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

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

シンゾウ ノ フクハイソク ケッテイ ト チュウカク ケイセイ ニ オケル Hand1 eHAND ノ ヤクワリ

京都大学0048新制・課程博士博士(医学)甲第11064号医博第2777号新制||医||876(附属図書館)22596UT51-2004-J736京都大学大学院医学研究科内科系専攻(主査)教授 長澤 丘司, 教授 米田 正始, 教授 塩田 浩平学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

〈Original〉Atorvastatin promoted in vitro angiogenesis by reduction of geranylgeranyl pyrophosphate in a dose-dependent manner and protected against rho kinase-mediated endothelial cell damage caused by thromboxane A2

[Abstract]Background: Atorvastatin can inactivate Rho/Rho kinase via a reduction in the synthesis of geranylgeranyl pyrophosphate (GGPP).Thromboxane A2 (TxA2) causes endothelial cell (EC) apoptosis via Rho/Rho kinase activation.We tested the hypothesis that atorvastatin protects against the Rho kinase-mediated anti-angiogenic effect of TxA2. Methods: We used human coronary artery ECs to form tubular structures on plates coated with a basement membrane matrix gel. The number of tubular structure was counted under a microscope. The caspase-3 activity was used as a determinant of apoptosis.Results: Atorvastatin significantly increased the number of tubes in a dose-dependent manner, and this effect was blocked by mevalonate or geranylgeranyl pyrophosphate (GGPP). Similar to atorvastatin, a potent selective inhibitor of geranylgeranyl transferase type I enhanced tubular formation. A TxA2 mimetic (IBOP) inhibited formation of EC tubular structures. The inhibitory effect was completely blocked by a TxA2 antagonist (SQ29548), a Rho kinase inhibitor (Y27632), and by atorvastatin. The IBOP-induced increase in caspase-3 activity was attenuated by atorvastatin. Conclusions: Atorvastatin promoted in vitro angiogenesis of ECs in a dose-dependent manner and reversed the TxA2 receptor-mediated antiangiogenic effect. We suggest that reduction of GGPP and inactivation of Rho kinase plays an important role in the proangiogenic effect of atorvastatin

〈Case Reports〉Catheter Ablation of Dual-Loop Macro-Reentrant Tachycardia under Electroanatomical Mapping Guidance Using Multiple-Electrode Sampling Catheter in Enlarged Right Atrium after Repair of Tetralogy of Fallot : A Case Report

〈Abstract〉We describe a 47-year-old woman who underwent tetralogy of Fallot repair at the age of 6 years and radiofrequency catheter ablation of macro-reentrant right atrial tachycardia (rt-AT) 41 years after surgery. A three-dimensional electroanatomical mapping system helped to determine the macroreentrant circuit. Although the right atrium was enlarged by the burden on the right side of the heart, multiple samplings on contact bipolar electrograms generated using a multipolar catheter enabled the production of high-density activation and voltage maps (429 points) within 30 minutes. The activation map revealed a dualloop reentrant circuit surrounding the superior and inferior vena cava, and clarified a critical isthmus located in the low-voltage area on the postero-lateral side of the right atrium. The rt-AT was terminated by ablation of the isthmus without damaging the nearby right phrenic nerve

Cancer-Associated Venous Thromboembolism in the Real World --From the COMMAND VTE Registry--

Background:There is a paucity of data on the management and prognosis of cancer-associated venous thromboembolism (VTE), leading to uncertainty about optimal management strategies. Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3, 027 consecutive acute symptomatic VTE patients in Japan between 2010 and 2014. We divided the entire cohort into 3 groups: active cancer (n=695, 23%), history of cancer (n=243, 8%), and no history of cancer (n=2089, 69%). The rate of anticoagulation discontinuation was higher in patients with active cancer (43.5%, 27.0%, and 27.0%, respectively, at 1 year, P<0.001). The cumulative 5-year incidences of recurrent VTE, major bleeding, and all-cause death were higher in patients with active cancer (recurrent VTE: 17.7%, 10.2%, and 8.6%, P<0.001; major bleeding: 26.6%, 8.8%, and 9.3%, P<0.001; all-cause death: 73.1%, 28.6%, 14.6%, P<0.001). Among the 4 groups classified according to active cancer status, the cumulative 1-year incidence of recurrent VTE was higher in the metastasis group (terminal stage group: 6.4%, metastasis group: 22.1%, under chemotherapy group: 10.8%, and other group: 5.8%, P<0.001). Conclusions:In a current real-world VTE registry, patients with active cancer had higher risk for VTE recurrence, bleeding, and death, with variations according to cancer status, than patients without active cancer. Anticoagulation therapy was frequently discontinued prematurely in patients with active cancer in discordance with current guideline recommendations