans with metabolic syndrome and insulin resistance, conditions that are associated with increased risk of cardiovascular disease. Fetuin-A is a natural inhibitor of the insulin-stimulated insulin receptor tyrosine kinase and was shown to induce insulin resistance in rodents.^, Studies in humans have demonstrated that circulating fetuin-A levels are positively associated with fat accumulation in the liver, insulin resistance, and metabolic syndrome. To our knowledge, the potential association between fetuin-A and atrial fibrillation (AF) has not been studied to date. Therefore, the present study aimed to determine circulating fetuin-A levels in AF patients and revealed that higher plasma fetuin-A levels were associated with AF after adjustments for some confounding factors.

Fetuin-A seems to be involved in many normal and pathological processes, such as in response to systemic inflammation, hepatocyte-growth-factor activity and regulation of insulin activity, inhibition of unwanted mineralization, osteogenesis, and bone resorption.

[…]

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Original Article

Adherence and Quality of Life in Non-Valvular Atrial Fibrillation With Direct Oral Anticoagulants Versus Vitamin K Antagonists: A Systematic Review

Vanelise Zortea et al. Karine Duarte Curvello Diogo Pilger Antonios Douros … Lisiane Freitas Leal Tatiana da Silva Sempé Tatiane da Silva Dal Pizzol

Abstract

Background

Direct anticoagulants (DOACs) and vitamin K antagonists (VKAs) differ in pharmacokinetic characteristics, intensity of required laboratory monitoring, and costs. These differences could affect patients’ adherence to treatment and quality of life (QoL).

Objective

To assess whether patients with non-valvular atrial fibrillation (AF) using DOACs have better treatment adherence and QoL when compared to patients using VKAs.

Methods

We conducted a systematic review in Medline, Embase, LILACS, SciELO, CINAHL, and Cochrane Central, until June 9, 2021. We included studies that estimated and compared treatment adherence and QoL between DOACs and VKAs in adults with non-valvular AF. The methodological quality of the studies was assessed using the Joanna Briggs Institute (JBI) tools. The protocol was registered in the PROSPERO (CRD 42020165238).

Results

Sixteen studies, including 122,458 patients with non-valvular AF, evaluated adherence, and eleven studies, including 5,687 patients, assessed QoL. A variety of methods was used to measure adherence. Eleven studies showed no difference in adherence between DOACs and VKAs, while three studies favored VKAs over DOACs and two studies favored DOACs over VKAs. QoL was measured by specific (n = 3) or generic questionnaires (n = 8); results favored DOACs over VKAs in four studies, while in the other seven studies the results showed no difference between the groups. Meta-analyses were not performed due to high methodological heterogeneity among studies.

Conclusions

Available evidence regarding treatment adherence and QoL with DOACs and VKAs is characterized by methodological heterogeneity and conflicting findings.

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Original Article

Prevalence of Atrial Fibrillation in Patients With end Stage Renal Disease

Maria da Graça Lepre Hawerroth et al. Lucas Yuji Sonoda Jean José Silva Walter Alvarenga de Oliveira

Abstract

Background

Atrial fibrillation (AF) is the most common arrhythmia in patients with end-stage renal disease (ESRD). The coexistence of high thromboembolic and hemorrhagic risks, added to the lack of strong scientific evidence on the safety of anticoagulants in the setting of renal failure, makes this a clinically challenging situation.

Objectives

To describe the clinical-demographic profile and prevalence of AF in the population with ESRD undergoing dialysis. Secondary objectives include the assessment of thromboembolic (CHA₂DS₂VASC) and bleeding (HASBLED) risk scores.

Methods

Cross-sectional analytical-descriptive study, carried out between January and March 2020. Patients with ESRD were evaluated by means of a medical history questionnaire, physical examination, and 12-lead electrocardiogram. A chi-square (χ2) association test was applied to calculate association between clinical variables and AF, with a significance level of α = 0.05.

Results

This study evaluated 295 patients, most of whom were men (170), elderly (63, IQR 53-71), current smokers (130), with associated cardio-endocrine comorbidities. The prevalence of AF was 6.7% (20). Heart failure (HF) (χ2=15.417; p<0.001), age of 65 years or older (χ2=14.584; p<0.001), and anticoagulation (χ2=5.715; p<0.01) were associated with AF. The median CHA₂DS₂VASC and HASBLED was 4 and 3, respectively. Eight patients were taking warfarin and five were receiving apixaban.

Conclusion

The prevalence of AF in this study is similar to that reported in other published articles on the subject, and patients were at high risk for cardiovascular outcomes. Non-anticoagulation strategy was commonly adopted due to controversies in the literature as well as the absence of published randomized clinical trials.

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Review Article

Exercise Stress Test in The Assessment of Brugada Syndrome Patients

Camila Pinto Cavalcante Miná et al. Eduardo Augusto Quidute Rocha Daniela Gardano Bucharles Mont’Alverne Eduardo Arrais Rocha

Abstract

Brugada syndrome (BS) is a genetic channelopathy, clinically characterized by an increased risk of sudden cardiac death. The diagnosis requires a typical electrocardiographic pattern, and data on risk stratification are limited in the literature. The aim of this study was to conduct a review on the importance of exercise stress test (EST) in risk stratification in BS. Articles were searched in the PubMed, Scielo and Google Scholar databases. From the 200 articles retrieved, eight were included, with a total of 712 patients (95% men) aged between 35 and 60 years. Severe symptoms and ventricular arrhythmias were reported by 256 patients before the EST, with syncope being reported in 70% of cases. The reviewed articles suggest that the EST is a safe method that can help in the diagnosis and risk stratification for malignant arrhythmias in patients with BS. Potential predictors of poor prognosis were: augmentation in ST-segment elevation > 0.5 mV in V1, V2 or V3 in early recovery; J-point elevation in lead > 2mm in aVR in late recovery; heart rate reduction < 40% from maximum heart rate in late recovery and occurrence of ventricular extrasystoles in early recovery.

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Editorial

Atrial Fibrillation and Hemodialysis – Should we Anticoagulate These Patients? Ischemic Versus Hemorrhagic Risk

Iara Atié Malan

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide, and it is a very frequent cause of increased morbidity and mortality in adults. This arrhythmia favors the formation of thrombi, which can lead to systemic embolism, such as ischemic stroke.

To identify patients with thromboembolic risk, the most used score is the CHA2DS2VASC, which takes the following factors in consideration: heart failure, arterial hypertension, age, diabetes, previous stroke, vascular disease, and sex. It is worth emphasizing that this score does not take renal function or dialysis treatment into consideration.

[…]

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Original Article

Hemorrhagic Versus Ischemic Risk in Patients with Atrial Fibrillation on Hemodialysis

Mariana Sousa et al. Gonçalo Cruz Sara Vilela Catarina Cardoso … Pedro Bravo José Paulo Santos Cristina Santos Jorge Silva

Abstract

Background

Hemodialysis (HD) patients with atrial fibrillation (AF) have a particularly high risk of stroke and bleeding, but no high-quality evidence-based recommendations exist to properly manage these patients.

Objectives

We aim to evaluate the ischemic versus the hemorrhagic risk in a HD population with AF.

Methods

We selected incident patients that started hemodialysis between 2011 and 2015. All patients that had AF before HD, or developed AF during the follow-up, were included. Both CHA₂DS₂ -VASC and HAS-BLED scores were calculated at the time of beginning of HD or AF diagnosis and correlated with the outcomes using a logistic regression model. The outcomes were hemorrhagic events, ischemic events and death related to any of these events. A p-value < 0.05 was set as statistically significant.

Results

Forty-six patients were included. Most of them had had AF before they started hemodialysis. Twenty-two patients were on oral anticoagulation (OAC). There was no significant difference between the incidence of ischemic and hemorrhagic events, regardless of the use of OAC. Previous stroke, transient ischemic attack, and thromboembolic event significantly increased the risk of an ischemic event (OR 6.78, p=0.028).

Conclusions

In this population, we did not observe any difference between the incidence of ischemic and hemorrhagic events, which was also true in patients with OAC. Therefore, the benefit of OAC in such patients remains questionable. However, patients with previous stroke, transient ischemic attack, or thromboembolic event seem to have a higher risk of new ischemic events and might benefit from anticoagulation.

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Original Article

Prevalence of Atrial Fibrillation in Pacemaker Patients

Mario Augusto Cray da Costa et al. Jorge Felipe do Lago Pereira dos Santos Marcelo Derbli Schafranski

Abstract

Background:

Current pacemakers allow for the continuous recording of the occurrence of arrhythmic events. One of the most frequent arrhythmias after implantation of a device is atrial fibrillation (AF), an important risk factor for embolic events. The frequency of this arrhythmia in pacemaker patients has not been widely studied.

Objectives:

This study aimed to evaluate the prevalence, incidence, and predictors of the occurrence of AF in patients with double-chamber pacemakers and without a history of atrial fibrillation prior to implantation.

Methods:

A dynamic, retrospective, and prospective cohort study was carried out with 186 patients undergoing biannual follow-up of the double-chamber pacemaker, without previous AF, in a single service, between 2016 and 2018. Clinical data were collected from the medical records and the telemetry of the device and the prevalence, incidence rate, relative risk by univariate analysis (by chi-square), and risk ratio were calculated by multivariate analysis (by Cox regression); values of p<0.05 were considered significant.

Results:

There was a prevalence of 25.3% FA, with an incidence of 5.64 cases / 100 persons-year. The median time for the development of arrhythmia was 27.5 months. Multivariate analysis identified 5 statistically significant predictors: male gender, OR: 2.54 [1.04–6.15]; coronary artery disease, OR: 2.98 [1.20–7.41]; hypothyroidism, OR: 3.63 [1.46–9.07]; prior heart surgery, OR: 2.67 [1.01–7]; and left atrial enlargement, OR: 2.72 [1.25–5.92].

Conclusions:

The prevalence and incidence of AF in this population are high. Risk factors for AF were: male gender, coronary artery disease, hypothyroidism, prior heart surgery, and left atrial enlargement.

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Original Article

Epicardial Fat Tissue Thickness and Omentin in Patients with Atrial Fibrillation

Ibrahim Etem Dural et al. Ersel Onrat Sefa Çelik Serkan Gokaslan … Ayhan Vurmaz Sadık Volkan Emren Zafer Yalım Alaeddin Avşar

Abstract

Background:

Although electrical and structural remodeling has been recognized to be important in the pathophysiology of atrial fibrillation, the mechanisms underlying remodeling process are unknown. There has been increasing interest in the involvement of inflammatory molecules and adipokines released from the epicardial fat tissue in the pathophysiology of atrial fibrillation.

Objectives:

In our study, we aimed to investigate the relationship of atrial fibrillation with increased epicardial adipose tissue, inflammatory molecules released from this tissue and omentin.

Methods:

Thirty-six patients who were followed up with a diagnosis of permanent AF at the cardiology outpatient clinic 33 individuals without atrial fibrillation (controls) were included in the study. Epicardial adipose tissue thickness of patients was measured by echocardiography. Serum omentin, IL 6, IL 1 beta, TNF alpha and CRP levels were measured. Man-Whitney U test was performed for comparisons and significance was established at 5% (p<0.05).

Results:

Epicardial adipose tissue thickness was significantly greater in the patient group (6mm [4-5.5]) than controls (4mm [3-5.5]) (p <0.001). No significant difference was found in the concentrations of omentin or inflammatory molecules between the groups.

Conclusion:

No relationship was found between atrial fibrillation and serum levels or omentin or inflammatory markers. A relationship between epicardial adipose tissue thickness measured by echocardiography and atrial fibrillation was determined.

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Original Article

Embolic Stroke of Undetermined Source (ESUS) and Stroke in Atrial Fibrillation Patients: not so Different after all?

Valeria Cristina Scavasine et al. Gustavo da Cunha Ribas Rebeca Teixeira Costa Guilherme Henrique Weiler Ceccato … Viviane de Hiroki Flumignan Zétola Marcos Christiano Lange

Abstract

Background:

Stroke related to atrial fibrillation (AF) is associated with high recurrence and mortality rates. Embolic Stroke of Undetermined Source (ESUS) is associated with fewer vascular risk factors, less disability, and a high recurrence rate.

Objective:

To compare risk factors, functional outcomes and the occurrence of primary endpoint (a composite of recurrent stroke, cardiovascular death, and myocardial infarction) between AF stroke and ESUS patients.

Method:

A retrospective analysis was conducted including all consecutive patients with first-ever ischemic stroke admitted to the Hospital de Clinicas (Clinical Hospital) of the Federal University of Paraná from October 2012 to January 2017 (n=554). There were 61 patients with stroke due to AF and 43 due to ESUS. Both groups were compared for demographic characteristics and vascular risk factors. Logistic regression models were performed to assess the impact of each variable on the primary endpoint in a 12-month follow-up. Statistical significance was considered for p-values < 0.05.

Results:

ESUS patients, as compared to AF patients, were younger and more likely to be smokers. ESUS patients presented a mean CHADS2VASc score of 4, while the AF group presented a score of 5 (p <0.001). The primary endpoint was observed in 9 (20.9%) ESUS and 11 (18.0%) AF patients over a 12-month period (p=0.802). Higher glucose levels upon hospital admission (p=0.020) and a higher modified Rankin Scale upon hospital discharge (p=0.020) were predictors of the primary endpoint occurrence.

