Long-term Safety and Efficacy of Benralizumab for Eosinophilic Granulomatosis with Polyangiitis Complicated with Severe Neuropathy.

The efficacy of benralizumab, as well as mepolizumab, to granulomatosis with polyangiitis (EGPA) involved with mononeuritis multiplex remains unclear. We experienced a case of EGPA presenting neuropathy with severe asthma. Muscle weakness due to neuropathy involved with gait disturbance was partly ameliorated by intravenous immunoglobulin therapy. Mepolizumab (100 mg/day) did not promote further improvement of neuropathy. However, the administration of benralizumab instead of mepolizumab improved neuropathy quickly and enabled walking alone. The efficacy of benralizumab for EGPA and its complication has been maintained for over four years. Benralizumab may be a possible treatment for EGPA presenting neuropathy with severe asthma.

Body size and atrial fibrillation in Japanese outpatients.

BACKGROUND: Although recent studies have suggested that height and body mass index (BMI) independently affect the prevalence of atrial fibrillation (AF), their combined effects have not been fully examined in Japanese patients. METHODS AND RESULTS: Patients without organic cardiac diseases, hypertension and diabetes mellitus were screened from a prospective, single hospital-based cohort of the Shinken Database 2004-2007 (n=4,719). Both height and BMI significantly increased the crude rate of AF prevalence and the effects were significant even after adjustment by age, sex and left atrial dimension. The relative risks (RRs) for AF in the height and BMI categories were 2.07 (95% confidence interval [CI] 1.70-2.52) and 1.78 (95%CI 1.46-2.17), respectively, in the highest tertile compared with the lowest tertile. The RRs in the highest combined tertile was high to 2.98 (95%CI 2.07-4.28) compared with the lowest combined tertile, an unignorable figure for AF prevalence in the future. CONCLUSIONS: Height and BMI synergistically affected the prevalence of AF in Japanese patients. With respect to the recent increase in body size of the Japanese population, the present study predicts that there will be more occurrences of AF than previously predicted. (Circ J 2010; 74: 66 - 70).

Relation between frequency of activated partial prothrombin time measurements and clinical outcomes in patients after initiation of dabigatran: A two-center cooperative study.

BACKGROUND: Although activated partial prothrombin time (aPTT) has often been used as a biomarker for evaluating the safety of dabigatran use in patients with non-valvular atrial fibrillation (NVAF), the optimal frequency of aPTT measurements is unclear. This study aimed to identify the frequency distribution of aPTT measurements in clinical practice and its clinical significance. METHODS: This was a retrospective cooperative study conducted in 2 sites. All NVAF patients who underwent aPTT measurements before and after dabigatran treatment were included (n=380). The patients were divided into 2 groups according to the frequency of aPTT measurements during the first 3 months after drug prescription: Group A: infrequent group with only 1 measurement; and Group B: frequent group with ≥2 measurements. The clinical characteristics and outcomes were compared between the groups. RESULTS: The frequency of aPTT measurements in the 3 months after dabigatran initiation varied: 240 patients underwent 1 measurement (Group A), and the remaining 140 patients underwent repeated measurements (Group B). There were significant differences in age and creatinine clearance (Ccr) between the groups (Group A vs. Group B: age 64.0±11.7 vs. 67.0±11.1 years, p=0.01; Ccr 83.8±30.3 vs.76.7±31.1 mL/min, p=0.03). During the mean follow-up period of 310 days, there were no significant differences in the discontinuation rate and incidence of bleeding (17% vs. 15% and 5% vs. 3%, respectively; both not significant). In Group B, the aPTT rarely increased beyond twice the upper normal limit within the 3 months (2.1%), although the correlation between the initial and subsequent aPTT measurements was low (r=0.366). CONCLUSIONS: In this retrospective study, the frequency of aPTT measurements after dabigatran initiation might have been dependent on patient characteristics. However, frequent aPTT measurements did not lead to a reduction in adverse clinical events.

Enlargement of the left atrium is associated with increased infiltration of immune cells in patients with atrial fibrillation who had undergone surgery.

