Aishin Memorial Hospital

The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181–0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [−5.49–4.12]; LVDd, −0.55 [−3.24–2.15]; LVDd index, −0.25 [−1.92–1.43]; LVDs, −0.03 [−3.84–3.90]; LVDs index, −0.04 [−2.38–2.30]; heart rate, 1.62 [−3.07–6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol.

筋周皮腫は成人の四肢に好発する良性皮下腫瘍であり，まれに血管内に発生する．症例は 46歳男．3年前より右大腿内側に15 mmの皮下腫瘤を自覚し，徐々に増大し圧痛を伴うようになった．外傷歴はないが，1日8時間以上の立ち仕事をしていた．病理組織では，皮下脂肪組織に複数の腫瘍胞巣が散在し，異型を伴わない卵形〜紡錘細胞が内皮細胞の周囲に同心円状に配列していた．免疫染色では腫瘍細胞はsmooth muscle actin（αSMA）陽性，desmin，CD31，CD34，および第Ⅷ因子に対して陰性であり，CD34は内皮細胞で陽性であった．これは腫瘍が血管内に存在することを示唆した．これより血管内筋周皮腫と診断した．成因を明らかにするために，過去に報告された15例と年齢，性別，期間，部位および形態において比較し，本症例では，長時間の立位による静脈鬱滞・逆流が下肢の血管内筋周皮腫の誘因であると考察した．

Behçet's disease (BD) is a chronic, relapsing inflammatory, multisystem disease of unknown etiology. The disease has a wide clinical spectrum of mucocutaneous lesions and ocular, vascular, articular, neurologic, gastrointestinal and cardiac involvement. Although the number of effective drugs used in the disease's treatment has increased in recent years, BD is still associated with severe morbidity because of mainly mucocutaneous, articular and ocular symptoms and an increased mortality because of large vessel, neurological, gastrointestinal and cardiac involvement. Many factors are associated with a more serious course, such as male gender and a younger age of onset. While the severity of the disease is more pronounced in the first years of the disease, it decreases in most patients after the age of forties. The primary goal of treatment should be the prevention of irreversible organ damage. Therefore, early diagnosis and appropriate treatment and close follow-up are mandatory to reduce the morbidity and mortality of the disease. Treatment varies depending on the organ involved and the severity of the involvement. For all these reasons, the treatment should be personalized and arranged with a multidisciplinary approach according to the organs involved. Treatment is mainly based on suppression of the inflammatory attacks of the disease using local and systemic immunomodulatory and immunosuppressive drugs. In this review, based on the mainly controlled studies and personal experience in clinical practice and basic research in this field, we propose a stepwise, symptom-based, algorithmic approach for the management of BD with a holistic perspective.

Early administration of direct oral anticoagulants in patients with acute large vessel occlusion (LVO) and nonvalvular atrial fibrillation (NVAF) is a concern, as endovascular therapy (EVT) became highly utilized. We conducted a historical and prospective multicenter registry at 38 centers in Japan from July 2016 to February 2018. Patients aged ≥ 20 years with NVAF and acute LVO or stenosis who received apixaban within 14 days from onset were included. We compared patients who received apixaban < 48 h (Early group) and ≥ 48 h (Late group) after onset in terms of the primary outcome (a composite of ischemic events, major bleeding events, and all-cause deaths). The secondary outcomes were each component of the primary outcome. Among the 686 patients, the median time from onset to administration was 2.5 days (range, 0–14; Early 263, Late 423). The Alberta Stroke Program Early CT Score (ASPECTS) and diffusion-weighted imaging (DWI)-ASPECTS) were significantly higher in the Early group than in the Late group. Recombinant tissue plasminogen activator (rt-PA) and EVT were more utilized in the Early group (rt-PA 46% vs. 35%, p = 0.003; EVT 62% vs. 46%, p < 0.0001). The cumulative incidence of primary outcome was similar between groups (ischemic events: Early 1.9% vs. Late 0.5% at 30 days; 3.5% vs. 0.7% at 90 days, major bleeding 3.4% vs. 2.9% at 30 days; 5.0% vs. 3.4% at 90 days). Early administration of apixaban (< 48 h), after onset of acute LVO in patients with NVAF, was generally safe compared with those who received it Late (≥ 48 h). http://www.clinicaltrials.gov. Unique identifier: NCT02818868 (June 30, 2016)

