Thrombosis and Anticoagulation Strategies in Patients with COVID-19 Including Japanese Perspective

Coronavirus disease 2019 (COVID-19) has become a major health problem worldwide since 2020. Although the main pathophysiology of COVID-19 is a respiratory infectious disease, it could also cause cardiovascular complications, including thrombosis. Thus, anticoagulation therapy has been thought to help prevent thrombosis, leading to improved survival. However, to date, several aspects of the optimal anticoagulation strategies for COVID-19 remain unclear. Considering the status of COVID-19-related thrombosis and some domestic issues in Japan, the optimal anticoagulation strategies for COVID-19 might have to be based on Japanese domestic clinical data considering racial difference. Racial disparities in terms of thromboembolic risk have been well known in the pre-COVID-19 era, and the risk of COVID-19-associated thrombosis depending on race could be an important issue. Considering a potential higher risk of bleeding with anticoagulation therapy in the Asian population, it might be important to maintain a good balance between the risks of thrombosis and bleeding. Latest evidences of COVID-19-related thrombosis and anticoagulation strategies, including some domestic issues in Japan, showed a different status of COVID-19-related thrombosis in Japan from that in Western countries, suggesting the potential benefit of different anticoagulation strategies, specifically for the Japanese population. Although these insights could be useful for the consideration of anticoagulation strategies for the Japanese population, the final decision should be based on balancing the benefits and risks of anticoagulation therapy in each patient

Magnetic resonance imaging in sudden deafness

The etiology of sudden deafness can remain undetermined despite extensive investigation. This study addresses the value of magnetic resonance imaging in the analysis of sudden deafness patients. STUDY DESIGN: transversal cohort. MATERIAL AND METHOD: In a prospective study, 49 patients attended at otolaryngology emergency room of Federal University of São Paulo - Escola Paulista de Medicina, from April 2001 to May 2003, were submitted to magnetic resonance imaging. RESULTS: Magnetic Resonance abnormalities were seen in 23 (46.9%) patients and revealed two tumors suggestive of meningioma, three vestibular schwannomas, thirteen microangiopathic changes of the brain and five (21.7%) pathological conditions of the labyrinth. CONCLUSION: Sudden deafness should be approached as a symptom common to different diseases. The presence of cerebellopontine angle tumors in 10.2% of our cases, among other treatable causes, justifies the recommendation of gadolinium-enhanced magnetic resonance use, not only to study the auditory peripheral pathway, but to study the whole auditory pathway including the brain.A surdez súbita é um sintoma cuja etiologia nem sempre é elucidada mesmo dispondo-se de toda propedêutica atual. Neste estudo avaliaremos as alterações encontradas em ressonância magnética de pacientes portadores de surdez súbita. FORMA DE ESTUDO: coorte transversal. MATERIAL E MÉTODO: Estudo prospectivo com realização de RM em 49 dos 61 pacientes com surdez súbita atendidos no pronto socorro de Otorrinolaringologia do Hospital São Paulo, no período de abril de 2001 a maio de 2003. Doze pacientes abandonaram ou não foram submetidos à ressonância magnética por outros motivos. RESULTADOS: 23 (46,9%) pacientes apresentaram alterações à ressonância magnética. Foram encontrados dois tumores sugestivos de meningioma e três schwannomas do oitavo par craniano. Lesões subcorticais e periventriculares esparsas e hiperintensas em FLAIR foram encontradas em 13 pacientes. Cinco (21,7%) pacientes apresentaram alterações periféricas. CONCLUSÃO: A surdez súbita deve ser abordada como um sintoma comum a diferentes doenças. A presença de tumores do ângulo pontocerebelar em 10,2% dos nossos casos, entre outras causas tratáveis, justifica o uso da ressonância magnética com contraste tanto para o estudo do sistema auditivo periférico quanto para o estudo das vias auditivas centrais, incluindo o cérebro.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Otorrinolaringologia e Cirurgia de Cabeça e PescoçoUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Diagnóstico por Imagem Departamento de Diagnóstico por ImagemUNIFESP, EPM, Depto. de Otorrinolaringologia e Cirurgia de Cabeça e PescoçoUNIFESP, EPM, Depto. de Diagnóstico por Imagem Depto. de Diagnóstico por ImagemSciEL

