Plasma B-type Natriuretic Peptide Levels Research Articles

Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease

ObjectiveTo analyze plasma myostatin levels and investigate their relationship with right ventricular (RV) function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD).MethodsThe study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE) less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP) levels were analyzed as a comparison of myostatin.ResultsThe data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL) were significantly higher in patients with cor pulmonale (16.68 ± 2.95) than in those without (13.56 ± 3.09), and much higher than in controls (8.79±2.79), with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05). Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05.ConclusionsPlasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD.

Brain natriuretic peptide in acute myocardial infarction: a marker of cardio-renal interaction.

Cardiac and renal functions are major independent predictors of outcomes in both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). As B-type natriuretic peptide (BNP) seems to be a major mediator in the cross-talk between heart and kidneys, we aimed at evaluating its capacity to reflect cardiac and renal function in patients with STEMI and NSTEMI. We measured BNP plasma levels at hospital admission in 619 patients with STEMI (n = 346) and NSTEMI (n = 273), grouped according to left ventricular ejection fraction (LVEF; > or ≤40%) and estimated glomerular filtration rate (eGFR; > or ≤ 60 ml/min/1.73 m). Median BNP values were 82 (38-186), 121 (40-342), 219 (80-685), and 474 (124-1263) pg/ml in patients with normal LVEF and eGFR (n = 347), with LVEF 40% or less and eGFR higher than 60 ml/min/1.73 m (n = 120), with LVEF higher than 40% and eGFR 60 ml/min/1.73 m or less (n = 86), and with combined LVEF and eGFR reductions (n = 66), respectively (P < 0.0001). At general linear model, both LVEF higher than 40% (P < 0.0001) and eGFR 60 ml/min/1.73 m or less (P < 0.0001) independently predicted BNP values. At multivariable analysis, BNP, LVEF 40% or less, and eGFR 60 ml/min/1.73 m or less were found to be independent predictors of the combined end point of in-hospital death, cardiogenic shock, need for renal replacement therapy, or mechanical ventilation (P = 0.003; P < 0.0001; P = 0.01, respectively). BNP plasma levels are closely related to LVEF and eGFR at hospital admission, in both STEMI and NSTEMI patients. Future studies should investigate whether BNP levels can summarize in a single parameter the prognostic information provided separately by cardiac and renal dysfunction.

Plasma B-Type Natriuretic Peptide Levels May Increase Because of Fat Mass Loss by Metformin or Sodium-Glucose Transporter 2 Inhibitors Treatment

Background: Cardiovascular disease (CVD) is the leading cause of death in type 2 diabetes. Metformin reduces cardiovascular events in obese patients with type 2 diabetes, and sodium-glucose transporter 2 (SGLT2) inhibitors decrease cardiovascular events in type 2 diabetic patients with established CVD. However, the underlying mechanisms behind the cardioprotective effects of metformin and SGLT2 inhibitors are unknown. Methods: Fifteen patients with newly diagnosed type 2 diabetes receiving metformin monotherapy, and seven patients with type 2 diabetes receiving SGLT2 inhibitors combined with other hypoglycemic agents were studied. We investigated changes in glycemic control, plasma B-type natriuretic peptide (BNP) levels, and body composition, 3 and 6 months after starting metformin administration, and 3 months after starting SGLT2 inhibitor administration. Results: Plasma BNP levels significantly increased after 3 months in both metformin and SGLT2 inhibitors treatment groups (7.9 ± 7.9 pg/mL to 17 ± 16.9 pg/mL, P = 0.012; 8.8 ± 7.2 pg/mL to 15.5 ± 14.3 pg/mL, P = 0.018, respectively). Fat mass significantly decreased in the first 3 months of metformin administration (25.7 ± 10.3 kg to 23.0 ± 11.4 kg, P = 0.046), while fat mass and visceral fat area decreased in three patients receiving SGLT2 inhibitors. Conclusions: Plasma BNP levels increased because of fat mass loss caused by treatment with metformin and SGLT2 inhibitors. Our results suggest that metformin and SGLT2 inhibitors could reduce the risk of CVD by exerting cardioprotective effects through elevated BNP levels in patients with type 2 diabetes. J Endocrinol Metab. 2016;6(1):12-17 doi: http://dx.doi.org/10.14740/jem333w

Sex differences in clinical characteristics and long-term outcome in acute decompensated heart failure patients with preserved and reduced ejection fraction.

In patients with acute decompensated heart failure (ADHF), sex differences considering clinical and pathophysiologic features are not fully understood. We investigated sex differences in left ventricular (LV) ejection fraction (LVEF), plasma B-type natriuretic peptide (BNP) levels, and prognostic factors in patients with ADHF in Japan. We studied 748 consecutive ADHF patients of 821 patients registered in the ADHF registry between January 2007 and December 2014. Patients were divided into four groups based on sex and LVEF [reduced (ejection fraction, or EF, <50%, heart failure with reduced EF, or HFrEF) or preserved (EF ≥50%, heart failure with preserved LVEF, or HFpEF)]. The primary endpoint was the combination of cardiovascular death and heart failure (HF) admission. The present study consisted of 311 female patients (50% HFrEF, 50% HFpEF) and 437 male patients (63% HFrEF, 37% HFpEF). There was significant difference between sexes in the LVEF distribution profile. The ratio of HFpEF patients was significantly higher in female patients than in male patients (P= 0.0004). Although there were no significant sex differences in median plasma BNP levels, the prognostic value of BNP levels was different between sexes. Kaplan-Meier analysis revealed that the high BNP group had worse prognosis than the low BNP group in male but not in female patients. In multivariate analysis, log transformed BNP at discharge predicted cardiovascular events in male but not in female HF patients (female, hazard ratio: 1.169; 95% confidence interval: 0.981-1.399;P= 0.0806; male, hazard ratio: 1.289; 95% confidence interval: 1.120-1.481;P= 0.0004). In patients with ADHF, the distribution of LV function and the prognostic significance of plasma BNP levels for long-term outcome were different between the sexes.

Interrelationship between the Myocardial Mass, Fibrosis, BNP, and Clinical Outcomes in Hypertrophic Cardiomyopathy.

Objective Increased left ventricular mass (LVM) and LV fibrosis mass (LVFM) are characteristics of hypertrophic cardiomyopathy (HCM). Additionally, a substantial increase in the plasma B-type natriuretic peptide (BNP) level is observed. Therefore, we investigated the interrelationship and clinical significances of these parameters in a HCM cohort that underwent cardiac MRI (CMR). Methods Patients with HCM (n=109) receiving regular outpatient treatment underwent CMR and follow-up through 2015 from CMR examinations. The clinical outcome measures were all-cause mortality, admission for worsening heart failure, and ventricular tachycardia/fibrillation. Results The baseline body mass index (BMI), LV outflow tract (LVOT) obstruction, New York Heart Association (NYHA) class, and increased left atrial dimension (LAD) index were associated with the plasma BNP level. In the CMR analysis, LVM and LVFM indices significantly correlated with the BNP level (r=0.422 and 0.368, respectively), which were independent determinants according to a multivariate analysis (p=0.009 and 0.023, respectively). A Kaplan-Meier analysis during a median follow-up of 19.4 months showed that the baseline LVM or LVFM index was not associated with the clinical outcomes. However, the baseline BNP level was significantly associated with them (p<0.001). In addition, a multivariate Cox proportional hazard analysis showed that plasma BNP was an independent predictor for the clinical outcomes after adjusting for age, sex, LVM, and LVFM. Conclusion The LVM and LVFM are determinants of the BNP level independent of the BMI, LVOT obstruction, LAD, and NYHA class in patients with HCM. However, plasma BNP may be a more sensitive integrated-marker for the clinical outcomes than LVM or LVFM.

Plasma B-Type Natriuretic Peptide Levels May Increase Because of Fat Mass Loss by Metformin or Sodium-Glucose Transporter 2 Inhibitors Treatment

Background: Cardiovascular disease (CVD) is the leading cause of death in type 2 diabetes. Metformin reduces cardiovascular events in obese patients with type 2 diabetes, and sodium-glucose transporter 2 (SGLT2) inhibitors decrease cardiovascular events in type 2 diabetic patients with established CVD. However, the underlying mechanisms behind the cardioprotective effects of metformin and SGLT2 inhibitors are unknown. Methods: Fifteen patients with newly diagnosed type 2 diabetes receiving metformin monotherapy, and seven patients with type 2 diabetes receiving SGLT2 inhibitors combined with other hypoglycemic agents were studied. We investigated changes in glycemic control, plasma B-type natriuretic peptide (BNP) levels, and body composition, 3 and 6 months after starting metformin administration, and 3 months after starting SGLT2 inhibitor administration. Results: Plasma BNP levels significantly increased after 3 months in both metformin and SGLT2 inhibitors treatment groups (7.9 ± 7.9 pg/mL to 17 ± 16.9 pg/mL, P = 0.012; 8.8 ± 7.2 pg/mL to 15.5 ± 14.3 pg/mL, P = 0.018, respectively). Fat mass significantly decreased in the first 3 months of metformin administration (25.7 ± 10.3 kg to 23.0 ± 11.4 kg, P = 0.046), while fat mass and visceral fat area decreased in three patients receiving SGLT2 inhibitors. Conclusions: Plasma BNP levels increased because of fat mass loss caused by treatment with metformin and SGLT2 inhibitors. Our results suggest that metformin and SGLT2 inhibitors could reduce the risk of CVD by exerting cardioprotective effects through elevated BNP levels in patients with type 2 diabetes. J Endocrinol Metab. 2016;6(1):12-17 doi: http://dx.doi.org/10.14740/jem333w

B-type Natriuretic Peptide and RISK-PCI Score in the Risk Assessment in Patients with STEMI Treated by Primary Percutaneous Coronary Intervention.

RISK-PCI score is a novel score for risk stratification of patients with ST elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). The aim of this study was to evaluate the role of B-type natriuretic peptide (BNP) and the RISK-PCI score for early risk assessment in patients with STEMI treated by pPCI. In 120 patients with STEMI treated by pPCI, BNP was measured on admission before pPCI. The primary end point was 30-day mortality. The ROC curve analysis revealed that the most powerful predictive factors of 30-day mortality were the plasma level of BNP ≥ 206.6 pg/mL with the sensitivity of 75% and specificity of 87.5% and the RISK-PCI score ≥ 5.25 with the sensitivity of 75% and specificity of 85.7%. Thirty-day mortality was 6.7%. After multivariate adjustment, admission BNP (≥ 206.6 pg/mL) (OR 2.952, 95% CI 1.072 - 8.133, p = 0.036) and the RISK-PCI score (≥ 5.25) (OR 2.284, 95% CI 1.140-4.578, p = 0.020) were independent predictors of 30-day mortality. The area under the ROC curve using the RISK-PCI score and BNP to detect mortality was 0.828 (p = 0.002) and 0.903 (p < 0.001), respectively. Addition of BNP to RISK-PCI score increased the area under the ROC to 0.949 (p < 0.001), but this increase measured by the c-statistic was not significant (p = 0.107). Furthermore, the significant improvement in risk reclassification (p < 0.001) and the integrated discrimination index (p = 0.042) were observed with the addition of BNP to RISK-PCI score for 30-day mortality. BNP on admission and the RISK-PCI score were the independent predictors of 30-day mortality in patients with the STEMI treated by pPCI. BNP in combination with the RISK-PCI score showed the way to more accurate risk assessment in patients with STEMI treated by pPCI.

Plasma B-type natriuretic peptide levels are poorly related to the occurrence of ischemia or ventricular arrhythmias during symptom-limited exercise in low-risk patients.

IntroductionThe usefulness of B-type natriuretic peptide (BNP) as a marker of ischemia is controversial. BNP levels have predicted arrhythmias in various settings, but it is unknown whether they are related to exercise-induced ischemic ventricular arrhythmias.Material and methodsWe analyzed in 63 patients (64 ±14 years, 65% male, 62% with known coronary disease) undergoing exercise stress single-photon emission computed tomography (SPECT) the association between plasma BNP values (before and 15 min after exercise) and the occurrence of ischemia or ventricular arrhythmias during the test.ResultsExercise test (8.1 ±2.7 min, 7.4 ±8.1 metabolic equivalents, 82 ±12% of maximal predicted heart rate) induced reversible perfusion defects in 23 (36%) patients. Eight (13%) patients presented significant arrhythmias (≥ 7 ventricular premature complexes/min, couplets, or non-sustained ventricular tachycardia during exercise or in the first minute of recovery). Median baseline BNP levels were 17.5 (12.4–66.4) pg/ml in patients developing scintigraphic ischemia and 45.6 (13.2–107.4) pg/ml in those without ischemia (p = 0.137). The BNP levels increased after exercise (34.4 (15.3–65.4)% increment over baseline, p < 0.001), but the magnitude of this increase was not related to SPECT positivity (35.7 (18.8–65.4)% vs. 27.9 (5.6–64.0)% in patients with and without ischemia, respectively, p = 0.304). No significant association was found between BNP values (at baseline or their change during the test) and ventricular arrhythmias.ConclusionsPlasma BNP values – at baseline or after exercise – were not associated with myocardial ischemia or with ventricular arrhythmia during exercise SPECT. These results highlight the limited usefulness of this biomarker to assess acute ischemia.

