Prophylactic Anticoagulation and Thrombosis in Hospitalized Patients with Clinically Stable COVID-19 at Admission: From the Practice-Based Observational Study.

Objectives: The potential benefit of routine prophylactic anticoagulation for all hospitalized patients with clinically stable coronavirus disease 2019 (COVID-19) is still controversial. Method: The CLOT-COVID Study was a multicenter observational study enrolling 2894 consecutive hospitalized patients with COVID-19. The current study population consisted of 1738 hospitalized patients with mild COVID-19 at admission not requiring oxygen administration, who were divided into 2 groups: patients with prophylactic anticoagulation (n = 326) and those without (n = 1412). Results: Patients with prophylactic anticoagulation had more severe status of the worst severity of COVID-19 during hospitalization compared with those without (mild: 38% versus 82%, moderate: 55% versus 17%, and severe or death at discharge: 6.4% versus 0.7%, P <0.001). During hospitalization, 8 patients (0.5%) developed thrombosis, and the incidences of thrombosis were numerically higher in patients with more severe status of worst severity of COVID-19 during hospitalization (mild: 0.2%, moderate: 1.2%, and severe or death at discharge: 3.2%). Conclusions: Among hospitalized patients with clinically stable COVID-19 at admission, patients who did not worsen in COVID-19 severity after admission rarely developed thrombosis, although patients with worsening of COVID-19 severity after admission more often received prophylactic anticoagulation and might have a higher risk of thrombosis.

Deep learning to assess right ventricular ejection fraction from two-dimensional echocardiograms in precapillary pulmonary hypertension.

BACKGROUND: Precapillary pulmonary hypertension (PH) is characterized by a sustained increase in right ventricular (RV) afterload, impairing systolic function. Two-dimensional (2D) echocardiography is the most performed cardiac imaging tool to assess RV systolic function; however, an accurate evaluation requires expertise. We aimed to develop a fully automated deep learning (DL)-based tool to estimate the RV ejection fraction (RVEF) from 2D echocardiographic videos of apical four-chamber views in patients with precapillary PH. METHODS: We identified 85 patients with suspected precapillary PH who underwent cardiac magnetic resonance imaging (MRI) and echocardiography. The data was divided into training (80%) and testing (20%) datasets, and a regression model was constructed using 3D-ResNet50. Accuracy was assessed using five-fold cross validation. RESULTS: The DL model predicted the cardiac MRI-derived RVEF with a mean absolute error of 7.67%. The DL model identified severe RV systolic dysfunction (defined as cardiac MRI-derived RVEF < 37%) with an area under the curve (AUC) of .84, which was comparable to the AUC of RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) measured by experienced sonographers (.87 and .72, respectively). To detect mild RV systolic dysfunction (defined as RVEF ≤ 45%), the AUC from the DL-predicted RVEF also demonstrated a high discriminatory power of .87, comparable to that of FAC (.90), and significantly higher than that of TAPSE (.67). CONCLUSION: The fully automated DL-based tool using 2D echocardiography could accurately estimate RVEF and exhibited a diagnostic performance for RV systolic dysfunction comparable to that of human readers.

Echocardiographic estimation of right ventricular diastolic stiffness based on pulmonary regurgitant velocity waveform analysis in precapillary pulmonary hypertension.

Right ventricular (RV) diastolic stiffness is an independent predictor of survival and is strongly associated with disease severity in patients with precapillary pulmonary hypertension (PH). Therefore, a fully validated echocardiographic method for assessing RV diastolic stiffness needs to be established. This study aimed to compare echocardiography-derived RV diastolic stiffness and invasively measured pressure-volume loop-derived RV diastolic stiffness in patients with precapillary PH. We studied 50 consecutive patients with suspected or confirmed precapillary PH who underwent cardiac catheterization, magnetic resonance imaging, and echocardiography within a 1-week interval. Single-beat RV pressure-volume analysis was performed to determine the gold standard for RV diastolic stiffness. Elevated RV end-diastolic pressure (RVEDP) was defined as RVEDP ≥ 8 mmHg. Using continuous-wave Doppler and M-mode echocardiography, an echocardiographic index of RV diastolic stiffness was calculated as the ratio of the atrial-systolic descent of the pulmonary artery-RV pressure gradient derived from pulmonary regurgitant velocity (PRPGDAC) to the tricuspid annular plane movement during atrial contraction (TAPMAC). PRPGDAC/TAPMAC showed significant correlation with ß (r = 0.54, p < 0.001) and RVEDP (r = 0.61, p < 0.001). A cut-off value of 0.74 mmHg/mm for PRPGDAC/TAPMAC showed 83% sensitivity and 93% specificity for identifying elevated RVEDP. Multivariate analyses indicated that PRPGDAC/TAPMAC was independently associated with disease severity in patients with precapillary PH, including substantial PH symptoms, stroke volume index, right atrial size, and pressure. PRPGDAC/TAPMAC, based on pulmonary regurgitation velocity waveform analysis, is useful for the noninvasive assessment of RV diastolic stiffness and is associated with prognostic risk factors in precapillary PH.