Incidence, clinical characteristics and long-term prognosis of postoperative symptomatic venous thromboembolism: a retrospective cohort study

OBJECTIVES: The purpose of this study was to evaluate the incidence, clinical characteristics and prognosis of postoperative symptomatic venous thromboembolism (VTE) in Japan. DESIGN: Retrospective observational study. Two data sets, Contemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND VTE) Registry and Japanese Society of Anesthesiologists (JSA) annual report, were used for current analyses. SETTING: Eighteen of 29 centres participated in the COMMAND VTE Registry. PARTICIPANTS: Acute symptomatic patients with VTE who had undergone surgery 2 months prior to the diagnosis at 18 centres from January 2010 to December 2013 were identified in the COMMAND VTE Registry. From each centre's JSA annual report, the overall population that had received anaesthetic management during this period was retrieved. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the incidences and clinical characteristics of postoperative symptomatic VTE. The secondary outcomes were recurrent VTE, major bleeding and all-cause death. RESULTS: We identified 137 patients with postoperative symptomatic VTE, including 57 patients with pulmonary embolism. The incidences of postoperative symptomatic VTE and pulmonary embolism were 0.067% and 0.028%, respectively, based on data from 2 03 943 patients who underwent surgery, managed by anaesthesiologists, during the study period. The incidences of postoperative symptomatic VTE varied widely, depending on surgical and anaesthetic characteristics. Postoperative symptomatic VTE occurred at a median of 8 days after surgery, with 58 patients (42%) diagnosed within 7 days. The cumulative incidence, 30 days after VTE, of recurrent VTE, major bleeding, and all-cause death was 3.0%, 5.2%, and 3.7%, respectively. CONCLUSION: This study, combining the large real-world VTE and anaesthesiology databases in Japan revealed the incidence, clinical features and prognosis of postoperative symptomatic VTE, providing useful insights for all healthcare providers involved in various surgeries. TRIAL REGISTRATION: Not applicable

Machine learning to predict major bleeding during anticoagulation for venous thromboembolism: possibilities and limitations

Predictive tools for major bleeding (MB) using machine learning (ML) might be advantageous over traditional methods. We used data from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) to develop ML algorithms to identify patients with venous thromboembolism (VTE) at increased risk of MB during the first 3 months of anticoagulation. A total of 55 baseline variables were used as predictors. New data prospectively collected from the RIETE were used for further validation. The RIETE and VTE-BLEED scores were used for comparisons. External validation was performed with the COMMAND-VTE database. Learning was carried out with data from 49 587 patients, of whom 873 (1.8%) had MB. The best performing ML method was XGBoost. In the prospective validation cohort the sensitivity, specificity, positive predictive value and F1 score were: 33.2%, 93%, 10%, and 15.4% respectively. F1 value for the RIETE and VTE-BLEED scores were 8.6% and 6.4% respectively. In the external validation cohort the metrics were 10.3%, 87.6%, 3.5% and 5.2% respectively. In that cohort, the F1 value for the RIETE score was 17.3% and for the VTE-BLEED score 9.75%. The performance of the XGBoost algorithm was better than that from the RIETE and VTE-BLEED scores only in the prospective validation cohort, but not in the external validation cohort

Prognostic value of reduction in left atrial size during a follow-up of heart failure: an observational study

