Shinya Hiramitsu

Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone

Cardiac involvement is an important prognostic factor in sarcoidosis, but reliable indicators of mortality risk in cardiac sarcoidosis are unstudied in a large number of patients. To determine the significant predictors of mortality and to assess the efficacy of corticosteroids, we analyzed clinical findings, treatment, and prognosis in 95 Japanese patients with cardiac sarcoidosis. Twenty of these 95 patients had cardiac sarcoidosis proven by autopsy; none of these patients had received corticosteroids. We assessed 12 clinical variables as possible predictors of mortality by Cox proportional hazards model in 75 steroid-treated patients. During the mean follow-up of 68 months, 29 patients (73%) died of congestive heart failure and 11 (27%) experienced sudden death. Kaplan-Meier survival curves showed 5-year survival rates of 75% in the steroid-treated patients and of 89% in patients with a left ventricular ejection fraction > or = 50%, whereas there was only 10% 5-year survival rate in autopsy subjects. There was no significant difference in survival curves of patients treated with a high initial dose (> 30 mg) and a low initial dose (> or = 30 mg) of prednisone. Multivariate analysis identified New York Heart Association functional class (hazard ratio 7.72 per class I increase, p = 0.0008), left ventricular end-diastolic diameter (hazard ratio 2.60/10 mm increase, p = 0.02), and sustained ventricular tachycardia (hazard ratio 7.20, p = 0.03) as independent predictors of mortality. In conclusion, the severity of heart failure was one of the most significant independent predictors of mortality for cardiac sarcoidosis. Starting corticosteroids before the occurrence of systolic dysfunction resulted in an excellent clinical outcome. A high initial dose of prednisone may not be essential for treatment of cardiac sarcoidosis.

Histologic diagnostic rate of cardiac sarcoidosis: Evaluation of endomyocardial biopsies

BACKGROUND An early diagnosis of cardiac sarcoidosis is important, particularly when considering the need for administering corticosteroid therapy. However, no reports are available on the success rate of diagnosis on the basis of biopsy findings in patients with cardiac sarcoidosis. This study investigated the diagnostic success rate of histologic evaluation of endomyocardial biopsy specimens in patients with this disease. METHODS AND RESULTS Right ventricular endomyocardial biopsy was performed in 26 patients in whom cardiac sarcoidosis was strongly suspected according to the Diagnostic Criteria of Sarcoidosis, plus abnormalities on the electrocardiogram, cardiac radionuclide images, or in left ventricular wall motion. A mean of 4.0 sites were sampled per patient. In each case we determined whether a definitive diagnosis of cardiac sarcoidosis could be made histologically. Noncaseating granulomas were found in only 5 (19.2%) of the 26 cases, thus permitting a histologic diagnosis of cardiac sarcoidosis. A histologic diagnosis was made in 4 (36.4%) of 11 patients who exhibited a dilated cardiomyopathy-like clinical picture, in contrast to only 1 (6.7%) of 15 patients in whom conduction disturbances were the major clinical feature and whose left ventricular ejection fraction was within normal limits. CONCLUSIONS The diagnostic rate achieved with biopsy in cardiac sarcoidosis is low; the patients with sarcoidosis and evidence of significant cardiac involvement should be treated for cardiac sarcoidosis despite negative myocardial biopsies for this disease.

Comparison of clinical features and prognosis of cardiac sarcoidosis and idiopathic dilated cardiomyopathy

In the present study, clinical findings of 15 patients with cardiac sarcoidosis presenting as dilated cardiomyopathy were compared with those of 30 consecutive patients with idiopathic dilated cardiomyopathy. The sarcoidosis patients had different clinical features, including female predominance, a high incidence of grave conduction disturbance and abnormal wall thickness, uneven wall motion abnormalities, and perfusion defects preferentially affecting the anteroseptal and apical regions, and poor prognosis compared with those with idiopathic dilated cardiomyopathy.

Use of percutaneous cardiopulmonary support of patients with fulminant myocarditis and cardiogenic shock for improving prognosis.

Percutaneous cardiopulmonary support was used in 9 patients with fulminant myocarditis and cardiogenic shock. Although 2 of the patients died, 7 improved and were able to resume social activities. Percutaneous cardiopulmonary support should be administered routinely to patients with fulminant myocarditis developing into cardiogenic shock.

Diagnostic utility of tenascin‐C for evaluation of the activity of human acute myocarditis

Tenascin‐C (TN‐C) is an extracellular matrix protein that is expressed transiently in close association with tissue remodelling in various body sites. In the heart, TN‐C is only present during early stages of development, is not expressed in the normal adult, but reappears in pathological states. The purpose of this study was to analyse the expression of TN‐C in myocardial tissue from myocarditis patients, and to evaluate the diagnostic value of immunostaining for TN‐C in the assessment of inflammatory activity in biopsy specimens. A total of 113 biopsy specimens obtained from 32 patients with a clinical diagnosis of acute myocarditis were examined by immunohistochemistry and in situ hybridization for TN‐C. The immunostaining was semi‐quantified and compared with histological diagnosis according to the Dallas criteria. Furthermore, serial biopsies from 22 patients were taken during convalescence, and sequential changes in TN‐C levels were analysed. Expression of TN‐C was specifically detected in endomyocardial biopsy specimens from patients with active‐stage inflammation, and disappeared in healed stages. The degree of expression of TN‐C correlated with the severity of histological lesions. These data suggest that TN‐C reflects disease activity in cases of human myocarditis. Immunostaining for TN‐C could enhance the sensitivity and accuracy of diagnosis using biopsy specimens. Copyright

Can β-blocker therapy be withdrawn from patients with dilated cardiomyopathy? ☆ ☆☆ ★

Abstract Background It has yet to be determined whether withdrawing β-blocker therapy from patients with dilated cardiomyopathy (DCM) is safe. Methods The influence of tapering and then stopping metoprolol was clarified in 13 patients with DCM who had been receiving this agent for ≥30 months. Results Seven of the 13 patients deteriorated, including 4 who died suddenly or of congestive heart failure during the 4-month period after metoprolol cessation. Conclusion In patients with DCM in whom β-blocker therapy is effective, withdrawal of these agents may lead to death. We conclude that β-blockers should not be stopped in this patient group. (Am Heart J 1999;137:456-9.)

FABP4 is secreted from adipocytes by adenyl cyclase‐PKA‐ and guanylyl cyclase‐PKG‐dependent lipolytic mechanisms

Fatty acid‐binding protein 4 (FABP4) is expressed in adipocytes, and elevated plasma FABP4 level is associated with obesity‐mediated metabolic phenotype. Postprandial regulation and secretory signaling of FABP4 has been investigated.

Changes in the peripheral eosinophil count in patients with acute eosinophilic myocarditis

In many cases, the diagnosis of eosinophilic myocarditis is suggested by an elevated peripheral blood eosinophil count. However, no detailed studies have been performed on the sequential changes in the initial peripheral blood eosinophil count over the course of the disease. We measured the peripheral blood eosinophil count at the time of presentation in eight patients with eosinophilic myocarditis proven by endomyocardial biopsy and intermittently thereafter. The eosinophil count at the time of onset was ≪500/mm3 in four patients, ≫500/mm3 but ≪1 000/mm3 in three patients, and ≧1 000/mm3 in one patient. In three of the four patients with an initial eosinophil count of ≪500/mm3, an increase to ≧500/mm3 occurred 7–12 days after the onset. The remaining patient did not develop peripheral eosinophilia. In conclusion, in the early stage of eosinophilic myocarditis, peripheral hypereosinophilia is not present initially in some patients, and may not develop during the course of the illness in a subset of these patients.

The effect of ezetimibe on lipid and glucose metabolism after a fat and glucose load

OBJECTIVES The clinical benefit of ezetimibe, an intestinal cholesterol transporter inhibitor, for treatment of postprandial hyperlipidemia was assessed in subjects who ingested a high-fat and high-glucose test meal to mimic westernized diet. METHODS We enrolled 20 male volunteers who had at least one of the following: waist circumference ≥ 85 cm, body mass index ≥ 25 kg/m(2), or triglycerides (TG) from 150 to 400mg/dL. After 4 weeks of treatment with ezetimibe (10mg/day), the subjects ingested a high-fat and high-glucose meal. Then changes in serum lipid and glucose levels were monitored after 0, 2, 4, and 6h, and the area under the curve (AUC) was calculated for the change in each parameter. RESULTS AND CONCLUSION At 4 and 6h postprandially, TG levels were decreased (p<0.01) after 4 weeks of ezetimibe treatment, and the AUC for TG was also decreased (p<0.01). Apolipoprotein B48 (apo-B48) levels at 4 and 6h postprandially were significantly decreased after ezetimibe treatment (p<0.01 and p<0.001, respectively), and the AUC for apo-B48 was also significantly decreased (p<0.01). Blood glucose and insulin levels at 2h postprandially were significantly decreased by ezetimibe (p<0.05). The AUCs for blood glucose and insulin were also significantly decreased (p<0.05 and p<0.01, respectively). Since ezetimibe improved postprandial lipid and glucose metabolism, this drug is likely to be beneficial for dyslipidemia in patients with postprandial metabolic abnormalities.

Efficacy of Atorvastatin Therapy in Ischaemic Heart Disease – Effects on Oxidized Low-density Lipoprotein and Adiponectin

The lipid-lowering and anti-atherosclerotic effects of atorvastatin (10 mg/day) were investigated by measuring changes in the levels of oxidized low-density lipoprotein (LDL), serum lipids (total cholesterol [TC], LDL-cholesterol [LDL-C] and triglycerides [TG]), and in the protein adiponectin. This was undertaken in 22 patients with ischaemic heart disease and serum LDL-C levels > 100 mg/dl. After 3 months of therapy, atorvastatin significantly decreased serum lipids, oxidized LDL was reduced from 457.0 ± 148.6 to 286.9 ± 88.5 nmol/l, and adiponectin increased from 9.7 ± 7.4 to 13.9 ± 9.98 μg/ml. No significant correlation was observed between adiponectin and LDL-C, TG and high-density lipoprotein cholesterol. Atorvastatin therapy was not associated with side-effects, such as myalgia and gastrointestinal disorders, and did not give abnormal laboratory test results. It is concluded that atorvastatin decreases serum lipid and oxidized LDL levels, and increases adiponectin levels in patients with ischaemic heart disease.