Tetsuo Hashimoto

Current status of clinical background of patients with atrial fibrillation in a community-based survey:The Fushimi AF Registry

BACKGROUNDnAtrial fibrillation (AF) increases the risks of stroke and death, and the prevalence of AF is increasing significantly. Until recently, warfarin was the only oral anticoagulant for stroke prevention, but novel anticoagulants are now under development.nnnMETHODS AND RESULTSnThe Fushimi AF Registry is a community-based survey of AF patients. We aimed to enroll all of the AF patients in Fushimi-ku, which is located at the southern end of the city of Kyoto. Fushimi-ku is densely populated with a total population of 283,000, and is assumed to represent a typical urban community in Japan. On the basis of the general prevalence of AF in the Japanese (0.6%), we estimated the total number of AF patients as 1700. A total of 76 institutions, a large proportion of which were private clinics, participated in the study. At present, we have enrolled 3183 patients from March 2011 to June 2012 (approximately 1.12% of total population). The mean age was 74.2±11.0 years, and 59.3% of subjects were male. The mean body weight was 58.5±13.2 kg, and the proportions with a body weight of less than 50 kg and 60 kg were 25.7% and 55.0%, respectively. The type of AF was paroxysmal in 46.0%, persistent in 7.3%, and permanent in 46.7%. Major co-existing diseases were hypertension (60.6%), heart failure (27.9%), diabetes (23.2%), stroke (19.4%), coronary artery disease (15.0%), myocardial infarction (6.4%), dyslipidemia (42.4%), and chronic kidney disease (26.4%). The mean CHADS2 score was 2.09±1.35: 0 in 11.8% of patients, 1 in 27.1%, and 2 in 29.1%. Warfarin was prescribed in only 48.5% of patients, whereas anti-platelet drugs, mainly aspirin, were prescribed for more than 30% of the patients.nnnCONCLUSIONSnThe Fushimi AF Registry provides a unique snapshot of current AF management in an urban community in Japan.

Treatment of acute inflammatory cardiomyopathy with intravenous immunoglobulin ameliorates left ventricular function associated with suppression of inflammatory cytokines and decreased oxidative stress

Although an autoimmune mechanism has been postulated for myocarditis and dilated cardiomyopathy, immunosuppressive agents had not been shown to be effective. Potential benefits of intravenous immunoglobulin (IVIg) in the therapy of patients with myocarditis and recent onset of dilated cardiomyopathy were reported. Also, experimental studies showed that IVIg is an effective therapy for viral myocarditis by antiviral and anti-inflammatory effects. Accordingly, in the current study, the effects of IVIg in the patients were investigated with the analyses of inflammatory cytokines and oxidative stress. Nine patients (six in myocarditis, three in acute dilated cardiomyopathy) were treated with high-dose intravenous IVIg (1-2 g/kg, over 2 days). All were hospitalized with New York Heart Association (NYHA) class III to IV heart failure, left ventricular ejection fraction (LVEF) <40%, and symptoms for <6 months at the time of presentation. Five patients were diagnosed using endomyocardial biopsy. LVEF determined by echocardiography improved from 19.0+/-7.5% (mean+/-S.D.) at baseline to 35.4+/-9.1% at follow up (12.2+/-5.8 days after the treatment) (P<0.01). C-reactive protein and plasma inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) were decreased by this treatment. In addition, plasma level of thioredoxin, which regulates the cellular state of oxidative stress, was decreased by the treatment. All nine patients improved functionally to NYHA class I to II, and were discharged without side-effects. There have been no subsequent hospitalizations for heart failure during the course of follow-up (3 months-4.5 years). LVEF improved 16% of EF in the patients with myocarditis and acute dilated cardiomyopathy with the reduction of cytokines associated with improvement of oxidative stress state by high-dose of IVIg. Thus, IVIg seems to be a promising agent in the therapy of acute inflammatory cardiomyopathy in view of not only suppression of inflammatory cytokines but a reduction of oxidative stress.

Upregulation of redox-regulating protein, thioredoxin, in endomyocardial biopsy samples of patients with myocarditis and cardiomyopathies.

An important role of redox regulation in myocardial diseases and heart failure has been postulated. Thioredoxin (TRX) is a redox-regulating protein. Recent studies indicated a possible association between plasma TRX concentrations and the severity of heart failure. Accordingly, we investigated the myocardial expression of TRX in patients with myocarditis and cardiomyopathies. Four cases of hypertrophic cardiomyopathy (HCM), 10 of dilated cardiomyopathy (DCM), 6 of myocarditis, and 5 of controls were studied. Right and left ventricular endomyocardial biopsy samples were obtained at the diagnostic cardiac catheterization. The samples were processed for immunohistological staining for TRX, which was done by the indirect immunoperoxidase technique. 8-hydoxy-2′-deoxyguanosine (8-OHdG), one of the major DNA base-modified products, was also detected for an established marker for oxidative stress. TRX immunoreactivity was none or trivial in control specimens. Positive TRX staining was found in 6 cases; 3 in active myocarditis and 3 in DCM. The positive staining was found in infiltrating cells and damaged myocytes in the perinecrotic lesions. Damaged myocytes were also positive for 8-OHdG. All the 3 cases of DCM positive for TRX stain showed severe left ventricular hypertrophy on electrocardiogram and highly elevated left ventricular end-diastolic pressure (> 24 mmHg), suggesting the overload of oxidative stress by hemodynamic impairment. Myocardial TRX was upregulated in myocarditis and cardiomyopathies with active necrotic stage associated with DNA damage, which may reflect the oxidative stress overload in hemodynamically uncontrolled status.

Relationship between natural killer activity and anger expression in patients with coronary heart disease.

Abstractu2002Recently, the contribution of the immune system in the development and progression of arteriosclerosis has been suggested. Moreover, psychological stress has also been reported to affect the immune response. Thus, psychological factors are considered to influence the immune response, and an excessive immune response promotes the progression of arteriosclerosis, resulting in the development of coronary heart disease (CHD). In this study, the relationship between the immune response and psychological factors was investigated in CHD patients (n = 74) and normal controls (n = 64). Natural killer (NK) activity was significantly higher in the CHD group than the normal control (CHD vs normal: 8151.39 vs 6653.06, P < 0.05), and was significantly elevated by the suppression of anger and negative emotions (P < 0.05). These results indicate that the characteristic process of psychological response in CHD patients is related to an overresponse of NK activity. We speculate that this linkage significantly influences the development of CHD.

Therapy with immunoglobulin in patients with acute myocarditis and cardiomyopathy: analysis of leukocyte balance

Intravenous immunoglobulin (IVIG) therapy has been used to treat several autoimmune or inflammatory diseases. We conducted a clinical trial of immunoglobulin therapy for acute myocarditis. The study consisted of two projects: (1) a comparison of prognosis between patients treated with and those not treated with IVIG in a multi-center study; (2) analyses of inflammatory cytokines and blood cell profiles in a substudy. In (1), 15 patients were treated with IVIG (1–2xa0g/kg, over 2xa0days), whereas 26 were untreated. There was a statistically significant difference between the survival curves of the patients treated with IVIG and the survival curves of those not treated with IVIG. There was no significant difference between the IVIG-treated and untreated groups in terms of clinical parameters of the acute and chronic phases. In (2), 10 patients were treated with IVIG and 6 were untreated. In both groups, all of the data except for changes in the fraction of lymphocytes and the fraction of monocytes decreased due to the treatment or during the course. In patients in the IVIG group, the percentage of peripheral eosinophils was decreased and the percentage of peripheral monocytes was increased by this treatment when they were compared with the pretreatment data. Therefore, therapy with IVIG seems to be a promising treatment for acute myocarditis given that it improves the clinical course, which may be due to modulation of inflammatory cytokines and the peripheral leukocyte balance.

Long-term angiographic outcomes of post-Sirolimus-eluting stent restenosis in Japanese patients

Though restenosis after drug-eluting stent implantation is still observed, the factors affecting post-Sirolimus-eluting stent restenosis (re-restenosis) have not been fully determined. We evaluated the long-term angiographic outcomes and examined background factors affecting re-restenosis. We enrolled 51 patients with 68 Sirolimus-eluting stent (SES) restenosis lesions who underwent target lesion revascularization (TLR) and angiographic follow-up studies. Re-restenosis was observed in 29 of 68 restenosis lesions, and the rate was 42.6%. Study subjects were divided into two groups: a re-restenosis (Re-R) group (20 patients) with 29 lesions and a restenosis (R) group (31 patients) with 39 lesions with no re-restenosis. There were no differences in age, sex, coronary risk factors, past history, or medications between the two groups. Re-restenosis was observed more frequently in the right coronary artery (Re-R group vs. R group; 65.5 vs. 33.3%, Pxa0=xa00.009). The incidence of stent fracture was higher in the Re-R group (Re-R group vs. R group; 48.3 vs. 12.8%, Pxa0=xa00.003). QCA results showed that the initial lesion length at the time of first coronary intervention was significantly longer in the Re-R group (Re-R group vs. R group; 21.6xa0±xa03.37 vs. 12.6xa0±xa04.98xa0mm, Pxa0=xa00.049). The rate of re-restenosis was 47.1% when treated with POBA alone, while it was 36.7% with SES treatment. In multivariate analysis, the initial lesion length at the time of first coronary intervention (odds ratioxa0=xa01.64, 95% CI 1.29–2.06, Pxa0<xa00.001) and stent fracture (odds ratioxa0=xa012.42, 95% CI 1.89–81.4, Pxa0=xa00.009) were independent predictors of re-restenosis. This study demonstrates that recurrent restenosis with SES treatment is associated with lesion length and stent fracture, a finding that is beneficial in the management of restenosis after SES implantation.

Biopsy-Proven Loeffler Endocarditis Successfully Treated With Steroids

A 73-year-old Japanese woman was admitted to the intensive care unit of our hospital with the diagnosis of eosinophilic pneumonia and congestive heart failure. Laboratory examination revealed a white blood cell count of 8100/mm3 with 49% eosinophils, 1568 IU/mL IgE, 467 IU/L lactate dehydrogenase with 40% lactate dehydrogenase-1, a brain natriuretic peptide level of 1223 pg/mL, and 23.5 U/mL myeloperoxidase anti-neutrophil cytoplasmic antibody. Chest x-ray demonstrated bilateral perihilar opacities. ECG showed normal sinus rhythm and QS pattern in leads V1 through V5. Transthoracic echocardiography (TTE) demonstrated severe thickening and hyperkinesis of the posterior portion of the left ventricular (LV) wall during diastole and systole (Figure 1A and 1B, arrows and Movies I–III in the online-only Data Supplement), which caused the Doppler-derived systolic pressure gradient across the LV outflow tract of 74 mmu2009Hg. Transmitral flow pattern showed an E/A ratio of 2.1 with a deceleration time of 58 milliseconds, suggesting severe …