BACKGROUND: Enlargement of the left atrium (LA) is a risk factor of atrial fibrillation (AF) recurrence after pharmacological and nonpharmacological interventions for AF. However, structural changes associated with LA enlargement have not been fully elucidated. METHODS: To examine inflammation in the structural changes associated with LA enlargement, human left appendages obtained from 27 patients who underwent cardiac surgery by using the maze procedure were subjected to immunohistochemical analysis. RESULTS: The extent of interstitial fibrosis increased according to the increase in LA dimension (LAD) as assessed by using ultrasound echocardiography. The extent of the infiltration of CD68-positive macrophages and CD3-positive T cells increased simultaneously according to the increments in LAD. The areas infiltrated by immune cells were positively and significantly correlated with LAD (r (2)=0.58, p<0.01 for CD68; r (2)=0.49, p<0.01 for CD3). CONCLUSIONS: In the patients with AF, LA enlargement was associated not only with the increase in the extent of interstitial fibrosis but also with the changes in the LA component cells, including an increase in number of immune cells resident in tissues.

Primary idiopathic chylopericardium: report of two cases.

Primary chylopericardium is an extremely rare disease. This report presents two cases of this disease, in a 47-year-old man and 21 -year-old woman. Both cases were given diagnosis of primary chylopericardium by chylous pericardial fluid examination and lymphangio-scintigraphy which demonstrated abnormal communication between the left thoracic duct and the pericardial cavity.

Clinical outcome after acute coronary syndrome in Japanese patients: an observational cohort study.

BACKGROUND: Mortality and morbidity after acute coronary syndrome (ACS) in Japan appear to be different from those in Western countries due to different social healthcare systems, races, geographical locations, and interventional procedures, although data are limited in Japan. METHODS: With a hospital-based cohort study comprising all the new patients who had visited our hospital between 2004 and 2007 (n=6562), we identified all-cause mortality, the composite endpoint of cardiac death, non-fatal myocardial infarction (MI), or target vessel revascularization and the predictors. RESULTS: Of the total, 293 patients were included with a discharge diagnosis of ACS (median follow-up of 24.5 months). Non-ST elevation-ACS (NSTE-ACS) (unstable angina and non-ST elevation MI) and ST elevation MI (STEMI) were observed in 165 (56.3%) and 128 (43.7%) patients, respectively. Percutaneous coronary intervention or coronary artery bypass graft surgery was performed in 72.7% and 14.5% of NSTE-ACS patients, respectively and in 82.8% and 10.2% of STEMI patients. The use of aspirin, ticlopidine, and beta-blockers for NSTE-ACS patients were 93.3%, 66.9%, and 38.0%, respectively, with corresponding rates of 96.0%, 75.4%, and 57.1% for STEMI patients. All-cause mortality rates in NSTE-ACS and STEMI were 1.8% and 5.5% at 30 days, respectively, and 6.3% and 12.9% at 2 years, with corresponding rates of 3.7% and 8.7% at 30 days, respectively, and 23.4% and 35.6% at 2 years for the composite endpoint. Multivariate analysis showed that predictors for mortality were older age (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.018-1.244) and estimated glomerular filtration rate value (HR 0.96, 95% CI 0.929-0.988) in NSTE-ACS, and older age (HR 1.10, 95% CI 1.011-1.119) and congestive heart failure on admission (HR 20.0, 95% CI 2.439-164.4) in STEMI. CONCLUSIONS: The present study identified long-term mortality, morbidity, and predictors of adverse events for Japanese patients with ACS.

Heart failure with preserved versus reduced left ventricular systolic function: a prospective cohort of Shinken Database 2004-2005.

