Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

Guidelines on the Diagnosis and Treatment of Hypertrophic Cardiomyopathy ­ 2024 / Diretriz sobre Diagnóstico e Tratamento da Cardiomiopatia Hipertrófica ­ 2024

Hypertrophic cardiomyopathy (HCM) is a form of genetically caused heart muscle disease, characterized by the thickening of the ventricular walls. Diagnosis requires detection through imaging methods (Echocardiogram or Cardiac Magnetic Resonance) showing any segment of the left ventricular wall with a thickness > 15 mm, without any other probable cause. Genetic analysis allows the identification of mutations in genes encoding different structures of the sarcomere responsible for the development of HCM in about 60% of cases, enabling screening of family members and genetic counseling, as an important part of patient and family management. Several concepts about HCM have recently been reviewed, including its prevalence of 1 in 250 individuals, hence not a rare but rather underdiagnosed disease. The vast majority of patients are asymptomatic. In symptomatic cases, obstruction of the left ventricular outflow tract (LVOT) is the primary disorder responsible for symptoms, and its presence should be investigated in all cases. In those where resting echocardiogram or Valsalva maneuver does not detect significant intraventricular gradient (> 30 mmHg), they should undergo stress echocardiography to detect LVOT obstruction. Patients with limiting symptoms and severe LVOT obstruction, refractory to beta-blockers and verapamil, should receive septal reduction therapies or use new drugs inhibiting cardiac myosin. Finally, appropriately identified patients at increased risk of sudden death may receive prophylactic measure with implantable cardioverter-defibrillator (ICD) implantation.

La miocardiopatía hipertrófica (MCH) es una forma de enfermedad cardíaca de origen genético, caracterizada por el engrosamiento de las paredes ventriculares. El diagnóstico requiere la detección mediante métodos de imagen (Ecocardiograma o Resonancia Magnética Cardíaca) que muestren algún segmento de la pared ventricular izquierda con un grosor > 15 mm, sin otra causa probable. El análisis genético permite identificar mutaciones en genes que codifican diferentes estructuras del sarcómero responsables del desarrollo de la MCH en aproximadamente el 60% de los casos, lo que permite el tamizaje de familiares y el asesoramiento genético, como parte importante del manejo de pacientes y familiares. Varios conceptos sobre la MCH han sido revisados recientemente, incluida su prevalencia de 1 entre 250 individuos, por lo tanto, no es una enfermedad rara, sino subdiagnosticada. La gran mayoría de los pacientes son asintomáticos. En los casos sintomáticos, la obstrucción del tracto de salida ventricular izquierdo (TSVI) es el trastorno principal responsable de los síntomas, y su presencia debe investigarse en todos los casos. En aquellos en los que el ecocardiograma en reposo o la maniobra de Valsalva no detecta un gradiente intraventricular significativo (> 30 mmHg), deben someterse a ecocardiografía de esfuerzo para detectar la obstrucción del TSVI. Los pacientes con síntomas limitantes y obstrucción grave del TSVI, refractarios al uso de betabloqueantes y verapamilo, deben recibir terapias de reducción septal o usar nuevos medicamentos inhibidores de la miosina cardíaca. Finalmente, los pacientes adecuadamente identificados con un riesgo aumentado de muerte súbita pueden recibir medidas profilácticas con el implante de un cardioversor-desfibrilador implantable (CDI).

A cardiomiopatia hipertrófica (CMH) é uma forma de doença do músculo cardíaco de causa genética, caracterizada pela hipertrofia das paredes ventriculares. O diagnóstico requer detecção por métodos de imagem (Ecocardiograma ou Ressonância Magnética Cardíaca) de qualquer segmento da parede do ventrículo esquerdo com espessura > 15 mm, sem outra causa provável. A análise genética permite identificar mutações de genes codificantes de diferentes estruturas do sarcômero responsáveis pelo desenvolvimento da CMH em cerca de 60% dos casos, permitindo o rastreio de familiares e aconselhamento genético, como parte importante do manejo dos pacientes e familiares. Vários conceitos sobre a CMH foram recentemente revistos, incluindo sua prevalência de 1 em 250 indivíduos, não sendo, portanto, uma doença rara, mas subdiagnosticada. A vasta maioria dos pacientes é assintomática. Naqueles sintomáticos, a obstrução do trato de saída do ventrículo esquerdo (OTSVE) é o principal distúrbio responsável pelos sintomas, devendo-se investigar a sua presença em todos os casos. Naqueles em que o ecocardiograma em repouso ou com Manobra de Valsalva não detecta gradiente intraventricular significativo (> 30 mmHg), devem ser submetidos à ecocardiografia com esforço físico para detecção da OTSVE.   Pacientes com sintomas limitantes e grave OTSVE, refratários ao uso de betabloqueadores e verapamil, devem receber terapias de redução septal ou uso de novas drogas inibidoras da miosina cardíaca. Por fim, os pacientes adequadamente identificados com risco aumentado de morta súbita podem receber medida profilática com implante de cardiodesfibrilador implantável (CDI).

