Survival Rate of Cells Sent by a Low Mechanical Load Tube Pump: The "Ring Pump".

A ring pump (RP) is a useful tool for microchannels and automated cell culturing. We have been developing RPs (a full-press ring pump, FRP; and a mid-press ring pump, MRP). However, damage to cells which were sent by the RP and the MRP was not investigated, and no other studies have compared the damage to cells between RPs and peristaltic pumps (PPs). Therefore, first, we evaluated the damage to cells that were sent by a small size FRP (s-FRP) and small size MRPs (s-MRPs; gap = 25 or 50 µm, respectively). "Small size" means that the s-FRP and the s-MRPs are suitable for microchannel-scale applications. The survival rate of cells sent by the s-MRPs was higher than those sent by the s-FRP, and less damage caused by the former. Second, we compared the survival rate of cells that were sent by a large size FRP (l-FRP), a large size MRP (l-MRP) (gap = 50 µm) and a PP. "Large size" means that the l-FRP and the l-MRP are suitable for automated cell culture system applications. We could not confirm any differences among the cell survival rates. On the other hand, when cells suspended in Dulbecco's phosphate-buffered saline solution were circulated with the l-MRP (gap = 50 µm) and the PP, we confirmed a difference in cell survival rate, and less damage caused by the former.

Indolent primary effusion lymphoma-like lymphoma in the pericardium: A case report and review of the literature.

We report a rare case of a 75-year-old man with a history of mild-to-moderate pericardial effusion that was detected on echocardiography performed in October 2011 when the patient was 69 years old. Follow-up echocardiography was performed every 6 months thereafter, showing that the pericardial effusion gradually subsided. However, in April 2017 he started experiencing several episodes of dyspnea, which prompted him to visit our hospital's outpatient department on June 22, 2017. Echocardiography revealed a large amount of pericardial effusion; thus, he was immediately hospitalized. After undergoing pericardiocentesis and drainage, 1740-ml of bloody pericardial fluid was collected. Serum antibody tests for human immunodeficiency virus, hepatitis C virus, and human herpes virus 8 were negative, whereas that for Epstein-Barr virus (EBV) was positive, indicating a prior infection. Cytopathological examination, immunocytochemical staining, lymphocyte surface marker analysis, and cytogenetic assessment were performed. EBV-encoded small ribonucleic acid in situ hybridization was negative. He was diagnosed with primary effusion lymphoma (PEL)-like lymphoma (LL) and was treated with 8 doses of rituximab 375 mg/m2 over a 2-month period. He has remained in complete response for the past 12 months. Our case shows the possibility of long-term existence of indolent PEL-LL in patients with mild-to-moderate pericardial effusion. .

Prognostic value of serial measurements of highly sensitive cardiac troponin I in stable outpatients with nonischemic chronic heart failure.

BACKGROUND: Cardiac troponin I (cTnI) is a useful biomarker in patients with chronic heart failure (CHF), and a highly sensitive cTnI (hs-cTnI) commercial assay has become available. However, the prognostic role of serial measurements of hs-cTnI in stable outpatients with CHF remains unknown. METHODS: At entry to the study, we evaluated 95 stable outpatients with nonischemic CHF showing a serum hs-cTnI (Centaur TnI-Ultra [Siemens Medical Solution Diagnostics, New York, NY], lower limit of detection 0.006 ng/mL) value ≥0.006 ng/mL. To evaluate the role of repetitive measurements of hs-cTnI, we performed echocardiography and measured serum levels of cTnI and N-terminal proBNP at baseline and 6 months later and then prospectively followed up these patients for 4.25 years. RESULTS: During long-term follow-up, there were 27 cardiac deaths. On multivariate analyses, high plasma N-terminal pro-brain natriuretic peptide (≥711 pg/mL, P = .0008), high serum hs-cTnI at baseline (≥0.03 ng/mL, P = .0011), and an increase in hs-cTnI (Δhs-cTnI ≥0 ng/mL, P = .022) after 6 months were independent significant prognostic predictors. The hazard ratio for mortality of patients with high hs-cTnI (≥0.03 ng/mL) and an increase in hs-cTnI (Δhs-cTnI ≥0 ng/mL) was 3.59 (95% CI 1.3-9.9, P = .014) compared with that of those with high hs-cTnI (≥0.03 ng/mL) and a decrease in hs-cTnI (Δhs-cTnI <0 ng/mL). CONCLUSIONS: These findings indicated that not only the serum concentration of hs-cTnI at baseline but also an increase in hs-cTnI were independent and useful prognostic predictors in patients with nonischemic CHF.

