Thrombosis – ABC CARDIOL

IJCS

Review Article

The Role of Platelets in Long COVID Development: A Literature Review

Gabriel Ferreira Lima et al. Lucas Miossi Amanda Gonçalves Jesus Silva Olivia Barros Pedreira Novais Fernanda Carla Ferreira Brito

Abstract

At its peak during the pandemic, coronavirus disease 2019 profoundly impacted global populations and introduced numerous post-infection complications, collectively referred to as long coronavirus disease. The mechanisms underlying the syndrome’s chronicity are multifaceted; however, a notable aspect of long coronavirus disease pathophysiology is its intricate association with platelets. The chronic inflammatory response triggered by severe acute respiratory syndrome coronavirus 2 is closely related to platelet activity, wherein inflammatory molecules bind to specific platelet receptors, inducing the release of platelet granules containing procoagulant and proinflammatory molecules. Consequently, there is a marked elevation in coagulation-related proteins, fostering the development of abnormal microthrombi and a dysfunctional fibrinolytic system. All these changes are indicative of an imbalance in coagulation regulation. Therefore, investigating pharmacological targets linked to this process is crucial for syndrome management, aiming to enhance the quality of life for affected individuals. This review aimed to highlight the importance of platelet function and activity in the pathophysiology of long coronavirus disease, as well as to identify molecular targets directly related to long coronavirus disease or coronavirus disease 2019–related disturbances in platelet homeostasis.

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Left Atrial Septal Pouch Thrombosis Detected Before Electrical Cardioversion: a Rare Source of Embolism

Andre Barcellos Amon et al. Mariana De Castro Lopes Marina Petersen Saadi Willian R. Menegazzo Angela Barreto Santiago Santos

A 59-year-old male patient with a history of systemic arterial hypertension was admitted to the emergency department with a seven-day history of chest pain and palpitations. On examination, he was hypotensive (93/70 mmHg) and tachycardic (150 bpm). A prominent systolic–diastolic murmur was heard along the right upper sternal border.

The initial investigation included electrocardiography (ECG) and Transthoracic Echocardiography (TTE). The ECG revealed atrial flutter, and the TTE showed biventricular dilation [Left Ventricular (LV) end-diastolic/end-systolic diameters: 60/51 mm; right ventricular (RV) basal diameter: 54 mm] and severe systolic dysfunction (LV ejection fraction: 19%; RV fractional area change: 16%). Additionally, a bicuspid aortic valve with mixed disease was identified: low-flow, low-gradient aortic stenosis (peak velocity: 3.1 m/s; peak/mean gradients: 39/23 mmHg; velocity ratio: 0.15; valve area: 0.7 cm, stroke volume index: 17 ml/m) and severe aortic regurgitation (pressure half-time: 170 ms; holodiastolic reversal in the descending aorta, end-diastolic velocity: 24 cm/s).

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ABCIC

Case Report

Acute Thrombosis During Ductus Arteriosus Stenting Successfully Treated with Balloon Angioplasty and In Situ Alteplase Infusion: Case Report

Jonathan Guimarães Lombardi et al. Paulo Correia Calamita Mayra Rosana Palmeira Barreto Luiza Silveira Neves Ficht Giulliano Gardenghi

Introduction

Tricuspid atresia with pulmonary atresia is a rare congenital heart defect, representing about 1% to 3% of all congenital heart diseases. Tricuspid atresia is subdivided into type I (normal position of the great arteries) and type II (transposition of the great arteries), with type 1A characterized by the presence of associated pulmonary atresia or stenosis. Pulmonary blood flow in these patients is dependent on the patency of the ductus arteriosus, making its maintenance essential in the neonatal period.

The treatment of tricuspid atresia follows a staged surgical approach, aiming for a Fontan circulation as the final goal. In the neonatal period, the focus is to ensure adequate pulmonary blood flow through hemodynamic or surgical interventions, including systemic-pulmonary shunts or ductal interventions.

