Observation of terahertz coherent edge radiation amplified by infrared free-electron laser oscillations.

A coupling device, which can extract coherent edge radiation (CER) from an optical cavity for a free-electron laser (FEL) without damaging the FEL due to diffraction loss, was developed at Nihon University. We successfully observed the CER beam with a power of 1 mW or more in the terahertz range during FEL oscillation. It is revealed that the CER power changed with the detuning of the optical cavity and the dependence of the CER power on the detuning length differs from that of the FEL power. The measured CER spectra indicate that the longitudinal electron distribution in a bunch is modulated by the FEL oscillation with a period corresponding to the FEL slippage length. We herein report the characteristics of the CER with FEL oscillation in detail. These results demonstrate that the CER is excellent tool to reveal the overall effect of FEL interaction on electron distribution in a bunch.

Effect of carperitide on plasma adiponectin levels in acute decompensated heart failure patients with diabetes mellitus.

BACKGROUND: It is reported that adiponectin has a cardioprotective effect and is decreased in type 2 diabetes mellitus (DM). METHODS AND RESULTS: The effect of carperitide (atrial natriuretic peptide: ANP) on plasma adiponectin levels was evaluated in acute decompensated heart failure (ADHF) patients with and without DM. In 47 patients (DM: n=11) who were admitted with ADHF, blood samples were collected before and 7 days after administration of carperitide. The plasma levels of ANP, brain natriuretic peptide (BNP), aldosterone and adiponectin were measured. Plasma adiponectin levels were significantly increased (17.6 +/-1.5 to 19.6 +/-1.8 microg/ml, P=0.0003) concomitant with the increase in ANP and decrease in BNP 7 days after carperitide infusion. Although adiponectin levels before treatment were slightly lower in ADHF patients with DM, the % increase in adiponectin levels was significantly greater in ADHF patients with DM than in those without DM (26.7 vs 6.6%, P=0.007). In the stepwise multivariate analyses, a higher plasma aldosterone levels before treatment (P=0.04) and DM (P=0.01) were significant independent predictors of a greater % increase in adiponectin levels after treatment with carperitide. CONCLUSIONS: Carperitide infusion increases the plasma adiponectin level, especially in ADHF patients with DM.

Effect of atrial natriuretic peptide on adiponectin in patients with heart failure.

BACKGROUND: The adipocyte-specific cytokine adiponectin, has cardioprotective effects, correlates with endogenous cardiac natriuretic peptides and adipocyte has guanylyl cyclase-A receptors of natriuretic peptides. AIMS: To evaluate the effect of carperitide (atrial natriuretic peptide; ANP) on plasma adiponectin in patients with heart failure. METHODS AND RESULTS: Seventy-five patients admitted to our hospital with decompensated heart failure were randomised (1:2) to nitroglycerin (group I: n = 23) or carperitide infusion (group II: n = 52). Blood samples were collected at baseline and after 7 days. Plasma levels of total and high-molecular weight (HMW) adiponectin, ANP and brain natriuretic peptide (BNP) were measured. There were no differences in baseline characteristics between the two groups. In group I, plasma levels of total and HMW adiponectin were significantly decreased (21.1+/-2.5 to 18.6+/-2.5 microg/mL, p<0.05, 12.3+/-1.8 to 10.8+/-1.7 microg/mL, p<0.05, respectively) concomitant with the decrease in plasma levels of ANP and BNP. In group II, plasma levels of total and HMW adiponectin were significantly increased (17.3+/-1.3 to 19.7+/-1.6 microg/mL, p<0.0001, 9.8+/-1.0 to 10.5+/-1.0 microg/mL, p<0.05, respectively) concomitant with the increase in ANP. CONCLUSIONS: These findings indicate that carperitide infusion increases plasma levels of total and HMW adiponectin in patients with heart failure.

Transcardiac increase in norepinephrine and prognosis in patients with chronic heart failure.

