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Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

There is still a scarcity of data on causes of long-term mortality in patients with venous thromboembolism (VTE).The COMMAND VTE Registry is a physician-initiated, retrospective, multicenter cohort study in which consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan were included between January 2010 and August 2014. We investigated detailed causes and risk factors for long-term mortality.During a median observation period of 1218 days, a total of 764 patients died, and the prevalence of active cancer was higher in patients who died than in patients alive (61 % versus 10 %, P 0.001). The cumulative incidences of cardiac death, pulmonary embolism (PE)-related death, bleeding death, cancer death, and non-cardiovascular non-cancer death were 2.2 %, 2.9 %, 2.0 %, 16.1 %, and 6.7 % at 5 years, respectively. The incidence of cancer death increased gradually, which was the most common cause of long-term death. Among patients without active cancer, the incidence of PE-related death increased rapidly and became a plateau beyond the acute phase, whereas the incidence of non-cardiovascular non-cancer death kept increasing, which became most common in the long term. The separate multivariable analysis among patient with and without active cancer identified independent risk factors of all-cause death including a few patient characteristics among patients with active cancer and several patient characteristics among patients without active cancer.Cancer was the most common cause of long-term mortality, while non-cardiovascular non-cancer death became most common among patients without active cancer.

Cardiovascular disease and cancer share a number of risk factors and pathophysiologic mechanisms. Although risk management and early detection of cancer in patients with cardiovascular disease are important, preventive efforts in cardiology and oncology have been relatively disconnected. This study aimed to investigate the rate of cancer screening in a population of older adults with cardiovascular disease.This study used data from the 2019 Comprehensive Survey of Living Conditions. Data on participants aged 60 years or older were extracted. The rate of cancer screening and cancer type were investigated between participants with and without cardiovascular disease.Of the 132,442 individuals, participants with cardiovascular disease had a significantly lower rate of cancer screening than those without cardiovascular disease [male: 4401 of 7972 participants (55.2%) vs. 33,744 of 52,106 participants (64.8%), p 0.001; female: 2500 of 4984 participants (50.2%) vs. 41,319 of 67,380 participants (61.3%), p 0.001]. The rate of cancer screening was significantly lower in participants with cardiovascular disease than in those without cardiovascular disease, regardless of cancer type, including gastric, colorectal, lung, breast, and gynecologic cancer screening. A history of cardiovascular disease was a negative factor for cancer screening (odds ratio 0.71, 95% confidence interval 0.67-0.74 in male participants; odds ratio 0.80, 95% confidence interval, 0.75-0.85 in female participants).The rate of cancer screening in elderly participants with cardiovascular disease was lower than that in participants without cardiovascular disease. Physicians should raise awareness regarding early cancer detection in patients with cardiovascular disease.

Background There is a paucity of data on the long-term clinical outcomes according to the severity of pulmonary embolism (PE) at initial diagnosis. Methods The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE). After excluding 1312 patients without PE, the current study population consisted of 1715 patients with PE, who were divided into 3 groups according to the clinical severity; massive PE, sub-massive PE and low-risk PE. Results There were 179 patients (10%) with massive PE, 742 patients (43%) with sub-massive PE, and 794 patients (46%) with low-risk PE. By the landmark analysis at 3 months, the cumulative incidences of recurrent VTE were similar among the 3 groups both within and beyond 3 months (Massive PE: 2.9%, Sub-massive PE: 4.2%, and Low-risk PE: 3.3%, P = 0.61, and 4.3%, 8.8%, and 7.8% at 5 years, P = 0.47, respectively). After adjusting confounders, the risk of massive PE relative to low-risk PE for recurrent VTE beyond 3 months remained insignificant (adjusted HR 0.54, 95% CI: 0.13–1.51, P = 0.27). Patients with massive PE at initial diagnosis more often presented as severe recurrent PE events than those with sub-massive and low-risk PE. Conclusions In the current real-world large registry, the long-term risk of overall recurrent VTE in patients with massive PE at initial diagnosis did not significantly differ from those with sub-massive and low-risk PE beyond 3 months, although patients with massive PE at initial diagnosis more frequently developed recurrent VTE as PE with severe clinical presentation.

Anticoagulation therapy is prescribed for the prevention of recurrence in patients with venous thromboembolism, which could be temporarily interrupted during invasive procedures. The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We identified patients who underwent invasive procedures during the entire follow-up period and evaluated periprocedural managements and clinical outcomes at 30 days after invasive procedures. During a median follow-up period of 1213 (IQR: 847–1764) days, 518 patients underwent invasive procedures with the cumulative incidences of 5.8% at 3 months, 11.1% at 1 year, and 24.0% at 5 years. Among 382 patients in high bleeding-risk category of invasive procedures, anticoagulation therapy had been discontinued already in 62 patients (16%) and interrupted temporarily in 288 patients (75%) during the invasive procedures with bridging anticoagulation therapy with heparin in 214 patients (56%). Among 80 patients in low bleeding-risk category, anticoagulation therapy had been already discontinued in 15 patients (19%) and interrupted temporarily in 31 patients (39%) during invasive procedure with bridging anticoagulation therapy with heparin in 17 patients (21%). At 30 days after the invasive procedures, 14 patients (2.7%) experienced recurrent VTE, while 28 patients (5.4%) had major bleeding. This study elucidated the real-world features of peri-procedural management and prognosis in patients with VTE who underwent invasive procedures during follow-up in the large multicenter VTE registry. The 30-day incidence rates of recurrent VTE and major bleeding events were 2.7% and 5.4%.

Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97–14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56–7.50), while the independent risk factors for major bleeding were age ≥ 75 years (HR 2.04, 95% CI 1.36–3.07), men (HR 1.52, 95% CI 1.02–2.27), history of major bleeding (HR 3.48, 95% CI 1.82–6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04–6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm .

Background The majority of acute pulmonary embolism (PE) is caused by thrombus developed from leg veins. However, impact of concomitant deep venous thrombosis (DVT) on clinical outcomes has not been fully evaluated in patients with acute PE. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic venous thromboembolism (VTE) in Japan. The current study population consisted of 655 acute PE patients who underwent lower extremities ultrasound examination at diagnosis for the assessment of concomitant DVT status. Results There were 424 patients with proximal DVT (64.7%), 162 patients with distal DVT (24.7%), and 69 patients with no DVT (10.5%). The cumulative 90-day incidence of all-cause death was higher in proximal DVT patients than in distal DVT and no DVT patients (7.9%, 2.5%, and 1.4%, p = 0.01). Regarding the causes of death, the cumulative 90-day incidence of PE-related death was low, and not significantly different across the 3 groups (1.4%, 0.6%, and 1.7%, p = 0.62). The most frequent cause of death was cancer in proximal and distal DVT patients. There were no significant differences in 90-day rates of recurrent VTE and major bleeding, regardless of the status of concomitant DVT (2.9%, 3.2%, and 2.2%, p = 0.79, and 1.5%, 4.4%, and 4.9%, p = 0.46, respectively). Conclusions Acute PE with proximal DVT at diagnosis was associated with a higher risk for short-term mortality than in patients without DVT, while the risk for short-term mortality was not significantly different between distal DVT patients and patients without DVT.

There is a paucity of data on the influence of low body weight on clinical outcomes in patients with acute venous thromboembolism (VTE).The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2778 patients with available body weight value, who were divided into 2 groups; 1705 patients with lower body weight (≤60 kg) and 1073 patients with higher body weight (60 kg).Patients with lower body weight were older (70.8 versus 60.9 years, P 0.001), and more often women (75% versus 38%, P 0.001), and more often had active cancer (27% versus 19%, P 0.001) than those with higher body weight. The cumulative 5-year incidence of recurrent VTE was not significantly different between the 2 groups (10.6% versus 10.7%, P = 0.51). The cumulative 5-year incidences of major bleeding and all-cause death were significantly higher in patients with lower body weight than in those with higher body weight (14.6% versus 9.6%, P 0.001, and 35.8% versus 19.8%, P 0.001, respectively). The excess adjusted risk of patients with lower body weight relative to those with higher body weight remained significant for major bleeding and all-cause death (HR 1.57, 95%CI: 1.16-2.12, P = 0.003, and HR 1.50, 95%CI: 1.24-1.81, P 0.001, respectively).In the current Japanese real-world registry, there were a high proportion of patients with low body weight, who had a higher risk for major bleeding and mortality without significant excess risk for recurrent VTE.

Male patients with pulmonary hypertension have poor survival than their female counterparts. Poor right ventricular function in men may be one of the major determinants of poor prognosis. This study aimed to investigate the difference in hemodynamics during exercise between men and women by exercise echocardiography. Consecutive patients with pulmonary hypertension who underwent right heart catheterization were enrolled, and survival was analyzed. In patients who underwent exercise echocardiography, the change in tricuspid regurgitation pressure gradient during exercise was calculated at multiple stages (low-, moderate-, and high-load exercise), and the mortality was also recorded. In a total of 93 patients, although there were no differences in pulmonary artery pressure and vascular resistance between sexes, male patients showed poor survival. In patients with exercise echocardiography, change in tricuspid regurgitation pressure gradient at low-load (25 W) exercise was significantly lower in men, although that at maximum-load exercise was not different between men and women. In the Kaplan–Meier analysis, in a median follow-up duration of 1760 days, male patients and those with lower change in tricuspid regurgitation pressure gradient at low-load exercise showed poorer survival ( P = 0.002 and 0.026, respectively). In the Cox proportional hazards analysis, the change in tricuspid regurgitation pressure gradient at low-load exercise was independently associated with poor survival after adjustment for age and sex. In conclusion, a lower change in tricuspid regurgitation pressure gradient at low-load exercise was observed in male patients and was a prognostic marker, which may be associated, at least in part, with poorer prognosis in male patients with pulmonary hypertension.

Aims Psychological distress is associated with poor prognosis in patients with cardiovascular disease (CVD). However, factors related to psychological distress in elderly patients with CVD are less understood. We aim to investigate the rate of psychological distress in elderly patients with CVD in comparison with that of patients without CVD and to examine the clinical, socio-economic, and lifestyle factors associated with this condition. Methods and results Data from a nationwide population-based study in Japan of patients aged ≥60 years were extracted, and 1:1 propensity score matching was conducted of patients with and without CVD. Psychological distress was assessed using the K6 scale, on which a score ≥6 was defined as psychological distress. Of the 24 388 matched patients, the rate of psychological distress was significantly higher among patients with CVD compared with those without CVD (29.8 vs. 20.5%, P < 0.0001). The multivariate analysis revealed that female sex, comorbidities, except for hypertension, current smoking status, daily sleep duration of Conclusion Elderly patients with CVD were more likely to have psychological distress compared with those without CVD. Multiple factors, including clinical, socio-economic, and lifestyle variables, were associated with psychological distress. These analyses may help healthcare providers to identify high-risk patients with psychological distress in a population of older adults with CVD.

There are uncertainties on the influence of the days of diagnosis in a week (weekends versus weekdays) on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. We compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. The patients diagnosed on weekends more often presented with PE (72% vs. 55%, P

Introduction Patients with renal dysfunction are at high risk for developing venous thromboembolism (VTE). However, the impact of renal dysfunction on recurrent VTE remains to be clarified. We assessed the relationship between estimated glomerular filtration rate (eGFR) at diagnosis and long-term clinical outcomes in VTE patients. Materials and methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic VTE among 29 centers in Japan between January 2010 and August 2014. Patients with available creatinine values (N = 2829) were divided into the reference eGFR (≥60 mL/min/1.73 m2) group (N = 1760) and the low eGFR ( Results The low eGFR group was independently associated with the increased risk for recurrent VTE (adjusted HR 1.55, 95%CI 1.15–2.08). When the low eGFR group was subdivided into the moderately low and very low eGFR groups, the risk for recurrent VTE increased with decreasing eGFR (adjusted HR 1.43, 95%CI 1.04–1.95, and adjusted HR 2.54, 95%CI 1.42–4.28). The risk for major bleeding was higher in the very low eGFR group, but not in the moderately low eGFR group (adjusted HR 1.70, 95%CI 1.06–2.61, and adjusted HR 0.85, 95%CI 0.73–1.28). Conclusions Renal dysfunction measured by eGFR was associated with an increased risk for recurrent VTE, which was more prominent in severe renal dysfunction. Severe renal dysfunction was also associated with a higher risk for major bleeding.

Background The simplified Pulmonary Embolism Severity Index (sPESI) score is a practical score for identification of patients with low-risk pulmonary embolism (PE), although it has not been applied in patients with active cancer. The current study aimed to evaluate the usefulness of the sPESI score in patients with PE and active cancer. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic VTE. The current study population consisted of 368 patients with PE and active cancer. The 30-day clinical outcomes were compared between patients with sPESI score = 1 and patients with sPESI scores ≥ 2. Results Overall, 37 patients (10%) died during the 30 days after diagnosis. The cumulative 30-day incidences of mortality, and PE-related death, were lower in patients with sPESI score = 1 than in patients with sPESI scores ≥ 2 (6.3% vs 13.1%; log-rank P = .03; and 0.7% vs 3.9%; log-rank P = .046). Among patients with sPESI score = 1, the predominant cause of death was cancer. There were no significant differences in the cumulative 30-day incidence of recurrent VTE and major bleeding between the two groups (3.9% vs 5.6%; log-rank P = .46; and 6.4% vs 4.5%; log-rank P = .45). Conclusions Among patients with PE and active cancer, patients with sPESI score = 1 had a lower 30-day mortality rate compared with patients with sPESI scores ≥ 2, and they showed very low PE-related mortality risk, although the overall mortality rate remained high because of cancer-related mortality. They also showed relatively high risks for recurrence and major bleeding, suggesting the need for careful follow-up. Trial Registry UMIN Clinical Trials Registry; No.: UMIN000021132; URL: http://www.umin.ac.jp/ctr/index.htm

BACKGROUND Visual-functional mismatch between coronary angiography and fractional flow reserve (FFR) has been reported, and the underlying reason remains poorly understood. Therefore, the relationship between angiographic measurements and FFR was evaluated, and predictors for FFR in intermediate coronary artery stenosis were determined. METHODS Consecutive 314 patients (405 lesions) with a lesion of 30-80% angiographic diameter stenosis who underwent invasive FFR were recruited. The myocardial area supplied by the coronary artery distal to the stenosis was evaluated using a modified version of the Bypass Angioplasty Revascularization Investigation (BARI) score. Participants underwent follow-up, and major cardiovascular events (MACE), including all-cause death, myocardial infarction (MI), and unplanned revascularization were recorded. RESULTS Although % diameter stenosis was correlated with FFR (R = 0.279, P

Vitamin K antagonist (VKA) remains an essential option for venous thromboembolism (VTE), although direct oral anticoagulants have become available. However, there is a paucity of data on the optimal intensity and quality of control for VKA in Japanese.The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1938 patients who received VKA with prothrombin time-international normalized ratio (PT-INR) measurement5 times. The primary outcome measure was a composite of symptomatic VTE recurrence or major bleeding at 1 year. The presumed optimal quality of VKA therapy was defined as the combination of PT-INR range and time in therapeutic range (TTR) with the numerically lowest event rate.The group with TTR ≥70 % based on PT-INR range ≥1.5 and2.0 showed the lowest cumulative incidence rate. The cumulative 1-year incidence and the adjusted risk for the primary outcome measure were significantly lower in the optimal quality group than in the non-optimal quality group (5.2 % vs. 11.7 %, p = 0.001, and HR 0.49, 95%CI 0.28-0.81). Similarly, the cumulative 1-year incidences of a recurrent VTE, major bleeding, and all-cause death were significantly lower in the optimal quality group (recurrent VTE: 2.5 % vs. 6.0 %, p = 0.02; major bleeding: 2.8 % vs. 7.0 %, p = 0.008; and all-cause death: 2.8 % vs. 12.6 %, p 0.0001). The lower risk of the optimal quality group relative to non-optimal quality group for the clinical outcomes was consistent regardless of the etiology of VTE (active cancer, transient risk factor, and unprovoked).The current VTE registry showed the optimal intensity of VKA therapy was target PT-INR range ≥1.5 and2.0, which could support the current Japanese guideline recommendation, and the good quality of control for VKA therapy of TTR ≥70 % was independently associated with better outcomes.

The plaques with higher grade of yellow color by angioscopy are reported to be associated with vulnerability leading to adverse outcomes in coronary artery diseases. However, no studies have been performed for peripheral artery disease (PAD). We aimed to evaluate the relationship of angioscopic findings of peripheral arteries with the long-term prognosis.Angioscopy of iliac or femoropopliteal artery was performed before endovascular therapy in patients with PAD. The local plaque color and presence of thrombus were evaluated. Multivariable Cox regression models were used to estimate hazard ratio (HR) for all-cause mortality or major adverse cardiovascular event (MACE) related to the plaque colors as well as presence of thrombus.Among 67 patients, 49.3% had intensive yellow plaques (group H) and the rest had light yellow to yellow ones (group L). Thrombus was detected in 74.6% of the patients and the presence was not different between the two groups. In Kaplan-Meier analysis during a median follow-up of 976 days and 757 days, group H showed increased mortality and MACE compared with group L (p0.01 for both). Multivariable analysis demonstrated that the intensive yellow color of plaque was independently associated with mortality and MACE [HR: 11.48, 95% confidence interval (CI): 2.19-211.1 and HR: 3.81, 95% CI: 1.36-13.48, respectively] after adjusting for the presence of thrombus.The yellow color intensity in local plaques by angioscopy may be a novel predictor of long-term prognosis in patients with PAD, regardless of the presence of thrombus.

Pulmonary artery sarcoma (PAS) is considered a very rare tumor with a poor prognosis. We herein report two cases of PAS that were diagnosed by positron emission tomography (PET)/computed tomography (CT). In both cases, PET was an effective option for diagnosing tumors, and surgical resection was a valid treatment for these diseases. If a pulmonary artery tumor is suspected, PET/CT is useful for diagnosing PAS and very helpful for choosing the surgical treatment strategy.

Anticoagulation therapy is prescribed for the prevention of recurrence in patients with venous thromboembolism, which could be temporarily interrupted during invasive procedures. The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We identified patients who underwent invasive procedures during the entire follow-up period and evaluated periprocedural managements and clinical outcomes at 30 days after invasive procedures. During a median follow-up period of 1213 (IQR: 847-1764) days, 518 patients underwent invasive procedures with the cumulative incidences of 5.8% at 3 months, 11.1% at 1 year, and 24.0% at 5 years. Among 382 patients in high bleeding-risk category of invasive procedures, anticoagulation therapy had been discontinued already in 62 patients (16%) and interrupted temporarily in 288 patients (75%) during the invasive procedures with bridging anticoagulation therapy with heparin in 214 patients (56%). Among 80 patients in low bleeding-risk category, anticoagulation therapy had been already discontinued in 15 patients (19%) and interrupted temporarily in 31 patients (39%) during invasive procedure with bridging anticoagulation therapy with heparin in 17 patients (21%). At 30 days after the invasive procedures, 14 patients (2.7%) experienced recurrent VTE, while 28 patients (5.4%) had major bleeding. This study elucidated the real-world features of peri-procedural management and prognosis in patients with VTE who underwent invasive procedures during follow-up in the large multicenter VTE registry. The 30-day incidence rates of recurrent VTE and major bleeding events were 2.7% and 5.4%.

The duration of anticoagulation therapy after venous thromboembolism (VTE) should be based on the balance between risks of recurrent VTE and bleeding. However, there is uncertainty about the impact of these events on subsequent mortality.We evaluated the association of recurrent VTE and major bleeding events with mortality among 3026 patients in the COMMAND VTE Registry. We estimated the risks of the recurrent VTE events and the major bleeding events for subsequent mortality by the time-updated multivariable Cox proportional hazard model.During the median follow-up period of 1218 days, 225 patients developed recurrent VTE events, 274 patients developed major bleeding events, and 763 patients died. The multivariable Cox proportional hazard model revealed that both the recurrent VTE and major bleeding events were strongly associated with subsequent mortality risk (recurrent VTE: HR 3.24, 95%CI 2.57-4.08, P 0.001; major bleeding: HR 3.53, 95%CI 2.88-4.31, P 0.001). Both the recurrent pulmonary embolism (PE) and recurrent deep vein thrombosis (DVT) events were associated with subsequent mortality risk (recurrent PE events: HR 4.42, 95%CI 3.28-5.95, P 0.001; recurrent DVT events: HR 2.42, 95%CI 1.75-3.36, P 0.001).In the real-world patients with VTE, both the recurrent VTE events and the major bleeding events were strongly associated with subsequent mortality risk with the comparable effect size. The recurrent PE and recurrent DVT events were also associated with increased risks for mortality, although the magnitude of the effect on mortality was numerically greater with the recurrent PE events than with the recurrent DVT events.

The relationship between D-dimer level at diagnosis and long-term clinical outcomes has not been fully evaluated in venous thromboembolism (VTE). The COMMAND VTE Registry is a multicenter registry enrolling consecutive acute symptomatic VTE patients in Japan. Patients with available D-dimer levels at diagnosis (N = 2852) were divided into 4 groups according to the D-dimer levels; Quartile 1 (0.0–4.9 µg/mL): N = 682, Quartile 2 (5.0–9.9 µg/mL) N = 694, Quartile 3 (10.0–19.9 µg/mL) N = 710, and Quartile 4 (≥ 20.0 µg/mL): N = 766. The cumulative incidence of all-cause death was higher in Quartile 4 throughout the entire follow-up period (19.9%, 24.9%, 28.8%, and 41.5% at 5-year, P

Background There are limited data assessing the risk for bleeding on anticoagulation therapy beyond the acute phase in patients with venous thromboembolism (VTE). The present study aimed to identify risk factors for major bleeding during prolonged anticoagulation therapy in VTE patients. Patients and Methods The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2,728 patients who received anticoagulation therapy beyond the acute phase, after excluding those patients with major bleeding events (n = 48), death (n = 66), or loss to follow-up (n = 32) during the initial parenteral anticoagulation period within 10 days after diagnosis, and those without anticoagulation therapy beyond 10 days after diagnosis (n = 153). Results During the median follow-up period of 555 days, major bleeding occurred in 189 patients (70 patients within 3 months; 119 patients beyond 3 months) with fatal bleeding in 24 patients (13%). The cumulative incidence of major bleeding was 2.7% at 3 months, 5.2% at 1 year, and 11.8% at 5 years. Active cancer (hazard ratio [HR], 3.06, 95% confidence interval [CI], 2.23–4.18), previous major bleeding (HR, 2.38, 95% CI, 1.51–3.59), anemia (HR, 1.75, 95% CI, 1.27–2.43), thrombocytopenia (HR, 2.11, 95% CI, 1.27–3.33), and age ≥75 years (HR, 1.64, 95% CI, 1.22–2.20) were independently associated with an increased risk for major bleeding by the multivariable Cox regression model. Conclusion Major bleeding events were not uncommon during prolonged anticoagulation therapy in real-world VTE patients. Active cancer, previous major bleeding, anemia, thrombocytopenia, and old age were the independent risk factors for major bleeding.

BACKGROUND Differences in the clinical characteristics and outcomes of venous thromboembolisms (VTEs) based on different clinical situations surrounding the onset might be important for directing appropriate treatment strategies, but have not yet been appropriately evaluated. Methods and Results: The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTEs in Japan between January 2010 and August 2014. We divided the study population into 3 groups: Out-of-hospital onset (n=2,308), In-hospital onset with recent surgery (n=310), and In-hospital onset without recent surgery (n=374). Active cancer was most prevalent in the In-hospital onset without recent surgery group, and least in the Out-of-hospital onset group (Out-of-hospital onset group: 20%, In-hospital onset with recent surgery group: 26%, and In-hospital onset without recent surgery group: 38%, P

Background Although the incidence of very late stent failure (VLSF) is reduced with newer generation drug-eluting stent (DES), the mechanism of VLSF has not been fully explored.Methods and Results:This study evaluated both local vascular healing using coronary angioscopy and systemic factors determined by platelet reactivity at long-term follow-up after 2nd- and 3rd-generation DES implantation in patients with acute coronary syndrome. Coronary angioscopy was performed to assess neointimal coverage (NIC), yellow color (YC) grade and presence of thrombus. The obtained findings were compared with 2nd- and 3rd-DES. Platelet aggregation was assessed by light transmittance aggregometry. 100 consecutive patients were prospectively enrolled: 2nd- (n=50) and 3rd-DES (n=50). 3rd-DES patients had significantly higher NIC grade and lower YC grade compared with 2nd-DES. The presence of thrombus was tended to be lower with 3rd-DES than with 2nd-DES (8% vs. 18%, P=0.11). Patients with thrombus had significantly higher maximum platelet aggregation and higher prevalence of high on-treatment platelet reactivity (HPR) than those without thrombus. Multivariable analysis showed stent strut exposure and HPR as independent predictors of thrombus. Conclusions Newer generation DES contribute to better vascular healing depending on the degree of neointimal coverage. In addition to local factors at the stented lesion, systemic factors such as degree of platelet reactivity might also contribute to VLSF.

BACKGROUND Patients with cancer-associated venous thromboembolism (VTE) are at high risk for recurrent VTE and are recommended to receive prolonged anticoagulation therapy if they are at a low risk for bleeding. However, there are no established risk factors for bleeding during anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3,027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the potential risk factors for major bleeding. During a median follow-up period of 199 days, major bleeding occurred in 72 patients. The cumulative incidence of major bleeding was 5.8% at 3 months, 13.8% at 1 year, 17.5% at 2 years, and 28.1% at 5 years. The most frequent major bleeding site was gastrointestinal tract (47%). Terminal cancer (adjusted HR, 4.17; 95% CI, 2.22-7.85, P

The instantaneous wave-free ratio (iFR) is used for assessing the hemodynamic severity of a lesion, as an alternative to the fractional flow reserve (FFR). We evaluated the relationship between iFR and FFR in detail and the clinical significance of iFR in patients with mild to intermediate coronary artery stenosis. We recruited consecutive 323 patients (421 lesions) with lesions exhibiting 30% to 80% diameter stenosis on angiography in whom FFR and iFR were measured. In the total lesions, mean diameter stenosis was 48.6% ± 9.0%, and physiological significance, defined by FFR of 0.80 or less or by iFR of 0.92 or less, was observed in 32.5% or 33.5%, respectively. Mismatch between iFR and FFR was observed in 18.1% of the lesions. Clinical factors did not predict FFR value; however, gender, diabetes mellitus, aortic stenosis, anemia, high-sensitivity CRP value, and renal function predicted iFR value. In multivariate logistic analysis after adjustment for FFR value, gender (p < 0.001), diabetes mellitus (p = 0.005), aortic stenosis (p = 0.016), high-sensitivity CRP (p < 0.001), and renal function (p = 0.003) were all independent predictors of iFR value. In Kaplan-Meier analysis, the baseline iFR predicted the subsequent major cardiovascular events (MACE) (hazard ratio, 2.40; 95% CI, 1.16-4.93; p = 0.018) and the results of the iFR-guided strategy for predicting rates of MACE and myocardial infarction/revascularization were superior to those of the FFR-guided strategy. In conclusion, significant clinical factors predicted iFR value, which affected the prognostic capacity. The iFR-guided strategy may be superior in patients with mild to intermediate stenosis.

Introduction The external validation of the modified Ottawa score to predict the risk of recurrence in patients with cancer-associated venous thromboembolism (VTE) has not yet been firmly established. The present study aimed to evaluate the utility and limitations of the modified Ottawa score in the risk stratification of recurrent VTE in patients with cancer-associated VTE. Materials and methods The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 614 cancer-associated VTE patients, who were divided into 3 groups; High-risk group: 202 patients (33%) with a modified Ottawa score ≥ 1, Intermediate-risk group: 269 patients (44%) with a score = 0, and Low-risk group: 143 patients (23%) with a score ≤ −1. Results Recurrent VTE occurred in 39 patients on anticoagulation therapy within 6 months. The cumulative incidence of recurrent VTE substantially increased in the higher risk categories by the modified Ottawa score (high-risk group: 13.6% [95%CI, 8.9%–20.2%], intermediate-risk group: 5.9% [95%CI, 3.5%–9.8%], and low-risk group: 3.0% [95%CI, 1.1%–7.8%], P = .02). The discriminating power of the score was modest with a C-statistic of 0.63. Each score component of the score had a different impact on recurrent events with a variable effect size. Conclusions The risks of recurrence in patients with cancer-associated VTE substantially increased in the higher risk categories by using the modified Ottawa score, but the discriminating power of the score for recurrence was modest with a variable impact of each score component on recurrent events.

Background: The simplified pulmonary embolism severity index (sPESI) score has been reported to be useful in predicting 30-day mortality for patients with pulmonary embolism, which helps the identification of low-risk patients for early hospital discharge or home treatment. However, therapeutic decision-making should also be based on the risks of adverse events other than mortality. Methods: The COMMAND VTE Registry is a multicentre registry enrolling consecutive patients with acute symptomatic venous thromboembolism in Japan between January 2010 and August 2014, and the current study population consisted of 1715 patients with pulmonary embolism. We calculated the sPESI score for each patient, and compared 30-day rates of mortality, recurrent venous thromboembolism and major bleeding between sPESI scores of 0 and 1 or greater. Results: Patients with a sPESI score of 0 accounted for 383 (22%) patients, and 110 (6.4%) patients died within 30 days. The cumulative 30-day incidence of mortality was lower in patients with a sPESI score of 0 than those with a sPESI score of 1 or greater (0.5% vs. 8.1%, log rank PConclusions: In patients with a sPESI score of 0, the 30-day mortality, recurrent venous thromboembolism and major bleeding rates were reasonably low. The sPESI score could be useful to identify candidates for early hospital discharge or home treatment.

In recent years, due to a remarkable progress of qualified mesh generation algorithms combinedwith computational image processing technologies, a complex shaped 3D crack analysis has been carried out more and more easily by finite element method. Generally speaking, in order to assess thereliability of numerical solution, existence of a closed-form solution or a practically exact numericalsolution is important and thank-worthy. In contrast with 2D problems, however, there are very fewnumber of closed form solutions regarding to 3D crack problems. In the present analysis, we examineda highly accurate body force method (BFM) analysis for a partially cylindrical 3D surface crackin which a suitable basic density function can be supposed reasonably by taking account the crackgeometry. The present SIF solution could be used effectively for the purpose of benchmark the finiteelement solution for general non-planar crack problems.

Background Although drug-eluting stents (DES) have substantially reduced the need for early target lesion revascularization (TLR) compared with bare-metal stents (BMS) by inhibiting neointima hyperplasia, early generation DES have been associated with an increased risk of very late stent failure (VLSF) due to stent thrombosis and TLR after 1 year. Although the incidence of VLSF is reduced with newer generation DES, VLSF remains an unresolved problem and its mechanisms are not fully explored. Purpose The purpose of this study was to evaluate quality and quantity of neointima and presence of thrombus by using coronary angioscopy at long-term follow-up in patients who experienced an acute coronary syndrome (ACS) treated with BMS and DES on dual antiplatelet therapy. Methods Coronary angioscopy was performed at 6 and 10 months after BMS and DES implantation, respectively, in ACS patients. We assessed neointimal coverage (NC) of the stent struts, yellow color grade (YG) of stented segment and the existence of thrombus. Angioscopic NC was defined as follows: grade 0= fully visible struts; grade 1= visible struts through thin neointima; grade 2= no visible struts. We determined maximum (Max-NC) and minimum coverage (Min-NC) grades and the dominant NC grades. YG was classified into 4 grades (0= white; 1= slight yellow; 2= yellow; 3= intensive yellow). The obtained findings were compared with BMS, first-generation (1st-) DES, second-generation (2nd-) DES and third-generation (3rd-) DES. Results A total of 212 patients were enrolled: BMS (n=127), 1st DES (n=26, sirolimus-eluting stent), 2nd-DES (n=38, permanent polymer everolimus-eluting stent), and 3rd-DES (n=21, bioresorbable polymer everolimus-eluting stent). Max-NC and Min-NC grade were significantly lower with 1st- and 2nd-DES than with BMS and 3rd-DES (Figure). The same trend was also observed in the dominant NC grades. There was a lower trend of YG in BMS and 3rd-DES than in 1st or 2nd-DES (Figure). The presence of thrombus was significantly lower in 3rd-DES in comparison with BMS, 1st-, and 2nd-DES (3rd-DES 0%, BMS 20.5%, 1st-DES 24%, 2nd-DES 13.5%, P=0.01). Figure 1 Conclusion Patients treated with 3rd-DES have higher NC grade, lower incidence of intrastent thrombus, and lower YG than in 1st and 2nd-DES. These findings may explain the lower incidence of VLSF associated with these newer generation stent platforms.

Background/Introduction There is still uncertainty about the optimal usage of thrombolysis for acute pulmonary embolisms (PEs), leading to widely varying usage of thrombolysis in the real world. However, these have not been fully evaluated yet. Purpose We sought to evaluate the management strategies and clinical outcomes of thrombolysis for acute PEs in the real world. Methods The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic venous thromboembolisms in Japan between January 2010 and August 2014. The present study population consisted of 1,549 patients with PEs who received tissue plasminogen activator (t-PA) thrombolysis (N=180, 12%), or those who did not (N=1,369). The effectiveness outcome was all-cause death. The safety outcome was major bleeding. We used a multivariable logistic regression analysis to estimate the odds ratio (OR) and 95% confidence intervals (CI), to adjust clinically relevant confounders (age, sex, history of major bleeding, active cancer, and anemia). Additionally, we conducted stratified analysis by clinical severity, and we also evaluated clinical outcomes according to dosages of t-PA. Results Patients with t-PA thrombolysis were younger, and more frequently had higher body weight, but less frequently had active cancer, history of major bleeding, and anemia. More than half of patients with t-PA thrombolysis were patients with mild PEs, and the proportions of t-PA thrombolysis varied widely across the participating centers. More than half of patients received low-dose of t-PA ( Conclusions In the present real-world registry, relatively large number of patients received t-PA thrombolysis with wide variation across the participating centers. T-PA thrombolysis was significantly associated with a higher risk for major bleeding, but not a lower risk for mortality, although there appeared to be a benefit of t-PA thrombolysis in decreasing the risk for mortality in patients with severe PEs. Acknowledgement/Funding Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Background/Introduction Pulmonary embolism (PE) is caused by blockage of pulmonary arteries by thrombus. The sources of thrombus are thought to be mostly veins in lower extremities, whereas deep vein thrombosis (DVT) in upper extremities rarely occurs spontaneously. Recent studies reported that DVT in upper extremities might have significant complications, and DVT in upper extremities could be increasing. However, there is a paucity of data on patients with DVT in upper extremities, leading to uncertainty in optimal treatment strategies including anticoagulation therapy. Purpose We sought to evaluate the clinical characteristics, management strategies, and long-term outcomes of patients with DVT in upper extremities in a large observational database in Japan. Methods The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE) objectively confirmed by imaging examination or by autopsy among 29 centers in Japan between January 2010 and August 2014. The current study population consisted of 2498 patients with DVT in upper or lower extremities, after excluding 381 patients with PE only, 144 patients who had thrombus in locations other than upper or lower extremities, and 4 patients with DVT in both upper and lower extremities. The study patients were divided into 2 groups: patients with DVT in upper extremities and patients with DVT in lower extremities. We compared the clinical characteristics, management strategies and long-term outcomes between the 2 groups. Results There were 74 patients (3.0%) with upper extremities DVT and 2498 patients (97%) with lower extremities DVT. Patients with upper extremities DVT more often had active cancer at diagnosis (58%) and central venous catheter use (22%). The proportion of concomitant PE at diagnosis was lower in patients with upper extremities DVT than in those with lower extremities DVT (14% and 51%, P Kaplan-Meier event curves for recurrence Conclusions The prevalence of patients with DVT in upper extremities was 3.0% in the current large-scale real-world registry. Patients with DVT in upper extremities more often had active cancer at diagnosis and central venous catheter use as a transient risk factor for VTE, and less often had concomitant PE. Patients with DVT in upper extremities had similar long-term risk for recurrent VTE as those with DVT in lower extremities despite shorter duration of anticoagulation. Acknowledgement/Funding Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Background Statin prevents occurrence and recurrence of atherosclerotic events. With regard to venous thromboembolism (VTE), a randomized controlled trial suggested that statin reduced occurrence of VTE, whereas its usefulness as secondary prevention of VTE remains to be elucidated. Purpose This study aimed to assess the association between statin prescription, recurrent VTE and bleeding events in patients with VTE. Methods The COMMAND VTE Registry is a multicentre registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centres in Japan. We divided the cohort into the patients who were prescribed statin (N=437) and those not (N=2590), and compared the two groups. We assessed hazard ratios (HRs) of those with statin relative to those without for long-term clinical outcomes (recurrent symptomatic VTE and International Society of Thrombosis and Hemostasis [ISTH] major bleeding). Because the durations of anticoagulation therapy were widely different between the two groups, we constructed Cox's proportional hazard model incorporating status of anticoagulation during the follow-up period as a time-varying covariate. Also, because the incidences of death were strikingly different between the two groups due to the difference in the prevalence of active cancer, we used Fine-Gray's subdistribution hazard model in the presence of competing risks. We incorporated clinically relevant factors into these two models as covariates (10 factors for recurrent VTE and 11 for major bleeding). Results The statin group was significantly older than the non-statin group (statin 71.2±11.8 vs. non-statin 66.5±15.8, P Adjusted hazard ratios Outcome measures Model 1 P value Model 2 P value Adjusted HR [95% CI] Adjusted HR [95% CI] Recurrent VTE 0.59 [0.36–0.98] 0.042 0.53 [0.32–0.89] 0.02 Major bleeding 0.87 [0.60–1.24] 0.43 0.997 [0.69–1.43] 0.99 Model 1 derived from Cox's model with time-varying covariate of anticoagulation status. Model 2 derived from Fine-Gray's model. Study flowchart Conclusions Prescription of satin was associated with significantly low risks for recurrent VTE, whereas that was not for major bleeding events. Statin could be a potential treatment option for secondary prevention of VTE.

Background Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), has significant morbidity and mortality. Acute PE, in particular, is fatal if we miss it, and symptomatic patients of PE sometimes have concomitant DVT. Purpose This study compared the risk of mortality in symptomatic patients of PE with and those without DVT in the long term. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE objectively confirmed by imaging examination or by autopsy among 29 centers in Japan between January 2010 and August 2014. Patients with both PE and DVT (N=1334) were regarded as PE patients, and the current study population consisted of 1715 PE patients and 1312 DVT patients. Results There were 1203 symptomatic patients of PE, including 381 without and 822 with DVT. In our cohort, the mean age was 67.9±14.9 years, 63% was female, 44% had hypertension, 12% diabetes mellitus, 5% history of VTE. There were 20% of active cancer. Baseline characteristics were well matched except for dyslipidemia (18% vs. 23%, p=0.021) and atrial fibrillation (8% vs. 5%, p=0.045). Patients without DVT had a more severe clinical presentation compared to those with DVT, including hypoxemia, shock and arrest. Moreover, Initial parenteral anticoagulation therapy in the acute phase was administered less frequently in patients without DVT (89% vs. 96%, P=0.0001). Two groups received thrombolysis (20% vs. 26%, P=0.18) and mechanical supports (Ventilator 14% vs. 5%, p Landmark analysis Conclusions In symptomatic patients of PE, there was a difference in mortality between groups, but no difference in recurrent VTE. Patients without DVT had a more severe clinical presentation compared to those with DVT, and many VTE-related deaths in the acute phase. The one-month mortality rate differed statistically between groups, but there was no significant difference in long-term survival beyond one month. Most of deaths were due to underlying diseases, mainly cancer, and less commonly due to VTE in the long term. Acknowledgement/Funding Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation