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BACKGROUND AND PURPOSE: To assess effects of long-term anemia management on left ventricular hypertrophy in patients with chronic kidney disease (CKD) not on dialysis, we performed secondary outcome analyses of a randomized controlled study that evaluated effects of anemia management with erythropoiesis stimulating agents in this population. METHODS AND SUBJECTS: Subjects [hemoglobin (Hb)<10.0 g/dL, 2.0 ≤ serum creatinine<6.0mg/dL] were randomized either to high Hb (11.0 ≤ target Hb ≤ 13.0 g/dL with darbepoetin alfa), or to low Hb group (9.0 ≤ target Hb ≤ 11.0 g/dL with recombinant human erythropoietin), and followed up to 48 weeks. Data from echocardiographic evaluation and values of neurohumoral factors associated with heart failure were assessed in subjects whose data were evaluable both at the baseline and at the end point. RESULTS: The high Hb group achieved target range Hb levels (12.1 ± 1.1g/dL, at 32 weeks, N=111), which was significantly higher (p<0.001) than the low Hb group (N=95). Though blood pressure and renal function changes were similar between the groups, left ventricular diastolic dimension was significantly decreased only in the high Hb group (p < 0.001), and the change in left ventricular mass index (LVMI) correlated coarsely but significantly with the achieved Hb levels (r = 0.147, p = 0.032). The higher Hb levels were associated with greater reduction in LVMI and left ventricular wall thickness, and the lower Hb levels with the greater increase in human arterial- or brain natriuretic polypeptide levels. CONCLUSIONS: Anemia correction targeting modestly higher Hb levels better preserves cardiac function in CKD patients not on dialysis.

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Anemia is a significant risk factor for patients with chronic kidney disease (CKD). Here, we investigated the effects of anemia correction on cardiac functions in CKD patients. Pre-dialysis CKD patients (n = 171) without known risk factors for cardiovascular disease (CVD) other than CKD with hemoglobin (Hb) concentrations < 10.0 g/dL were enrolled for evaluation of cardiac functions and biomarkers before and after the 16-week treatment of erythropoiesis-stimulating agents. The treatment significantly increased Hb concentrations in all patients who completed the study (n = 143, 8.91 ± 0.87 versus 11.27 ± 1.31 g/dL; n < 0.001) and among patients whose echocardiograms were available for evaluation (n = 77, 8.92 ± 0.94 versus 11.24 ± 1.13 g/dL; P < 0.001). The left ventricular mass index (LVMI) was decreased (121.3 ± 25.8 versus 114.7 ± 25.1 g/m(2), n = 77, P = 0.012) and significant correlation between the change in the LVMI and Hb concentration was noted (P = 0.011). The levels of B-type natriuretic peptide and human atrial natriuretic peptide, and the cardio-thoracic ratio were significantly increased among subjects with Hb concentrations < 11.0 g/dL at completion of the study. The changes in these parameters were significantly correlated with the Hb concentrations (P = 0.033, P = 0.011, and P < 0.001, respectively). No significant differences were observed in the electrocardiographic parameters. Correcting Hb levels higher than those conventionally recommended reduced left ventricular hypertrophy and myocardial stress, lowering risks for CVD in pre-dialysis CKD patients.

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Correcting anemia in patients with chronic kidney disease (CKD) to higher hemoglobin (Hb) levels may be associated with increased risk. No optimal target for Hb has been established. This controlled study examined 321 patients with CKD who were not on dialysis, had a Hb level of <10g/dL, and a serum creatinine of 2.0 to 6.0mg/dL. They were randomized into two target Hb groups: 161 to high Hb (11.0-13.0g/dL) to receive darbepoetin alfa and low Hb to 160 (9.0-11.0g/dL) to receive recombinant erythropoietin. The study lasted 48weeks. Of 154 and 153 patients with adverse events, cardiovascular adverse events developed in 42 and 51 patients in the high and low Hb groups, respectively, with no significant difference in the incidence. All quality of life scores improved in the high Hb group and vitality improved significantly more with high Hb (P=0.025). The left ventricular mass index (LVMI) remained stable in the low Hb group, but there was a significant decrease in LVMI in the high group (P<0.001). There were no safety concerns with targeting a higher Hb level during the 48weeks of this study. Patients with a higher Hb target had comparatively better outcomes with respect to quality of life and LVMI.

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BACKGROUND: Anemia is common among patients with chronic kidney disease (CKD). The introduction of erythropoietin treatment has changed anemia management, but the therapeutic hemoglobin (Hb) target is still under debate, and clinical evidence for its effect on cardiac functions and QOL is sparse. METHODS: A 16-week dose-response study and a 32-week follow-Up study were combined. After correcting anemia of less than 10 g/dl in pre-dialysis Japanese CKD patients, a higher Hb target (12-13 g/dl) by darbepoetin alfa (DPO) was compared with the conventional Hb target by epoetin alfa (EPO). Outcomes were anemia correction, management of the left ventricular mass index (LVMI) and QOL scores. RESULTS: No significant difference was seen in Hb at baseline and week 16, but a significant difference was recorded at week 34 (12.34 +/- 0.93 g/dl for DPO and 10.43 +/- 0.90 g/dl for EPO). In both groups, LVMI decreased similarly until week 16, but the decrease of EPO was retarded, and a significant difference between LVMI was seen only in DPO at week 34 (100.7 +/- 16.6 g/m(2) for DPO and 110.9 +/- 25.2 g/m(2) for EPO). Relationships between Hb and LVMI change at week 34 were examined by stratifying Hb into four groups (Hb <10 g/dl, 10 g/dl < or = Hb <11 g/dl, 11 g/dl < or = Hb <12 g/dl and 12 g/dl < or = Hb), and a decrease of LVMI was prominent in the 12 g/dl < or = Hb group. Correction of anemia to 11 g/dl or more led to improved QOL scores. No safety difference was observed among the treatments. CONCLUSIONS: Targeting a higher Hb around 12 g/dl was more beneficial than targeting conventional Hb in terms of reduction of LVMI and QOL. Further studies to determine the appropriate Hb target are necessary.