Adult-onset idiopathic peripheral pulmonary artery stenosis.

BACKGROUND: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. METHODS: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. RESULTS: 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. CONCLUSIONS: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.

The chest CT signs for pulmonary veno-occlusive disease correlate with pulmonary haemodynamics in systemic sclerosis.

OBJECTIVE: Pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) sometimes accompanies pulmonary veno-occlusive disease (PVOD). We aimed to reveal the relation between clinical signs of PVOD and severing of pulmonary vasculopathy in SSc. METHODS: This study comprised 52 consecutive SSc patients who had pulmonary haemodynamic abnormalities (mPAP > 20 mmHg, PVR > 2 W.U. or PAWP > 15 mmHg). The chest CT scan was evaluated in all patients. Patients were divided into two groups, the 0-1 group and the 2-3 group, according to the number of chest CT signs for PVOD, including 1) mediastinal lymph node enlargement, 2) thickened interlobular septal wall, and 3) ground glass opacity. Pulmonary haemodynamics, echocardiography and MRI-based cardiac function, pulmonary function, and serum biomarkers were compared between the two groups. RESULTS: Mediastinal lymph node enlargement, thickened interlobular septal wall, and ground glass opacity were observed in 11 (21%), 32 (62%), and 11 (21%) patients, respectively. The 2-3 group (n = 15) had higher mPAP (p= 0.02) while lower DLco/VA (p= 0.02) compared with the 0-1 group (n = 37). Other parameters, including PAWP, cardiac output, left ventricular ejection fraction, left atrial diameter, forced vital capacity, brain natriuretic peptide, and Krebs von den Lunge-6 were not different between the two groups. CONCLUSION: The CT signs for PVOD had positive correlation with mPAP but negative correlation with DLco in SSc patients, indicating that PAH-SSc may reflect a spectrum of pulmonary vascular disease that ranges from the pulmonary artery to the vein.

Impact of cancer on the prevalence, management, and outcome of patients with chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved thrombotic obstruction of the pulmonary vasculature. Cancer is a known risk factor for CTEPH. This study aimed to determine the impact of cancer on the prevalence, management, and outcomes of patients with CTEPH. MATERIALS AND METHODS: In this retrospective study involving 99 patients sequentially diagnosed with CTEPH in our hospital, the prevalence of 10 comorbid conditions including a past history of cancer at the time of CTEPH diagnosis were calculated. RESULTS: Among the 99 patients, 17 (17%) had a history of cancer. Breast cancer (n = 6) was the most common cancer type, followed by gastrointestinal cancer (n = 3), uterine cancer (n = 2), and malignant lymphoma (n = 2). Between patients with and without cancer, there were no differences in the demographics, severity of CTEPH, and management; however, the 5-year survival rate was lower for patients with cancer (65%) than for those without (89%). In addition, patients with cancer had significantly worse survival than those without (p = 0.03 by log-rank test). During follow-up, nine patients developed cancer after the diagnosis of CTEPH. Among the 99 patients, 13 died during follow-up, 6 (46%) of whom died of cancer. CONCLUSIONS: 17% of our patients with CETPH were diagnosed with cancer, with breast and gastrointestinal tract cancers being the most common. Cancer comorbidity was associated with a poor prognosis and contributed to death in 46% of deceased patients. The impact of cancer on CTEPH should be further evaluated in the future.

Association of longitudinal cardiac troponin trajectory with adverse events in patients with cardiac sarcoidosis.