Some intracranial aneurysms treated by stent-assisted coiling (SAC) with incomplete occlusion undergo progressive occlusion (PO) during follow-up period. We analyzed the predictors for the occurrence of PO. Among 74 cerebral aneurysms treated by SAC using the Enterprise or Neuroform stents from 2010 to 2015, we included 43 aneurysms with occlusion grade of neck remnant (NR, n=36) or residual aneurysm (RA, n=7) at the post-procedure. We defined PO as improvement in occlusion grade from RA to NR, or from NR or RA to complete occlusion on angiographic follow-up imaging at 6months after the procedure. We analyzed the independent predictors for PO using a multivariate logistic regression model and receiver operating characteristic (ROC) curve analysis. Forty-three aneurysms were analyzed, with mean volume embolization ratio of 30.3±6.7%. Twenty aneurysms (47%) achieved PO. Univariate analysis found that the median neck diameter of the aneurysms was smaller in aneurysms with PO than others. Multivariate logistic regression analysis also found that the odds ratio of neck diameter of the aneurysm for PO was 0.44 (95% CI, 0.19-0.82, p<0.01). Moreover, ROC curve analysis for PO found that the optimal cut-off value of the neck diameter was 5.5mm, with a sensitivity of 95%, specificity of 57% (p<0.01). Incompletely occluded aneurysms with a neck diameter of 5.5mm or less might be more likely to develop PO within 6months after SAC by using Enterprise or Neuroform stents.

To determine the predictive value of serum lipid levels on the development of later cardiovascular events after abdominal aortic aneurysm (AAA) surgery. A total of 101 patients under 70 undergoing an elective AAA surgery were divided into the following two groups: 1) those who developed later cardiovascular events after AAA surgery, including cerebral infarction (n = 4), catheter intervention (PCI) or surgery for coronary artery disease (CAD) (n = 9) and other vascular disease. (CVE group; n = 19); 2) those without later events (NoCVE group: n = 82). Preoperative atherosclerotic risk factors including serum lipid levels were subjected to univariate and multivariate analysis. The CVE group showed a significantly lower high-density lipoprotein cholesterol (HDL-C) level (32.9 ± 6.6 vs 41.6 ± 12.1 mg/dL; p <0.001), higher low-density lipoprotein cholesterol (LDL-C) / HDL-C ratio (4.30 ± 1.01 vs 3.24 ± 1.15; p = 0.001), and higher prevalence of mild CAD (without an indication of PCI) (p = 0.029) preoperatively. Cox hazard analysis indicated that preexistent mild CAD (hazard ratio 4.70) and preoperative HDL-C <35 mg/dL (hazard ratio 3.07) were significant predictors for later cardiovascular events after AAA surgery. Patients at high risk for later cardiovascular events should require a careful follow-up and may also require an aggressive lipid-modifying therapy.

Antithrombin III (AT III) deficiency is a rare hereditary disease that predisposes to thromboembolic complications. We report a case of AT III deficiency complicated with acute pulmonary thromboembolism, successfully treated with emergency pulmonary thromboembolectomy after insertion of an inferior vena cava filter. AT III activity before treatment was found to be 44% of normal value and remained less than 50% of normal throughout the postoperative course. In his family line, both the patient's aunt and deceased father had a history of pulmonary infarction. AT III activity of the patient's aunt was 47 to 58% of normal value. The patient was discharged on the 15th day after surgery and has been doing well for four years receiving warfarin as anticoagulant therapy. Careful follow-up is essential for early detection of the recurrent pulmonary thromboembolism resulting in pulmonary hypertension and/or right heart failure.

The control strategy for ventricular support with a centrifugal blood pump was examined in this study. The control parameter was the pump rpm that determines pump flow. Optimum control of pump rpm that reflects the body's demand is important for long-term, effective, and safe circulatory support. Moreover, continuous, reliable monitoring of ventricular function will help successfully wean the patients from the ventricular assist device (VAD). The control strategy in this study includes determination of the target pump rpm that can provide the flow required by the body, fine-rpm-tuning to minimize deleterious effects such as suction in the ventricle, and assessment of ventricular function for successful weaning from VADs. To determine the target pump rpm, we proposed to use the relation between the native heart rate and cardiac output, and the relation between the pump rpm and centrifugal pump output. For fine-tuning of the pump rpm, the motor current waveform was used. We computed the power spectral density of the motor current waveform and calculated the ratio of the fundamental to the higher order components. When this ratio was larger than approximately 0.2, we assumed there would be a suction effect in the ventricle. As for assessment of ventricular function, we used the amplitude of the motor current waveform. The control system implemented using a DSP functioned properly in the mock circulatory loop as well as in acute animal experiments. The motor current also showed a good correlation with the ventricular pressure in acute animal experiments.