Conclusion:

AF and ESUS stroke patients presented very similar independence rates upon hospital discharge and outcomes after 12 months, despite some baseline differences, including stroke recurrence, vascular death, and myocardial infarction.

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Editorial

Rivaroxaban: is it Really Need to Monitor its Anticoagulant Effect in Clinical Practice?

Luiz Eduardo Montenegro Camanho et al. Gustavo Vignoli dos Santos

Oral anticoagulation (OAC) has been the cornerstone for the treatment of atrial fibrillation (AF) patients. The vitamin K antagonist warfarin has been considered the drug of choice in stroke prevention with proven efficacy for more than 60 years. The great inter-patient and intra-patient dose variability and need for routine International Normalized Ratio (INR), are among the main disadvantages of warfarin. The direct-acting oral anticoagulants (DOACs), including direct thrombin inhibitors (dabigatran) and factors Xa inhibitors (apixaban, edoxaban, and rivaroxaban), are currently the therapy of choice for preventing thromboembolic events in patients with atrial fibrillation. Unlike warfarin and other vitamin K antagonists, the DOACs are administered in fixed doses and do not require routine laboratory monitoring.

Rivaroxaban is an oral inhibitor of free and clot-associated factor Xa through reversible, competitive interactions with its active site. Bioavailability following oral administration is dose-dependent, and it is highly bound to plasma proteins. Plasma levels peak 2 to 4 h following oral administration, partially excreted by the kidneys, and has a half-life depending on the dose and age. Factor Xa inhibitors variably affect prothrombin time (PT), with concentration-dependent PT prolongation. The sensitivity of the different assays varies widely, depending on the thromboplastin reagent, and it is recommended to check the sensitivity of PT in each institution. At therapeutic doses, rivaroxaban has a relatively weak effect on PT, but there is a more pronounced effect on supratherapeutic doses.

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Original Article

Atrial Fibrillation and Use of Rivaroxaban: Performance of the Prothrombin Time / INR as a Function of Time After Blood Collection

Rita Carolina Figueiredo Duarte et al. Priscila Samara Sérgio Moreira Cláudia Natália Ferreira Estevão Lanna Figueiredo … Eduardo Sternick Francisco Rezende Silveira Luan Carlos Vieira Alves Ana Paula Lucas Mota Edna Afonso Reis Maria das Graças Carvalho Helton José dos Reis

Abstract

Background

Traditionally, the most effective therapy in the prevention of stroke in patients with atrial fibrillation (AF) has been oral anticoagulation with vitamin K inhibitors, particularly warfarin, whose disadvantages and adverse effects have led to their replacement by “direct oral anticoagulants”, as factor X inhibitor.

Objectives

This study aimed to conduct a brief approach on atrial fibrillation (AF) and use of Rivaroxaban, and to comparatively evaluate the prothrombin time / International Normalized Ratio (PT/INR) in patients with AF in use of this oral anticoagulant, depending on the time elapsed between the last administration of the drug and the time of blood sample venipuncture.

Methods

We evaluated 34 patients with AF in use of Rivaroxaban by using PT / INR, distributed into a subgroup with blood collection time ≤ 12 hours (n = 7) and > 12 hours after the last drug intake (n = 27). Mann-Whitney test was used to compare the groups and p < 0.05 was considered significant.

Results

An analysis as a function of time between the Rivaroxaban intake and blood collection, revealed that PT / INR suffers the greatest effect up to 12 hours after ingestion of the drug, dropping to levels close to normal in subsequent hours before the next dose.

Conclusion

We concluded that, in contrast to warfarin, the knowledge of the time interval between drug intake and blood collection from patients taking Rivaroxaban is essential to properly interpret a laboratory test to assess hemostasis, particularly PT and its derivatives. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

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Editorial

To Close or not to Close PFOs in Cryptogenic Stroke, an Evolving Question

Alex Felix et al. Monica Luiza de Alcantara

A matter of intense debate in the last decades, the ideal strategy for secondary prevention in patients with cryptogenic stroke and patent foramen ovale (PFO) is not yet clearly defined. PFOs are prevalent in the general population and can be found in up to 40% of patients with cryptogenic stroke. Although in some cases of cryptogenic stroke PFO might be just an innocent bystander, paradoxical embolism is a well-known potential causative mechanism, especially in patients with concomitant deep venous thrombosis, whereby PFO closure may represent an effective measure to avoid recurrences. Even among patients with PFO, phenotypical heterogeneity may also determine percutaneous treatment suitability and directly impact on results, whereas the presence of large shunts, atrial septal aneurysm or associated complex septal defects must also be taken into account.

