Changes In Natriuretic Peptide Levels Research Articles

Changes in Natriuretic Peptide Levels and Subsequent Kidney Function Decline in SPRINT

Rationale & ObjectiveNovel approaches to assessing kidney disease risk during hypertension treatment are needed given the uncertainty in how intensive blood pressure (BP) lowering impacts kidney outcomes. We determined whether longitudinal N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements during hypertension treatment are associated with kidney function decline. Study DesignProspective observational study. Setting& Participants: 8005 Systolic Blood Pressure Intervention Trial (SPRINT) participants with NT-proBNP measurements at baseline and 1 year. Exposure1-year change in NT-proBNP categorized as ≥25% decrease, ≥25% increase, and <25% change (stable). OutcomeAnnualized change in estimated glomerular filtration rate (eGFR) and ≥30% decline in eGFR. Analytical ApproachLinear mixed-effect and logistic regression models were used to evaluate the association of change in NT-proBNP with subsequent annualized change in eGFR and ≥30% decline in eGFR, respectively. Analyses stratified by baseline chronic kidney disease (CKD) status. ResultsCompared with stable 1-year NT-proBNP levels, a ≥25% decrease in NT-proBNP was associated with slower decline in eGFR in those with CKD (adjusted difference [% per year] =1.09 [95% CI, 0.35-1.83]) and without CKD (adjusted difference [% per year] =0.51 [95% CI, 0.21-0.81]; P for interaction =0.4). Meanwhile, ≥25% increase in NT-proBNP in those with CKD was associated with faster decline in eGFR (adjusted difference [% per year] = -1.04 [95% CI, -1.72 to -0.36]) and risk of ≥30% decline in eGFR (adjusted odds ratio: 1.44 [95% CI, 1.06-1.96]); associations were stronger in those with CKD versus without CKD (P for interactions =0.01 and <0.001, respectively). Relationships were similar irrespective of the randomized BP arm in SPRINT (P for interactions >0.2). LimitationsPersons with diabetes and proteinuria > 1 g/d were excluded. ConclusionsChanges in NT-proBNP during BP treatment are independently associated with subsequent kidney function decline, particularly in people with CKD. Studies should assess if dynamic NT-proBNP may be useful in monitoring kidney risk during hypertension treatment.

Effects of Mineralocorticoid Receptor Antagonists in Early-Stage Heart Failure With Preserved Ejection Fraction

BackgroundHospitalization with a first episode of heart failure (HF) is a serious event associated with poor clinical outcomes in HF with preserved ejection fraction (HFpEF). Identification of HFpEF via detection of elevated left ventricular filling pressure at rest or during exercise may allow early intervention. Benefits of treatment with mineralocorticoid receptor antagonists (MRAs) in established HFpEF have been reported, but use of MRAs is not well studied in early HFpEF without prior HF hospitalization. MethodsWe retrospectively studied 197 patients with HFpEF who did not have prior hospitalization but had been diagnosed by exercise stress echocardiography or catheterization. We examined changes in natriuretic peptide levels and echocardiographic parameters reflecting diastolic function following MRA initiation. ResultsOf the 197 patients with HFpEF, MRA treatment was initiated for 47 patients. After a median 3-month follow-up, reduction in N-terminal pro-B-type natriuretic peptide levels from baseline to follow-up was greater in patients treated with MRA than in those who were not (median, -200 pg/mL [interquartile range, -544 to -31] vs 67 pg/mL [interquartile range, -95 to 456], P < 0.0001 in 50 patients with paired data). Similar results were observed for the changes in B-type natriuretic peptide levels. Reduction in the left atrial volume index was also greater in the MRA-treated group than in the non-MRA-treated group after a median 7-month follow-up (77 patients with paired echocardiographic data). Patients with lower left ventricular global longitudinal strain experienced a greater reduction in N-terminal pro-B-type natriuretic peptide levels following MRA treatment. In the safety assessment, MRA modestly decreased renal function but did not change potassium levels. ConclusionsOur results suggest that MRA treatment has potential benefits for early-stage HFpEF.

Periprocedural changes in natriuretic peptide levels and clinical outcome after transcatheter mitral valve repair.

AimsThis multicentre study investigated the association of periprocedural changes in the levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) with clinical outcomes after transcatheter edge‐to‐edge mitral valve repair (TMVR).Methods and resultsPatients were retrospectively analysed who underwent TMVR with the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) and had available sequential NT‐proBNP testing at baseline and 2 months after TMVR. Periprocedural changes in NT‐proBNP following TMVR were assessed as the percent change in NT‐proBNP between baseline and the 2 month follow‐up, and the significant reduction in NT‐proBNP was defined as a decrease of >30% in the follow‐up NT‐proBNP compared with the pre‐procedural NT‐proBNP level. Primary outcome was defined as a composite outcome consisting of all‐cause mortality and hospitalization due to heart failure from 2 months to 2 years after TMVR. Additionally, we identified the cut‐off value of pre‐procedural NT‐proBNP to predict the composite outcome using a receiver operating characteristic analysis (cut‐off: 2485 pg/mL). Of 485 patients undergoing TMVR (age: 76.2 ± 9.2 years, female: 42.1%, secondary mitral regurgitation: 67.2%), 150 patients (30.9%) had the significant reduction in NT‐proBNP (>30%) following the procedure. Patients with the NT‐proBNP reduction had a lower incidence of the composite outcome, compared with those without the reduction in NT‐proBNP (31.4% vs. 40.2%; log‐rank P = 0.03). The significant reduction in NT‐proBNP was also associated with a lower risk of the composite outcome [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.45–0.97; P = 0.04], independently of pre‐procedural NT‐proBNP levels and other clinical parameters. The percent change in NT‐proBNP was associated with a linear trend of the incidence of the composite outcome (adjusted HR per 10% decrease: 0.96; 95% CI: 0.94–0.98; P < 0.001). A stratified analysis revealed that the prognostic impact of the significant reduction in NT‐proBNP was consistent among clinical subgroups, including aetiology of mitral regurgitation (P for interaction = 0.99). Higher pre‐procedural NT‐proBNP level (>2485 pg/mL) was associated with the increased risk of the composite outcome (adjusted HR: 1.50; 95% CI: 1.03–2.17; P = 0.03); however, patients with a higher pre‐procedural NT‐proBNP who achieved the significant reduction in NT‐proBNP had a similar risk of the composite outcome to those with a lower pre‐procedural NT‐proBNP.ConclusionsChanges in sequential NT‐proBNP measurements were associated with clinical outcomes within 2 years after TMVR. The assessment of NT‐proBNP dynamics may be valuable to assess the residual risk for patients undergoing TMVR and could assist with post‐procedural management after TMVR.

The Effect of Minimally Invasive Thoracoscopic Left Atrial Appendage Excision on Cardiac Dynamic and Endocrine Function.

Purpose: Left atrial appendage (LAA) isolation is an effective surgical treatment for decreasing thromboembolic risk. We sought to evaluate the short-term effect of minimally invasive surgery with LAA excision on left atrial dynamic and endocrine function in atrial fibrillation (AF) patients.Methods: A total of 52 patients with paroxysmal AF undergoing minimally invasive surgery with LAA excision in Anzhen Hospital from October 2012 to June 2014 were enrolled in the study. The natriuretic peptide plasma level was determined by enzyme-linked immunosorbent assay (ELISA), and left atrial dynamic function was measured preprocedure by real-time three-dimensional echocardiography and postprocedure after 7 days and 3 months.Results: With the exception of six recurrences, 88.5% (46/52) of the patients were prospectively followed over 3 months in terms of their sinus rhythm postprocedure. No severe operative complications or embolism events occurred within those 3 months. Echocardiography showed a 3–6% decrease in left atrial volume postprocedure, and dynamic function was largely restored by 3 months. There was no significant change in natriuretic peptide levels, although a slight decrease was detected 7 days postprocedure, which gradually recovered by 3 months (P = 0.350).Conclusions: There are no significant differences in left atrial dynamics and natriuretic peptide secretion in AF patients after minimally invasive surgery with LAA excision.

Relation between therapy-induced changes in natriuretic peptide levels and long-term therapeutic effects on mortality in patients with heart failure and reduced ejection fraction.

To assess whether natriuretic peptides (NPs) can be used to reliably predict long-term therapeutic effect on clinical outcomes for patients with heart failure and reduced ejection fraction (HFrEF). HFrEF intervention trials with mortality data were identified. Subsequently, we identified trials assessing therapy-induced changes in NPs. We assessed the correlation between the average short-term placebo-corrected drug or device effect on NPs and the longer-term therapeutic effect on clinical outcomes. Of 35 distinct therapies with an identifiable mortality result (n = 105 062 patients), 20 therapies had corresponding data on therapeutic effect on NPs. No correlation was observed between therapy-induced placebo-corrected change in brain natriuretic peptide or N-terminal pro-brain natriuretic peptide and therapeutic effect on all-cause mortality (ACM) (Spearman r = -0.32, P = 0.18 and r = -0.20, P = 0.47, respectively). There was no correlation between therapy-induced placebo-corrected per cent change in NP and intervention effect on ACM or ACM-heart failure hospitalizations (r = -0.30, P = 0.11 and r = 0.10, P = 0.75, respectively). Short-term intervention-induced changes in NP levels are not reliable predictors of therapeutic long-term effect on mortality or morbidity outcomes for patients with HFrEF.

The value of early repeated N-terminal pro-B-type natriuretic peptide measurement in acute heart failure

The determination of natriuretic peptide levels in patients hospitalized for suspected acute heart failure is important for the confirmation of the diagnosis and for the prognosis. Changes in natriuretic peptide levels in response to therapy have a strong prognostic value. To decide whether repeated natriuretic peptide measurements for acute heart failure show changes that could influence the diagnosis and/or the prognosis. Prospective data collection was carried out of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels on admission and within 12 hours in patients hospitalized for acute heart failure. Only the data of those patients were analyzed whose symptoms started within 24 hours prior to admission and were due to acute heart failure. The 23 patients whose data we analyzed had an average age of 77.9 ± 8.3 years. Most of them had left ventricular systolic dysfunction with an average ejection fraction of 34.1 ± 3.9%. The time between the start of symptoms and the first measurement was 6.7 ± 2.2 hours, while the time until the repeated determination was 6.5 ± 2.2 hours after the first measurement. The median value of the NT-proBNP levels in the 6 hours control showed an increase from 5064 pg/mL to 8847 pg/mL (p<0.0005), which amounts to a 75 percent increase - mean hs-troponin T showed an increase from 46 ± 25 ng/L to 78 ± 51 ng/L (p<0.002). A significant increase in NT-proBNP levels is to be expected in early repeated measurement after hospital admission. This fact could have diagnostic and prognostic consequences if validated in a larger patient population. Orv Hetil. 2018; 159(25): 1009-1012.

The prognostic role of extremely high levels of the B-type natriuretic prohormone with regard to the in-hospital mortality of patients hospitalized for heart failure

Patients hospitalized for heart failure have a very high in-hospital as well as one-year mortality. Natriuretic peptides play both a diagnostic and a prognostic role in this disease. Changes of natriuretic peptide levels in response to therapy are a well-known prognostic marker. Regarding in-hospital mortality, however, little is known about the prognostic value of extremely high levels of natriuretic peptides measured on admission. To decide whether extremely high levels of B-type natriuretic peptide have a prognostic value with regard to in-hospital mortality. NT-proBNP levels on admission and in-hospital mortality were extracted retrospectively from the data of patients treated with heart failure in the cardiology department of the Hospital of St. John of God in Budapest. We separately analyzed the data of patients hospitalized for heart failure in 2015 with extremely high initial NT-proBNP levels. The cut-off value in this regard was 10 000 ng/l. We also analyzed the comorbidities of these patients. The median NT-proBNP level of those patients who survived beyond the index hospital stay in the last 10 years was 4842 ng/l, whereas the median NT-proBNP level of those 182 patients who died during their hospital stay was 10 688 ng/l (p<0.001). In the year 2015, we treated 118 patients with an NT-proBNP level above 10 000 ng/l. Thirteen of these patients died, which means that their in-hospital mortality exceeded 10%. In comparison, the in-hospital mortality of all heart failure patients was 5.8%. The difference of median NT-proBNP levels of surviving versus deceased patients in this group with extremely high NT-proBNP levels was no longer significant (17 080 ng/l vs. 19 152 ng/l). Patients with an NT-proBNP level of >10 000 ng/l on admission have a significantly higher in-hospital mortality. The difference of NT-proBNP levels of surviving versus deceased patients in the group with admission NT-proBNP levels >10 000 ng/l is no longer significant. We could not identify any etiological factors that would explain these extremely high NT-proBNP levels or the excess in-hospital mortality. Orv Hetil. 2017; 158(20): 779-782.

Changes in Serum NT-Pro BNP and Left Atrial BNP Levels after Percutaneous Transvenous Mitral Commissurotomy in Sinus Rhythm Versus Atrial Firilation.

Introduction: Natriuretic peptides are secreted from the heart in response to increased wall stress. Their levels are expected to be increased in patients with mitral stenosis (MS) due to high left atrium (LA) pressure and pulmonary artery pressure (PAP). Percutaneous transvenous mitral commissurotomy (PTMC) if successful is pursued by a rapid decrease in LA pressure and subsequent decrease in pulmonary artery pressure. The concurrent changes in natriuretic peptide levels could be affected with heart rhythm. Methods: Forty five patients with severe rheumatic MS undergoing PTMC were enrolled. We evaluated the serum NT-Pro BNP levels before and 24 hours after PTMC. BNP levels were also measured from the blood samples obtained from LA before and 20 minutes after the procedure. Changes in biomarkers were assessed based on heart rhythm and success of the procedure. Results: While serum NT-Pro BNP levels showed significant decrease 24 hours after the procedure (P= 0.04), BNP levels taken 20 minutes after PTMC from LA were similar to their baseline concentrations (P= 0.26). NT-Pro BNP levels decreased 51.7±182.86 pg/ml for sinus rhythm (SR) and 123.4±520 pg/ml for atrial fibrillation (AF) (P= 0.68). Conclusion: Immediate changes in BNP levels did not predict the success of procedure probably due to the additional balloon inflation attempts in LA in several patients and half-life of BNP. BNP levels obtained later may be of more value considering the half-life of this marker. Heart rhythm was not found to influence the changes in biomarker levels. BNP and NT-pro BNP changes were not found to predict success of the procedure.

Natriuretic peptide levels in intrauterine growth-restricted fetuses with absent and reversed end-diastolic flow of the umbilical artery in relation to ductus venosus flow velocities

To determine if changes in natriuretic peptide levels [propeptide of atrial natriuretic peptide (proANP) and N-terminal propeptide of brain natriuretic peptide (NT-proBNP)] can be demonstrated in fetuses with serious growth restriction and Doppler ultrasonographic findings of hemodynamic compromise. Natriuretic peptides of the umbilical vein (proANP and NT-proBNP), arterial and venous blood gases, as well as lactate levels of the umbilical vein were determined in 38 appropriate for gestational age (AGA) fetuses, and 24 intrauterine growth-restricted (IUGR) fetuses with absent (zero-flow) and 17 IUGR fetuses with reversed end-diastolic flow (reverse-flow) of the umbilical artery. A continuous increase in natriuretic peptides in the presence of progressive deterioration was shown. ANP concentrations were significantly lower in the AGA group (mean 818 fmol/mL; range 508-991 fmol/mL) than the zero-flow group (mean 19,680 fmol/mL; range 13,680-25,080 fmol/mL) and the reverse-flow group (mean 33,880 fmol/mL; range 24,365-41,786 fmol/mL). Significant differences were further demonstrated in BNP concentrations of the AGA group (mean 32 fmol/L; range 25-38 fmol/L), zero-flow group (mean 1191 fmol/L; range 908-1655 fmol/L), and reverse-flow group (mean 3063 fmol/L; range 1281-4968 fmol/L). Additionally, significant differences in lactate concentrations were observed for the three groups: AGA, 2.6 mmol/L (range 2-3 mmol/L); zero-flow group, 4.1 mmol/L (range 3.3-5 mmol/L); and reverse-flow group, 7.7 mmol/L (range 5.9-13.7 mmol/L). Increased ANP levels correlated with the arterial base excess and lactate concentrations, as well as with the flow velocities in the ductus venosus during atrial contraction (a-wave), and both ductus venosus indices (S-a)/D and (S-a)/V(mean). No correlations were established for BNP. As components of a compensatory mechanism, natriuretic peptides exert an influence on the cardiovascular function of the fetus.

Natriuretic peptides in hormonal regulation of hypoxia responses

The possibility that natriuretic peptides' effects are important in hypoxia responses of vertebrates is reviewed. Both the transcription and release of natriuretic peptides are affected by oxygen tension. Furthermore, many of the effects observed in hypoxia, such as diuresis and a reduction of plasma volume, are also caused by treatment of the animal with natriuretic peptides. Also, several clinical observations about changes in natriuretic peptide levels in, e.g., sleep apnea and cyanotic congenital heart disease, are consistent with the idea that hypoxia is involved in the etiology of conditions, in which natriuretic peptide levels increase. Virtually all published information on the relationship between oxygen and natriuretic peptides is based on human studies. Because hypoxic conditions are more common in aquatic than terrestrial environments, future studies about the possible role of natriuretic peptides in hypoxia, as well as the role of hypoxia in the evolution of natriuretic peptides, including the different subtypes, should increasingly involve also aquatic organisms.

Review on natriuretic peptides: where we are, where we are going

Tremendous advances have been made in our understanding of the pathophysiology and treatment of congestive heart failure. However, diagnosis of the disease still remains difficult, even with a comprehensive physical examination. Symptoms such as dyspnea are nonspecific and insensitive indicators for heart failure, which can go largely undetected. Several studies have suggested the need for new diagnostic capabilities, especially with the increasing prevalence of heart failure in the US. The discovery of natriuretic peptides as diagnostic biomarkers has been one of the most critical advances for the management of heart failure. Both B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide have the potential to diagnose heart failure, assess prognostic risk of rehospitalization and mortality, and even help guide treatment. Their relative cost-effectiveness and availability have also facilitated their acceptance into many emergency departments, clinics and in-patient units as standard care when evaluating patients with suspected heart failure. Our understanding of the natriuretic peptide system is still in its infancy, but natriuretic peptides have emerged as important diagnostic and prognostic tools that have generated interest in finding broader applications for their use. The purpose of this review is to discuss the clinical approaches and future applications of natriuretic peptides in diagnosing and managing treatment of congestive heart failure. A comprehensive review of studies to assess the utility of natriuretic peptides for diagnosis and prognosis of heart failure and other conditions. Natriuretic peptides are powerful tools to aid the physician in the diagnosis, prognosis and management of heart failure in both in-patient and out-patient settings. However, natriuretic peptides should be used as an adjunct test as many circumstances can also influence changes in natriuretic peptide levels.

Levosimendan-induced reduction in natriuretic peptide levels during the treatment of decompensated heart failure: Clinical implications — Reply

Although, the potential use of natriuretic peptide testing in treatment monitoring of heart failure remains to be fully clarified, levosimendan-induced reduction in natriuretic peptide levels has consistently been reported to be associated with favorable clinical, hemodynamic, anti-inflammatory and anti-apoptotic effects. Several studies demonstrated that not only is plasma natriuretic peptide level important predictor of long-term outcomes, but changes in natriuretic peptide levels during the treatment of heart failure are also associated with corresponding changes in morbidity and mortality. Re-analysis of the data from our previously published study suggested a greater percentage of NT-proBNP reduction at 48 h in patients who survived compared to those who died in both levosimendan (− 36 ± 8% vs − 24 ± 13%, respectively) and dobutamine (− 32 ± 8% vs + 9 ± 32%, respectively) treatment groups, although not statistically different. The changes in natriuretic peptide levels during therapy reflect short-term hemodynamic improvements and effectiveness of drug regimens, but also may have a role in predicting long-term outcomes.

Serum levels of natriuretic peptides in patients with Behcet’s disease

The objective of our study was to elucidate serum levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) in Behcet's disease (BD) patients with active and inactive period. The multicenter study included 53 patients with active (n = 28) and inactive (n = 25) BD (mean age, 34.3 +/- 9 years; 15 men and 38 women) satisfying the International Study Group criteria and 26 healthy controls (mean age, 34.4 +/- 6.1 years; seven men and 19 women) matched for age and gender from a similar ethnic background. Serum natriuretic peptides levels were determined by enzyme immunoassay kit. Mean serum ANP concentrations in the active patients (4.01 +/- 1.21 ng/ml) were significantly lower than in the healthy controls (5.76 +/- 1.99 ng/ml, p = 0.004). Mean serum BNP levels were found to be significantly higher in both the active (6.19 +/- 2.97 ng/ml) and inactive (6.49 +/- 2.88 ng/ml) BD groups compared with the control group (3.82 +/- 1.1 ng/ml, p = 0.004 and p = 0.001, respectively). Mean serum CNP concentrations in the active patients (0.49 +/- 0.12 ng/ml) were significantly lower than in the inactive patients (0.65 +/- 0.2 ng/ml, p = 0.017) and the healthy controls (0.8 +/- 0.27 ng/ml, p < 0.001). Our results suggest that changes in natriuretic peptide levels may be associated with vasculitis that play role in the etiopathogenesis of the BD.

The effect of 24 h intravenous infusion of levosimendan on changes of natriuretic peptide levels in patients with congestive heart failure

Introduction: Natriuretic peptides have been suggested to serve as diagnostic markers and indicators of therapeutic response in patients with congestive heart failure (CHF). Levosimendan (LS) is a calcium sensitizer with inotropic and vasodilatory effects for the treatment of CHF. An active metabolite, OR-1896, prolongs the hemodynamic effects of LS by several days. Objectives: The suitability of natriuretic peptides (NT-proANP and NT-proBNP) as markers for the duration of LS effect was investigated. Methods: 22 patients with NYHA II-IV CHF were randomised to receive either LS or placebo in 1:1 ratio. LS dose was 12 mcg/kg bolus followed by 0.1 mcg/kg/min infusion for 50min and 0.2 mcg/kg/min infusion for 23h. Plasma NT-proANP and NT-proBNP samples were analysed from baseline up to 14 days after the start of the infusions using radioimmunoassay. Invasive PCWP and PAP was measured up to 6h after infusion start using Swan-Ganz catheter. Results: A rapid decrease in NT-proANP was evident in the LS treated patients already at 2h compared with placebo (median change −36% vs 0%, p=0.02). NT-proANP levels remained statistically significantly lower in LS than in placebo treated patients up to day 7 (median change −36% vs −8%, p=0.007). The decrease in NT-proBNP in response to LS came slower than in NT-proANP, with a significant difference at 24h after infusion start (median change −50% vs −19%, p=0.03). The decrease of NT-proBNP remained significantly lower in LS treated patients up to day 2 (median change −52% vs- −41%, p=0.02). The mean correlation during 6h between NT-proANP and PCWP was 0.634 and between NT-proBNP and PCWP 0.650. Conclusions: According to changes in natriuretic peptide levels the hemodynamic effects of LS last at least up to seven days. Natriuretic peptide levels correlated well to invasively evaluated PCWP. Natriuretic peptides seem to serve as good surrogate markers for the evaluation of the hemodynamic response to LS.