BACKGROUND: Although high-sensitivity cardiac troponins may be sensitive and easily repeatable markers of disease activity in patients with cardiac sarcoidosis (CS), the association between longitudinal cardiac troponin trajectory and adverse events remains unclear. This study aimed to clarify whether longitudinal cardiac troponin levels were associated with adverse events in patients with CS. METHODS: We examined 63 consecutive CS-initiated prednisolone (PSL) patients with available longitudinal high-sensitivity cardiac troponin T (cTnT) data between December 2013 and March 2023. The area under the cTnT trajectory, which reflected cumulative cTnT release, was calculated to assess the association between longitudinal cTnT levels and adverse events. Patients were divided into two groups according to the median area under the cTnT trajectory per month. The primary outcome was a composite of sustained ventricular tachycardia or fibrillation, worsening heart failure, and sudden cardiac death (SCD). RESULTS: In total, 463 cTnT measurements were collected over a median follow-up period of 30.4 (interquartile range [IQR] 15.6-34.2) months. The primary outcome was observed in 12 (19%) patients. A higher area under the cTnT trajectory was significantly associated with an increased incidence of the primary outcome (P = 0.027), while cTnT levels before and one month after initiation of PSL, and these changes were not related to adverse events (P = 0.179, 0.096, and 0.95, respectively). CONCLUSIONS: Longitudinal cTnT trajectory following PSL initiation was associated with adverse cardiac events in patients with CS, suggesting that longitudinal measurement of cTnT would be useful for the early identification of high-risk patients.

Initial Triple Combination Therapy Including Intravenous Prostaglandin I2 for the Treatment of Patients with Severe Pulmonary Arterial Hypertension.

Upfront combination therapy including intravenous prostaglandin I2 (PGI2-IV) is recognized as the most appropriate treatment for patients with severe pulmonary arterial hypertension (PAH). This retrospective study aimed to determine reasons why this therapy is not used for some patients with severe PAH and describe the hemodynamic and clinical prognoses of patients receiving initial combination treatment with (PGI2-IV+) or without (PGI2-IV-) PGI2-IV.Data for patients with severe PAH (World Health Organization Functional Class III/IV and mean pulmonary arterial pressure [mPAP] ≥ 40 mmHg) were extracted from the Japan Pulmonary Hypertension Registry. Overall, 73 patients were included (PGI2-IV + n = 17; PGI2-IV- n = 56). The PGI2-IV+ cohort was younger than the PGI2-IV- cohort (33.8 ± 10.6 versus 52.6 ± 18.2 years) and had higher mPAP (58.1 ± 12.9 versus 51.8 ± 9.0 mmHg), greater prevalence of idiopathic PAH (88% versus 32%), and less prevalence of connective tissue disease-associated PAH (0% versus 29%). Hemodynamic measures, including mPAP, showed improvement in both cohorts (post-treatment median [interquartile range] 38.5 [17.0-40.0] for the PGI2-IV + cohort and 33.0 [25.0-43.0] mmHg for the PGI2-IV - cohort). Deaths (8/56) and lung transplantation (1/56) occurred only in the PGI2-IV - cohort.These Japanese registry data indicate that older age, lower mPAP, and non-idiopathic PAH may influence clinicians against using upfront combination therapy including PGI2-IV for patients with severe PAH. Early combination therapy including PGI2-IV was associated with improved hemodynamics from baseline, but interpretation is limited by the small sample size.

Clinical Features Comparing Arterial Thrombosis and Venous Thromboembolism in Hospitalized Patients with COVID-19: Result from the CLOT-COVID Study.

Objectives: This study aimed to investigate the clinical features of arterial thrombosis and venous thromboembolism (VTE) in coronavirus disease 2019 (COVID-19). Methods: The CLOT-COVID Study was a retrospective, multicenter cohort study that enrolled 2,894 consecutively hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We compared the clinical features of arterial thrombosis and VTE. Results: Thrombosis was observed in 55 patients (1.9%) during hospitalization. Arterial thrombosis and VTE occurred in 12 (0.4%) and 36 (1.2%) patients, respectively. Among the 12 patients with arterial thrombosis, 9 (75%), 2 (17%), and 1 developed ischemic cerebral infarction, myocardial infarction, and acute limb ischemia, respectively, and there were five patients (42%) without comorbidities. Among 36 patients with VTE, 19 (53%) and 17 (47%) developed pulmonary embolism (PE) and deep vein thrombosis (DVT), respectively. PE was common in the early stages of hospitalization; whereas, DVT was common beyond the early stages of hospitalization. Conclusion: Among patients with COVID-19, arterial thrombosis was less common than VTE, although ischemic cerebral infarction seemed to be relatively common, and a certain number of patients developed arterial thrombosis even in the absence of known atherosclerosis risk factors.

SATISFY-JP, a phase II multicenter open-label study on Satralizumab, an anti-IL-6 receptor antibody, use for the treatment of pulmonary arterial hypertension in patients with an immune-responsive-phenotype: Study protocol.

Pulmonary arterial hypertension (PAH), an intractable disease with a poor prognosis, is commonly treated using pulmonary vasodilators modulating the endothelin, cGMP, and prostacyclin pathway. Since the 2010s, drugs for treating pulmonary hypertension based on mechanisms other than pulmonary vasodilation have been actively developed. However, precision medicine is based on tailoring disease treatment to particular phenotypes by molecular-targeted drugs. Since interleukin-6 (IL-6) is involved in the development of PAH in animal models, and some patients with PAH have elevated IL-6 levels, the cytokine is expected to obtain potentials for therapeutic targeting. Accordingly, we identified a phenotype with elevated cytokine activity of the IL-6 family in the PAH population by combining case data extracted from the Japan Pulmonary Hypertension Registry with a comprehensive analysis of 48 cytokines using artificial intelligence clustering techniques. Including an IL-6 threshold ≥2.73 pg/mL as inclusion criteria for reducing the risk of insufficient efficacy, an investigator-initiated clinical study using satralizumab, a recycling anti-IL6 receptor monoclonal antibody, for patients with an immune-responsive phenotype is underway. This study is intended to test whether use of patient biomarker profile can identify a phenotype responsive to anti-IL6 therapy.

Pulmonary arterial hypertension in an 80-year-old man with long-term use of cyclophosphamide.

An 80-year-old man diagnosed with primary macroglobulinemia 7 years earlier had been treated with cyclophosphamide, following which he developed dyspnea on exertion. Cyclophosphamide was discontinued. The patient's dyspnea, however, failed to improve. Right heart catheterization (RHC) revealed precapillary pulmonary hypertension (PH). He was transferred to our institution for further examination. Prior use of cyclophosphamide was the patient's only risk factor for PH, and cyclophosphamide use was considered as a possible cause of PH in this case. He was treated with tadalafil and dyspnea gradually improved. A follow-up RHC exhibited improvement in mean pulmonary arterial pressure and pulmonary vascular resistance.

Risk Factors and Impact on Outcomes of Thrombosis in Patients with COVID-19 in Japan: From the CLOT-COVID Study.

Objectives: The relationship between the thrombotic event and prognosis in patients with coronavirus disease 2019 (COVID-19) has not yet been fully investigated in Japan. Our study aimed to investigate the clinical outcomes and risk factors for thrombosis in hospitalized patients with COVID-19 in Japan. Materials and Methods: We compared the patient characteristics and clinical outcomes among patients with thrombosis (N=55) and those without thrombosis (N=2839) by using a large-scale data of CLOT-COVID study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800). Thrombosis included venous thromboembolism, ischemic stroke, myocardial infarction, and systemic arterial thromboembolism. Results: Higher rates of mortality and bleeding events were shown in hospitalized patients with COVID-19 with thrombosis compared to those without thrombosis (all-cause mortality, 23.6% vs. 5.1%, P<0.001; major bleeding, 23.6% vs. 1.6%, P<0.001). Multivariable analysis revealed that the independent risk factors of thrombosis were male sex, D-dimer level on admission>1.0 µg/mL, and moderate and severe COVID-19 status on admission. Conclusions: The development of thrombosis in hospitalized patients with COVID-19 was related to higher mortality and major bleeding, and several independent risk factors for thrombosis could help determine the patient-appropriate treatment for COVID-19.

Long-term outcome of chronic thromboembolic pulmonary hypertension using direct oral anticoagulants and warfarin: a Japanese prospective cohort study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear. OBJECTIVES: The CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH. PATIENTS/METHODS: Patients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding. RESULTS: Nine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032). CONCLUSION: This registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin.

Clinical and Hemodynamic Responses to Imatinib in Pulmonary Veno-Occlusive Disease/Pulmonary Capillary Hemangiomatosis: A Retrospective Pilot Study of Five Cases and Review of the Literature.

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare types of pulmonary arterial hypertension with dismal prognoses; there is no established medical treatment for these conditions. Possible efficacy of imatinib against these conditions has been reported in 15 cases; however, how and in whom imatinib is effective remain unknown. METHODS: We retrospectively evaluated clinical data from consecutive patients with PVOD/PCH treated with imatinib at our institution. The diagnosis of PVOD/PCH was established using the following criteria: pre-capillary pulmonary hypertension; diffusion capacity of the lung for carbon monoxide < 60%; and two or more high-resolution computed tomography findings of interlobular septal thickening, centrilobular opacities, and mediastinal lymphadenopathy. The dose of pulmonary vasodilators remained unchanged during the assessment of imatinib. RESULTS: The medical records of five patients with PVOD/PCH were reviewed. The patients were aged 67 ± 13 years, their diffusion capacity of the lung for carbon monoxide was 29 ± 8%, and their mean pulmonary artery pressure was 40 ± 7 mmHg. Imatinib was administered at 50-100 mg/day; consequently, the World Health Organization functional class improved in one patient. In addition, imatinib improved the arterial oxygen partial pressure in this and another patient (these two also experienced a decreased mean pulmonary artery pressure and pulmonary vascular resistance after imatinib usage). CONCLUSIONS: This study indicated that imatinib improves the clinical condition, including pulmonary hemodynamics, of some patients with PVOD/PCH. In addition, patients with a certain high-resolution computed tomography pattern or PCH-dominant vasculopathy may respond favorably to imatinib.

Efficacy, safety, and pharmacokinetics of inhaled treprostinil in Japanese patients with pulmonary arterial hypertension.

Treprostinil is a chemically stable analog of prostacyclin, and inhaled treprostinil was developed to deliver the effects directly to the pulmonary vasculature while minimizing systemic side effects. The objective of the study was to evaluate the efficacy on hemodynamics and exercise capacity, safety, and pharmacokinetics (PK) of inhaled treprostinil in Japanese patients with pulmonary arterial hypertension (PAH). Inhaled treprostinil was administered at three breaths (18 µg)/session four times daily, and the dose was gradually increased to a maximum of nine breaths (54 µg)/session. Endpoints included change in pulmonary vascular resistance index (PVRI) as primary, other efficacy parameters, safety, and PK. Seventeen PAH patients, the majority of whom (76.5%) had been receiving both an endothelin receptor antagonist (ERA) and a phosphodiesterase type-5 (PDE5) inhibitor/soluble guanylate cyclase (sGC) stimulator, received inhaled treprostinil. At Week 12, PVRI statistically decreased by -39.4 ± 25.5% (95% confidence interval: -52.6 to -26.3). The most frequently reported adverse events related to treprostinil were headache, cough, throat irritation, and hot flush. Regarding PK, there were no notable differences in the geometric mean C max and AUClast between Japanese and non-Japanese patients. Treatment with inhaled treprostinil using the dosing regimen approved in the United States resulted in significant improvement in hemodynamics, exercise capacity, and symptoms with a favorable tolerability and safety profile in Japanese patients. Inhaled treprostinil could be a valuable therapeutic option for Japanese patients with PAH, including those receiving a combination therapy with an ERA and a PDE5 inhibitor/sGC stimulator. Trial registration: JAPIC Clinical Trials Information [JapicCTI-194651].

Mortality-associated Risk Factors in Hospitalized COVID-19 Patients in Japan: Findings of the CLOT-COVID Study.

BACKGROUND: Reports of mortality-associated risk factors in patients with the novel coronavirus disease 2019 (COVID-19) are limited. METHODS: We evaluated the clinical features that were associated with mortality among patients who died during hospitalization (n = 158) and those who were alive at discharge (n = 2,736) from the large-scale, multicenter, retrospective, observational cohort CLOT-COVID study, which enrolled consecutively hospitalized COVID-19 patients from 16 centers in Japan from April to September 2021. Data from 2,894 hospitalized COVID-19 participants of the CLOT-COVID study were analyzed in this study. RESULTS: Patients who died were older (71.1 years vs 51.6 years, P < 0.001), had higher median D-dimer values on admission (1.7 µg/mL vs 0.8 µg/mL, P < 0.001), and had more comorbidities. On admission, the patients who died had more severe COVID-19 than did those who survived (mild: 16% vs 63%, moderate: 47% vs 31%, and severe: 37% vs 6.2%, P < 0.001). In patients who died, the incidence of thrombosis and major bleeding during hospitalization was significantly higher than that in those who survived (thrombosis: 8.2% vs 1.5%, P < 0.001; major bleeding: 12.7% vs 1.4%, P < 0.001). Multivariable logistic regression analysis revealed that age >70 years, high D-dimer values on admission, heart disease, active cancer, higher COVID-19 severity on admission, and development of major bleeding during hospitalization were independently associated with a higher mortality risk. CONCLUSION: This large-scale observational study in Japan identified several independent risk factors for mortality in hospitalized patients with COVID-19 that could facilitate appropriate risk stratification of patients with COVID-19.

An Adult Case of Unilateral Left Pulmonary Artery Agenesis Presenting with Hemoptysis.

Pulmonary artery agenesis (PAA) is a rare congenital vascular anomaly usually diagnosed during infancy. We herein report a 67-year-old man with PAA manifesting as massive hemoptysis. Contrast-enhanced computed tomography of the chest revealed the diagnosis of PAA, which we speculated to have resulted in the present event. Detailed angiography provided more accurate information on the pulmonary vasculature and collateral circulation, which helped us plan tailored treatment. Although very rare, we must consider the possibility of PAA in adults with unexplained hemoptysis.

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.