In-Hospital Management and Long-term Clinical Outcomes and Adherence in Patients With Acute Decompensated Heart Failure: Primary Results of the First Brazilian Registry of Heart Failure (BREATHE).

BACKGROUND: Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognoses of patients with HF in Latin America. METHODS: BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute heart failure (HF). Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018 SUGGESTION FOR REPHRASING: In-hospital management, 12-month clinical outcomes and adherence to evidence-based therapies were evaluated. RESULTS: A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors and spironolactone decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months. CONCLUSIONS: In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and at 12 months of follow-up.

In-Hospital Management and Long-term clinical outcomes and adherence in patients with acute decompensated heart failure: primary results of the first brazilian registry of heart failure (BREATHE)

BACKGROUND: Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognosis of patients with HF in Latin America. METHODS: BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute HF. Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018. In-hospital management and 12-month clinical outcomes were assessed, and adherence to evidence-based therapies was evaluated. RESULTS: A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors, and spironolactone numerical decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months. CONCLUSIONS: In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and 12 months of follow-up.

First Evaluation of the Brazilian Advanced Life Support Training (TECA A)

Abstract Background Cardiac arrest (CA) is a common condition associated with high mortality. The Brazilian advanced life support training TECA A (Treinamento em Emergências Cardiovasculares Avançado — Advanced Cardiovascular Emergency Training) was created to train healthcare professionals in the management of CA. However, there are no studies evaluating the effectiveness of TECA A. Objective To assess the impact of TECA A on the management of CA using a simulated CA situation. Methods Fifty-six students underwent a simulated case of CA in a manikin. The students' performance in the management of CA was assessed for the time to first chest compression and defibrillation and for a global assessment score using a structured tool. These items were assessed and compared before and after the TECA A. Exclusion criteria were previous participation in CA trainings and absence from class. Categorical variables were compared using the McNemar test and quantitative variables using the Wilcoxon test. All tests were two-tailed, and statistical significance was set at p < 0.05. Results Compared with before TECA A, median global assessment scores were higher after TECA A (pre-training: 4.0 points [2.0-5.0] vs. 10 points [9.0-10.0]; p<0.001), the time to start chest compressions was shorter (pre-training: 25 seconds [15-34] vs. 19 seconds [16.2-23.0]; p=0.002) and so was the time to defibrillation (pre-training: 82.5 seconds [65.0-108.0] vs. 48 seconds [39.0-53.0]; p<0.001). Conclusions The TECA A promoted a higher adherence to cardiopulmonary resuscitation (CPR) guidelines and a reduction in the time elapsed from CA to first chest compression and defibrillation.

Learning: New Strategy for Humanized Digital Medical Education and Training in Cardiology. / Virtual Case-Based Learning: Nova Estratégia de Ensino e de Treinamento Médico Digital Humanizado em Cardiologia.

BACKGROUND: The consolidation of new educational paradigms requires the implementation of innovative strategies to transform students into competent professionals. OBJECTIVES: To assess knowledge and satisfaction of medical students before and after the use of a new humanized digital model of active learning, called virtual case-based learning (VCBL). METHODS: This was a descriptive, documentary analysis of the teaching-learning process of medical students. Data obtained from theoretical knowledge assessment and satisfaction evaluation questionnaires applied in 2018 and 2019 were analyzed, and the new VCBL was compared with the traditional active methodology PBL (problem-based learning). Descriptive and association analyses were made using the Statistical Package for the Social Sciences. RESULTS: A total of 167 evaluation forms administered to medical students were analyzed. In the evaluation of theoretical knowledge, the 2018 and the 2019 student groups had a mean of 41.7% and 73.3%, respectively (p<0.001). Among the students who responded to the satisfaction evaluation form, 76.0% gave the highest rating to question one, and 83.0% to question two. Nearly 70.0% of students positively evaluated knowledge acquisition with the Paciente 360 platform; 78.0% reported to feel prepared for working in outpatient care; and 94.0% positively evaluated the new method. CONCLUSION: In this initial study, the results indicate that the new active method for humanized digital medical education, the VCBL, can help in the betterment of the teaching-learning process, promoting knowledge and satisfaction by the students.

FUNDAMENTO: A consolidação de novos paradigmas educacionais exige a implantação de estratégias inovadoras com potencial de transformar estudantes em profissionais competentes. OBJETIVOS: Analisar o conhecimento e a satisfação de estudantes antes e após a utilização de uma nova metodologia ativa de ensino médico de modelo digital humanizado chamada Virtual Case-Based Learning (VCBL). MÉTODOS: Estudo descritivo com análise documental sobre o processo de ensino-aprendizagem de estudantes de medicina. Dados obtidos da avaliação de conhecimento teórico e do instrumento de satisfação dos alunos nos anos de 2018 e 2019 foram analisados, e a nova metodologia proposta VCBL foi comparada com a metodologia ativa de ensino tradicional, o Problem-Based Learning (PBL). As análises descritivas e de associação foram realizadas utilizando o programa Statistical Package for the Social Sciences. RESULTADOS: Foram analisados 167 documentos aplicados a estudantes de medicina. Em relação à avaliação do conhecimento teórico, os alunos avaliados em 2018 obtiveram média 41,7%, comparados aos alunos de 2019 que alcançaram 73,3% (p<0,001). Entre os estudantes submetidos à avaliação da satisfação com a metodologia de aprendizagem proposta, 76,0% pontuaram o valor máximo para a questão um, e 83,0% para a questão número dois. Cerca de 70,0% dos estudantes classificaram positivamente o aprendizado adquirido após utilização da plataforma Paciente 360; 78,0% responderam que se sentem preparados para o atendimento ambulatorial; e 94,0% pontuaram de forma positiva a metodologia empregada. CONCLUSÃO: Neste estudo inicial, os resultados indicaram que a nova ferramenta em metodologia ativa de ensino médico digital humanizado, o VCBL, pode auxiliar no aprimoramento do processo de ensino-aprendizagem, proporcionando conhecimento e satisfação dos estudantes.

Virtual Case-Based Learning: Nova Estratégia de Ensino e de Treinamento Médico Digital Humanizado em Cardiologia / Learning: New Strategy for Humanized Digital Medical Education and Training in Cardiology

Resumo Fundamento A consolidação de novos paradigmas educacionais exige a implantação de estratégias inovadoras com potencial de transformar estudantes em profissionais competentes. Objetivos Analisar o conhecimento e a satisfação de estudantes antes e após a utilização de uma nova metodologia ativa de ensino médico de modelo digital humanizado chamada Virtual Case-Based Learning (VCBL). Métodos Estudo descritivo com análise documental sobre o processo de ensino-aprendizagem de estudantes de medicina. Dados obtidos da avaliação de conhecimento teórico e do instrumento de satisfação dos alunos nos anos de 2018 e 2019 foram analisados, e a nova metodologia proposta VCBL foi comparada com a metodologia ativa de ensino tradicional, o Problem-Based Learning (PBL). As análises descritivas e de associação foram realizadas utilizando o programa Statistical Package for the Social Sciences. Resultados Foram analisados 167 documentos aplicados a estudantes de medicina. Em relação à avaliação do conhecimento teórico, os alunos avaliados em 2018 obtiveram média 41,7%, comparados aos alunos de 2019 que alcançaram 73,3% (p<0,001). Entre os estudantes submetidos à avaliação da satisfação com a metodologia de aprendizagem proposta, 76,0% pontuaram o valor máximo para a questão um, e 83,0% para a questão número dois. Cerca de 70,0% dos estudantes classificaram positivamente o aprendizado adquirido após utilização da plataforma Paciente 360; 78,0% responderam que se sentem preparados para o atendimento ambulatorial; e 94,0% pontuaram de forma positiva a metodologia empregada. Conclusão Neste estudo inicial, os resultados indicaram que a nova ferramenta em metodologia ativa de ensino médico digital humanizado, o VCBL, pode auxiliar no aprimoramento do processo de ensino-aprendizagem, proporcionando conhecimento e satisfação dos estudantes.

Abstract Background The consolidation of new educational paradigms requires the implementation of innovative strategies to transform students into competent professionals. Objectives To assess knowledge and satisfaction of medical students before and after the use of a new humanized digital model of active learning, called virtual case-based learning (VCBL). Methods This was a descriptive, documentary analysis of the teaching-learning process of medical students. Data obtained from theoretical knowledge assessment and satisfaction evaluation questionnaires applied in 2018 and 2019 were analyzed, and the new VCBL was compared with the traditional active methodology PBL (problem-based learning). Descriptive and association analyses were made using the Statistical Package for the Social Sciences. Results A total of 167 evaluation forms administered to medical students were analyzed. In the evaluation of theoretical knowledge, the 2018 and the 2019 student groups had a mean of 41.7% and 73.3%, respectively (p<0.001). Among the students who responded to the satisfaction evaluation form, 76.0% gave the highest rating to question one, and 83.0% to question two. Nearly 70.0% of students positively evaluated knowledge acquisition with the Paciente 360 platform; 78.0% reported to feel prepared for working in outpatient care; and 94.0% positively evaluated the new method. Conclusion In this initial study, the results indicate that the new active method for humanized digital medical education, the VCBL, can help in the betterment of the teaching-learning process, promoting knowledge and satisfaction by the students.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59-1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61-8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. FUNDING: Coalition COVID-19 Brazil, Bayer SA.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3­0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59­1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61­8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation.