Discharge use of carvedilol is associated with higher survival in Japanese elderly patients with heart failure regardless of left ventricular ejection fraction.

Previous clinical trials have proven beneficial effects of beta-blockers in patients with heart failure (HF) with reduced ejection fraction (EF). However, those studies excluded elderly patients from the subjects or included only a small number of them. We assessed whether beta-blocker treatment with carvedilol improves survival in elderly patients with HF regardless of left ventricular EF (LVEF). We retrospectively analyzed a total of 189 patients older than 75 years who were hospitalized with HF from January 2004 to December 2010. Of these, 84 patients (44%) had been treated with carvedilol at discharge. Patients treated with carvedilol were younger, were less likely to have chronic obstructive pulmonary disease, and had lower LVEF compared with those without carvedilol (all P < 0.05). During the median follow-up of 2.5 years after discharge, 92 patients died. Cox hazard analysis showed that, even after adjustment for covariates, carvedilol significantly decreased all-cause mortality in this cohort (P < 0.01). Furthermore, a beneficial effect on outcome was found in patients with reduced (LVEF ≤ 40%) and preserved (LVEF > 40%) EF (all P < 0.05). In conclusion, Beta-blockers may provide beneficial effects on Japanese elderly patients with HF regardless of LVEF.

Effects of cilnidipine on serum uric acid level and urinary nitrogen monoxide excretion in patients with hypertension.

The effects of cilnidipine on the serum uric acid level and urinary NO excretion in hypertensive patients were investigated. Blood and urine samples of 16 hypertensive outpatients were collected before and 2 months after cilnidipine therapy (10 mg). The serum uric acid level decreased significantly after cilnidipine treatment, while the uric acid-creatinine clearance ratio was unaffected. The cilnidipine medication produced a significant increase in urinary NO excretion, although amlodipine did not change it significantly. Therefore, cilnidipine has a profound antihypertensive effect and may reduce the serum uric acid level and increase NO production in the kidney.

Right- and left-sided carcinoid heart disease without intracardiac shunting.

We present a case of a 54-year-old man with carcinoid heart disease and mitral valve involvement. He had hepatic carcinoid with an extremely elevated urinary excretion of 5-hydroxyindole acetic acid and was referred to our division for shortness of breath and leg edema. Transthoracic echocardiography showed the thickened and retracted tricuspid valve leaflets and severe tricuspid regurgitation. Moderate mitral regurgitation was observed, with the involvement of mitral valve leaflets. A patent foramen ovale was not detected on transesophageal echocardiography. The extremely high concentration of circulating serotonin and/or other vasoactive substances may have contributed to left- as well as right-sided carcinoid heart disease.

Addition of losartan to angiotensin-converting enzyme inhibitors improves insulin resistance in patients with chronic heart failure treated without ß-blockers.

BACKGROUND: Angiotensin II and insulin resistance (IR) have clinical implications in the pathophysiology of chronic heart failure (CHF). However, it is still unclear whether the combination of an angiotensin-receptor blocker and angiotensin-converting enzyme inhibitor (ACEI) improves IR in CHF patients who do not receive ß-blockers. Thus, the aim of the present study was to evaluate the effects of losartan on glucose metabolism and inflammatory cytokines in CHF patients treated with ACEI but not ß-blockers. METHODS AND RESULTS: The effect of losartan treatment for 16 weeks on IR was analyzed in 16 CHF patients in a randomized crossover trial. Insulin level and homeostasis model IR index (HOMA-IR) decreased significantly (P<0.05), but fasting plasma glucose did not change significantly. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels were significantly decreased with losartan (P<0.05). Furthermore, the changes in IL-6 and MCP-1 levels were significantly correlated with the reduction in HOMA-IR (P<0.05), but the change in TNF-α levels was not significantly correlated. CONCLUSIONS: The addition of losartan to ACEI therapy improved IR and decreased inflammatory cytokines in CHF patients who did not receive ß-blockers.

Uric acid-lowering treatment with benzbromarone in patients with heart failure: a double-blind placebo-controlled crossover preliminary study.

