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Background: Although diuretic resistance leading to residual congestion is a known predictor of a poorer heart failure (HF) prognosis, better therapeutic strategies for effective and safe decongestion have not been established. Methods and Results:In this study, 81 HF patients with fluid retention (despite taking ≥40 mg/day furosemide (FUR)), with an estimated glomerular filtration rate <45 mL/min/1.73 m 2 , were randomized into 2 groups and administered either ≤15 mg/day additive tolvaptan (TLV) or ≤40 mg/day increased FUR for 7 days. Changes in urine volume between baseline and mean urine volume during treatment were significantly higher in the TLV than FUR group (P=0.0003). Although there was no significant decrease in body weight or improved signs and symptoms of congestion between the 2 groups, the increase in serum creatinine on Day 7 from baseline was significantly smaller in the TLV than FUR group (P=0.038). Multiple logistic regression analysis revealed that additive TLV (odds ratio 0.157, 95% confidence interval 0.043-0.605, P=0.001) was an independent clinical factor for improved renal function during treatment compared with increased FUR. Conclusions:In HF patients with residual congestion and renal dysfunction refractory to standard therapy, additive TLV increased urine volume without further renal impairment compared with patients who received an increased dose of FUR.

We investigated the lipid lowering and anti-atherosclerotic effects of atorvastatin in patients with hypercholesterolemia. Thirty patients were given atorvastatin 10 mg daily, and assessed for serum lipids, intima-media thickness (IMT), and brachial-ankle pulse wave velocity (ba-PWV) at the baseline, 6 months, and 12 months. Remnant-like particle-cholesterol (RLP-C), lipoprotein (a) (Lp(a)), and high-sensitivity C-reactive protein (hs-CRP) were measured in some patients at the baseline and at 6 months. Total cholesterol, triglyceride and low-density lipoprotein cholesterol were significantly decreased by 32%, 23% and 44% at 6 months, respectively, and these effects were sustained at 12 months. There was no change in high-density lipoprotein cholesterol. IMT at the baseline was 0.

Myocardial infarction (MI) leads to necrosis and uncontrolled release of cellular content. Binucleated and polyploid cardiomyocytes contain high amounts of chromatin, a DNA polymer of histones which are cytotoxic. We hypothesized that chromatin from necrotic cells accumulates in the non-perfused, ischemic infarct region, causing local high concentrations of cytotoxic histones, thereby potentiating damage to the heart after MI. The endonuclease DNase1 is capable of dispersing extracellular chromatin through linker DNA digestion which could lead to a decrease in local histone concentrations and cytotoxicity. It was confirmed that after permanent coronary artery ligation in mice, extracellular histones accumulated within the infarcted myocardium. In vitro, histones caused myocyte cytotoxicity. For protection against histone-mediated cytotoxicity after MI in vivo, DNase1 was administered within the first 6 h after induction. Indeed, DNase1 accumulation in the infarcted region of the heart was observed, as well as effective disruption of extracellular cytotoxic chromatin and subsequent reduction of high local histone concentrations. Functionally, acute DNase1 treatment resulted in significantly improved left ventricular remodeling in mice as measured by serial echocardiography, while mortality, infarct size and inflammatory parameters were unaffected. Notably, improved cardiomyocyte survival within the infarct region was observed and might account for the protective effects in acutely DNase1-treated animals. Disruption of extracellular cytotoxic chromatin within the infarcted heart by acute DNase1 treatment is a promising approach to protect myocytes from histone-induced cell death and subsequent left ventricular dysfunction after MI.

SummaryThe recommended treatment for eosinophilic myocarditis (EM), pathologically defined as myocardial inflammation with eosinophil infiltration, is corticosteroids. Although EM has a wide variety of clinical features including the degree of eosinophilic infiltration, there have been no reports on how patients with EM should be treated with corticosteroids irrespective of their pathological findings.Thirty-seven consecutive patients with acute myocarditis hospitalized in our institute between 1996-2009 were enrolled. Excluding those with secondary EM such as Loeffler's endocarditis, hypereosinophilic syndrome, and ChurgStrauss Syndrome, together with drug-induced allergic myocarditis, the subjects were divided into 2 groups according to the existence of eosinophils in the myocardial interstitium observed in endomyocardial biopsy specimens. There were no differences in the clinical characteristics on admission between the 2 groups: with (group EM, n = 22) and without (group lymphocytic myocarditis (LM), n = 7) eosinophilic infiltrates irrespective of pathological differences. The treatment policy has been consistent in our institution: intensive hemodynamic observation and support without corticosteroid administration, not only in LM but also in idiopathic EM. There was no significant difference in clinical recovery in the acute phase as indicated by the hospitalization period, left ventricular ejection fraction, or long-term prognosis in EM compared to LM.A conventional management strategy for idiopathic EM without corticosteroid administration can improve the prognosis in the acute and chronic phases, similar to that of LM. (Int Heart J 2011; 52: 110-113) Key words: Eosinophilic myocarditis, Endomyocardial biopsy, Corticosteroid therapy E osinophilic myocarditis (EM) is a relatively rare condition. Although the etiology of EM is not always apparent, several causes have been identified, including hypersensitivity to medicine or some other substance with the heart as the target organ. The spectrum of clinical presentation is wide, and EM is likely to lead to progressive myocardial damage with destruction of the conduction system and then refractory heart failure. It is widely known that EM demonstrates cardiac symptoms with pathological findings of infiltration of eosinophils and degranulation in the myocardium. It has been recommended EM be treated with corticosteroid therapy, according to the guidelines 1) but such is not the case regarding viral myocarditis. In previous reports, some cases of EM, including those with a history of severe left ventricle (LV) dysfunction and aborted sudden death, showed dramatic responses to corticosteroid therapy.2,3) In one case report, an intravenous bolus of methylprednisolone (1 g/day for three days) followed by 1 mg/kg/day oral prednisolone with gradual tapering for one year resulted in an improvement of symptoms, a reduction in the eosinophil count, and increased LV ejection fraction as shown by echocardiography. 4) Also, some reports have shown that conventional managem...