OBJECTIVE: The association between sequential changes in left atrial diameter (LAD) and prognosis in heart failure (HF) remains to be elucidated. The present study aimed to investigate the link between reduction in LAD and clinical outcomes in patients with HF. DESIGN: A multicentre prospective cohort study. SETTING: This study was nested from the Kyoto Congestive Heart Failure registry including consecutive patients admitted for acute decompensated heart failure (ADHF) in 19 hospitals throughout Japan. PARTICIPANTS: The current study population included 673 patients with HF who underwent both baseline and 6-month follow-up echocardiography with available paired LAD data. We divided them into two groups: the reduction in the LAD group (change <0 mm) (n=398) and the no-reduction in the LAD group (change ≥0 mm) (n=275). PRIMARY AND SECONDARY OUTCOMES: The primary outcome measure was a composite of all-cause death or hospitalisation for HF during 180 days after 6-month follow-up echocardiography. The secondary outcome measures were defined as the individual components of the primary composite outcome measure and a composite of cardiovascular death or hospitalisation for HF. RESULTS: The cumulative 180-day incidence of the primary outcome measure was significantly lower in the reduction in the LAD group than in the no-reduction in the LAD group (13.3% vs 22.2%, p=0.002). Even after adjusting 15 confounders, the lower risk of reduction in LAD relative to no-reduction in LAD for the primary outcome measure remained significant (HR 0.59, 95% CI 0.36 to 0.97 p=0.04). CONCLUSION: Patients with reduction in LAD during follow-up after ADHF hospitalisation had a lower risk for a composite endpoint of all-cause death or HF hospitalisation, suggesting that the change of LAD might be a simple and useful echocardiographic marker during follow-up

Improved and new-onset anemia during follow-up in patients with acute decompensated heart failure

There was no previous report on the prognostic impact of new-onset or improved anemia after discharge from acute decompensated heart failure (ADHF).We analyzed 771 patients with ADHF and who were followed in multicenters in Japan was divided into 4 groups based on the hemoglobin values at discharge and 6-month index visit: 373 patients (48.4%) with persistent anemia, 87 patients (11.3%) with new-onset anemia, 91 patients (11.8%) with improved anemia, and 220 patients (28.5%) without anemia.The primary outcome measure was a composite of all-cause death or HF hospitalization after index visit. The cumulative 6-month incidences of the primary outcome measure were 25.2% for persistent anemia, 18.5% for new onset anemia, 9.0% for improved anemia, and 9.2% for no anemia (log-rank P < .001). Compared with the no anemia group, the excess risk for the primary outcome measure remained significant in the persistent anemia group [hazard ratio (HR) 2.70, 95% confidence interval (95% CI), 1.45-5.44, P = .001] and in the new-onset anemia group (HR 2.73, 95% CI 1.19-6.25, P = .02), while it was not significant in the improved anemia group (HR 1.69, 95% CI 0.68-4.03, P = .25).Persistent and new-onset anemia at 6-month visit were associated with a subsequent higher risk for all-cause death or HF hospitalization in patients with ADHF, suggesting the importance of detecting anemia during follow-up

Left atrial reverse remodeling improves risk stratification in patients with heart failure with recovered ejection fraction

We aimed to investigate the relationship between left atrial (LA) reverse remodeling and prognosis of heart failure (HF) with recovered ejection fraction (EF) (HFrecEF). Among 1, 246 patients with acute heart failure enrolled in the prospective longitudinal follow-up study, 397 patients with HF with mildly-reduced EF and with reduced EF at discharge were analyzed. Echocardiography was performed during the index hospitalization and at the 6-month follow-up after discharge. They were divided into non-HFrecEF (n = 227) and HFrecEF (n = 170) groups. The primary outcome measure was a composite of all-cause death or hospitalization for HF. The cumulative 180-day incidence of the primary outcome measure after follow-up echocardiography was significantly lower in the HFrecEF group than in the non-HFrecEF group (8.9% versus 23.4%, log-rank P = 0.0002). LA reverse remodeling was associated with a lower cumulative 6-month incidence of the primary outcome measure in the HFrecEF group (4.7% versus 18.0%; HR: 0.27, 95%CI: 0.09-0.79, P = 0.01), but not in the non-HFrecEF group (24.4% versus 22.6%; HR: 1.13, 95%CI: 0.65-1.96, P = 0.28) with a significant LA reverse remodeling-by-HFrecEF interaction (P for interaction = 0.02). Combination of left ventricular and atrial reverse remodeling may help in improving HF risk stratification