BACKGROUND: Hyperuricemia is common in chronic heart failure (CHF), and it is a strong independent marker of prognosis. Upregulated xanthine oxidase (XO) activity and impaired renal excretion have been shown to account for increased serum uric acid (UA) levels in CHF. Therapeutic interventions with allopurinol to reduce UA levels by XO inhibition have been shown to be beneficial. Discussions are ongoing whether UA itself is actively involved or it is a mere marker of upregulated XO activity within CHF pathophysiology. Therefore, the aim of this study was to test the effect of lowering UA by uricosuric treatment without XO inhibition on hemodynamic and metabolic characteristics of CHF. Impaired renal excretion of UA was taken into account. METHODS AND RESULTS: Serum UA (SUA), urinary UA (uUA) excretion, and renal clearance test for UA (Cl(UA)) were measured in 82 patients with CHF. SUA was significantly increased compared with controls of similar age (control, 5.45+/-0.70 mg/dL; New York Heart Association I, 6.48+/-1.70 mg/dL; New York Heart Association II, 7.34+/-1.94 mg/dL; New York Heart Association III, 7.61+/-2.11 mg/dL; P<0.01). Patients with CHF showed lower uUA excretion and Cl(UA). On multivariate analysis, insulin, brain natriuretic peptide (P<0.01), and creatinine levels (P=0.05) showed independent correlation with SUA. The treatment effect of the uricosuric agent benzbromarone was tested in 14 patients with CHF with hyperuricemia in a double-blind, placebo-controlled, randomized crossover study design. Benzbromarone significantly decreased SUA (P<0.01). Brain natriuretic peptide, left ventricular ejection fraction, and dimensions in echocardiographic assessment did not change after benzbromarone therapy. In contrast, fasting insulin (placebo, 18.8+/-8.9 microU/mL; benzbromarone, 11.0+/-6.2 microU/mL; P<0.05), homeostasis model assessment of insulin resistance index (placebo, 5.4+/-2.6; benzbromarone, 3.0+/-1.7; P<0.05), and tumor necrosis factor-alpha (placebo, 2.59+/-0.63 pg/mL; benzbromarone, 2.14+/-0.51 pg/mL; P<0.05) improved after benzbromarone, and the changes in tumor necrosis factor-alpha levels were correlated with reduction of SUA (P<0.05). CONCLUSIONS: These results show that UA lowering without XO inhibition may not have an effect on hemodynamic impairment in CHF pathophysiology. To the extent that these data are correct, this finding suggests that upregulated XO activity rather than UA itself is actively involved in hemodynamic impairment in CHF. Clinical Trial Registration- clinical trials.gov. Identifier: NCT00422318.

A simple risk score to predict in-hospital death of elderly patients with acute decompensated heart failure--hypoalbuminemia as an additional prognostic factor.

BACKGROUND: Risk stratification for elderly patients with acute decompensated heart failure (ADHF) may help clinicians to select the appropriate therapy and raise the quality of care. METHODS AND RESULTS: The present study enrolled 349 patients aged over 65 years who were hospitalized with ADHF from January 2004 to October 2008. Five independent prognostic factors were identified by multivariate logistic regression analysis, and each factor was assigned a number of points proportional to its regression coefficient: prior heart failure hospitalization (2 points), sodium or=35 mg/dl (2 points), albumin or=980 pg/ml (2 points); in particular, hypoalbuminemia was identified as the strongest prognostic factor. The patients were stratified into 3 groups: low risk (0-4 points), moderate risk (5-7 points), and high risk (8-11 points). The respective in-hospital mortality rates were 1.6%, 15.8%, and 42.1% (P<0.05). CONCLUSIONS: In addition to known prognostic factors, hypoalbuminemia may provide important information for elderly patients with ADHF. A simple risk score may help to stratify the risk of in-hospital mortality and contribute to better clinical management of these elderly patients.

Appropriate use of nasal continuous positive airway pressure decreases elevated C-reactive protein in patients with obstructive sleep apnea.

