N-terminal Pro Natriuretic Peptide Levels Research Articles

Dapagliflozin and sacubitril on myocardial microperfusion in patients with post-acute myocardial infarction heart failure and type 2 diabetes.

Coronary heart disease and type 2 diabetes mellitus (T2DM) frequently coexist, creating a complex and challenging clinical scenario, particularly when complicated with acute myocardial infarction (AMI). To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion. In total, 98 patients were categorized into control (n = 47) and observation (n = 51) groups. The control group received noxital, while the observation group was treated with dapagliflozin combined with noxital for 6 months. Changes in myocardial microperfusion, blood glucose level, cardiac function, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, growth differentiation factor-15 (GDF-15) level, and other related factors were compared between the two groups. Additionally, the incidence of major adverse cardiovascular events (MACE) and adverse reactions were calculated. After treatment, in the observation and control groups, the corrected thrombolysis in myocardial infarction frame counts were 37.12 ± 5.02 and 48.23 ± 4.66, respectively. The NT-proBNP levels were 1502.65 ± 255.87 and 2015.23 ± 286.31 pg/mL, the N-terminal pro-atrial natriuretic peptide (NT-proANP) levels were 1415.69 ± 213.05 and 1875.52 ± 241.02 ng/mL, the GDF-15 levels were 0.87 ± 0.43 and 1.21 ± 0.56 g/L, and the high-sensitivity C-reactive protein (hs-CRP) levels were 6.54 ± 1.56 and 8.77 ± 1.94 mg/L, respectively, with statistically significant differences (P < 0.05). The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group (P < 0.05). The incidence of adverse reactions was 13.73% (7/51) in the observation group and 10.64% (5/47) in the control group, with no statistically significant difference (P > 0.05). Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM. The underlying mechanism may be related to the reduction in the expression levels of NT-proANP, GDF-15, and hs-CRP.

Abstract P157: Racial Differences In Atrial Natriuretic Peptide And Insulin

Low circulating concentrations of the natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). As a group, African Americans (AA) have lower NP levels and are disproportionately burdened by T2D. Insulin, which is higher in AA, has been shown to regulate NP concentration by increasing the NP clearance receptor. This secondary analysis tests the hypothesis that higher insulin in AA will be associated with lower levels of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP). Participants were 120 AA and European American (EA) men and women ages 19-45 years. Measures of insulin, including fasting insulin and insulin total and incremental area under the curve (AUC and iAUC, respectively, at 30 and 120 m), were derived from an oral glucose tolerance test (OGTT). Insulin sensitivity (SI Clamp ) was assessed using the euglycemic glucose clamp. NT-proANP was measured from fasting samples obtained during the OGTT. Differences in NT-proANP by race was evaluated with analysis of covariance while adjusting for age, sex, and BMI. Linear regression models were used to examine associations between NT-proANP and insulin measures while adjusting for age, sex, race, and BMI. Relative to EA, AA had higher insulin concentrations, lower insulin sensitivity, and lower NT-proANP levels (p&lt;0.05). Fasting insulin and 30 m insulin AUC were inversely associated with NT-proANP (p=0.02, p=0.02, and p=0.04, respectively). These results suggest that the lower NT-proANP observed in AA is related to higher insulin. Future research is needed to investigate the relationship between insulin, ANP, and the NP clearance receptor, particularly in populations at risk for chronic disease.

Correlation between N-terminal pro-atrial natriuretic peptide, corin, and target organ damage in hypertensive disorders of pregnancy.

The objective was to evaluate the correlation between N‐terminal pro‐atrial natriuretic peptide (NT‐proANP), corin and the severity of target organ injury in hypertensive disorders of pregnancy. A total of 78 women with hypertensive disorders of pregnancy and 49 normotensive pregnancies were enrolled. The clinical characteristics, laboratory index and echocardiogram results were collected. NT‐proANP, corin, sFlt‐1 and PlGF levels were measured. A receiver's operating characteristics (ROC) curve was performed to evaluate the efficacy of predicting target organ injury in the HDP group. The NT‐proANP, corin, and sFlt‐1/PlGF ratio were increased in the HDP group (p < .05). The area under the curve (AUC) predicted by NT‐proANP and corin were larger than sFlt‐1/PlGF ratio (0.779, 0.867, and 0.766, respectively). The creatinine and urine protein were significantly increased, while the estimated glomerular filtration rate (eGFR) was dramatically decreased in the HDP group (p < .05 each). The left atrial diameter (LAD), left atrial volume index (LAVI), left ventricular posterior wall thickness (LVPWT), and left ventricular septal thickness (LVST) were larger in the HDP group (p < .001 each). The NT‐proANP/corin levels were positively correlated with LAD, creatinine, and urine protein, and negatively correlated with eGFR in HDP group (p < .05 each). Multiple regressions demonstrated that NT‐proANP was an independent risk factor of LAD and urine protein, and corin was an independent risk factor of creatinine and eGFR in HDP group. NT‐proANP and corin may be reliable biomarkers for evaluating the severity of target organ damage in the hypertensive disorders of pregnant patients.

Gender difference of association between plasma N-terminal pro-atrial natriuretic peptide and metabolic syndrome.

The natriuretic peptides (NPs) system, and mainly atrial natriuretic peptide (ANP), plays a key role in human metabolism and cardiometabolic disorders. Due to differences in NP levels and in prevalence of metabolic syndrome (MetS) between men and women, we aimed to explore the gender difference of association between N-terminal pro-atrial natriuretic peptide (NT-proANP) and MetS in a general population in China. Participants' weight, height, waist circumference, blood pressure, plasma NT-proANP, and other traditional biomarkers were measured. Multivariate logistic regression models were used to determine the association between plasma NT-proANP and MetS, and the odds ratio (OR) and 95% confidence interval (CI) were calculated for men and women, respectively. Among 2203 participants, 1361 (61.78%) were women, 687(30.77%) participants had MetS, and the average age was 53years. Women had a higher level of NT-proANP than men. However, adjusted logistic regression demonstrated that men in the upper quartile group of NT-proANP had 0.60 (95% CI 0.39-0.92) times the risk of having MetS, while women in the upper quartile group had 1.10 (95% CI 0.77-1.56) times the risk of having MetS compared to the lower quartile group. Furthermore, with the increase of the level of NT-proANP, the ORs showed a declining trend in men (P = 0.017), but it was not statistically significant among women (P = 0.700). There are gender differences in the relationship between NT-proANP and MetS, while an inverse association between plasma NT-proANP and MetS in men suggests that higher levels of NT-proANP may be a protective factor for MetS.

Serum 25-Hydroxy Vitamin D Levels in Japanese Infants with Respiratory Syncytial Virus Infection Younger than 3 Months of Age.

Low blood levels of vitamin D have been reported in children who have frequent respiratory tract infections. We measured serum concentrations of 25-hydroxy (OH) vitamin D in Japanese infants under 3 months of age who had respiratory syncytial virus (RSV) infection. Serum levels of 25-OH vitamin D in the 10 infants, excluding those with underlying diseases, were between < 4 and 29.8 ng/mL. In 8 out of 10 subjects (80.0%), serum 25-OH vitamin D levels were lower than 20 ng/mL. There was no statistically significant association between the levels of 25-OH vitamin D and age, duration of admission, respiratory severity score, white blood cell count, blood gas levels, and N-terminal pro-natriuretic peptide levels. Levels of serum 25-OH vitamin D in children who required hospitalization owing to RSV infection were low, indicating deficiency. These results suggest that vitamin D deficiency affects the susceptibility to RSV infection, but not the severity of the infection.