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ABC

Letter to the Editor

Analysis of Factors Affecting False Lumen Thrombosis in Type B Aortic Dissection

Beatriz Vitória Carvalho Lordêlo et al. Álvaro Eduardo Santos Oliveira Henri Jun Iti Okubo Luana Macedo da Silva Nascimento … Luiz Henrique Cardoso da Silva Pedro Pereira Tenório

Dear editor,

The study published by Tang et al., entitled “Factors Affecting False Lumen Thrombosis in Type B Aortic Dissection,” highlighted the influence of morphological aspects of type B aortic dissection (TBAD), according to the Stanford classification, on false lumen thrombosis prior to treatment with endovascular repair of the thoracic aorta. It has been shown that false lumen thrombosis occurs significantly less frequently in patients with TBAD and renal failure, when compared with those with TBAD and normal renal function.

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Multiple Thrombotic Complications in a Patient With Polycythemia Vera

Barbara Zdzierak et al. Bernadeta Chyrchel Andrzej Surdacki Stanisław Bartuś Artur Dziewierz

Introduction

Polycythemia vera (PV) is a rare Philadelphia chromosome–negative myeloproliferative neoplasm characterized by the clonal proliferation of multipotent bone marrow progenitor cells, leading to erythrocytosis and increased red blood cell mass. It may coexist with other hematologic disorders. PV results in blood hyperviscosity, which predisposes patients to thrombosis — the most common and clinically significant complication of PV. Post-PV myelofibrosis (post-PV MF) represents an advanced stage in the natural progression of PV. In patients with post-PV MF, thrombosis also remains one of the major complications. We present a case of multiple thrombotic events, namely acute coronary syndrome, digital arterial thrombosis, and ischemic stroke, in a patient with PV.

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IJCS

Editorial

Systemic Biomarkers in Heart Failure: To Measure or Not to Measure?

Humberto Villacorta

Heart failure (HF) is an aggressive disease with unfavorable prognosis if not treated properly. Even after optimal medical treatment, some patients may remain at high risk for clinical events. As such, it is important to identify patients at risk of death or hospitalization. Biomarkers have been used to establish prognosis in HF, and natriuretic peptides (NP) are considered the gold standard biomarker in HF, not only for diagnosis but also for prognosis.

NP are cardiac biomarkers, produced by the heart ventricles in response to wall stretch. However, several systemic biomarkers, reflecting different pathways, have been shown to be elevated in HF with the potential to add information on top of NP ().^– Nevertheless, these biomarkers have not been strongly recommended in HF guidelines because their utility in aiding decision-making is unclear.

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Editorial

Does One Size Fit All? – Refining Parenteral Anticoagulant Therapy According to Body Weight

Remo Holanda de Mendonça Furtado

Parenteral anticoagulant is widely used in medicine. In acute coronary syndromes (ACS), the use of intravenous unfractionated heparin (UFH) has been largely replaced by low molecular weight heparins (LMWH) due to the ease of administration, more predictable effect, and superior efficacy of the latter in patients with ST-elevation myocardial infarction submitted to fibrinolysis. Current guidelines recommend anticoagulation with enoxaparin (class I) in a broad range of patients with ACS.^, However, one of the major limitations of LMWH remains in its use in patients with extremes of body weight. Some studies suggest a less trustable anticoagulation among patients weighing more than 100 kilograms or with body mass index (BMI) above 40 kg/m. Whether 1 mg/kg every 12 hours dosing for therapeutic anticoagulation should remain in extremely obese patients is still controversial.^, Currently, the Brazilian label from enoxaparin recommends a maximum dose of 100 mg every 12 hours, with additional dosing adjustments for patients older than 75 years and those with moderate to severe renal dysfunction.

The current issue of the Arquivos Brasileiros de Cardiologia brings an important meta-analysis that can help, in part, to clarify these questions. The authors performed a systematic review of studies enrolling patients being treated for several different conditions, most of them (87%) for ACS, with a parenteral anticoagulant (UFH, enoxaparin, or fondaparinux). Eligible studies compared two exposure groups (obese versus non-obese, being obese defined as a BMI ≥ 30 kg/m) in terms of death and bleeding outcomes. Because few studies reported endpoints of myocardial infarction and none analyzed stroke, these outcomes were not part of the current meta-analysis. Authors have found 6 studies, three of them secondary analyses from randomized clinical trials (RCT) and three retrospective cohort studies. The rates of bleeding did not differ according to the obesity status (with no apparent heterogeneity according to UFH versus LMWH). However, obesity was associated with lower mortality on parenteral anticoagulation. This last finding is not entirely surprising given it has been demonstrated before (the so called “obesity paradox”). The strengths of the current meta-analysis were the rigorous selection of studies in different databases, assessment of risk of bias, and estimates of heterogeneity with proper methods. The main limitation was that, although RCTs were included, the essential information, that is, the comparison between obese and non-obese patients, was based on observational data, with the inherent risk of bias due to unknown, unmeasured confounders. Apparent lower mortality in obese patients could be explained by the usually younger age (since aging is, in fact, a factor that may decrease body weight over time) and thus the lower prevalence of other age-related co-morbidities that per si are associated with higher mortality, thus creating this apparent paradox. This same issue may cover a potential signal for an increase in bleeding (if it does exist) among obese patients. If obesity were protective against death, we would not expect a mortality reduction favoring weight loss in RCTs testing a weight reduction medication, such as subcutaneous semaglutide, among patients with high cardiovascular risk.