Risk Factors and Clinical Outcomes of Nonhome Discharge in Patients With Acute Decompensated Heart Failure: An Observational Study

Background: No clinical studies have focused on the factors associated with discharge destination in patients with acute decompensated heart failure. Methods and Results: Of 4056 consecutive patients hospitalized for acute decompensated heart failure in the KCHF (Kyoto Congestive Heart Failure) registry, we analyzed 3460 patients hospitalized from their homes and discharged alive. There were 3009 and 451 patients who were discharged to home and nonhome, respectively. We investigated the factors associated with nonhome discharge and compared the outcomes between home discharge and nonhome discharge. Factors independently and positively associated with nonhome discharge were age ≥80 years (odds ratio [OR], 1.76; 95% CI, 1.28–2.42), body mass index ≤22 kg/m2 (OR, 1.49; 95% CI, 1.12–1.97), poor medication adherence (OR, 2.08; 95% CI, 1.49–2.88), worsening heart failure (OR, 2.02; 95% CI, 1.46–2.82), stroke during hospitalization (OR, 3.74; 95% CI, 1.75–8.00), functional decline (OR, 12.24; 95% CI, 8.74–17.14), and length of hospital stay >16 days (OR, 4.14; 95% CI, 3.01–5.69), while those negatively associated were diabetes mellitus (OR, 0.69; 95% CI, 0.51–0.94), cohabitants (OR, 0.62; 95% CI, 0.46–0.85), and ambulatory state before admission (OR, 0.25; 95% CI, 0.18–0.36). The cumulative 1‐year incidence of all‐cause death was significantly higher in the nonhome discharge group than in the home discharge group. The nonhome discharge group compared with the nonhome discharge group was associated with a higher adjusted risk for all‐cause death (hazard ratio, 1.66; P<0.001). Conclusions: The discharge destination of patients with acute decompensated heart failure is influenced by factors such as prehospital social background, age, body mass index, low self‐care ability, events during hospitalization (worsening heart failure, stroke, etc), functional decline, and length of hospital stay; moreover, the prognosis of nonhome discharge patients is worse than that of home discharge patients. Registration Information: clinicaltrials.gov. Identifier: NCT02334891

Significant Impact of Age on Mortality and Non-significant Impact of Age on Thrombosis and Major Bleeding in Patients with COVID-19: From the CLOT-COVID Study.

AIM: There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20-39, 40-59, 60-79, and 80- years. RESULTS: Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20-39, 40-59, 60-79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity. CONCLUSIONS: In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission

Clinical characteristics, management strategies and outcomes of patients with recurrent venous thromboembolism in the real world

There is a paucity of data on management strategies and clinical outcomes after recurrent venous thromboembolism (VTE). In a multicenter registry enrolling 3027 patients with acute symptomatic VTE, the current study population was divided into the following 3 groups: (1) First recurrent VTE during anticoagulation therapy (N = 110); (2) First recurrent VTE after discontinuation of anticoagulation therapy (N = 116); and (3) No recurrent VTE (N = 2801). Patients with first recurrent VTE during anticoagulation therapy more often had active cancer (45, 25 and 22%, P < 0.001). Among 110 patients with first recurrent VTE during anticoagulation therapy, 84 patients (76%) received warfarin at recurrent VTE with the median prothrombin time-international normalized ratio (PT-INR) value at recurrent VTE of 1.6, although patients with active cancer had a significantly higher median PT-INR value at recurrent VTE compared with those without active cancer (2.0 versus 1.4, P < 0.001). Within 90 days after recurrent VTE, 23 patients (20.9%) during anticoagulation therapy and 24 patients (20.7%) after discontinuation of anticoagulation therapy died. Active cancer was a major cause of recurrent VTE during anticoagulation therapy as a patient-related factor, while sub-optimal intensity of anticoagulation therapy was a major cause of recurrent VTE during anticoagulation therapy as a treatment-related factor, particularly in patients without active cancer