Atrial natriuretic peptide predicts disease progression and digital ulcers development in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune disease characterized by micro/macrovascular damage due to the underlying fibrosis. Markers able to predict the progression of cardiovascular damage, including digital ulcers, in SSc are warranted. We aimed at characterizing the relevance of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide plasma levels in relation to cardiovascular damage and digital ulcers in a cohort of Italian SSc patients. Seventy patients were enrolled (64 women and six men; mean age 56.7 ± 14 years) with a disease duration of 11.1 ± 8.3 years. Clinical, instrumental (nailfold videocapillaroscopy, ECG, transthoracic echocardiography, pulmonary function test with diffusion lung CO), NT-proANP and N-terminal probrain natriuretic peptide plasma levels measurement were performed at baseline. The clinical follow-up lasted 24 months. The statistical approach used to achieve the study objectives included multivariate analysis, receiver operating characteristic curve, Kaplan-Meier and Cox regression analyses. Both NT-proNPs levels correlated with systolic pulmonary arterial pressure, but only the NT-proANP level correlated with right heart dimension. Both NT-proNPs levels were higher in patients experiencing events at follow-up but only the NT-proANP level significantly predicted the progression of cardiovascular damage, including development of pulmonary arterial hypertension (PAH). NT-proANP levels were higher in patients with digital ulcers and strongly predicted their development. Our results show that the NT-proANP plasma level significantly correlates with disease progression such as new onset of PAH, worsening of pulmonary hypertension and development of digital ulcers in a cohort of SSc Italian patients. If future studies will confirm our findings, the plasma NT-proANP level could be used in clinical practice as a novel sensitive marker for PAH and digital ulcers development in SSc.

SAT-080 Dexamethasone Administration Stimulates Acute Increases in Natriuretic Peptides in Humans: A Potential Diagnostic Test for "Natriuretic Peptide Hormone Deficiency"?

Background: Animal models and human genetic investigations suggest that lower levels of natriuretic peptides (NP), which are cardiac-derived hormones, are associated with the development of obesity, insulin resistance, type 2 diabetes, and hypertension. However, whether lower resting NP levels in humans reflect a true hormone deficiency (analogous to other hormone deficiencies like adrenal insufficiency) is unknown, in part, because a diagnostic test for NP deficiency is currently lacking. One strategy for developing a diagnostic test for NP deficiency is to identify a stimulus that provokes an increase in NP concentrations. Dexamethasone is a potent stimulus for NP production in animals, but its effect on NP levels in humans is not well defined. Objective: We sought to define the effects of dexamethasone on circulating NPs over time in healthy humans. We hypothesized that dexamethasone would stimulate increases in NP levels, and that we could characterize the magnitude and timing of the changes as a primary step toward developing a diagnostic test for NP deficiency. Methods: 10 healthy, lean women (mean age 28 + 5 years, mean BMI 22.5 + 1.6 kg/m2) received a single 4 mg IV dose of dexamethasone after an overnight fast. Plasma levels of N-terminal pro-atrial natriuretic peptide (NT-proANP) and N-terminal pro- b-type natriuretic peptide (NT-proBNP) were serially measured during 2 time periods following dexamethasone: 1) “Acute Phase”: 0-8 hours, and 2) “Extended Phase”: at 24, 48, and 72 hours. Changes in NPs were analyzed using a piecewise random effects model for the 2 time periods. Results: During the Acute Phase after dexamethasone, a biphasic change in NT-proANP was observed (nonlinear, p<0.001). Median NT-proANP initially increased, with a peak increase of 24% occurring at 2.5 hours, and thereafter decreased until 8 hours (to 21% below baseline). During the “Extended Phase,” NT-proANP levels rebounded (p<0.001) and returned to near baseline by 72 hours. Next, median NT-proBNP increased during the Acute Phase (p= 0.016), with a peak increase of 27% occurring at 8 hours, and subsequently declined during the Extended Phase (p= 0.04) to a median value 24% lower than baseline at 72 hours. Discussion: Dexamethasone appears to acutely stimulate NP production in humans, as evidenced by an initial increase, followed by a subsequent decline, in circulating NP levels. The time course differs between NT-proANP and NT-proBNP, with NT-proANP peaking earlier than NT-proBNP. These pilot data may inform larger studies for establishing population norms for the NP response to glucocorticoids and evaluating whether a NP stimulation test with glucocorticoids may be a useful test for diagnosing NP deficiency.

Abstract 17240: A Pilot Clinical Trial to Study Racial Differences in Natriuretic Peptide Response to a High-Carbohydrate Challenge

Introduction: Human genetic studies have shown a greater risk of cardiometabolic disease with genetically lower natriuretic peptide (NP) levels. We have previously shown that blacks have lower NP levels than whites albeit in older individuals, which is partly explained by genetic factors. A high-carbohydrate challenge in young healthy whites was associated with a reduction in N-terminal pro atrial NP (NTproANP) levels, but no data exist in blacks. Hypothesis: We hypothesized that 1) the baseline differences in NP levels by race would be evident in young adults with no comorbidities; 2) blacks would have a reduction in NTproANP levels in response to high-carbohydrate challenge similar to whites but the magnitude of change would differ. Methods: Healthy self-identified blacks and whites were screened for the presence of laboratory abnormalities. Each eligible participant was provided 3 days of study diet to standardize salt intake. After the dietary intervention, subjects were brought to the clinical research unit for a high-carbohydrate challenge. Venous blood was collected every hour for 8 hours to perform biochemical assays. African ancestry proportions among self-identified blacks were also determined. Results: We recruited 56 healthy participants with a mean age of 26 years, 48% female, 54% whites, mean body mass index 26 kg/m 2 , and an average proportion of 90% African ancestry among self-identified blacks. We found that BNP levels were 24% (95% CI 53 to 6) and N-terminal-proB-type NP (NTproBNP) levels were 44% (95% CI 99 to 17) lower in blacks compared with whites. The decrease in NTproANP levels in response to carbohydrate challenge differed by race (p for interaction=0.03). In response to a carbohydrate challenge, blacks had a 24% reduction in the NTproANP levels (p=0.01) vs. a 47% decrease in the NTproANP in whites (p&lt;0.001) ( Figure, Panel A ), with no change in NTproBNP levels in both races ( Figure, Panel B ). Conclusions: Blacks have an endogenously suppressed NP system which may be a biologic determinant contributing to racial disparities in cardiometabolic disease. We have shown that high-carbohydrate diet has a differential effect on NP system by race which needs to be considered while individualizing strategies for disease prevention. ( NCT# 03072602 ).

Acute effects of insulin on circulating natriuretic peptide levels in humans

BackgroundThe natriuretic peptide hormones play an important role in salt and blood pressure regulation. In observational studies, obesity and insulin resistance have been consistently associated with lower concentrations of natriuretic peptides. It has been proposed that insulin influences natriuretic peptide production.ObjectiveWe sought to determine the acute effects of insulin administration on natriuretic peptide concentrations.Methods31 men and women (11 lean, 10 overweight, and 10 obese), ages 30–70 years, without cardiovascular disease or overt diabetes underwent a hyperinsulinemic-euglycemic insulin clamp. Plasma concentrations of N-terminal pro atrial natriuretic peptide (NT-proANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured at baseline and steady-state (the final 30 minutes of the clamp protocol).ResultsFrom baseline to steady-state, insulin levels increased from a mean level of 9.5 to 176.7 μU/ml (p<0.001). Over this period, circulating NT-proANP concentrations decreased by 9% (-1933 ng/L, p = 0.01). The changes in NT-proANP did not differ between lean, overweight, and obese individuals. Steady-state NT-proANP levels, adjusted for baseline, were lower in individuals with greater insulin resistance, independent of BMI. In contrast to NT-proANP, NT-proBNP levels did not change significantly during the clamp (p = 0.41).ConclusionInsulin administration was associated with a moderate decrease in circulating NT-proANP, but not NT-proBNP. The lowest NT-proANP concentrations were found in insulin-resistant individuals. Further investigations are warranted to elucidate potential mechanisms underlying the effects of insulin on the cardiac hormonal axis.

Assessment of left atrial volume and function by real time three-dimensional echocardiography in obese patients.

To evaluate left atrial (LA) volume and functions in obese subjects using real time three-dimensional echocardiography (RT3DE) and also the relationship between LA mechanical functions and N-terminal pro-atrial natriuretic peptide (NT-proANP). This study included 40 obese (26 females and 14 males, mean age 51.9years) and 40 normal weight subjects (23 females and 16 males, mean age 53.5years) with normal coronary angiograms. All the study participants underwent RT3DE to assess LA volume and mechanical function. Plasma NT-proANP was determined by ELISA method. There was no significant difference between groups in left ventricular (LV) diameters and ejection fraction, which reflect LV systolic function. However, transmitral deceleration time, isovolumetric relaxation time, and peak late diastolic tissue Doppler velocity values, which reflect LV diastolic function, were found to be significantly higher in obese subjects when compared with controls. LA maximum volume (LAVmax), LAVmax index (LAVI), LA minimal volume (LAVmin), before atrial contraction volume (LAVpreA), LA active emptying volume, LA total emptying volume, and LA active emptying fraction, which reflect LA reservoir and pump functions, were also higher in obese subjects when compared with controls. LA passive emptying fraction was significantly lower in obese subjects than in controls. NT-proANP levels were similar between groups. There were positive correlations between NT-proANP level and LAVI, LAVmax, LAVmin, LAVpreA, and LA total and active emptying volumes. Left atrial mechanical functions and volumes are impaired in obese subjects. These findings may be regarded as early markers of subclinical cardiac failure in obese subjects who have not yet exhibited any clinical evidence of cardiovascular disease.

Cross-laboratory analytical validation of the cardiac biomarker NT-proANP in rat

Natriuretic peptides, including N-terminal-proatrial natriuretic peptide (NT-proANP) are cardiac hormones that are produced in response to myocardial stretch and have been used in rats and humans as blood based functional cardiac biomarkers. There are limited validation data of these assays in rats and therefore the Predictive Safety Testing Consortium, Cardiac Hypertrophy Working Group (PSTC-CHWG) performed a cross-laboratory (5 laboratories) analytical evaluation of a commercially available NT-proANP ELISA for use with rat samples. Serum samples were collected from normal Sprague Dawley (SD) rats and were spiked with kit calibrator material or rat heart tissue extracts to provide specimens for the validation. In addition, the cardiotoxicant, isoproterenol, was used to induce elevated endogenous NT-proANP levels in a subgroup of rats for additional validation specimens. The Biomedica™ (BI-20892, Vienna, Austria) proANP (1-98) enzyme-linked immunoabsorbent assay (ELISA) kit was used to measure NT-proANP. Intra-assay and inter-assay precisions, accuracy, sample linearity, recovery, limit of detection, upper and lower limits of quantitation (ULOQ and LLOQ, respectively), sample-freeze/thaw stability and stored sample stability were assessed and compared to pre-determined acceptance criteria. The majority of the experimental assessments met the established validation criteria, however there were individual results that did not meet these standards. Overall, acceptable intra- and inter-assay precisions and accuracies as well as inter-laboratory precision and accuracy were demonstrated. Linearity and recovery values fell within the pre-determined acceptance criteria, samples remained stable for up to three freeze-thaw cycles and frozen samples were stable at ~-70 °C for 12 months. The limit of detection (LOD) and LLOQ and ULOQ were similar to those specified by the manufacturer. Overall, the assay was demonstrated to be technically adequate for the detection of NT-proANP serum levels in SD rats.

Plasma concentration of N-terminal pro-atrial and N-terminal pro-brain natriuretic peptides and fluid balance in children with bronchiolitis.

The aim of this study was to evaluate the plasma levels of N-Terminal pro-brain natriuretic peptide (N-BNP), N-Terminal pro-atrial natriuretic peptide (N-ANP) and antidiuretic hormone (ADH) over time and their relationship to clinical indicators in hospitalized children with bronchiolitis. Prospective crossover clinical investigation. Hospitalized children in a university-affiliated hospital. Twenty-seven children (birth to 24 mo) with first episode of bronchiolitis and 34 age-matched healthy controls. Daily blood samples up to five consecutive days were obtained for N-BNP, N-ANP and ADH in the bronchiolitis group and on the initial blood draw in the control group. Daily total fluid intake, net fluid balance and clinical bronchiolitis severity levels were recorded. N-BNP and N-ANP levels were measured by enzyme-linked immunosorbent assay. ADH levels were measured by a double antibody technique. The mean age (months ± SD) in the bronchiolitis group was 4.2 ± 5.9 mo and 12.0 ± 6.1 mo in the control group; 51.9% of bronchiolitis patients were positive for respiratory syncytial virus (RSV). In patients with bronchiolitis on admission, plasma N-BNP measurements (mean ± SD) were elevated (996.0 ± 570.2 fmol/mL) compared to controls (552.7 ± 264.7 fmol/mL P < 0.005). Serum N-ANP levels were also initially elevated (3,889 ± 1,769.7 fmol/mL) compared to controls (2,173 ± 912 fmol/mL P < 0.005). The serum levels of N-BNP and N-ANP remained significantly elevated from day 2 through day 5. Similarly, ADH levels were significantly higher on admission in the bronchiolitis group (10 ± 7.49 pg/mL) vs. the control group (5.8 ± 5.5 pg/mL P < 0.05), but quickly decreased from day 2 through day 5. N-BNP, N-ANP and ADH concentrations were elevated in hospitalized children with bronchiolitis at admission. Based on our observation, judicious fluid management is indicated in children hospitalized with bronchiolitis.

Circulating atrial natriuretic peptide genetic association study identifies a novel gene cluster associated with stroke in whites.

The goal of this study was to identify genetic determinants of plasma N-terminal proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in vitro cell studies and on disease susceptibility. Genotyping was performed across 16 000 genes in 893 randomly selected individuals, with replication in 891 subjects from the community. Plasma NT-proANP1-98 concentrations were determined using a radioimmunoassay. Thirty-three genome-wide significant single-nucleotide polymorphisms were identified in the MTHFR-CLCN6-NPPA-NPPB locus and were all replicated. To assess the significance, in vitro functional genomic studies and clinical outcomes for carriers of a single-nucleotide polymorphism rs5063 (V32M) located in NPPA that represented the most significant variation in this genetic locus were assessed. The rs5063 variant allozyme in transfected HEK293 cells was decreased to 55±8% of wild-type protein (P=0.01) as assessed by quantitative western blots. Carriers of rs5063 had lower NT-proANP levels (1427 versus 2291 pmol/L; P<0.001) and higher diastolic blood pressures (75 versus 73 mm Hg; P=0.009) and were at an increased risk of stroke when compared with wild-type subjects independent of age, sex, diabetes mellitus, hypertension, atrial fibrillation, and cholesterol levels (hazard ratio, 1.6; P=0.004). This is the first large-scale genetic association study of circulating NT-proANP levels performed with replication and functional assessment that identified genetic variants in the MTHFR-CLCN6-NPPA-NPPB cluster to be significantly associated with NT-proANP levels. The clinical significance of this variation is related to lower NT-proANP levels, higher blood pressures, and an increased risk of stroke in the general community.

Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease

To evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease. Seventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease. Prospective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed. The hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6-12.5; p < 0.001). The median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95% confidence interval, 5.6-12.6 months), compared to 54 months (46 - infinity) for dogs with concentrations ≤ 1000 pmol/l (p < 0.001). Due to intra- and inter-individual variability, most corresponding analyses for NOx were insignificant but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching CHF (23 vs. 28 μmol/l, p = 0.016). Risk of CHF increased with increase in heart rate (>130 beats per minute) and grade of murmur (≥ 3/6). The risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months.

0283: Correlation between N-terminal pro-natriuretic peptide levels and left atrial size in patients with left ventricular systolic dysfunction

Elevated N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP) levels are correlated with the severity of left ventricular systolic dysfunction and left ventricular filling alterations. Besides, left atrial (LA) size is believed to reflect chronic diastolic dysfunction. Evaluate the relationship between NT Pro-BNP and LA size. 81 patients (77.7% males; mean age, 61.55±15 years), with left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] <55%), underwent transthoracic echocardiography to evaluate LA size and venous blood sampling to determine NT-pro-BNP levels. Mean LVEF was 35.6±10.8 % (LVEF <35% in 32 patients). The NT Pro-BNP values were elevated (mean 3304±4218.9 pg/ml). Higher NT Pro-BNP was significantly correlated to LA size (r=0.56, p<0.001). The optimal cut-off value to predict LA size >20 cm2 was 1188 pg/mL (area under the receiver-operating characteristic curve [AUC] 0.83 [0.71–0.93], p<0.0001, sensitivity 77.6%, specificity 75%). The present study shows that plasma NT Pro-BNP levels is strongly correlated to LA size. NT-proBNP level more than 1188 pg/mL may suggest LA dilatation.

GW24-e2957 Efficacy of ivabradine in combination with metoprolol versus uptitration of metoprolol in patients after Q-wave myocardial infarction with early left ventricular systolic dysfunction

ObjectivesThe purpose of the study was to evaluate the effect of combination of ivabradine with metoprolol tartrate versus uptitration of metoprolol tartrate on left ventricular (LV) systolic function and plasma...

Neurohormonal and cytokine fluctuations following transcatheter closure for an atrial septal defect

Inflammation and neurohormonal activation are considered to be involved in the development of earlier and/or later complications in congenital heart disease patients, even after a successful repair of the lesion. It is not yet clarified what is the role of the therapeutic interventions in the occurrence of such a response and how it could be associated with possible postoperative complications. We sought to assess the inflammatory and neurohormonal response to transcatheter closure of secundum type atrial septal defects (ASD) over a six-month follow-up period. We also evaluated the association between the respective markers and catheterization data as well as echocardiographic measurements. Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), N-terminal-proatrial natriuretic peptide (NT-proANP) and N-terminal-probrain natriuretic peptide (NT-proBNP) were assessed and echocardiographic measurements were performed in twenty-eight patients with atrial septal defect prior to, and at the first, second and sixth months post transcatheter closure. Thirty-three age-matched healthy volunteers were also enrolled. IL-6 plasma levels, although higher preoperatively, [physical logarithm (ln) IL-6: 3.37±0.66 vs 2.92±0.44 pg/ml, p=0.015], reached control levels postoperatively, at the end of the third month, whereas TNF-α and IL-10 were not influenced by the procedure. NT-proANP levels were elevated preoperatively compared to the control group (ln NT-proANP 3.78±0.572 vs 3.48±0.30, p=0.031), with a further significant increase during the 1st month (ln NT-proANP 3.78±0.572 vs 4.2±0.42, p=0.006), following the pattern of the left atrial volume enlargement, and remained high even 6 months after the procedure .On the other hand, the initially normal concentrations of NT-proBNP, after a transient significant increase during the first month postoperatively (ln NT-proBNP 3.56±0.94 vs 4.58±0.91, p<0.0001) returned to the controls' levels at the end of the third month. Preoperative concentrations of NT-proANP positively correlated with NT-proBNP concentrations and pulmonary to systemic flow ratio (Qp/Qs). Transcatheter closure could improve, on a mid- term basis, the inflammatory process but natriuretic peptides' secretion continues in parallel with left atrial volume increase. Further follow up is required to determine the long-term progress of the inflammatory and neurohormonal response to the procedure.

Plasma soluble corin and N-terminal pro-atrial natriuretic peptide levels in pregnancy induced hypertension

One of the theories involved in the pathogenesis of pregnancy induced hypertension involves salt and water retention. We aimed to measure the proenzyme convertase corin, responsible for pro-atrial natriuretic peptide (ANP) cleavage to active ANP, in plasma of hypertensive pregnant females. Sixty pregnant females suffering from pregnancy induced hypertension in second and third trimesters of pregnancy were compared to twenty eight healthy pregnant females of the same gestational period. Concomitant urine and plasma samples were collected for the determination of some biochemical parameters. Plasma soluble corin and N-terminal (NT) pro-ANP (1-98) values were determined in both groups using enzyme immunoassays. Plasma soluble corin mean value was significantly higher in the patient group compared to the control group. Upon dividing the patient group according to blood pressure, plasma NT pro-ANP showed significantly higher mean value in the group with blood pressure⩾140/90mmHg compared to the group with blood pressure<140/90mmHg and control group. High plasma soluble corin and NT pro-ANP values in hypertensive pregnant females particularly those with blood pressure⩾140/90mmHg speculates an ANP receptor/ post receptor signaling defect, which would aggravate the pregnancy induced hypertensive state.

Characterization of End-Stage Renal Disease After Liver Transplantation in Transthyretin Amyloidosis (ATTR V30M)

Transthyretin (TTR) amyloidosis, an autosomal-dominant disease, is characterized by peripheral and autonomic neuropathy--familial amyloidotic polyneuropathy (FAP). End-stage renal disease (ESRD) occurs at 10 years after the onset of neuropathy. Orthotopic liver transplantation (OLT) is the usual treatment of choice. We evaluated FAP patients, ATTR V30M, before and after OLT who started dialysis within 3 months after surgery. The 11 patients had an age at the onset of neuropathy of 31.9 ± 6.3 years with a mean evolution of disease to OLT of 4.54 ± 2.5 years. The glomerular filtration rate was <60 mL/min in 2 patients, 2 displayed nephrotic range proteinuria, and 3 had microalbuminuria. Elective pacemaker implantation was necessary in 8 subjects. Post-OLT 3 patients developed proteinuria, 2 of whom showed increasing nephrotic syndrome. Dysautonomia worsened leading to bladder catheterization in 6. In patients with previous normal renal function and proteinuria <3 g/d, the evolution of neuropathy to the first dialysis was 14.6 ± 4.2 years versus 7.5 ± 1.1 among the other subjects. Overall, dialysis was implemented at 7.4 ± 4.9 years after surgery. There was no liver graft dysfunction. The heart evaluation post-OLT showed the following: 3 patients with de novo dysrhythmias requiring pacemaker implantation and 3 with N-terminal pro-natriuretic peptide levels >10,000 pg/mL. Death occurred in 4 subjects at an average of 26 months after initiation of dialysis. Concerning ESRD, there was no clear benefit of transplantation in the early stages. Patients with normal renal function and lower levels of proteinuria showed slower progression to ESRD, irrespective of their duration of neuropathy.

Hypertension During Pregnancy

Hypertension during pregnancy remains a common and potentially devastating complication.1,2 Hypertension can be isolated (gestational hypertension) or associated with proteinuria (preeclampsia) and, rarely, can manifest as a consequence of either preexisting or new onset renal (usually glomerular) disease. Preeclampsia is a particularly worrisome diagnosis, because it carries increased risk for morbidity to the mother and child and may accelerate to the condition of eclampsia in which seizures develop in association with a high risk for fetal and maternal mortality. Although, ideally, the diagnosis of these conditions should involve the use of biomarkers that reflect the underlying pathophysiology of the disease process, the lack of clinically available assays has forced the clinician to diagnose the condition based solely on the clinical presentation. Unfortunately, although establishing cut points for elevated blood pressure and urine protein excretion appears to be straightforward, these continuous variables lend themselves to arbitrary definitions, and this likely explains why the precise definition of preeclampsia has changed several times and why different organizations continue to classify preeclampsia differently.3 A recent report from the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy3 nicely summarized the current status of diagnosing preeclampsia: “Although our current understanding of this syndrome has increased, the criteria used to identify the disorder remain subject to confusion and controversy. The confusion doubtless reflects the fact that preeclampsia is a syndrome, which means that attempts at definition use arbitrarily selected markers rather than changes of pathophysiologic importance.” Adding to this confusion is the fact that a …