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ABCIC

Case Report

Large Heterogeneous Mass in the Right Chambers: A Case Report in Cardio-Oncology

João Pedro Perfeito Frigo et al. Themissa Helena Voss

Abstract

Renal cell carcinoma (RCC) is one of the most lethal cancers. It is frequently associated with the formation of tumor thrombi (TT), an intravascular extension of the tumor. Approximately 4% to 10% of patients with RCC have TT, which can reach the renal vein (10% to 18%), the inferior vena cava (4% to 23%), and, rarely, the right atrium (1%). These thrombi generally accompany advanced tumors, with distant metastases, and they reflect an aggressive biology. Treatment is challenging, especially in metastatic cases, and surgical resection is indicated in the absence of metastases. Anticoagulation remains controversial due to the neoplastic composition of TT. We report the case of a 51-year-old male patient with clear cell RCC and lung and liver metastases treated with pazopanib. The patient presented right heart failure and was diagnosed with extensive TT up to the right atrium, identified by transthoracic echocardiography. In an advanced stage, with clinical deterioration, palliative care was chosen, and the patient died within a few weeks. The diagnosis of TT is crucial to define prognosis and therapeutic strategies. Echocardiography, combined with advanced imaging techniques, plays a fundamental role in differentiating between TT and thromboembolism. This case highlights the importance of a multidisciplinary approach and technological advances for managing complex conditions such as TT, with the goals of early diagnosis and reduced complications.

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ABCIC

Case Report

Successful Occlusion of a Giant Subclavian Artery Aneurysm Sac with a Vascular Plug: A Case Report

Fuat Polat et al. Osman Eren Karpuzoğlu

Abstract

Subclavian artery aneurysms are rare vascular anomalies that carry significant risks, including thromboembolism, ischemia, and rupture. This case report describes a 71-year-old female patient presenting with left arm ischemia, including pain, numbness, and weakness, caused by a left subclavian artery aneurysm complicated by distal thrombosis. Imaging revealed a 65 × 55 mm aneurysm with a 2.5 cm thrombotic occlusion. The aneurysm was treated with an endovascular approach, utilizing a vascular plug deployed via femoral access. This was preceded by failed attempts to access the lesion through the radial approach due to the presence of thrombotic occlusion and complex vascular anatomy. After the procedure, the patient experienced significant symptom relief, and follow-up imaging confirmed thrombosis of the aneurysm sac. This case highlights the effectiveness of endovascular techniques in managing complex subclavian artery aneurysms and emphasizes the importance of individualized treatment strategies and close follow-up.

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A Prosthetic Dysfunction Earlier Than Expected

Mariana Laranjeira et al. Maria Inês Bertão Rodolfo Pereira Olga Sousa

Prosthetic Heart Valves, despite their improvements over the last few decades, can be subject to complications and dysfunction. Mechanical prosthetic valves have an expected lifespan of approximately 10 to 20 years, with many lasting longer. For biological valves, the lifespan is generally shorter (5 to 15 years). However, the durability varies according to individual factors, valve type, and patient health. Although their greater durability, Mechanical Heart Valves are more pro-thrombotic than biological valves, and their dysfunction may be associated, for example, with thrombotic events and the formation of pannus. Pannus is an inflammatory tissue composed of inflammatory cells, fibroblasts, and blood vessels, and its presence can lead to dysfunction or other complications such as valve obstruction or endocarditis. The prevalence of pannus in cardiac valve prostheses varies depending on several factors, such as the type of prosthesis (biological or mechanical) and the patients’ clinical conditions. It is estimated that the formation of pannus occurs in about 1% to 5% of patients with valve prostheses, although it may be more common in biological ones. The annual rate of thrombus formation can reach 5.7-8%, being higher in tricuspid and mitral valve prostheses.^, A multimodality-based approach can provide useful data for differential diagnosis, complementing clinical assessment and offering an appropriate and optimized therapeutic approach. Valve dysfunction, in case of delayed diagnosis, can progress to cardiogenic shock. Valvular dysfunctions can be structural (valve dysfunction due to changes related to the valve itself) or non-structural (dysfunctions not related to the valve resulting in stenosis or regurgitation, which include the formation of pannus), which arises from the accumulation of fibrous tissue in the valve, causing its dysfunction. It forms less frequently than thrombi and its risk is higher in the mitral position compared to the tricuspid.

The authors present a case of mechanical mitral valve prosthesis dysfunction due to pannus. A Caucasian 43 years-old woman, with dyslipidaemia and hypertension with a history of infectious endocarditis of the mitral valve in 04/2022, presented with signs of infectious infiltration of both leaflets and severe mitral regurgitation. At this point, a cycle of antibiotic therapy was performed with ampicillin and flucloxacillin, with no agent being isolated (neither in blood cultures nor microbiological examination of the explanted valve). A double-disc mechanical valve prosthesis was implanted in the mitral position. The patients were hypocoagulated with a vitamin K antagonist (warfarin, with target INR levels of 2.5-3.5) and discharged from the hospital for outpatient follow-up.

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IJCS

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

Fixed-Dose Antiplatelet Dual Combination in Patients with Coronary Artery Disease in Turkish Population: DAPT-TR

Ahmet Öz et al. Kenan Toprak Ertan Aydin İbrahim Saraç … Mustafa Doğduş Selçuk Opan Mustafa Yenerçağ Mustafa Begenc Tascanov Ömer Kümet Miraç Karaağaç Murat Özmen Bektaş Murat Ömer Kertmen Özkan Bekler Sinan İnci Mustafa Ahmet Huyut Ahmet Özderya Fahri Er Mustafa Duran İsa Ardahanlı Mehmet Memduh Baş Tuncay Güzel Gökhan Ceyhun İbrahim Halil Özdemir Mehmet Burak Özen Ramazan Gündüz Aslan Erdoğan İlyas Çetin Veysel Özgür Barış Çağrı Yayla Medeni Karaduman Lütfü Aşkın Lütfü Bekar Okan Tanrıverdi Eyüp Özkan Emrah Yeşil Serhat Çalışkan Zülfiye Kuzu Berat Uğuz Ferit Böyük Ayşegül Ülgen Kunak Selda Murat Serkan Asil Özkan Kayhan Emrah Erdoğan Ramazan Duz Fahrettin Katkat Tuba Ekin Ersin İbişoğlu Bilge Nazar Ateş Burak Ayça Asım Oktay Ergene Mehdi Zoghi

Abstract

Background

Dual antiplatelet therapy (DAPT) is the treatment of choice for patients with acute and chronic coronary syndromes as it reduces mortality and prevents recurrent thrombotic complications. The assessment of both ischaemic burden and bleeding risk is crucial in deciding which DAPT to choose and how long it should be continued.

Objectives

The aim of our study was to perform prospective clinical follow-up of patients receiving fixed-dose combination therapy (ASA 75 mg + clopidogrel 75 mg). Our study is a multicentric, cross-sectional, observational, cohort study.

Methods

A total of 1500 patients who were started on fixed-dose combination DAPT for acute or chronic coronary syndrome were included in the study. Primary endpoints were hospitalization for any reason, hospitalization for cardiovascular cause, acute myocardial infarction, stent thrombosis, target vessel revascularization and bleeding; the secondary endpoints were death for any reason or cardiovascular cause and stroke. The significance level adopted in the statistical analysis was 5%.

Results

Median age was 63 years; 78.5% of the patients were receiving DAPT treatment for acute coronary syndrome. The rates of hospitalization for cardiovascular reasons, acute myocardial infartion, stent thrombosis and target-vessel revascularization were 7.9%, 2.3%, 1.3% and 4.2%, respectively. While the rate of BARC type 1 bleeding was 3.3%, the rate of BARC type 5, 3, or 2 bleeding was 0.6%. The secondary endpoints which were death from any cause, cardiovascular death and stroke were 0.5%, 0.3% and 0.3%, respectively. Conclusion: Our study shows that fixed-dose combination therapy is effective and safe in appropriately selected patients with acute or chronic coronary syndromes.

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Original Article

Direct Oral Anticoagulants versus Vitamin K Antagonists for Left Ventricular Thrombus: A Meta-Analysis with Trial Sequential Analysis

Eric Pasqualotto et al. Douglas Mesadri Gewehr Rafael Oliva Morgado Ferreira Matheus Pedrotti Chavez … Caroliny Hellen Silva Sara Almeida Cruz Jhonny Limachi-Choque Amanda Park Mário Sérgio Soares de Azeredo Coutinho Luiz Fernando Kubrusly

Abstract

Background

Vitamin K antagonists (VKAs) are the recommended first-line treatment for left ventricular thrombus (LVT); however, direct oral anticoagulants (DOACs) have been considered an alternative therapy.

Objectives

To evaluate the efficacy and safety of DOACs compared with VKAs therapy in patients with LVT.

Methods

PubMed, Embase, and Cochrane were systematically searched for randomized clinical trials or cohort studies that compared DOACs versus VKAs for LVT. Risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (95% CIs). Statistical significance was defined as p value < 0.05.

Results

A total of 4 randomized clinical trials and 29 cohort studies were included, with 4,450 patients assigned to either DOACs or VKAs. There was no significant difference between groups for stroke or systemic embolic (SSE) events (RR 0.84; 95% CI 0.65 to 1.07; p = 0.157), stroke (RR 0.73; 95% CI 0.48 to 1.11; p = 0.140), systemic embolic (SE) events (RR 0.69; 95% CI 0.40 to 1.17; p = 0.166), thrombus resolution (RR 1.05; 95% CI 0.99 to 1.11; p = 0.077), any bleeding (RR 0.78; 95% CI 0.60 to 1.00; p = 0.054), clinically relevant bleeding (RR 0.69; 95% CI 0.46 to 1.03; p = 0.066), minor bleeding (RR 0.73; 95% CI 0.43 to 1.23; p = 0.234), major bleeding (RR 0.87; 95% CI 0.42 to 1.80; p = 0.705), and all-cause mortality (RR 1.05; 95% CI 0.79 to 1.39; p = 0.752). Compared with VKAs, rivaroxaban significantly reduced SSE events (RR 0.35; 95% CI 0.16 to 0.91; p = 0.029) and SE events (RR 0.39; 95% CI 0.16 to 0.95; p = 0.037).

Conclusions

DOACs had a similar rate of thromboembolic and hemorrhagic events, as well as thrombus resolution, compared to VKAs in the treatment of LVTs. Rivaroxaban therapy had a significant reduction in thromboembolic events, compared to VKAs.

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Original Article

Factors Affecting False Lumen Thrombosis In Type B Aortic Dissection

Qian-hui Tang et al. Jing Chen Han Yang Zhong Qin … Qiu-ning Lin Xiao Qin

Abstract

Background

Complete thrombosis of the false lumen facilitates remodeling of type B aortic dissection (TBAD). Morphological characteristics affect thrombosis in the false lumen.

Objectives

Discuss the factors present before admission that influence false lumen thrombosis in patients with TBAD.

Methods

We studied 282 patients diagnosed with TBAD in our hospital between January 2008 and December 2017. We divided the subjects into a thrombotic group and a non-thrombotic group based on whether any thrombus was detectable in the false lumen. We analyzed the differences between the two groups with respect to clinical data, the vertical length of the dissection, and the diameter of the aorta. P values < 0.05 were considered statistically significantly different.

Results

Significant differences between the thrombotic group and non-thrombotic group were found with respect to age (53.92 ± 11.40 vs. 50.36 ± 10.71, p = 0.009) and proportion of patients with renal insufficiency (7.83% vs. 16.38%, p = 0.026). In zones 3–9, the true lumen diameter of the thrombotic group was significantly larger than in the non-thrombotic group (p < 0.05). Binary logistic regression analysis showed that true lumen diameter in zone 5 and renal insufficiency were independent predictors of false lumen thrombosis.

Conclusions

Age and renal function were associated with thrombosis in the false lumen. Potentially, the difference between the diameter of the true lumen diameter and that of the false lumen may influence the thrombosis of the false lumen.

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Letter to the Editor

Mechanical Valve Implants: What Are Their Long-Term Effects?

Eldys Myler Santos Marinho et al. Júlio Martinez Martinez Santos Bruno da Silva Brito Achilles de Souza Andrade Johnnatas Mikael Lopes

Surgical procedures for replacing body structures through prostheses are perhaps the medical interventions that require great expertise and continuous monitoring, prolonging the lives and health of countless people. This was a theme of the research entitled “ Clinical Features and Survival Analysis of Patients after Mechanical Heart Valve Replacement, with an Emphasis on Prosthetic Valve Thrombosis ” by Tagliari et al. published in volume 119, number 5 of this journal.

Among the various contributions the study brings us, some findings need further clarification so mechanical valve implant interventions can be useful clinically and in public health.

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Original Article

Rivaroxaban in Outpatients with Mild or Moderate COVID-19: Rationale and Design of the Study CARE (CARE – Coalition COVID-19 Brazil VIII)

Gustavo B. F. Oliveira et al. Precil Diego M. M. Neves Haliton A. Oliveira Daniela Ghidetti Mangas Catarino … Lucas B. O. Alves Alexandre B. Cavalcanti Regis G. Rosa Viviane C. Veiga Luciano C.P. Azevedo Otávio Berwanger Renato D. Lopes Álvaro Avezum

Abstract

Background

Previous studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting.

Objective

To assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients.

Methods

The COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests.

Results

Major thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups.

Conclusion

The CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.

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Original Article

Clinical Features and Survival Analysis of Patients after Mechanical Heart Valve Replacement, with an Emphasis on Prosthetic Valve Thrombosis

Fábio Tagliari et al. Marcelo Goulart Correia Guilherme Dalcol Amorim Alexandre Siciliano Colafranceschi … João Manoel Pedroso Luiz Fernando Rodrigues Junior Thaisa Rodrigues Tagliari Clara Weksler Cristiane Lamas

Abstract

Background

Valvular heart diseases are highly prevalent in the world, and surgical valve replacement has improved patients’ survival.

Objectives

To describe clinical and laboratory data of patients undergoing mechanical valve replacement, and to determine the incidence of prosthetic valve thrombosis (PVT).

Methods

Retrospective cohort study with a follow-up of up to nine years. The study variables were collected from conventional and electronic medical charts. Statistical calculations were performed using the Jamovi software version 1.2.2.; a p<0.05 was considered statistically significant. Kaplan Meier curves were constructed, and Cox regression analysis was performed for analysis of factors related to mortality.

Results

A total of 473 patients were included, mean age of 46.9 ±11.3 years. Rheumatic disease was the most common etiology. In a mean follow-up period of 4.43 years, mortality rate was 16.1%. Patients with aortic prosthesis showed higher survival than patients with double implant (mitral and aortic) (p=0.026). Of the factors adjusted for mortality, only functional class and chronic renal failure showed statistically significant association. The incidence of PVT was 0.24/100 patients/year, and the first event occurred more than 1000 days after the implant. Smoking and pannus formation were significantly associated with PVT. No differences were found in INR variability between patients with and without thrombosis by prosthetic position, but significant differences were found in INR before thrombosis as compared with patients without thrombosis (INR= 2.20 [1.80-2.20] vs. 2.80 [2.20-3.40]; p= 0.040). The incidence of stroke and bleeding was 4.4% and 5.2% respectively.

Conclusions

The study population was young, and rheumatic valve disease was common in this group. The prevalence of PVT was similar to that described in the literature, despite the low income and low educational level of our sample.

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Editorial

Prognosis and Characteristics Associated with Prosthetic Valve Thrombosis: Insights from a Brazilian Study

Giovanni Possamai Dutra et al. Bruno Ferraz de Oliveira Gomes

Since the 1960s, heart valve disease has undergone critical changes in its therapeutic strategy. The beginning of valve replacement surgeries using prostheses changed the prognosis of patients with valve disease worldwide. Annually, more than 280 thousand valve prostheses are implanted.