In the past years, several evidence-based guidelines and expert consensus on the management of patients with PFO and prevention of recurrent stroke have been published by international scientific societies, including a position paper sponsored by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), with the participation of eight European scientific societies. A recent guideline by the American Academy of Neurology (AAN) was published online last April.

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Editorial

Challenges for Anticoagulation in Atrial Fibrillation

Ana Inês da Costa Bronchtein

Atrial fibrillation (AF) is the most prevalent arrhythmia in the world. It is considered a current epidemic and one of the main causes of ischemic stroke, usually with severe and debilitating conditions, and is responsible for systemic cardioembolic phenomena, increased number of cases of congestive heart failure (CHF), cognitive impairment related to silent embolic phenomena, and increased overall mortality in affected patients.

Vitamin K antagonists (VKA) represented in the vast majority of studies with warfarin have been widely used for many years; however, they have complex adherence due to several factors, including the need for frequent INR monitoring, regular dose adjustments for maintaining a suitable time in therapeutic range (TTR) (>= 70%) and interactions with a number of drugs and foods, which contributed to its ever decreasing use. Direct-acting anticoagulants (DACs), represented by dabigatran, rivaroxaban, apixaban and, more recently, edoxaban, offer an alternative to VKA, without the disadvantages presented by the latter.

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Original Article

The Role of Patent Foramen Ovale Closure in the Secondary Prevention of Cryptogenic Stroke: a Meta-Analysis Report

Sónia P. Pinto Pereira et al. Alzira Nunes Cristina Santos Scott E Kasner José P. L Nunes

Abstract

Background:

Patent foramen ovale (PFO) closure has been compared to medical therapy for secondary prevention of recurrent cryptogenic stroke.

Objectives:

To produce an updated meta-analysis including only data from the primary analyses of clinical trials and to evaluate the role of PFO closure in the secondary prevention of recurrent stroke.

Methods:

Search in Medline (PubMed) and in ISI Web of Knowledge. Parameters under analysis and meta-analyses were: stroke, transient ischemic attack (TIA) and atrial fibrillation (AF). Comprehensive Meta-analysis Software V.2.0 (Biostat) was used. Random-effects analyses were carried out. A level of significance of 5% was used.

Results:

In this study six, randomized trials enrolling 3,750 patients were included. Unlike other published meta-analyses on the same topic, in this case, only clinical trial data, and not follow-up data, were used. PFO closure, as compared with medical therapy alone, demonstrated superiority in reducing the rate of recurrent stroke (risk ratio with PFO closure vs. medical therapy, 0.37; 95% confidence interval [CI], 0.17 to 0.78; p = 0.01). PFO closure did not offer a significant benefit in prevention of TIA (risk ratio with PFO closure vs. medical therapy, 0.96; 95% CI, 0.64 to 1.44; p = 0.85). Among patients assigned to closure group, an increased risk of atrial fibrillation was seen (risk ratio with PFO closure vs. medical therapy, 4.64; 95% CI, 2.38 to 9.01; p < 0.01).

Conclusions:

In patients with cryptogenic stroke who had a patent foramen ovale, a protective effect of closure was seen concerning the risk of recurrent stroke, but not regarding the prevention of TIA.

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IJCS

Original Article

Internal Validation of a Risk Score for Prediction of Postoperative Atrial Fibrillation after Cardiac Surgery

Rafael de March Ronsoni et al. Tiago Luiz Luz Leiria Leonardo Martins Pires Marcelo Lapa Kruse … Edemar Pereira Rogerio Gomes da Silva Gustavo Glotz de Lima

Abstract

Background:

Postoperative atrial fibrillation (POAF) after cardiac surgery has great clinical and economic implications. Many attempts have been made to identify risk factors aiming at a better evaluation of prophylactic treatment strategies.

Objective:

To perform an internal validation of a risk score for POAF.

Methods:

A prospective cohort of 1,054 patients who underwent myocardial revascularization and/or valve surgery was included. The risk score model was developed in 448 patients, and its performance was tested in the remaining 606 patients. Variables with a significance level of 5% in the cohort were included and subjected to a multiple logistic regression model with backward selection. Performance statistics was performed using the c-statistic, the chi-square and the Hosmer-Lemeshow (HL) goodness-of-ﬁt, Pearson’s correlation coefﬁcient.

Results:

Four variables were considered predictors of outcome: age (≥ 70 years), mitral valve disease, the non-use or discontinuation of beta-blockers and a positive water balance (> 1,500 mL). The ROC curve was 0.76 (95% confidence interval [CI]: 0.72-0.79). The risk model showed a good ability according to the performance statistics – HL test x⁽²⁾ = 0.93; p = 0.983 and r = 0.99 (Pearson’s coefficient). There was an increase in the frequency of POAF with the increase of the score: very low risk = 0.0%; low risk = 3.9%; intermediate risk = 10.9%; and high risk = 60.0%; p < 0.0001.

Conclusion:

The predictive variables of POAF allowed us to construct a simplified risk score. This scoring system showed good accuracy and can be used in routine clinical practice.

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IJCS

Original Article

Trends and Predictors of Oral Anticoagulation in Patients with Atrial Fibrillation: A Serial Cross-Sectional Study from 2011 to 2016

Maria de Fátima de Araújo Geraldes et al. Eduardo Sahade Darze Paulo Novis Rocha

Abstract

Background:

Despite the efficacy of vitamin K antagonists against stroke in patients with atrial fibrillation (AF), the underuse of this therapy is well documented.

Objectives:

To evaluate trends and predictors of oral anticoagulants utilization in patients with AF.

Methods:

Observational, retrospective, serial cross-sectional study between 2011-2016. Comparisons between groups were performed using the Student t, Mann-Whitney and Chi-square tests. Logistic regression was used to identify independent predictors of anticoagulation. A p value < 0.05 was considered significant.

Results:

A total of 377 patients were analyzed. The mean age was 70 ± 15 years; 52% were male and 75% were anticoagulated (20% with VKA and 55% with DOAC). Over 5 years, the overall frequency of anticoagulation increased by 22.4%. The use of DOACs increased from 29% to 70%, whereas the use of VKA decreased from 36% to 17%. The use of antiplatelet agents alone also fell from 21% to 6%. The predictors of anticoagulation were previous episodes of AF (OR 3.1, p < 0.001), hypertension (OR 3.0, p < 0.001) and HASBLED score (OR 0.5, p < 0.001). The predictors of DOAC use were serum creatinine (OR 0.2, p = 0.002), left atrial size (OR 0.9, p = 0.003) and biological valve prosthesis (OR 0.1, p = 0.007). Of the 208 patients using DOACs, 63 (30%) received inadequate prescriptions: 5 with severe drug interactions and 58 with incorrect dosing.

Conclusions:

Between 2011 and 2016, DOACs were rapidly incorporated into clinical practice, replacing AVKs and antiplatelets, and contributing to greater use of anticoagulation in patients with AF.

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IJCS

Editorial

Risk Scores for Stroke Prevention in Patients with Non-Valvular Atrial Prevention: Is it Time to Put Parameters of Left Atrial Appendage Morphology and Function Into Clinical Practice?

Angelo A. V. de Paola

Overall, one-third of thromboembolic events originated from the heart. Left atrial appendage (LAA) and its anatomic complexity has been implicated in 90% of cases of thrombus formation and cardioembolic events in patients with non-valvular atrial fibrillation (AF). Risk scores to predict thromboembolism from AF, such as CHADS₂ and CHA₂DS₂VASc are widely used to guide anticoagulation therapy and varies in relation to comorbidities associated with the thrombogenic substrate; however, because of its clinical conception, they did not include atrial anatomy (atrial enlargement), function (flow velocities) and electrophysiology (atrial fibrillation burden). Patients with CHA₂DS₂VASc score ≥ 2 are at intermediate or higher risk (event rate ≥ 2-3%/year) and anticoagulation is recommended. Left atrial variables such as LAA function and morphology, routinely studied by transesophageal echocardiography (TEE), were not considered in these scores.

In 2012, Di Biase et al.; published a retrospective study of 932 patients with AF and computed tomography (CT)/magnetic resonance imaging (MRI) classification of four different types of LAA morphologies: chicken wing, cactus, windsock and cauliflower. Non-chicken wing categories were 4 to 8 times more likely to have had stroke/TIA. Eight additional cross-sectional studies utilizing this classification for LAA morphology in 2,210 patients (6 with CT and 2 with TEE), found a significant association with non-chicken-wing morphology and stroke in 5 series^– and no significant difference in 3 other studies.^–

[…]

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