Gestational Weight Gain in a Woman with Peripartum Cardiomyopathy

Greater gestational weight gain (GWG) may be a risk factor for peripartum cardiomyopathy (PPCM). In counseling, women with a prior history of PPCM associated with greater GWG should be advised to avoid excessive GWG in subsequent pregnancies. The third pregnancy occurred in a 36-year-old Japanese woman with height of 1.48 m and left ventricular ejection fraction (LVEF) of 62% following the first and second pregnancies complicated with PPCM and spontaneous abortion, respectively. She exhibited GWG of 14.7 kg (from 37.0 to 51.7 kg) and normal or nearly normal plasma B-type natriuretic peptide levels and LVEF (>55%) throughout the current pregnancy. In her first pregnancy at the age of 33 years, extraordinary GWG of 30 kg (from 38.5 to 69.1 kg) preceded PPCM with nadir LVEF of 22% at 6 weeks postpartum followed by more than 18-month LVEF of <55%.

Correlation of B-type natriuretic peptide levels and echocardiographic parameters in preterm infants with patent ductus arteriosus.

PurposeThis study aimed to evaluate the correlation, according to postnatal age, between plasma B-type natriuretic peptide (BNP) levels and echocardiographic parameters for the assessment of patent ductus arteriosus (PDA) in preterm infants with respiratory distress.MethodsWe enrolled 42 preterm infants with respiratory distress who underwent serial echocardiographic evaluation with simultaneous plasma BNP measurements until ductal closure. The correlations between BNP levels and the following 4 representative echocardiographic parameters were studied: diameter of the ductus arteriosus (DA), ratio of the left atrial diameter to the aortic diameter (LA/Ao), ratio of the PDA diameter to the infant's left pulmonary artery diameter (PDA/LPA), and the antegrade diastolic flow of LPA (DFLPA).ResultsBNP levels were significantly correlated to the magnitude of the ductal shunt, comprising the DA diameter, PDA/LPA ratio, LA/Ao ratio, and antegrade DFLPA for the overall study period. The earliest significant correlation, starting from postnatal day 2, was observed between the LA/Ao ratio and BNP levels. The PDA/LPA ratio and the antegrade DFLPA showed significant correlations with BNP levels postnatal day 3 onward, and with the DA diameter, postnatal day 5 onward.ConclusionBNP levels and echocardiographic parameters showed a positive correlation, but the significance of the correlations differed according to the postnatal age, especially during the first few days of life.

Renal Denervation Attenuates Multi-Organ Fibrosis and Improves Vascular Remodeling in Rats with Transverse Aortic Constriction Induced Cardiomyopathy

Background/Aims: To investigate the effects of renal denervation (RDN) on multi-organ fibrosis and vascular remodeling in cardiomyopathy. Methods: Thirty-six male Sprague-Dawley rats underwent transverse aortic constriction (TAC). Five weeks later, 28 surviving TAC rats were randomly assigned to three groups: (1) RDN, (2) Sham, (3) Carvedilol. Six male Sham TAC rats served as the Control. Ten weeks after TAC, samples were collected. Results: TAC rats showed an increased diastolic interventricular septal thickness at week 5. At 10 weeks, Masson staining showed that left ventricular and renal glomerular fibrosis were significantly reduced in RDN compared with Sham group. In comparison to Sham group, hepatic perivascular fibrosis was attenuated in both RDN and Carvedilol group, so were the media thickness and the media/lumen of aorta. The plasma levels of B-type natriuretic peptide (BNP), Cystatin C (Cys-C), Alanine Transaminase, angiotensin II (Ang II), transforming growth factor beta 1 (TGF-β1), and malondialdehyde increased, and total superoxide dismutase (T-SOD) decreased in Sham but not in RDN group, compared with Control group. Both RDN and Carvedilol reduced the Cys-C and TGF-β1 levels, and restored T-SOD concentration, compared with Sham group. While only RDN lowered the plasma levels of BNP and Ang II. No significant effects of RDN on blood pressure (BP) and heart rate (HR) were oberved. Conclusions: RDN can attenuate multi-organ fibrosis and improve vascular remodeling independent of BP and HR change in TAC-induced cardiomyopathy. These effects of RDN may be associated with the direct inhibition of renin-angiotensin-aldosterone system and oxidative stress.

Abstract 15352: Plasma Levels of BNP are Lower in Patients With Heart failure With Preserved EF (HFpEF) as Compared With Those With Reduced EF (HFrEF)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence and causes substantial morbidity, mortality, and resource utilization in the aging population. The plasma level of B-type natriuretic peptide (BNP) is used as a marker of HF with reduced EF (HFrEF). However, the role of BNP in HFpEF is not well known. The purpose of the present study was to compare the levels of BNP together with the echocardiographic findings between HFpEF and HFrEF. Methods: The study subjects consisted of 1574 patients with HF and early diastolic flow velocity (E)/velocity of early diastolic mitral annular motion (e′) or E/e′≥15 (as a measure of elevated left atrial pressure) (574 men and 1000 women, mean age 78.8±10.7) admitted at our hospital. They were divided into 1238 patients with HFpEF (373 men and 865 women, mean age 79.7±10.2) [left ventricular (LV) EF≥50% and E/e′≥15] and 336 patients with HFrEF (201 men and 135 women, mean age 75.4±11.8) (LVEF&lt;50%). Echocardiographic parameters, age, gender, and BNP were examined. Results: The levels of BNP were lower [107(47, 225) pg/ml vs. 296(121, 626) pg/ml, P&lt;0.001] in the HFpEF group than in the HFrEF group. The frequencies of female gender, age, EF, LV posterior wall thickness were higher (all P&lt;0.001, respectively) and LV mass, LV end-diastolic diameter (LVDd), LV end-systolic diameter (LVDs) and left atrial diameter (LAD) were lower (all P&lt;0.001, respectively) in the HFpEF group than in the HFrEF group. A multiple regression analysis revealed EF (t=-17.0), age (t=11.2), E/e′ (t=10.5), LAD (t=9.0), LV mass (t=7.9), and LVDd (t=-5.3) were independent predictors (all P&lt;0.001, respectively) for the BNP level (P&lt;0.001, R2=0.40) in this order. Conclusions: HFpEF was associated with lower levels of BNP and smaller heart and was more prevalent in the elders and women as compared with HFrEF. Predictors for the levels of BNP were EF, age, and E/e′ in this order. These findings imply that the plasma levels of BNP reflect LVEF more than LV diastolic function (E/e′) and thus are lower in the HFpEF group than in the HFrEF group. These findings suggest that the role of BNP in HF may be different between HFpEF and HFrEF.

Abstract 10036: Olmesartan Improves Not Only Vascular Endothelial Dysfunction but Cardiac Diastolic Dysfunction in Hypertensive Heart Failure With Preserved Ejection Fraction - ORION Study

Introduction: The optimal treatment for heart failure (HF) with preserved left ventricular (LV) ejection fraction (EF) (HFpEF) has not been established. Using an experimental model of HFpEF, we previously reported a novel mechanism underlying reversal of endothelial dysfunction and HFpEF by AT1 receptor blocker (ARB). By performing this study (ORION: OlmesaRtan Improvement endothelial functiON with hypertension study), we examined the effects of ARB on hypertensive HFpEF patients, focusing on reactive oxygen species (ROS). Methods and Results: We examined prospectively 20 hypertensive HFpEF patients, taking any renin-angiotensin system inhibitors, switched to appreciable amounts of highly-selective ARB; olmesartan (average dosage amounts: 22.9 mg/day) for 3 months. Despite no additive hypotensive effects of olmesartan, endothelial dysfunction assessed by fingertrip digital reactive hyperemia (RH) peripheral arterial tonometry using Endo-PAT2000 was significantly reversed (RH-index; 1.57±0.34 to 1.87±0.50, P=0.034), accompanied by significant reduction of serum derivatives of reactive oxidative metabolites levels, novel biomarker of ROS (362.8±13.7 to 302.1±9.4 unit called the Carratelli unit [U.CARR], P=0.001). Olmesartan treatments significantly improved cardiac diastolic function evaluated by the ratio of early transmitral flow velocity to tissue doppler early diastolic mitral annular velocity (15.4 to 11.0, P&lt;0.001) but not LVEF and LV anterior wall thickness in echocardiography, and decreased plasma B-type natriuretic peptide levels (214.9 to 191.4, P&lt;0.05) in HFpEF patients. Additionaly, olmesartan significantly increased plasma superoxide dismutase activity (2.39±0.73 to 3.06±0.78 U/mL, P=0.02) and adiponectin levels (2.66±1.55 to 4.12±1.99 μg/mL, P&lt;0.05), but not affect plasma nitrates and nitrites (NO3-/NO2-) levels (53.2±28.1 to 62.9±28.4 μmol/L). Conclusions: These data suggested that strong AT1 receptor blockade by olmesartan restored not only endothelial dysfunction but cardiac diastolic dysfunction in HFpEF beyond hypotensive effects. Increased in SOD activities and adiponectin levels, but not nitric oxide levels, might contribute to these beneficial effects of olmesartan.

Abstract 13459: Usefulness of B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin for Risk Stratification in Low Flow, Low Gradient Aortic Stenosis -A Substudy of the TOPAS Study

Background: B-type natriuretic peptide (BNP) and troponin T (TNT) have been shown to be associated with outcome in several clinical conditions. However the prognostic value of these 2 biomarkers combined together remains unclear. We aimed to explore the prognostic value of combined BNP and high-sensitivity TNT (hsTNT) in patients with low flow low gradient aortic stenosis (LGLG AS). Methods: Ninety eight patients (74±10 year; 75% men) with LFLG AS (LVEF &lt;50% and/or SVi&lt;35 ml/m2, mean gradient&lt;40 mmHg, AVAi&lt;0.6 cm2/m2) were prospectively enrolled in the TOPAS study and included in this analysis. The cohort was divided into three groups according to BNP and hsTNT plasma levels: Group A, patients with BNP&lt;550 pg/mL and undetectable TNT (hsTNT&lt;0.015 ng/mL); Group B, with BNP≥550 pg/mL or hsTNT≥0.015 ng/mL and Group C, patients with BNP≥550 pg/mL and hsTNT≥0.015 ng/mL. The primary endpoint was all-cause mortality. Results: Among the 98 patients, 32 (33%) were in Group A, 39 (40%) in Group B and 24 (27%) in Group C. During a median follow up of 2.8 [IQR=1.1-4.1] years, 55 patients died. Patients in Group C were older and had lower LVEF (all p&lt;0.05). Two-year mortality was higher in Group C (41±9%) than in Group B (23±7) and Group A (5±4%) (p=0.0019). In Group B, there was no significant difference in 2-year mortality rates between the subgroup with hsTNT≥0.015 ng/mL versus that with BNP≥550 pg/mL (26±9% vs. 11±10%, respectively, p=0.21). In multivariable analysis adjusted for age, type of treatment (AVR vs. conservative), coronary artery disease and LVEF, Group C remained independently associated with increased risk of mortality (HR= 4.25; p=0.023), and Group B tended to have higher mortality (HR=3.63; p=0.058) as compared to Group A. Conclusion: The results of this study demonstrate the usefulness of combined measures of BNP and hsTNT to enhance risk stratification in patients with LFLG AS. Patients having activation of both BNP and hsTNT have a 4-fold increase risk of mortality.

Early Elevated B-Type Natriuretic Peptide Levels are Associated with Cardiac Dysfunction and Poor Clinical Outcome in Pediatric Septic Patients.

To determine the B-type natriuretic peptide (BNP) level in pediatric septic patients, and to investigate its association with cardiovascular dysfunction and clinical outcome. Pediatric patients with sepsis or septic shock were prospectively enrolled in our pediatric intensive care unit (PICU). On day 1 of admission, plasma BNP levels were measured at the time-point of echocardiography. Myocardial dysfunction was defined as left ventricular fractional shortening (FS) < 30%. Inotropic support was quantified by inotropic scores and disease severity was assessed by Pediatric Risk of Mortality (PRISM) III scores. Therafter, associations between BNP levels and clinical parameters were analyzed. There were 94 patients (mean: 5.6 yr, range: 2 mo-17 yr) that were consecutively enrolled in this study. The median BNP level was 127 pg/ml (range: 5 to 4950 pg/ml). BNP levels were correlated with PRISM III (rho = 0.36, p = 0.001) and C-reactive protein level (r = 0.39, p = 0.001). The median BNP levels were not only higher in patients with septic shock (n = 34) than those with sepsis (n = 58) (213 vs. 54 pg/ml, p = 0.0004), but also higher in patients with myocardial dysfunction (n = 18) than those with preserved myocardial function (n = 66) (765 vs. 65 pg/ml, p < 0.001). We also found that BNP levels correlated negatively with FS (r = -0.56, p < 0.001) and positively with inotropic scores (r = 0.34, p = 0.04). Most importantly, the median BNP levels were higher in non-survivors (n = 13) than survivors (n = 81) (367 vs. 106 pg/ml, p = 0.003). BNP levels are elevated in pediatric septic patients early in the disease course, and increased levels are associated with cardiovascular dysfunction and worse clinical outcome. B-type natriuretic peptide; Cardiac function; Pediatric; Sepsis; Septic shock.

Renal sympathetic denervation improves cardiac dysfunction in rats with chronic pressure overload.

Varied causative and risk factors can lead to cardiac dysfunction. Cardiac dysfunction often evolves into heart failure by cardiac remodeling due to autonomic nervous system disturbance and neurohumoral abnormalities, even if the detriment factors are removed. Renal sympathetic nerve activity plays a pivotal regulatory role in neurohumoral mechanisms. The present study was designed to determine the therapeutic effects of renal sympathetic denervation (RSD) on cardiac dysfunction, fibrosis, and neurohumoral response in transverse aortic constriction (TAC) rats with chronic pressure overload. The present study demonstrated that RSD attenuated myocardial fibrosis and hypertrophy, and structural remodeling of the left atrium and ventricle, up-regulated cardiac beta adrenoceptor (beta-AR, including beta(1)AR and beta(2)AR) and sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) while down-regulated angiotensin II type 1 receptor (AT(1)R), and decreased plasma B-type natriuretic peptide (BNP), norepinephrine (NE), angiotensin II (Ang II), and arginine vasopressin (AVP) levels in TAC rats with chronic pressure overload. We conclude that RSD attenuates myocardial fibrosis, the left atrial enlargement, and the left ventricular wall hypertrophy; inhibits the overdrive of the sympathetic nervous system (SNS), renin-angiotensin-aldosterone system (RAAS), and AVP system in TAC rats with chronic pressure overload. RSD could be a promising non-pharmacological approach to control the progression of cardiac dysfunction.

Diagnostic utility of BNP, corin and furin as biomarkers for cardiovascular complications in type 2 diabetes mellitus patients

Context: The number of patients with type 2 diabetes mellitus (T2DM) is progressively increasing, and diabetic cardiovascular complications have become a public health problem. Brain or B-type natriuretic peptide (BNP) is a cardiac hormone synthesized as a pre-pro-peptide. pro-BNP is produced by cleaving the signal peptide then two proprotein convertases, corin and furin cleave pro-BNP to form a biologically active hormone. Two corin single nucleotide polymorphisms (SNPs) have been reported to alter corin protein conformation and impair its biological activity.Objective: We aimed to investigate the potential role of corin and furin in comparison to BNP as biomarkers for predicting cardiovascular complications in T2DM patients. The association of corin gene SNPs with corin levels was also examined.Methods: Seventy-five subjects were recruited in this study, including 25 T2DM patients with complications, 25 T2DM patients without complications as well as 25 healthy subjects. Plasma BNP, corin and furin levels were measured using enzyme-linked immunosorbent assays. Two corin SNPs were genotyped using allele specific oligonucleotide-polymerase chain reaction.Results: Both furin and BNP were found to be more sensitive than corin (80% versus 56%, p = 0.008), whereas furin showed higher specificity when compared to BNP (96% versus 84%, p = 0.041) and corin (96% versus 64%, p < 0.0001) in predicting cardiovascular complications in T2DM patients. Corin SNPs are not associated with corin levels, neither in the entire study cohort nor in the subgroup of T2DM patients with cardiovascular complications (p > 0.05).Conclusions: Furin may be useful, either alone or in combination with other biomarkers, for cardiovascular risk stratification assessment in T2DM patients.

Clinical value of plasma B-type natriuretic peptide assay in pediatric pneumonia accompanied by heart failure.

Previous studies have shown that B-type natriuretic peptide (BNP) is useful in differentiating cardiac from pulmonary causes of dyspnea in adults. To date, international guidelines have recommended measurements of circulating BNP as a biomarker for diagnostic and prognostic purposes, as well as therapeutic monitoring, in adults with cardiac diseases, particularly those suffering from acute and chronic heart failure (HF). The aim of the present study was to investigate the differential diagnostic and therapeutic analysis of BNP levels assayed in pediatric pneumonia accompanied by HF. The clinical data of 80 patients with pneumonia, aged 1-3 years, were analyzed. The patients were divided into two groups: Simple pneumonia (46 cases) and pneumonia accompanied by HF (34 cases). All patients underwent two plasma BNP assays: The first one upon admission to the hospital and the second one prior to discharge. The plasma BNP levels of 20 healthy children were used as the negative control. Plasma BNP levels were measured using the Triage® BNP automated immunoassay systems and reagents. Statistical analysis showed that the plasma BNP levels of the patients upon admission were higher in the pneumonia accompanied by HF group compared with those in the simple pneumonia group (750±120 vs. 135±50 pg/ml; P<0.05). In addition, in the pneumonia accompanied by HF group, the plasma BNP levels of the patients were higher upon admission to the hospital than they were prior to discharge (750±120 vs. 115±45 pg/ml; P<0.05); therefore, plasma BNP may comprise a sensitive diagnostic and therapeutic evaluative marker for pediatric patients with pneumonia accompanied by HF. This finding could prove invaluable in the clinical diagnosis and treatment of the disease.

A case of Werner's syndrome with cardiac syndrome X and heart failure with preserved ejection fraction

We herein report a case of Werner's syndrome (WS) with cardiac syndrome X (CSX) and heart failure with preserved ejection fraction (HFpEF), receiving nicorandil treatment.A 58-year-old woman with chest discomfort on exercise was suspected of having effort-angina pectoris because of broad ST-depression in electrocardiogram of exercise test and reversible defect in the posterior-wall portion of left ventricle in exercise thallium201 myocardial scintigraphy. This patient also exhibited HFpEF, diagnosed by increased ratio of early-transmitral-flow-velocity to tissue-Doppler early-diastolic mitral annular velocity (E/e′) in echocardiography and plasma B-type natriuretic peptide (BNP) levels. However, coronary angiography revealed no organic stenosis in epicardial coronary arteries, and coronary physiological measurements by PressureWire™ (St. Jude Medical, St Paul, MN, USA) demonstrated that coronary flow reserve (CFR) was greatly decreased. Because impaired CFR represents coronary microvascular dysfunction in the absence of obstructive coronary narrowing, we diagnosed CSX, and initiated the administration of nicorandil to improve coronary microcirculation. After three-month-treatment of nicorandil, the patient's symptoms were diminished, and reversible defect in exercise myocardial scintigraphy was improved. Furthermore, both E/e′ and BNP were decreased, indicating the improvement of HFpEF via the restoration of microvascular dysfunction.Thus, nicorandil administration could bring beneficial effects in WS with CSX and HFpEF, accompanied by coronary microcirculation dysfunction.<Learning objective: Contrary to previous case reports regarding Werner's syndrome (WS) with obstructive coronary artery disease (CAD), we herein report a case of WS with cardiac syndrome X (CSX) without obstructive CAD, complicated with heart failure with preserved ejection fraction (HFpEF). Because impaired coronary microcirculation is known to be associated with left ventricular hypertrophy and HFpEF, nicorandil could improve not only CSX but HFpEF via the restoration of coronary microvascular dysfunction.>

Bacteremic pneumococcal pneumonia: clinical outcomes and preliminary results of inflammatory response.

Further examination of clinical outcomes and inflammatory response of bacteremic pneumococcal community-acquired pneumonia (CAP) is of great interest to enhance the care of patients with pneumococcal CAP. This is a secondary analysis of the Community Acquired Pneumonia Organization (CAPO) to compare the time to clinical stability (TCS), length of hospital stay (LOS), and in-hospital mortality of hospitalized pneumococcal CAP patients with and without bacteremia. To measure the effect of bacteremia in pneumococcal CAP patients on outcomes, we modeled all-cause in-hospital mortality using a Poisson regression model, and TCS and LOS using Cox proportional hazards models. Adjusted multivariate regression models were also used to predict the probability of occurrence of each of the study outcomes. To investigate the inflammatory response, we measured the plasma levels of pro- and anti-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1rα, IL-6, IL-8, IL-10], inflammatory biomarkers [C-reactive protein (CRP), pro-calcitonin (PCT), and B-type natriuretic peptide (BNP)], and peripheral blood neutrophil responses in 10 patients, 4 bacteremic and 6 non-bacteremic pneumococcal CAP, upon admission and every other day during the first 6 days of hospitalization. Functional data were presented as median and standard error of the median (SEM); due to small number of samples no statistical comparisons were performed between groups. From 833 pneumococcal CAP patients, 394 patients (47 %) were bacteremic. Bacteremic pneumococcal CAP were less likely to reach TCS with an adjusted hazard ratio (AHR) of 0.82 (95 % CI 0.69-0.97; p = 0.02) and had higher in-hospital mortality with an AHR of 1.63 (95 % CI 1.06-2.50, p = 0.026). Bacteremic pneumococcal CAP patients had a longer LOS than non-bacteremic pneumococcal CAP (p < 0.003). Higher plasma levels of CRP, PCT, and BNP were found in bacteremic than in non-bacteremic patients. The bacteremic group had consistently higher plasma levels of both pro- and anti-inflammatory cytokines. The blood neutrophil functional responses were similar in both groups of patients. Bacteremic pneumococcal CAP patients were significantly associated with higher in-hospital mortality, lower TCS, and longer LOS. HIV-infected patients showed a greater mortality which was not statistically significant. Bacteremic pneumococcal CAP patients had higher levels of biomarkers and systemic cytokines.