The incidence of valvular disease of degenerative etiology has increased in industrialized countries while, unfortunately, rheumatic heart disease is still often observed in many parts of the world, being the most prevalent etiology of valvular heart disease in Brazil. The mechanical valve prosthesis is the most indicated for younger patients, often affected by the rheumatic disease, which explains its relevance in our country.^–

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Editorial

Rhythm Control Interventions in Patients with Atrial Fibrillation – Insights on Preprocedural Anticoagulation and Utility of Left Atrial Imaging

Mirella Facin et al. Nelson Samesima

The most common sustained arrhythmia in clinical practice is atrial fibrillation (AF),^, affecting 2-4% of the adult population worldwide. It is even more frequent with aging, with almost 10% prevalence in individuals older than 80. Current estimates state that one in every three adults aged 55 years will develop AF during their lifetime, leading to substantial healthcare and economic burden. Clinical issues relate primarily to thromboembolic events (TE) and arrhythmic symptoms, both central targets while managing patients with AF.^,

Overall, atrial fibrillation confers a 2-5-fold escalated risk of TE, which is not evenly distributed, depending on unique modifiers. Important risk factors abridged in the CHA₂DS₂-VASc score – Congestive heart failure, Hypertension, Age ≥75 years, Diabetes, Stroke/TIA, Vascular disease, Age 65-74 years, Sex (female) – may predict stroke risk, consistently mitigated in almost 70% by proper anticoagulation. Vitamin K antagonists (VKAs) were the only oral anticoagulants available for over half a century. From 2009 to 2013, pivotal randomized controlled trials acquainted the scientific community with the new/direct oral anticoagulants (DOACs).^– These drugs not only held similar efficacy to VKA in preventing thromboembolic events but also had a better safety profile against major bleeding – notably intracranial hemorrhage – and a more predictable pharmacokinetic and pharmacodynamic profile, ruling out the need for routine laboratory monitoring. However, the applicability of DOACs in off-label backgrounds, including stroke prevention during rhythm control interventions, remained unclear for many years.

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Symptomatic Aortic Mural Thrombus in a Patient With COVID-19

Milton Sérgio Bohatch Júnior et al. Amanda Fernandes Vidal da Silva Marcelo Bellini Dálio Mauricio Serra Ribeiro Edwaldo Edner Joviliano

A 56-year-old male former smoker with a history of diabetes mellitus developed flu-like symptoms (cough, fever, and myalgia) that worsened after nine days (dyspnea and asthenia) sought medical attention in an emergency care unit. He was hospitalized with novel coronavirus (sudden acute respiratory syndrome coronavirus 2) infection confirmed by polymerase chain reaction testing. His condition progressed with sudden pain in the left lower limb, toe coldness and paresthesia without motor changes, and pain in the third finger of the left hand associated with non-fixed cyanosis. The patient was referred to the emergency room of Hospital das Clínicas of Ribeirão Preto with acute arterial occlusion. On evaluation, he presented non-fixed cyanosis in the distal phalanx of the third finger of the left hand with no pulse or neurological changes throughout the limb. The left lower limb presented no pulse of or arterial flow in the anterior and posterior tibial arteries. He underwent urgent thrombectomy (Rutherford class 2A) with thrombus removal, and limb perfusion was restored with pulsatile tibial artery flow. The patient remained on anticoagulant therapy with unfractionated heparin. Computed tomography angioplasty used to analyze the embolism demonstrated mural thrombi at the origin of the left subclavian artery and in the infrarenal aorta (, ). The patient progressed with good arterial condition (resolution of left upper limb non-fixed cyanosis and presence of pulse in the left leg), stayed in the intensive care unit for three days, and was discharged after two days of anticoagulant treatment (rivaroxaban [Xarelto^®]). In outpatient follow-up, he remained asymptomatic and presented no new embolic events, and the mural thrombi resolved completely after one year of anticoagulant therapy (, ).

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Research Letter

Mechanical Mitral Valve Thrombosis in a Patient with COVID-19 Infection

Emre Aruğaslan et al. Yunus Çalapkulu Ender Örnek Mustafa Karanfil … Hüseyin Bayram Seref Alp Küçüker

Introduction

The novel coronavirus disease-2019 (COVID-19) caused by “Severe Acute Respiratory Syndrome Coronavirus-2” (SARS-CoV-2) became a global pandemic. Although respiratory involvement is the predominant presentation, current evidence has shown that COVID-19 is a multisystemic disease with coagulopathy and thromboembolic complications. Increased production of tissue factor and thrombin reduced fibrinolysis due to hyperinflammation are the proposed mechanisms of COVID-19 induced thrombosis.