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A 32 year-old woman with bilateral hilar lymphadenopathy suffered from syncopal attacks after her first delivery. Electrocardiograms showed complete atrioventricular block (AVB) and myocardial scintigrams demonstrated a decreased uptake in the anteroseptal area. She was diagnosed as having postpartal cardiac acceleration of sarcoidosis. Because she rejected permanent pacemaker implantation, we started steroid therapy under temporary pacing. Fortunately, the treatment was very effective. Even after tapering-off of the steroid, the AVB has never reappeared. Permanent pacemaker implantation with subsequent steroid therapy is generally recommended for complete AVB due to cardiac sarcoidosis. However, steroid therapy alone can be considered for some selected cases.

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Atrial fibrillation (AF) is well known to be male-dominant. Female sex hormones may be involved, since very few premenopausal women experience AF. However, a possible gender difference in older subjects has not been fully elucidated yet. We retrospectively reviewed the symptoms of 133 patients (111 males and 22 females) with paroxysmal AF (PAF) from the medical records at our hospital from 1995 to 2000, and classified the patients according to the time of the attacks as day type, night type, or unspecific type. In females, the age at the first diagnosis of PAF was significantly higher (males: 57 +/- 1 year old, females: 65 +/- 2 years old; P = 0.006) and the proportion of cases younger than 61 years old was significantly smaller (63%, 32%; P = 0.007). As in previous reports, the female group had more cases with unspecific type (26.5%, 47.6%) or with long duration (> 24 hours) (16.9%, 37.5%). In contrast to these published results, fewer women (10.5%) had frequent attacks (more than twice a week) than men (39.8%). The incidence of regular alcohol consumption, one of the most important PAF triggers, was significantly higher in men than women (84.7%, 13.6%; P < 0.0001). Even when we focused on cases older than 60 years old, the female group still had more cases with unspecific type (53.3% versus 23.1%) or with long duration (27.3% versus 14.7%) than men, and fewer with frequent attacks (0% versus 51.7%) or regular alcohol consumption (6.7% versus 82.9%; P < 0.0001) than men. The gender difference in symptoms related to PAF may depend not only on sex hormones, but also on intrinsic or social gender differences.

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A 15-year-old girl developed subacute constrictive pericarditis following successful surgical repair of double-chambered right ventricle. Two weeks after surgery, the patient had massive pericardial effusion, which acutely progressed to constrictive pericarditis with the symptoms of cardiac tamponade. Further surgery was necessary to resect the parietal pericardium. No blood transfusion was required for this patient, who was a Jehovah's Witness. She was doing well 9 months after the second operation, with residual pericardium of normal thickness.

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Calcification in the pulmonary artery (PA) occurs in rare cases. There have been no studies of calcification in the PA at the site of its contact with a left coronary artery bypass graft (CABG). In the present study, X-ray computed tomography (CT) was employed for examination of such calcification. The subjects were 53 patients (49 male and 4 female, mean age of 56.7 years) who underwent 74 left CABGs (69 saphenous veins and five internal thoracic arteries). Following surgery, non-contrasted CT was performed from the lower level of the aortic arch to the lower boundary of the left ventricle at 5-mm horizontal intervals, and contrasted CT was performed at the level of the PA; this procedure was repeated at approximately six-month intervals after the operation. In addition, aortography and selective graft angiography were carried out at 7.6 months postoperatively. The inner diameter of the grafts and the levels of serum cholesterol were also examined. Calcification in the PA was detected in 24 cases (all of them saphenous vein grafts), but graft angiography found no stenosis in those sites. Calcification size varied from 1 mm to 14 mm, with 10 of the cases at or exceeding 10 mm and showing high density. Only three of the cases enlarged with time. Calcification appeared at 2.9 to 54.3 months postoperatively and the mean time of onset was 10.0 +/- 15.7 months. The mean age of the patients with PA calcification was 58.7 +/- 5.9 years while that of the patients without calcification was 57.3 +/- 10.0 years. Graft diameter was 5.9 +/- 1.9 mm in the former group and 5.6 +/- 1.7 mm in the latter. Serum cholesterol level was 235 +/- 32 mg/dl in the former group and 243 +/- 42 mg/dl in the latter. There were three cases of occlusion in the calcification group, and four in the other. There were no significant intergroup differences in these four parameters. The incidence of CT-detected calcification in the PA was found to be high at its point of contact with saphenous vein grafts.