BACKGROUND: C-reactive protein (CRP) is an important risk factor for cardiovascular disease. Furthermore, it has been reported that levels of CRP are increased in patients with obstructive sleep apnea (OSA). The aim of this study was to examine the effects of long-term therapy with nasal continuous positive airway pressure (nCPAP) on CRP levels and to investigate whether compliance with nCPAP therapy more effectively attenuated markers of systemic inflammation in patients with OSA. METHODS AND RESULTS: Fifty-five patients (mean [+/- SEM] age, 55 +/- 2 years; 44 male patients, 11 female patients) with newly diagnosed moderate-to-severe OSA (apnea-hypopnea index > 20 events/h) were studied before and after 6 months of nCPAP treatment. There was a significant reduction in CRP levels after nCPAP therapy (before nCPAP therapy, 0.23 +/- 0.03 mg/dL; after nCPAP therapy, 0.17 +/- 0.02 mg/dL; p < 0.01). Additionally, we divided these patients into two groups based on adherence to nCPAP therapy. A group of patients using nCPAP > 4 h/d and > 5 d/wk were designated as the good compliance group. The decrease in CRP concentration was significant (before nCPAP therapy, 0.23 +/- 0.04 mg/dL; after nCPAP therapy, 0.16 +/- 0.03 mg/dL; p < 0.05) in the good compliance group but not in the poor compliance group (before nCPAP therapy, 0.24 +/- 0.05 mg/dL; after nCPAP therapy, 0.20 +/- 0.05 mg/dL; p = 0.21). Furthermore, we divided those patients into a high CRP group (>/= 0.2 mg/dL) and a normal CRP group (< 0.2 mg/dL) before nCPAP therapy. The significant decrease in CRP levels in the good compliance group was evident only in those patients with an initially elevated CRP level (before nCPAP therapy, 0.48 +/- 0.08 mg/dL; after nCPAP therapy, 0.29 +/- 0.06 mg/dL; p < 0.05). CONCLUSION: Appropriate use of nCPAP in patients with OSA may be required to decrease elevated CRP levels, with possible implications for cardiovascular morbidity and mortality.

Serum adiponectin levels and lifestyle factors in Japanese men.

Adiponectin plays an important role in the development of various lifestyle-related diseases such as obesity, hypertension, type II diabetes mellitus, hyperlipidemia, and metabolic syndrome, leading to the development of heart and vascular diseases. However, the determinants that affect circulating adiponectin levels, including lifestyle factors, have still not been thoroughly investigated, in a general male population in particular. A total of 109 healthy Japanese male subjects (mean age, 55 +/- 14 years) with constant lifestyles were enrolled. All were on no medication. Fasting serum adiponectin levels were measured with an enzyme-linked immunosorbent assay. Each subject's lifestyle was assessed by the self-administered Breslow Questionnaire (a well-established method to estimate various lifestyles) with minor modifications. Partial correlation analysis for serum adiponectin levels, after controlling age and all lifestyle factors, revealed a significant and independent negative correlation between serum adiponectin levels and body mass index (BMI) (r = -0.222, P = 0.025), and a significant and independent positive correlation between serum adiponectin levels and sleep duration (r = 0.252, P = 0.011). No significant correlations were observed between adiponectin and other lifestyle factors. These data suggest that increased BMI and shorter sleep duration may be significant independent risks for low serum adiponectin levels in healthy males. Therefore, these factors may be intervention targets to modulate adiponectin to its proper levels for the prevention of cardiovascular disorders.

Autoperipheral blood mononuclear cell transplantation improved giant ulcers due to chronic arteriosclerosis obliterans.

We report the case of a 74-year-old man with Fontaine stage IV chronic arteriosclerosis obliterans who had been suffering from inveterate giant skin ulcers on the dorsum and heel of the right foot. As conventional medical treatments had not improved these ulcers and surgical treatment was considered unfeasible, amputation of the right lower limb below the knee appeared to represent the only option. The patient was admitted to Tottori University Hospital to attempt a new angiogenic therapy using auto-mononuclear cell transplantation to avoid amputation. On admission, neither right ankle blood pressure nor transcutaneous partial pressure of oxygen at the right toe were detectable. The patient had a history of multiple cerebral infarctions, and collection of mononuclear cells from bone marrow was considered too difficult, so collection of peripheral blood mononuclear cells was selected. Transcutaneous partial pressure of oxygen and skin temperature in the treated limb started to improve from 2 weeks after implantation. Ulcer size was recognizably reduced by 1 month after treatment. Partial auto-skin implantation on the right heel was performed 2 months after treatment, and the giant skin ulcer was finally completely covered. No adverse effects were noted during follow-up lasting 1 year. These results suggest that peripheral blood mononuclear cell implantation may offer a suitable alternative rescue therapy for patients with critical limb ischemia whose general condition is not good.