We present a case of a COVID-19 infected patient with thrombosis of the mechanical mitral valve.

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Incidental Finding of Retroaortic Renal Vein ‘Posterior Nutcracker Phenomenon’ Associated with Thrombosis

Milton Sérgio Bohatch Júnior et al. Amanda Fernandes Vidal da Silva Carlos Diego Ribeiro Centellas Maurício Serra Ribeiro Edwaldo Edner Joviliano

A 56-year-old woman was admitted to the emergency room with acute obstructive abdomen. She denied comorbidities or previous surgeries. Abdominal computed tomography showed cecal volvulus and an incidental finding of chronic recanalized left renal vein thrombosis with a retroaortic trajectory (posterior “nutcracker” phenomenon). She underwent exploratory laparotomy with a right colectomy and transverse ileum anastomosis. After a gradually progressed diet, she was discharged from hospital ten days after surgery. In outpatient follow-up, she denied symptoms of abdominal or flank pain, and laboratory tests showed no signs of proteinuria or hematuria. Conservative treatment and periodic follow-up were chosen considering the incidental finding of nutcracker phenomenon.

A retroaortic left renal vein is a rare anatomical variation that is asymptomatic in most cases and called posterior nutcracker phenomenon. In symptomatic cases, the term posterior nutcracker syndrome is used.^, Its exact prevalence is unknown, but it is more commonly diagnosed in female patients between the third and fourth decades of life. This compressive disorder can result in venous hypertension with renal vein dilation and ureteral and renal pelvis varicose veins and present as macroscopic and microscopic hematuria, flank pain, and proteinuria.^, Conservative treatment is used for asymptomatic or oligosymptomatic patients as described in here.

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Case Report

Arrhythmogenic Right Ventricular Dysplasia with Right Atrial Thrombus

Clara Bernardy dos Santos et al. Angela Bolonhez Otavio Mangili

Abstract

Arrhythmogenic right ventricular dysplasia is an autosomal dominant genetic disease characterized by the progressive replacement of the myocardium with fibrous fat tissue. It is clinically characterized by arrhythmia, heart failure, syncope and, in some cases, sudden death. We report the case of a patient with such pathology, at an advanced stage, with atrial flutter and thrombus formation in the right atrial appendage, whose therapeutic option was anticoagulation and subsequent electrical cardioversion.

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Original Article

Association between Clinical Risk Score (Heart, Grace and TIMI) and Angiographic Complexity in Acute Coronary Syndrome without ST Segment Elevation

Alexandre Vianna Cedro et al. Diandro Marinho Mota Louis Nakayama Ohe Ari Timerman … José Ribamar Costa Laura de Siqueira Castro

Abstract

Background:

GRACE, TIMI and HEART scores have been previously validated to predict serious untoward events among patients with non-ST elevation acute coronary syndrome (Non-ST ACS). However, the ability of these scores to discriminate the angiographic complexity of coronary artery disease has not been clearly established.

Objectives:

We sought to evaluate the correlation between clinical scores (TIMI, GRACE and HEART) and the anatomical complexity assessed by SYNTAX score, among non-ST ACS patients undergoing cinecoronariography.

Methods:

Transversal cohort encompassing patients with diagnosis of Non-ST ACS referred to invasive stratification in our single center, between July 2018 and February 2019. Association between the scores was established by the Pearson’s linear correlation test while the accuracy of the clinical scores versus SYNTAX score was determined with the ROC curve.

Results:

A total of 138 patients were enrolled. Median GRACE, TIMI and HEART scores were 97, 3 and 5, respectively, whereas the median SYNTAX was 8. There was a positive correlation between the SYNTAX and the HEART (ρ =0.29; p<0.01) and GRACE (ρ =0.18; p 4 presented 100% sensitivity, with 50% specificity; and GRACE> 139 showed 55% sensitivity and 97% specificity for high SYNTAX.

Conclusion:

The clinical scores presented a positive, although modest, association with the SYNTAX score. The combined use of HEART and GRACE offers good accuracy for detecting angiographic complexity.

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