Relationship between biological variation in B-type natriuretic peptide and plasma renin concentration in stable outpatients with dilated cardiomyopathy.

BACKGROUND: The aim of the present study was to interpret B-type natriuretic peptide (BNP) level in outpatients with stable chronic heart failure (CHF); it is important to clarify whether the change in BNP represents disease progression or a range of biological variation. METHODS AND RESULTS: To compare biological variation in BNP and biological variation in factors of the renin-angiotensin-aldosterone system (RAS) in stable CHF patients with dilated cardiomyopathy (DCM), the BNP plasma levels and RAS factors were measured in 115 stable outpatients with DCM. According to stepwise multivariate analysis, plasma BNP at baseline (P=0.005), presence of atrial fibrillation (P=0.015), and a high biological variation in plasma renin concentration (PRC; P=0.002) were significant independent dominant factors related to a high biological variation in BNP. Although there was no change in body weight or blood pressure during the 2-month study period, the % change in hematocrit was negatively correlated with % change in BNP (r=-0.327, P=0.0008), and positively correlated with % change in PRC (r=0.671, P=0.001). CONCLUSIONS: There was a significant relationship between biological variation in BNP and biological variation in PRC, suggesting that the physiological interaction between the natriuretic peptide system and RAS may contribute to the biological variation in plasma BNP in stable outpatients with DCM.

Prognostic role of high-sensitivity cardiac troponin T in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Cardiac troponin T (cTnT) is useful biomarker in patients with chronic heart failure (CHF). However, its clinical use is limited by the low sensitivity of the conventional commercial assay system. Recently, a highly sensitive cTnT (hs-cTnT) assay has become commercially available. METHODS AND RESULTS: To compare the prognostic value of conventional cTnT and hs-cTnT in patients with nonischemic dilated cardiomyopathy (DCM), hemodynamic parameters and the serum levels of conventional cTnT, hs-cTnT and brain natriuretic peptide (BNP) were measured in 85 consecutive CHF patients with nonischemic DCM and then these patients were followed for a mean of 4.1 years. During long-term follow up, there were 20 cardiac deaths. In 85 DCM patients, conventional cTnT was elevated (≥0.03ng/ml) in 4 patients (5%) and hs-cTnT was elevated (≥0.01ng/ml) in 46 patients (54%). In non-survivors (n=20), conventional cTnT was elevated (≥0.03ng/ml) in 2 patients (2%) and hs-cTnT was elevated (≥0.01ng/ml) in 17 patients (85%). In the stepwise multivariate analyses, a high plasma level of BNP (P=0.002), low left ventricular ejection fraction (<30%, P=0.012) and high hs-cTnT (≥0.01ng/ml, P=0.006) were independent significant prognostic predictors, but conventional cTnT (≥0.03ng/ml) was not. CONCLUSIONS: The findings of the present study indicated that a high serum concentration of hs-cTnT is a useful prognostic predictor that is independent of LVEF or BNP in CHF patients with non-ischemic DCM, suggesting that an increased hs-cTnT concentration sensitively reflects ongoing myocardial damage.

Biological variation of brain natriuretic peptide and cardiac events in stable outpatients with nonischemic chronic heart failure.

BACKGROUND: To evaluate the biological variation and prognostic value of brain natriuretic peptide (BNP) for stable outpatients with nonischemic chronic heart failure (NICHF). METHODS AND RESULTS: Biological variation in BNP was evaluated using an automated assay system in 140 outpatients with NICHF. The stable clinical condition during the 2-month study period was defined as unchanged NYHA and unchanged left ventricular ejection fraction; therefore, 7 patients were excluded during the 2 months. Thereafter, 133 patients were prospectively followed and the relationship between cardiac events and the plasma BNP concentrations (at baseline and after 2 months) were evaluated as well as the changes in BNP. The biological variation in BNP (2-month interval) was calculated as 22.3%. During a mean follow-up period of 42 months, 26 patients had cardiac events. According to stepwise multivariate analyses, plasma BNP after 2 months (P=0.0002) and % change in BNP (P=0.0067) were significant independent predictors of cardiac events. CONCLUSIONS: These findings indicated that a combination of the absolute value of BNP after 2 months and % increase in BNP (2-month interval) is useful for predicting cardiac events in stable outpatients with NICHF.

Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1(c) levels in patients with chronic heart failure.

BACKGROUND: It has been reported that mineralocorticoid receptor antagonist improves the prognosis of chronic heart failure (CHF). Recently, hemoglobin A1(c) (HbA1(c)) levels have been reported to be an independent risk factor for mortality in CHF, suggesting the important role of insulin resistance in CHF. We compared the metabolic effect of a selective mineralocorticoid receptor blocker eplerenone with spironolactone in CHF patients. METHODS: One hundred seven stable outpatients with mild CHF, who were already receiving standard therapy for CHF, were randomized (1:2) to spironolactone (25 mg/d) or eplerenone (50 mg/d). Plasma levels of B-type natriuretic peptide, adiponectin, HbA1(c) and cortisol were measured before and after 4 months treatment with spironolactone or eplerenone. RESULTS: There were no differences in baseline characteristics including hemodynamic parameters and plasma levels of biomarkers between 2 groups. In both groups, plasma B-type natriuretic peptide levels were significantly decreased and plasma aldosterone levels were significantly increased after 4 months. In patients receiving spironolactone (n = 34), plasma adiponectin levels were significantly decreased (12.6 ± 1.4-11.2 ± 1.3 µg/mL, P < .0001) and HbA1(c) and cortisol levels were significantly increased (5.61 ± 0.1-5.8 ± 0.1%, P < .0001, 11.3 ± 0.8-14.7 ± 1.3 µg/dL, P = .003, respectively). In patients receiving spironolactone, there was a significant positive correlation between the change in cortisol and the change in HbA1(c) (r = 0.489, P = .003). In contrast, in patients receiving eplerenone (n = 73), plasma levels of adiponectin, HbA1(c) and cortisol did not change. CONCLUSION: These findings indicated that the metabolic effect of eplerenone differed from that of spironolactone and that eplerenone had a superior metabolic effect especially on HbA1(c) in CHF patients.

Prognostic role of highly sensitive cardiac troponin I in patients with systolic heart failure.

BACKGROUND: Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are useful biomarkers in patients with chronic heart failure (CHF). However, the clinical use has limitations due to the low sensitivity of a conventional commercial assay system. Recently, a high sensitive-cTnI (hs-cTnI) commercial assay has become available. METHODS: To compare the prognostic value of cTnT and hs-cTnI, we measured hemodynamic parameters and serum levels of cTnT, hs-cTnI and N-terminal pro-brain natriuretic peptide (NT-proBNP)in 258 consecutive CHF patients and then followed these patients for a mean period of 2.6 years. In both assays of cTnT and hs-cTnI, the lowest concentration at which the coeffi cient of variation was < or =10% were 0.03 ng/mL, respectively. Therefore, in the present study, an elevated cTnT or cTnI test was defined as a level of > or =0.03 ng/mL. RESULTS: During long-term follow up, there were 20 cardiac deaths. In 258 CHF patients, serum cTnT were elevated (> or =0.03 ng/mL) in 32 patients (12%) and serum hs-cTnI was elevated (> or =0.03 ng/mL) in 112 patients (43%). On stepwise multivariate analyses, high plasma NT-proBNP (> or =627 pg/mL, P = .0063) and hs-cTnI (> or =0.03 ng/mL) (P = .016) were independent significant prognostic predictors but cTnT (> or =0.03 ng/mL) was not. The hazard ratio for mortality of patients with high plasma NT-proBNP (> or =627 pg/mL) and hs-cTnI (> or =0.03 ng/mL) was 5.74 (95% CI, 2.33-14.28, P < .0001) compared to that of those with low NT-proBNP (<627 pg/mL) or hs-cTnI (<0.03 ng/mL). CONCLUSIONS: These findings indicate that a high plasma concentration of hs-cTnI is an independent and useful prognostic predictor in patients with CHF.

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension.

In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1-7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB.A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n=25): continuous candesartan treatment at a stable dose; and olmesartan group (n=25): candesartan (8 mg day(-1)) was changed to olmesartan given at a dose of 20 mg day(-1). There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135+/-36 vs. 123+/-29 g m(-2); P<0.01).These findings indicate that replacing candesartan with olmesartan decreased LVMI in association with a sustained decrease of plasma Ang II over a 12-month period without changing blood pressure or plasma aldosterone in patients with essential hypertension.

Serum cortisol as a useful predictor of cardiac events in patients with chronic heart failure: the impact of oxidative stress.

BACKGROUND: The pathophysiological role of cortisol, which binds to the mineralocorticoid receptor with an affinity equal to that of aldosterone (ALD), may be influenced by oxidative stress in patients with chronic heart failure. We evaluated cardiac event prediction using cortisol levels in chronic heart failure, in comparison with ALD, adrenocorticotropic hormone, and brain natriuretic peptide (BNP), and the impact of oxidative stress. METHODS AND RESULTS: We measured the plasma levels of biomarkers such as BNP, ALD, adrenocorticotropic hormone, serum cortisol, and oxidized low-density lipoprotein (oxLDL), a biomarker of oxidative stress, in 319 consecutive symptomatic patients with chronic heart failure, and we followed these patients for a mean period of 33 months. During the follow-up period, 29 patients had cardiac events (death or hospitalization). Plasma levels of BNP, ALD, adrenocorticotropic hormone, oxLDL, and serum cortisol (16.8+/-1.8 microg/dL versus 12.4+/-0.3 microg/dL, P=0.01) were significantly higher in patients with cardiac events than in those without cardiac events. On stepwise multivariate analyses, high levels of BNP (P=0.0003), renin (P=0.002), cortisol (P=0.02), and oxLDL (P=0.002) were independent predictors of cardiac events, but ALD and adrenocorticotropic hormone levels were not. In patients with serum cortisol > or =12.5 microg/dL, the hazard ratio of cardiac events in patients with oxLDL > or =12 U/mL was 3.5 compared with that in patients with oxLDL <12 U/mL (P=0.008). CONCLUSIONS: These findings indicate that serum cortisol levels were a complementary and incremental cardiac event risk predictor in combination with BNP in patients with chronic heart failure and that cardiac event prediction based on cortisol levels was influenced by oxidative stress.

Effect of simvastatin vs. rosuvastatin on adiponectin and haemoglobin A1c levels in patients with non-ischaemic chronic heart failure.

AIMS: To compare the effects of lipophilic simvastatin and hydrophilic rosuvastatin on plasma adiponectin and glycated haemoglobin A1c (HbA1c) levels in patients with non-ischaemic chronic heart failure (NICHF). METHODS AND RESULTS: Seventy-one stable outpatients with NICHF, who were already receiving standard therapy for CHF, were randomized to simvastatin (n = 35) or rosuvastatin (n = 36). Plasma levels of brain natriuretic peptide (BNP), total adiponectin, high-sensitive C-reactive protein, HbA1c, and oxidized low-density lipoprotein (oxLDL), a marker of oxidative stress, were measured before and 4 months after treatment with simvastatin or rosuvastatin. There was no difference in the baseline characteristics including left ventricular ejection fraction (LVEF) and biochemical parameters between the two groups. In both groups, plasma BNP levels and LVEF did not change after 4 months. Plasma levels of adiponectin and oxLDL did not change and HbA1c level was slightly increased (6.0 +/- 0.9 vs. 6.1 +/- 0.9%, P = 0.053) in the simvastatin group. In contrast, plasma adiponectin level was significantly increased (12.3 +/- 7.3 vs. 14.0 +/- 8.2 microg/mL, P = 0.012) concomitant with a significant reduction in oxLDL and HbA1c (oxLDL: 8.8 +/- 4.7 vs. 7.6 +/- 4.7 U/mL, P = 0.0059; HbA1c: 6.0 +/- 0.7 vs. 5.9 +/- 0.7%, P = 0.002) in the rosuvastatin group. CONCLUSION: These findings suggest that hydrophilic rosuvastatin but not lipophilic simvastatin increases adiponectin and decreases HbA1c levels in patients with NICHF.

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.

Dose-dependent prognostic effect of carvedilol in patients with chronic heart failure--special reference to transcardiac [corrected] gradient of norepinephrine.

BACKGROUND: The effect of the dose of carvedilol on cardiac sympathetic nerve activity (CSA) and mortality remain uncertain in patients with chronic heart failure (CHF). METHODS AND RESULTS: To compare the dose of carvedilol and the transcardiac gradient of norepinephrine (NE), a biomarker of CSA, and prognosis in patients with CHF, hemodynamic parameters and plasma levels of NE, N-terminal brain natriuretic peptide (NT-proBNP) in the aortic root and coronary sinus were measured in 107 patients with systolic CHF who received carvedilol. Patients were divided into 2 groups [group I: low dose (<10 mg/day, n=41) and group II: high dose (>or=10 mg/day, n=66)]. There was no difference between the 2 groups for the hemodynamic parameters. The dose of carvedilol did not correlate with plasma NE, but was significantly correlated with the transcardiac increase in NE. During a median follow-up of 4.3 years, 13 patients died of cardiac disease. In the Cox stepwise multivariate analyses, a high level of transcardiac increase in NE (P<0.001), high level of plasma log NT-proBNP (P=0.004) and low dose of carvedilol (P=0.012) were significant independent predictors. CONCLUSION: The carvedilol dose is important for the management of CSA and prognosis in patients with systolic CHF.

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.

Relationship between renal function and serum cardiac troponin T in patients with chronic heart failure.

AIMS: Both serum cardiac troponin T (cTnT) and renal function are prognostic predictors in patients with chronic heart failure (CHF). We aimed to evaluate the relationship between renal function and serum cTnT. METHODS AND RESULTS: We measured serum concentrations of cTnT in the aortic root (AO) and coronary sinus (CS) in 258 CHF patients. Patients were divided into two groups: patients with an estimated glomerular filtration rate (eGFR) >or= 60 mL/min/1.73 m(2) [chronic kidney disease (CKD)(-)], and patients with an eGFR < 60 mL/min/1.73 m(2) [CKD (+)]. In 32 (12%) of the 258 CHF patients, serum levels of cTnT were detectable (>or=0.03 ng/mL) in the AO and in the CS. There was no correlation between eGFR and the transcardiac increase in cTnT and there was a significant negative correlation between eGFR and the serum cTnT concentration (r = - 0.365, P = 0.039). There was no difference in the transcardiac gradient of cTnT between patients without CKD (n = 16) and patients with CKD (n = 16) (0.083 +/- 0.11 vs. 0.108 +/- 0.13 ng/mL, P = 0.55). However, the serum cTnT level in the AO was two-fold higher in CHF patients with CKD than patients without CKD (0.20 +/- 0.177 vs. 0.088 +/- 0.065 ng/mL, P < 0.05). CONCLUSION: These findings indicate that decreased clearance via the kidney contributes to the elevated cTnT in CHF patients with CKD.

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.

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.

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.

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.