Traumatic fracture of the stapes and perilymph fistula: report of a case.

We herein report a case of traumatic fracture of the stapes accompanying vestibular window rupture with perilymph fistula, and its diagnosis and surgical procedure were discussed. In the present case, a direct force through the external auditory canal damaged not only the ossicular chain but also the vestibular window. On the exploratory tympanotomy, the complete dislocation and fracture of the stapes with a relatively huge rupture was confirmed. Perilymph fistula was repaired with a connective tissue graft, which was inserted between disrupted vestibular window and the long process of the incus. Vestibular dysfunctions disappeared within 3 days, and a satisfactory audiologic result was obtained one month after surgery.

Status of endothelial dependent vasodilation in patients with hyperuricemia.

Hyperuricemia has been associated with an increased risk for cardiovascular disease and increased mortality. However, the biologic mechanisms that link elevated serum uric acid to cardiovascular disease are uncertain. This study tested the hypothesis that elevated serum uric acid is associated with impaired endothelial function in hyperuricemic patients without any overt cardiovascular disease. Seventeen male patients with hyperuricemia (mean age 42+/-4 years) and 9 control subjects (mean age 45+/-5 years) were studied. All subjects were nonsmokers. All patients had never been treated for hyperuricemia, were on no medications, and were free of any other known diseases. Endothelial function was evaluated by flow-mediated dilation measured by ultrasound. Flow-mediated dilation was significantly impaired in patients with hyperuricemia (4.0+/-0.7%) compared with control subjects (6.4+/-0.8%) (p=0.044). Flow-mediated dilation correlated inversely with uric acid levels (r=-0.4, p=0.05). Nitrate-induced dilation was 12.3+/-1.0% in patients with hyperuricemia and 11.8+/-2.3% in control subjects (p=0.82). Impaired endothelial-dependent vasodilation is present in hyperuricemic patients even in the absence of any overt cardiovascular disease. The elevated serum uric acid, per se, may constitute a novel risk factor for endothelial dysfunction.

Recurrent extrusion of cochlear implant at an interval of 5 years.

OBJECTIVE: To describe two different types of device extrusion occurring in the same patient 1 and 6 years after cochlear implantation and to discuss the relation between the two extrusions and problems of cochlear implantation in patients with chronic suppurative otitis media. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENT AND INTERVENTIONS: The patient was a 52-year-old man with profound hearing loss in the right ear caused by chronic otitis media and deafness in the left ear caused by removal of an acoustic neuroma. Surgery for cleaning the tympanic cavity and reconstruction of the bony canal after previous radical mastoidectomy was performed in the right ear first. One year later, cochlear implantation was performed in this ear. RESULTS: One year after implantation, the anterior edge of the internal device of cochlear implant was exposed along the skin incision. This site was stable after corrective surgery. Five years after this operation, however, the posterior edge of the internal device extruded, accompanied by infection around the device. CONCLUSION: The two extrusions occurred with a long interval in between and at two different sites. The first extrusion occurred along the skin incision, and the second extrusion occurred away from the skin incision with infection around the device. The authors assumed that the first and the second extrusion occurred independently; the first extrusion was caused by insufficient blood supply resulting from scar formation from repeated mastoid operations and by pressure on the skin from the internal and external devices, and the second extrusion was caused by proliferated tissue pushing the device upward and against the skin as a result of chronic middle ear infection. The clinical course indicates that sufficiently long follow-up periods are needed to determine the usefulness of the prevention techniques for cochlear implantation in patients with chronic suppurative otitis media.