Clinical outcomes of upfront combination therapy for portopulmonary hypertension.

Background: Limited data exists on upfront combination therapy for portopulmonary hypertension. We evaluated the clinical efficacy, long-term outcomes, and safety of upfront combination therapy in patients with portopulmonary hypertension. Methods: We performed a retrospective, single-center cohort study involving a final analysis of 33 consecutive patients diagnosed with portopulmonary hypertension who were taking pulmonary arterial hypertension-specific medication. We compared hemodynamic parameters, risk profiles, composite clinical worsening events, and safety between monotherapy (n = 23) and upfront combination therapy (n = 10). Results: Twenty-seven patients (82 %) were classified into the Child-Pugh A stage. The change ratios of pulmonary vascular resistance (-32 % vs. -57 %, P = 0.006) were significantly better with upfront combination therapy. Upfront combination therapy also showed significant improvement in risk profiles. Kaplan-Meier analysis showed that the composite event-free rate was significantly lower in patients who received upfront combination therapy than in those who received monotherapy (P = 0.016), although no statistical differences were observed in all-cause death. In the univariate Cox proportional hazards analysis, upfront combination therapy was a factor for decreasing composite clinical worsening outcomes (hazard ratio 0.190, 95 % confidence interval 0.042-0.854; P = 0.030). No significant hepatic impairments were observed over 2 years of follow-up in the upfront combination group. Conclusions: In patients with portopulmonary hypertension, upfront combination therapy significantly improved symptoms and short-term hemodynamics, and reduced long-term clinical worsening events without serious adverse effects. This study's findings suggest that patients with portopulmonary hypertension presenting with mild hepatic impairment benefit from upfront combination therapy.

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.

Exosomal miR206 Secreted From Growing Muscle Promotes Angiogenic Response in Endothelial Cells.

BACKGROUND: Resistance exercise is beneficial in patients with lower extremity arterial disease. Muscle-derived exosomes contain many types of signaling molecules, including microRNAs (miRNAs). Here, we tested the hypothesis that exosomal miRNAs secreted by growing muscles promote an angiogenic response in endothelial cells (ECs).Methods and Results: Skeletal muscle-specific conditional Akt1 transgenic (Akt1-TG) mice, in which skeletal muscle growth can be induced were used as a model of resistance training. Remarkable skeletal muscle growth was observed in mice 2 weeks after gene activation. The protein amount in exosomes secreted by growing muscles did not differ between Akt1-TG and control mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway frequency analysis of 4,665 target genes, identified using an miRNA array miRNAs, revealed a significant increase in Akt and its downstream signaling pathway genes. Among the upregulated miRNAs, miR1, miR133, and miR206 were significantly upregulated in the serum of Akt1-TG mice. miR206 was also increased in insulin-like growth factor (IGF)-1-stimulated hypertrophied myotubes. Exogenous supplementation of exosomal miR206 to human umbilical vein ECs promoted angiogenesis, as assessed using the spheroid assay, and increased the expression of angiogenesis-related transcripts. CONCLUSIONS: Exosomal miR206 is upregulated in the blood of Akt1-TG mice and in IGF-stimulated cultured myotubes. Exogenous supplementation of miR206 promoted an angiogenic response in ECs. Our data suggest that miR206 secreted from growing muscles acts on ECs and promotes angiogenesis.

Quantification of pulmonary perfusion using LSIM-CT correlates with pulmonary hemodynamics in patients with CTEPD.

Background: Lung subtraction iodine mapping (LSIM)-CT is a clinically useful technique that can visualize pulmonary mal-perfusion in patients with chronic thromboembolic pulmonary disease (CTEPD). However, little is known about the associations of LSIM images with hemodynamic parameters of patients with CTEPD. This study investigates a parameter of LSIM images associated with mean pulmonary arterial pressure (mPAP) and validates the association between pulmonary vascular resistance, right atrial pressure, cardiac index, and exercise capacity in patients with CTEPD. Methods: This single-center, prospective, observational study involved 30 patients diagnosed with CTEPD using lung perfusion scintigraphy. To examine the correlation of decreased pulmonary perfusion area (DPA) with mPAP, areas with 0-10, 0-15, 0-20, and 0-30 HU in lung subtraction images were adopted in statistical analysis. The DPA to total lung volume ratio (DPA ratio, %) was calculated as the ratio of each DPA volume to the total lung volume. To assess the correlation between DPA ratios of 0-10, 0-15, 0-20, and 0-30 HU and mPAP, Spearman's rank correlation coefficient was used. Results: The DPA ratio of 0-10 HU had the most preferable correlation with mPAP than DPA ratios of 0-15, 0-20, and 0-30 HU (ρ = 0.440, P = 0.015). The DPA ratio of 0-10 HU significantly correlates with pulmonary vascular resistance (ρ = 0.445, P = 0.015). The receiver operating characteristic curve analysis indicated that the best cutoff value of the DPA ratio of 0-10 HU for the prediction of an mPAP of ≥30 mmHg was 8.5% (AUC, 0.773; 95% CI, 0.572-0.974; sensitivity, 83.3%; specificity, 75.0%). Multivariate linear regression analysis, which was adjusted for the main pulmonary arterial to ascending aortic diameter ratio and right ventricular to left ventricular diameter ratio, indicated that the DPA ratio of 0-10 HU was independently and significantly associated with mPAP (B = 89.7; 95% CI, 46.3-133.1, P < 0.001). Conclusion: The DPA ratio calculated using LSIM-CT is possibly useful for estimating the hemodynamic status in patients with CTEPD.

Thrombus or tumor?

Key clinical message: Contrast defects in veins are often diagnosed as benign thrombi, but depending on the patient's background it is necessary to differentiate between tumor thrombi. It is difficult to differentiate between these using contrast-enhanced CT alone, but with angioscopy it is easy to visually distinguish between a benign and tumor thrombi. Abstract: Contrast-enhanced computer tomography (CT) performed on a male patient being treated for de-differentiated chondrosarcoma revealed contrast defects in the pulmonary artery and right femoral vein, and a diagnosis of pulmonary artery thromboembolism and venous thromboembolism was made, and oral anticoagulant therapy was started. However, a follow-up CT showed that the contrast defect had extended to the inferior vena cava. Observation using an angioscope revealed that it was not a benign thrombi but a tumor.

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.

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.

Association Between the Development of Thrombosis and Worsening of Disease Severity in Patients With Moderate COVID-19 on Admission　- From the CLOT-COVID Study.

BACKGROUND: The worsening of coronavirus disease 2019 (COVID-19) severity is a critical issue in current clinical settings and may be associated with the development of thrombosis.Methods and Results: This study used patient data obtained in the CLOT-COVID study, a retrospective multicenter cohort study. The demographics of patients with moderate COVID-19 on admission with and without worsened severity during hospitalization were compared and predictors were identified. Of 927 patients with moderate COVID-19 on admission, 182 (19.6%) had worsened severity during hospitalization. Patients with worsening of severity were older, more likely to have hypertension, diabetes, heart disease, and active cancer, and more likely to use pharmacological thromboprophylaxis. Patients with worsening of severity had higher D-dimer levels on admission and were more likely to develop thrombosis and major bleeding during hospitalization than those without worsening. Increased age (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03, P=0.005), diabetes (OR: 1.63, 95% CI: 1.11-2.33, P=0.012), D-dimer levels >1.0 µg/mL on admission (OR: 2.10, 95% CI: 1.45-3.03, P<0.001), and thrombosis (OR: 6.28, 95% CI: 2.72-14.53, P<0.001) were independently associated with worsening of COVID-19 severity. CONCLUSIONS: Approximately 20% of patients with moderate COVID-19 had worsened severity during hospitalization. Increased age, diabetes, D-dimer levels >1.0 µg/mL on admission, and the development of thrombosis during hospitalization were significantly associated with worsened COVID-19 severity.

Influence of obesity on incidence of thrombosis and disease severity in patients with COVID-19: From the CLOT-COVID study.

BACKGROUND: The influence of obesity on the development of thrombosis and severity of coronavirus disease 2019 (COVID-19) remains unclear. METHOD: The CLOT-COVID study was a retrospective multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 between April 2021 and September 2021 among 16 centers in Japan. The present study consisted of 2690 patients aged over 18 years with available body mass index (BMI), who were divided into an obesity group (BMI ≥30) (N = 457) and a non-obesity group (BMI <30) (N = 2233). RESULTS: The obesity group showed more severe status of COVID-19 at admission compared with the non-obesity group. The incidence of thrombosis was not significantly different between the groups (obesity group: 2.6 % versus non-obesity group: 1.9 %, p = 0.39), while the incidence of a composite outcome of all-cause death, or requirement of mechanical ventilation or extracorporeal membrane oxygenation during hospitalization was significantly higher in the obesity group (20.1 % versus 15.0 %, p < 0.01). After adjusting confounders in the multivariable logistic regression model, the risk of obesity relative to non-obesity for thrombosis was not significant (adjusted OR, 1.39; 95 % CI, 0.68-2.84, p = 0.37), while the adjusted risk of obesity relative to non-obesity for the composite outcome was significant (adjusted OR, 1.85; 95 % CI, 1.39-2.47, p < 0.001). CONCLUSIONS: In the present large-scale observational study, obesity was not significantly associated with the development of thrombosis during hospitalization; however, it was associated with severity of COVID-19.

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.

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.

Real-World Management of Pharmacological Thromboprophylactic Strategies for COVID-19 Patients in Japan: From the CLOT-COVID Study.

Background: Data on prophylactic anticoagulation are important in understanding the current issues, unmet needs, and optimal management of Japanese COVID-19 patients. Objectives: This study aimed to investigate the clinical management strategies for prophylactic anticoagulation of COVID-19 patients in Japan. Methods: The CLOT-COVID study was a multicenter observational study that enrolled 2,894 consecutive hospitalized patients with COVID-19. The study population consisted of 2,889 patients (after excluding 5 patients with missing data); it was divided into 2 groups: patients with pharmacological thromboprophylaxis (n = 1,240) and those without (n = 1,649). Furthermore, we evaluated the 1,233 patients who received prophylactic anticoagulation-excluding 7 patients who could not be classified based on the intensity of their anticoagulants-who were then divided into 2 groups: patients receiving prophylactic anticoagulant doses (n = 889) and therapeutic anticoagulant doses (n = 344). Results: The most common pharmacological thromboprophylaxis anticoagulant was unfractionated heparin (68.2%). The severity of COVID-19 at admission was a predictor of the implementation of pharmacological thromboprophylaxis in the multivariable analysis (moderate vs mild: OR: 16.6; 95% CI:13.2-21.0; P < 0.001, severe vs mild: OR: 342.6, 95% CI: 107.7-1090.2; P < 0.001). It was also a predictor of the usage of anticoagulants of therapeutic doses in the multivariable analysis (moderate vs mild: OR: 2.10; 95% CI: 1.46-3.02; P < 0.001, severe vs mild: OR: 5.96; 95% CI: 3.91-9.09; P < 0.001). Conclusions: In the current real-world Japanese registry, pharmacological thromboprophylaxis, especially anticoagulants at therapeutic doses, was selectively implemented in COVID-19 patients with comorbidities and severe COVID-19 status at admission.

Incidence, risk factors, and clinical impact of major bleeding in hospitalized patients with COVID-19: a sub-analysis of the CLOT-COVID Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) causes extensive coagulopathy and a potential benefit of anticoagulation therapy has been documented for prevention of thromboembolic events. Bleeding events has also been reported as a notable complication; whereas, the incidence, risks, and clinical impact of bleeding remain unclear. METHOD: The CLOT-COVID Study was a nationwide, retrospective, multicenter cohort study on consecutive hospitalized patients with COVID-19 in Japan between April 2021 and September 2021. In this sub-analysis, we compared the characteristics of patients with and without major bleeding; moreover, we examined the risk factors for and clinical impact of bleeding events. RESULTS: Among 2882 patients with COVID-19, 57 (2.0%) had major bleeding. The incidence of major bleeding increased with COVID-19 severity as follows: 0.5%, 2.3%, and 12.3% in patients with mild, moderate, and severe COVID-19, respectively. COVID-19 severity, history of major bleeding, and anticoagulant type/dose were independently and additively associated with the bleeding incidence. Compared with patients without major bleeding, those with major bleeding exhibited a longer duration of hospitalization (9 [6-14] vs 28 [19-43] days, P < 0.001) and higher mortality during hospitalization (4.9% vs. 35.1%, P < 0.001). CONCLUSIONS: In the real-world clinical practice, the incidence of major bleeding was not uncommon, especially in patients with severe COVID-19. Independent risk factors for major bleeding included history of major bleeding, COVID-19 severity, and anticoagulant use, which could be associated with poor clinical outcomes including higher mortality. Precise recognition of the risks for bleeding may be helpful for an optimal use of anticoagulants and for better outcomes in patients with COVID-19.

Therapeutic-Dose vs. Prophylactic-Dose Anticoagulation Therapy for Critically Ill Patients With COVID-19 in a Practice-Based Observational Study.

BACKGROUND: The potential benefit of therapeutic-dose anticoagulation for critically ill patients with coronavirus disease 2019 (COVID-19) is still controversial.Methods and Results: In the CLOT-COVID study, 225 patients with severe COVID-19 on admission requiring mechanical ventilation or extracorporeal membrane oxygenation were divided into patients with therapeutic-dose anticoagulation (N=110) and those with prophylactic-dose anticoagulation (N=115). There was no significant difference in the incidence of thrombosis between the groups (9.1% vs. 7.8%, P=0.73). CONCLUSIONS: Among a cohort of critically ill patients with COVID-19, approximately half received therapeutic-dose anticoagulation, although it did not show a potential benefit compared with prophylactic-dose anticoagulation.

D-Dimer Values and Venous Thromboembolism in Patients With COVID-19 in Japan　- From the CLOT-COVID Study.

Background: To date, there are no large-scale data on the association between D-dimer levels at admission and the occurrence of venous thromboembolism (VTE) in Japanese patients with coronavirus disease 2019 (COVID-19). Methods and Results: The CLOT-COVID study was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 across 16 centers in Japan from April 2021 to September 2021. Among 2,894 enrolled patients, 2,771 (96%) had D-dimer levels measured at admission. Patients were divided into 3 groups based on tertiles of D-dimer levels at admission (1st tertile, D-dimer ≤0.5 µg/mL, n=949; 2nd tertile, D-dimer 0.51-1.09 µg/mL, n=894; 3rd tertile, D-dimer ≥1.1 µg/mL, n=928). The higher the tertile group, the more severe the COVID-19 status at admission. The incidence of VTE during hospitalization was highest in the 3rd tertile group (1st tertile, 0.3%; 2nd tertile, 0.3%; 3rd tertile, 3.6%; P<0.001). Even after adjusting for confounders in the multivariable logistic regression model, the higher D-dimer levels in the 3rd tertile (≥1.1 µg/mL) were independently associated with a higher risk of VTE during hospitalization (adjusted odds ratio 4.83 [95% confidence interval 1.93-12.11; P<0.001]; reference=1st tertile). Conclusions: Higher D-dimer levels at admission were associated with a higher risk of VTE events during hospitalization in Japanese patients with COVID-19. This could be helpful in determining patient-specific anticoagulation management strategies for COVID-19 in Japan.

The current status of thrombosis and anticoagulation therapy in patients with COVID-19 in Japan: From the CLOT-COVID study.

BACKGROUND: Data on thrombosis and current real-world management strategies for anticoagulation therapy are scarce but important for understanding current issues and unmet needs of an optimal management of patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021, and we tried to capture the status of the patients in the fourth and fifth waves of the COVID-19 infections in Japan. We enrolled consecutive hospitalized patients who were diagnosed with COVID-19 and had a positive polymerase chain reaction test obtained from the hospital databases. RESULTS: Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in 9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. The types and doses of anticoagulants varied widely across the participating centers. During the hospitalization, 38 patients (1.3%) and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrast-enhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism (71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4% with moderate COVID-19, and 9.5% with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. CONCLUSIONS: In the present large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients with COVID-19 was common especially in patients with severe COVID-19, and management strategies varied widely across the participating centers. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19.

Influence of sex on development of thrombosis in patients with COVID-19: From the CLOT-COVID study.

INTRODUCTION: There has been limited data on the influence of sex on development of thrombosis in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: 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 the men (N = 1885) and women (N = 1009) groups. RESULTS: There were no significant differences in D-dimer levels at admission between men and women. Men had more severe status of the COVID-19 at admission compared with women (Mild: 57% versus 66%, Moderate: 34% versus 29%, and Severe: 9.1% versus 5.7%, P < 0.001). Men more often received pharmacological thromboprophylaxis than women (47% versus 35%, P < 0.001). During the hospitalization, men more often developed thrombosis than women (2.5% [95%CI, 1.9-3.3%] versus 0.8% [95%CI, 0.4-1.6%], P = 0.001). Men had numerically higher incidences of thrombosis than women in all subgroups of the worst severity of COVID-19 during the hospitalization (Mild: 0.3% versus 0.0%, Moderate: 1.6% versus 1.0%, and Severe: 11.1% versus 4.3%). Even after adjusting confounders in the multivariable logistic regression model, the excess risk of men relative to women remained significant for thrombosis (adjusted OR, 2.51; 95%CI, 1.16-5.43, P = 0.02). CONCLUSIONS: In the current large observational study of patients with COVID-19, men had more severe status of the COVID-19 than women, and the risk of development of thrombosis was higher in men compared with women, which could be helpful in determining the patient-specific optimal management strategies for COVID-19.

Vaso reactivity test using inhaled nitric oxide for pulmonary arterial hypertension accompanied by severe interstitial lung disease attributed to systemic sclerosis: A case report.

A 70-year-old man with severe interstitial pneumonia attributed to limited cutaneous systemic sclerosis was referred to our institution because of worsening dyspnea. High-resolution computed tomography did not show considerable progression compared with previous images, whereas transthoracic echocardiography showed severe right ventricular dysfunction. Oxygen saturation was decreased to 84% at room air. A blood test showed an increase in the plasma brain natriuretic peptide level (289.4 pg/mL). Right heart catheterization (RHC) showed a remarkably high mean pulmonary arterial pressure (mPAP) of 48 mmHg at room air. A vaso reactivity test using inhaled nitric oxide showed improvement of mPAP, pulmonary vascular resistance (PVR), and partial pressure of arterial oxygen. These findings suggested that the patient responded to pulmonary hypertension (PH)-targeted drugs. We then prescribed tadalafil 10 mg and inhaled iloprost 5 µg six times daily. Three weeks after initiating PH-targeted drugs, RHC indicated hemodynamic improvement similar to hemodynamic changes in the vaso reactivity test (mPAP: 28 mmHg; PVR: 4.2 W.U.). He was discharged with improved symptoms. Inhaled nitric oxide during RHC might be helpful to consider the treatment strategy when patients have PH comorbid systemic sclerosis and severe interstitial lung disease. .

Epicardial adipose tissue volume is an independent predictor of left ventricular reverse remodeling in patients with non-ischemic cardiomyopathy.

BACKGROUND: In some patients with non-ischemic cardiomyopathy, left ventricular (LV) contraction is improved by optimal medical therapy, leading to LV reverse remodeling (RR). Patients with heart failure with improved ejection fraction and LVRR have a good prognosis, but the factors that predict RR are not fully understood. The relationship between body composition and cardiovascular disease has been reported. The present study aimed to assess the clinical predictors of LVRR in association with body composition. METHODS: We recruited patients who were diagnosed with non-ischemic cardiomyopathy between September 2017 and January 2020. Finally, 89 patients with a reduced LV ejection fraction were enrolled in this prospective study. Body composition, including ectopic fat, was measured in all patients using computed tomography. Echocardiography was performed 6 months after enrollment to evaluate LVRR. RESULTS: LVRR was observed in 39 patients (43.8%) after 6 months. In terms of the demographic findings, epicardial adipose tissue volume was greater in the LVRR group than in the non-LVRR group (135.2 cm3 [SD 128.4 cm3] vs. 88.9 cm3 [SD 54.6 cm3]; p = 0.040). The Kaplan-Meier analysis demonstrated that adverse cardiac events were significantly less frequent in the LVRR group than in the non-LVRR group (log-rank test, p = 0.013). The multivariate logistic regression analysis identified epicardial adipose tissue volume as an independent predictor of LVRR (odds ratio [OR]: 1.010, 95% confidence interval [CI]: 1.001-1.01; p = 0.036). CONCLUSION: Epicardial adipose tissue volume is an independent predictor of LVRR in patients with non-ischemic cardiomyopathy.