BACKGROUND: No previous study has compared the transcardiac gradient of norepinephrine (NE) and the prognosis of patients with chronic heart failure (CHF). AIM: To evaluate the prognostic role of the transcardiac gradient of NE in patients with CHF. METHODS: We measured haemodynamic parameters and plasma levels of NE, brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the aortic root (AO) and coronary sinus (CS) in 356 consecutive patients with CHF. RESULTS: During a median follow-up of 3.5 years, 40 patients died. Transcardiac gradients of BNP (273+/-276 vs. 472+/-433 pg/mL, p<0.0001), NT-proBNP (417+/-700 vs. 928+/-1093 pg/mL, p<0.0001) and NE (114+/-160 vs. 473+/-992 pg/mL, p<0.0001) were significantly higher in non-survivors than survivors. After adjustment for clinical variables associated with CHF including haemodynamics and neurohumoral factors, the transcardiac gradient of NE (p<0.0001) and plasma log NT-proBNP (p<0.0001) were independent prognostic predictors. Among 67 patients in whom 123I-metaiodobenzylguanidine (MIBG) could be performed, transcardiac increase in NE was correlated with the washout rate (r=0.398, p=0.0009) and was a superior predictor of mortality than MIBG parameters on stepwise multivariable Cox proportional hazards regression analyses. CONCLUSION: The transcardiac increase in NE is an independent and useful prognostic predictor for evaluating the prognosis of CHF patients.

Plasma level of cardiotrophin-1 as a prognostic predictor in patients with chronic heart failure.

BACKGROUND: Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines and is increased in patients with chronic heart failure (CHF). AIMS: To evaluate the prognostic role of CT-1 in patients with CHF. METHODS AND RESULTS: We measured the plasma levels of CT-1, brain natriuretic peptide (BNP), and IL-6 in 125 patients with CHF. Patients were monitored for a mean follow-up period of 2.9 years. Plasma levels of CT-1 increased with severity of CHF. There was a significant negative correlation between plasma CT-1 and left ventricular ejection fraction. There was a significant correlation between plasma CT-1 and log IL-6. During the follow-up period, 37 patients died. High plasma levels of CT-1, BNP, and IL-6 were independent predictors of mortality on stepwise multivariate analysis. The hazard ratio for mortality in patients with plasma BNP>170 pg/mL and CT-1>658 fmol/mL was 2.48 (95% confidence interval, 1.217-5.060) compared to those with plasma BNP>170 pg/mL and CT-1<658 fmol/mL (p=0.0124). CONCLUSION: These findings indicate that plasma CT-1 measurement provides additional prognostic information and that combined levels of CT-1 and BNP are more accurate at predicting mortality in patients with CHF than either marker alone.

Direct comparison of transcardiac difference between brain natriuretic peptide (BNP) and N-terminal pro-BNP in patients with chronic heart failure.

BACKGROUND: Direct comparison of transcardiac increase in brain natriuretic peptide (BNP) and NT-pro-BNP has not been performed previously. AIMS: To evaluate the relation between BNP and NT-pro-BNP secretion, plasma levels and renal function. METHODS: We measured the plasma levels of BNP and NT-pro-BNP in the aortic root and coronary sinus in 326 consecutive patients with chronic heart failure (CHF). Patients were divided into two groups [group I: estimated glomerular filtration rate (eGFR)>or=60 mL/min and group II: eGFR<60 mL/min]. RESULTS: The molar level of the transcardiac increase in NT-pro-BNP is lower than that of BNP. There were no differences in haemodynamics or the transcardiac gradient of BNP and NT-pro-BNP between group I and group II. The molar ratio of the plasma NT-pro-BNP to BNP was significantly higher in group II than in group I. By stepwise multivariate analyses, not only the left ventricular (LV) ejection fraction and LV end-diastolic pressure, but also eGFR, LV mass index (LVMI) and haemoglobin were independent predictors of plasma NT-pro-BNP and BNP. CONCLUSION: The molar level of the transcardiac increase in NT-pro-BNP is lower than that of BNP; however, the influence of renal function on plasma NT-pro-BNP is greater than that on BNP.

Comparison of the effects of efonidipine and amlodipine on aldosterone in patients with hypertension.

To prevent cardiovascular disease, targeting aldosterone synthesis and release may be clinically important. Aldosterone production in the adrenal gland is mediated mainly by the T-type calcium channel in vitro. Efonidipine inhibits both L- and T-type Ca channels. To compare the effects of efonidipine on neurohumoral factors with those of amlodipine, an L-type Ca channel blocker, we studied 40 essential hypertensive outpatients. Forty patients who had been administered amlodipine for more than 1 year were treated with efonidipine for 6 months in place of amlodipine. Substituting efonidipine for amlodipine had no significant effect on clinic systolic blood pressure or the plasma levels of brain natriuretic peptide, norepinephrine or active renin. However, the heart rate was significantly decreased (72.0+/-1.3 vs. 69.8+/-1.3 beats/min, p<0.01) and the plasma aldosterone level was also significantly decreased after efonidipine treatment (97.7+/-7.9 vs. 79.7+/-5.6 pg/mL, p<0.0001). Changes in the aldosterone level correlated with the baseline value before the replacement of amlodipine by efonidipine (r=-0.769, p<0.0001). These findings indicate that at the effective antihypertensive doses of efonidipine and amlodipine, efonidipine significantly decreases heart rate and plasma aldosterone level compared with those under amlodipine treatment in hypertensive patients.

Long-term effect of efonidipine therapy on plasma aldosterone and left ventricular mass index in patients with essential hypertension.

A certain percentage of aldosterone (ALD) breakthrough generally occurs in patients with hypertension and chronic heart failure and is an important issue during long-term treatment with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB). It has been reported that efonidipine decreases the plasma levels of ALD. However, the long-term effects of efonidipine on the plasma levels of ALD and the left ventricular mass index (LVMI) remain unknown in patients with hypertension. Sixty stable outpatients with essential hypertension who had received amlodipine and ACE-I or ARB for more than 1 year were randomized into two groups (amlodipine group (n=30): continuous amlodipine treatment at a stable dose; efonidipine group (n=30): amlodipine (5 mg day(-1)) was changed to efonidipine at a dose of 40 mg day(-1)). There was no difference in their baseline characteristics including the LVMI and plasma levels of ALD. In the amlodipine group, there were no significant changes in blood pressure, LVMI or plasma levels of ALD for 18 months. In the efonidipine group, blood pressure did not change after replacement of amlodipine with efonidipine, although there was a significant decrease in the plasma levels of ALD after 6 months. The decrease in ALD was sustained for 18 months and LVMI was significantly decreased after 18 months (121+/-25 vs. 114+/-21 g m(-2), P<0.05). There was a significant correlation between the changes in LVMI and % changes of ALD in the efonidipine group. These findings indicate that the effect of efonidipine on the suppression of plasma ALD was sustained for at least 18 months and that long-term efonidipine therapy decreases LVMI in patients with essential hypertension.

Effect of carvedilol on plasma adiponectin concentration in patients with chronic heart failure.

BACKGROUND: Patients with a high plasma adiponectin have a poor prognosis in chronic heart failure (CHF). Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are reported to increase the plasma adiponectin concentration, but the effect of beta-blockers on plasma adiponectin in patients with CHF remains unknown. METHODS AND RESULTS: Blood samples were collected at before and 6 months after administration of carvedilol in 44 CHF patients. The hemodynamic parameters, echocardiography, plasma concentrations of brain natriuretic peptide (BNP), norepinephrine and adiponectin were measured. Six months after treatment, there were significantly decreased plasma concentrations of adiponectin (15.8 +/-1.4 to 11.0 +/-1.1 microg/ml, P<0.0001), BNP and norepinephrine and increased left ventricular ejection fraction (LVEF). On stepwise multivariable analyses, a higher plasma adiponectin concentration before treatment (rs=-0.561, P<0.0001) was a significant independent predictor of a greater decrease in adiponectin concentration and the decrease in plasma adiponectin concentration was significantly correlated with the improvement of LVEF (r=-0.561, P<0.0001). CONCLUSIONS: These findings indicate that carvedilol decreases plasma adiponectin concentration and that the decrease in plasma adiponectin is associated with the improvement of LVEF after treatment with carvedilol in CHF patients.

Plasma NT-proBNP as a more reliable biomarker of endogenous cardiac natriuretic peptides than BNP during carperitide infusion.

Because both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) competitively bind to natriuretic peptide receptors but not N-terminal proBNP (NT-proBNP), the diagnostic value of BNP as a marker of the severity of heart failure in comparison with NT-proBNP during exogenous ANP (carperitide) infusion remains unclear. Forty-two patients with CHF (NYHA class III or IV) treated with the infusion of carperitide were included in the present study. We measured plasma levels of BNP and NT-proBNP at baseline and after the improvement of symptoms. We also measured these parameters before and 1 hour after stopping the infusion of carperitide. After stopping the infusion of carperitide, the plasma BNP level was significantly decreased by about 20% (394 +/- 53.8 versus 312.8 +/- 46 pg/mL, P < 0.0001) but plasma NT-proBNP did not change (1674.5 +/- 282.1 versus 1777.5 +/- 300.3 pg/mL, P = 0.259). The molar ratio of plasma BNP/NT-proBNP was significantly higher during carperitide infusion (0.74 +/- 0.08) than those at baseline (0.63 +/- 0.06) and after stopping carperitide (0.59 +/- 0.07). During carperitide infusion, plasma NT-proBNP may be a more reliable marker of endogenous cardiac natriuretic peptides than plasmaBNP, which may be increased by carperitide infusion.

Impact of oxidative stress on plasma adiponectin in patients with chronic heart failure.

BACKGROUND: Adiponectin, which is an adipocyte-specific cytokine that has a beneficial effect in cardiovascular disease, may be downregulated by oxidative stress in patients with chronic heart failure (CHF). Plasma levels of both adiponectin and biomarkers of oxidative stress are increased and have a prognostic impact on CHF patients. METHODS AND RESULTS: The plasma adiponectin level was measured in 116 patients with CHF (left ventricular ejection fraction <45%) who underwent cardiac catheterization, and these findings were compared with the atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) levels, hemodynamic parameters and plasma oxidized low-density lipoprotein (oxLDL) level as a marker of oxidative stress. There was no correlation between the plasma adiponectin level and hemodynamic parameters, but there was a positive correlation with the cardiac natriuretic peptides [ANP (r(s)=0.464, p<0.0001) or BNP (r(s)=0.489, p<0.0001)]. There was a significant negative correlation between plasma adiponectin level and oxLDL (r=-0.245, p=0.0079). In the stepwise multivariate analysis, a high level of natriuretic peptide (log BNP) (p=0.0098), and a low level of oxLDL (p=0.0105) were independent predictors of a high adiponectin level in CHF patients. CONCLUSIONS: The plasma adiponectin level is regulated not only by cardiac natriuretic peptides but also by oxidative stress in patients with CHF.

Beneficial effect of perindopril on cardiac sympathetic nerve activity and brain natriuretic peptide in patients with chronic heart failure: comparison with enalapril.

BACKGROUND: In patients with chronic heart failure (CHF), it remains unclear whether perindopril is more cardioprotective than enalapril. METHODS AND RESULTS: Forty-five stable CHF outpatients undergoing conventional therapy including enalapril therapy were randomized to 2 groups [group I (n=24): continuous enalapril treatment; group II (n=21): enalapril was changed to perindopril]. Cardiac sympathetic nerve activity was evaluated using cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and 6 months after treatment. There was no difference in baseline characteristics between the 2 groups. In group I, there were no changes in MIBG parameters, left ventricular ejection fraction (LVEF) or plasma level of brain natriuretic peptide (BNP). In contrast, in group II the delayed heart/mediastinum count ratio was significantly increased (2.0+/-0.07 vs 2.15+/-0.07, p=0.013) and the washout rate was significantly decreased (33.0+/-1.4 vs 30.5+/-1.2, p=0.030) after 6 months compared with the baseline value. In addition, LVEF was significantly increased and the plasma BNP level was significantly decreased. CONCLUSION: These findings suggest that for the treatment of CHF, perindopril is superior to enalapril with respect of cardiac sympathetic nerve activity and BNP.

Direct comparison of transcardiac increase in brain natriuretic peptide (BNP) and N-terminal proBNP and prognosis in patients with chronic heart failure.

BACKGROUND: No previous study has compared the transcardiac gradient of cardiac natriuretic peptides and prognosis. METHODS AND RESULTS: To compare the prognostic value of the transcardiac increase in brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in patients with chronic heart failure (CHF), the hemodynamic parameters and plasma levels of BNP and NT-proBNP were measured in the aortic root (AO) and coronary sinus (CS) in 353 consecutive patients with CHF. During a median follow-up of 2.8 years, 35 patients died. The molar ratio of (CS-AO) NT-proBNP to (CS-AO) BNP correlated with hemodynamic abnormalities and it was significantly higher in non-survivors than in survivors (median value=0.702 vs 0.437, respectively; p=0.0009), suggesting that NT-proBNP is superior to BNP in terms of transcardiac increase. After adjustment for clinical variables associated with CHF, including hemodynamics and an estimated glomerular filtration rate, it was found that only the plasma NT-proBNP level was an independent prognostic predictor, even after considering the transcardiac increases in BNP and NT-proBNP. CONCLUSION: These findings suggest that the transcardiac gradient of NT-proBNP to BNP molar ratio increases with the severity of left ventricular dysfunction, and that plasma NT-proBNP level may be more useful than BNP for evaluating the prognosis of patients with CHF.

Total and high molecular weight adiponectin, haemodynamics, and mortality in patients with chronic heart failure.

AIMS: To evaluate whether plasma high molecular weight (HMW) adiponectin provides prognostic information in addition to that obtained from clinical, haemodynamic, and biochemical variables previously known to be associated with a high mortality in chronic heart failure (CHF) patients. METHODS AND RESULTS: We measured the plasma levels of total and HMW adiponectin, atrial natriuretic peptide, brain natriuretic peptide (BNP), and N-terminal-proBNP (NT-proBNP), and haemodynamic parameters in 449 consecutive CHF patients. Based on body mass index (BMI), patients were classified into three groups: low (<21 kg/m(2), n = 133), normal (21-25 kg/m(2), n = 205), and high (>25 kg/m(2), n = 111). After adjustment for clinical variables associated with CHF including haemodynamics, plasma total adiponectin level was an independent prognostic predictor but HMW adiponectin was not in the overall patient group. On subgroup analyses, in patients with abnormal BMI, plasma total adiponectin level was not an independent prognostic predictor, but in patients with normal BMI, plasma levels of log NT-proBNP (P = 0.017) and log total adiponectin (P = 0.003) were independent prognostic predictors. CONCLUSION: These findings indicate that total adiponectin is more useful for assessing mortality risk than HMW adiponectin and a high plasma total adiponectin is an independent prognostic predictor especially in CHF patients with normal BMI.

Comparison of active renin concentration and plasma renin activity as a prognostic predictor in patients with heart failure.

BACKGROUND: Plasma renin activity (PRA) may be limited to angiotensinogen levels, which decrease in patients with heart failure (HF) because of liver congestion. METHODS AND RESULTS: To evaluate whether the plasma active renin concentration (ARC) is a more useful prognostic predictor than PRA, the plasma levels of ARC, PRA, angiotensin II, aldosterone, brain natriuretic peptide (BNP), norepinephrine, and hemodynamic parameters were measured in 214 consecutive HF patients who were already taking angiotensin-converting enzyme inhibitors (ACEI) or angiotensin-receptor blockers (ARB). Median follow-up period was 1,197 days. Of the clinical variables, including pulmonary capillary wedge pressure, right atrial pressure, left ventricular ejection fraction, and neurohumoral factors, only high plasma levels of log ARC (p<0.0001) and log BNP (p=0.0009), but not log PRA, were significant independent prognostic predictors. Log ARC/PRA ratio was significantly higher in nonsurvivors than in survivors. Log ARC/PRA significantly correlated with pulmonary capillary wedge pressure (r=0.305, p<0.0001), right atrial pressure (r=0.222, p=0.0011), and log BNP (r=0.242, p=0.0004). CONCLUSIONS: Plasma ARC is superior to PRA and a high plasma ARC is an independent prognostic predictor in HF patients who are already receiving ACEI or ARB.

Direct comparison of brain natriuretic peptide (BNP) and N-terminal pro-BNP secretion and extent of coronary artery stenosis in patients with stable coronary artery disease.

BACKGROUND: It is unclear whether coronary artery stenosis affects the secretion of N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) from the heart independent of ventricular dysfunction. Therefore, this study evaluated the relationship between BNP and NT-proBNP secretion, plasma levels and the severity of coronary artery stenosis in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Plasma levels of BNP and NT-proBNP in the aortic root (AO) and coronary sinus (CS) in 251 consecutive patients with stable CAD were measured. The transcardiac increase of NT-proBNP was significantly increased with the severity of coronary artery stenosis (p=0.012), but that of BNP was not (p=0.116). The molar ratio of the (CS-AO) NT-pro-BNP/(CS-AO) BNP increased with the severity of coronary artery stenosis (p=0.019) and decreased after coronary revascularization (p=0.018, n=36). Step-wise multivariate linear regression analyses were used to detect independent predictors of the (CS-AO) NT-proBNP among 10 variables including hemodynamic parameters and the Gensini score, which is a measure of the extent and severity of CAD. Among these variables, left ventricular ejection fraction (p<0.0001), left ventricular end-diastolic pressure (p=0.003) and log Gensini score (p=0.008) were significant independent predictors. CONCLUSION: These findings suggest that the transcardiac increase of NT-proBNP from the heart increases with the severity of coronary artery stenosis independent of hemodynamic overload, and plasma NT-proBNP may be superior to BNP to assess disease severity in CAD patients.

Thermal ablation of FEL irradiation using gypsum as an indicator.

Thermal effects produced in a laser-irradiated sample were studied by micro-X-ray diffraction and micro-Fourier transform infrared spectroscopy (FTIR). Gypsum, transformed into bassanite at 124 degrees C and into anhydrite at 147 degrees C, was used as a thermal indicator. Pit formation by a wavelength-tunable free electron laser (FEL) irradiation on the gypsum pellet maximized at a wavelength of 3.0 microm, 2 mJ/shot, and pits were not detected in those irradiated at 2.6 or 3.8 microm compared with the maximum at 3.0 microm and diminished at 2.0 or 4.0 microm in the human tooth case. Micro-X-ray diffraction and micro-FTIR did not reveal any appreciable bassanite or anhydrite in the irradiated regions. From the laser ablation viewpoint, these results allow the FEL ablation to be considered as plasma or evaporative ones. This study indicated that the micro-pulse of laser was effective to prevent thermal damages of laser irradiation.

Prediction of mortality by high-sensitivity C-reactive protein and brain natriuretic peptide in patients with dilated cardiomyopathy.

BACKGROUND: The prognostic role of serum C-reactive protein (CRP) in chronic heart failure (CHF) patients, especially those with nonischemic dilated cardiomyopathy (DCM), remains unknown. In the present study, whether CRP provides prognostic information in DCM patients was evaluated. METHODS AND RESULTS: Neurohumoral factors and hemodynamics in 84 consecutive DCM patients were measured and these patients were followed up for a mean period of 42 months. During the follow-up period, 23 patients developed cardiac events and 18 patients died of cardiac causes. Using stepwise multivariate Cox proportional hazards regression analyses, log brain natriuretic peptide (BNP) (p = 0.007) and high-sensitivity CRP (hsCRP) > 1 mg/L (p = 0.008) were significant independent predictors of cardiac events. The patients were stratified into 4 groups based on the normal serum concentration of hsCRP (1 mg/L) and median plasma concentration of BNP (110 pg/ml). Survival rates were significantly higher in patients with hsCRP < 1 mg/L and BNP < 110 pg/ml. The hazard ratio of patients with BNP > 110 pg/ml and hsCRP > 1 mg/L was 15.8 (95% confidence interval, 1.9-127.2) compared with those with BNP < 110 pg/ml and hsCRP < 1 mg/L for cardiac death. CONCLUSIONS: Serum hsCRP level is an independent prognostic predictor in patients with DCM and the combination of hsCRP and BNP may be useful for the management of CHF patients with DCM.

Serum level of uric acid, partly secreted from the failing heart, is a prognostic marker in patients with congestive heart failure.

BACKGROUND: A recent study suggested that xanthine oxidase is activated in congestive heart failure (CHF). However, whether uric acid (UA) is secreted from the failing heart remains unknown, so it is currently unclear whether serum UA can provide prognostic information independent of brain natriuretic peptide (BNP). METHODS AND RESULTS: Serum UA was measured in the aortic root (AO) and the coronary sinus (CS) of 74 patients with CHF. The serum UA level was significantly higher in the CS than in the AO. The transcardiac gradient of UA (CS-AO) increased with the severity of CHF, inversely correlated with left ventricular ejection fraction (LVEF) and positively correlated with left ventricular end-diastolic volume index. The plasma levels of norepinephrine, BNP, UA, and LVEF were monitored prospectively in 150 CHF patients for a mean follow-up of 3 years. High plasma levels of UA (p<0.001) and BNP (p<0.001) were shown by multivariate stepwise analysis to be independent predictors of mortality. CONCLUSIONS: High plasma UA level, partly secreted from the failing heart, is a prognostic predictor independent of BNP in patients with CHF. Monitoring a combination of BNP and UA may be useful for the management of patients with CHF.

Relationship between renal function and plasma brain natriuretic peptide in patients with heart failure.

OBJECTIVES: This study sought to evaluate the relationship between brain natriuretic peptide (BNP), renal function, and the severity of congestive heart failure (CHF). BACKGROUND: Both BNP and renal function are prognostic predictors in CHF patients. METHODS: We measured the plasma BNP level in the aortic root and coronary sinus in 366 consecutive patients with CHF. Estimated glomerular filtration rate (eGFR) by the Cockcroft-Gault equation was used as an indicator of renal function. RESULTS: By stepwise multivariate analyses, hemodynamic parameters such as left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP) but not eGFR were independent predictors of a transcardiac increase (coronary sinus-aortic root) in BNP. Regarding the plasma level of BNP in the aortic root, not only LVEF (p < 0.0001) and LVEDP (p < 0.0001) but also eGFR (p < 0.0001) were independent predictors. Patients were divided into two groups, patients with an eGFR > or =60 ml/min (group 1, n = 229) and patients with an eGFR <60 ml/min (group 2, n = 137). There was no difference in LVEF, LVEDP, or the transcardiac gradient of BNP between the two groups, but the plasma level of BNP in the aortic root was approximately two-fold greater in group 2 than in the group 1. CONCLUSIONS: These findings suggest that decreased clearance from the kidney contributes to the elevated BNP in CHF patients with renal dysfunction, especially in patients with an eGFR <60 ml/min.