BACKGROUND: Several hospital-based investigations have reported that a high proportion of patients with heart failure (HF) have preserved left ventricular ejection fraction (LVEF). The purpose of this study was to determine the prevalence, prognosis, and predictors for mortality of Japanese HF patients with preserved versus reduced LVEF in a prospective cohort fashion. METHODS AND RESULTS: Our hospital-based database including inpatients and also outpatients was used for analysis. Out of 4255 new patients, 597 patients (male/female 414/183, age 65.1+/-12.9 years) were diagnosed as having symptomatic HF at the initial visit. Among 589 HF patients undergoing echocardiography, 398 (67.6%) showed a preserved LVEF (>50%) and 191 (32.4%) had a reduced LVEF (< or =50%). Patients with preserved LVEF were older (p=0.004) and more likely to be female (p=0.002). During follow-up of an average 539 days, 34 cardiovascular deaths occurred, and patients with preserved LVEF showed a better prognosis than those with reduced LVEF (3.2% vs. 7.4% per year, p=0.0097). Multivariate Cox hazards analysis identified LVEF as an independent predictor in all HF patients. Also, separated group analysis showed that presence of chronic kidney disease was independently associated with poor prognosis irrespective of HF types. CONCLUSIONS: This prospective cohort study identified prevalence and prognosis of HF in Japanese in- and outpatients, where patients with preserved LVEF showed a better prognosis than those with reduced LVEF.

Prevalence and prognosis of patients with heart failure in Tokyo: a prospective cohort of Shinken Database 2004-5.

Prognosis of patients with heart failure (HF) remains unclear in Japan and should be determined in a prospective fashion. A prospective cohort of The Shinken Database comprised details on all of the new patients, including both inpatients and outpatients, who visited The Cardiovascular Institute Hospital in 2004-2005. HF patients were defined as those with symptomatic HF coexisting with structural heart diseases. Among 4,255 patients who visited our hospital, 597 patients (male/female 414/183, age 65.1 +/- 12.9 years, LVEF 56.2 +/- 18.0%) were diagnosed as presenting symptomatic HF. Ischemic heart disease was present in 305 (51.1%), valvular heart disease in 212 (35.5%), dilated cardiomyopathy in 59 (9.9%), hypertrophic cardiomyopathy in 24 (4.0%), hypertensive heart disease in 14 (2.3%), and others in 67 (11.2%). Hypertension, atrial fibrillation, and diabetes were observed in 35.3%, 27.4%, and 23.7%, respectively. During the mean follow-up period of 539 +/- 257 days, 40 deaths (5.0% per year) occurred, including 34 cardiovascular deaths (4.5% per year, NYHA class II: 1.0%, III: 11.3%, IV: 36.6% per year, respectively). The present study showed that the prognosis of Japanese patients with HF among moderate to severe severity was found to be similar to that of Western countries. Multiple Cox hazard analysis identified the presence of chronic kidney disease and NYHA class as independent predictors for cardiovascular death. This prospective cohort study identified the prevalence, prognosis, and risk factors in HF patients to provide a basis for therapeutic management in Japan.

Prevalence and prognosis of patients with atrial fibrillation in Japan: a prospective cohort of Shinken Database 2004.

BACKGROUND: Prognosis of Japanese patients with atrial fibrillation (AF) should be determined in a prospective cohort study. METHODS AND RESULTS: A prospective cohort of The Shinken Database 2004 comprised details on all the new patients who visited The Cardiovascular Institute Hospital in 2004 (n=2,412), which included 286 AF patients (11.8%, 205 males, 64.1+/-12.3 years, 165 paroxysmal). In this Japanese cohort of AF patients, the prevalence of congestive heart failure (CHF) was low compared with that in Westerners. Total mortality and cardiovascular morbidity of these patients were also quite low, 1.7% and 11.2% at 1 year, respectively. However, patients with CHF exhibited higher mortality (7.3%), and hospitalization for CHF increased the rate to 22.6%. There was no significant difference in mortality between paroxysmal and persistent AF. Multiple Cox-hazard regression analysis identified hospitalization at initial visit and lack of anticoagulation as independent predictors for mortality, and existence of CHF as the only independent predictor for cardiovascular morbidity. CONCLUSIONS The present study identified the mortality (1.7%) and morbidity (11.2%) of Japanese AF patients during 1 year after initial visit. Hospitalization for CHF and lack of anticoagulation were independent predictors for mortality, suggesting important roles of co-morbidities of Japanese AF patients.