Change In NT-proBNP Levels Research Articles

Dapagliflozin cardiovascular effects on end-stage kidney disease (DARE-ESKD-2) trial: rationale and design.

ABSTRACT Background Dapagliflozin prevents myocardial dysfunction in chronic kidney disease patients regardless residual kidney function, We hypothesized that this effect is extensible also to patients on dialysis. Research design and methods The DARE-ESKD-2 is an ongoing, single-center, open-label randomized clinical trial designed to determine the effects of adding dapagliflozin to standard treatment on myocardial function and structure. Eligible patients were adults on a regular dialysis scheme for more than 3 months. Pregnancy, liver failure, allergy to the investigational drug, and prior use of SGLT2i were exclusion criteria. Participants were randomized in a 1:1 ratio to dapagliflozin or standard treatment groups for 24-weeks. The primary goal is to compare the change in NT-proBNP levels between study arms, and secondary goals include comparing the between-group difference in left ventricle global longitudinal strain, indexed mass, ejection fraction, and E/e` ratio, and on symptoms scale and 6-minute walk test distance. An exploratory analysis will evaluate changes in body composition and bone densitometry. Results The trial has finished the enrollment of 80 patients, that are currently being followed-up. Conclusions This trial will provide novel data on myocardial effects of SGLT2i in dialysis recipients. Results from this study may provide evidence to support SGLT2i use in ESKD.

Association Between Late Gadolinium Enhancement with or Without Reverse Remodeling and Prognosis.

Late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR) prevents left ventricular reverse remodeling (LVRR), resulting in a poor prognosis. However, the prognosis of patients who have LGE and achieve LVRR and patients who do not have LGE and do not achieve LVRR remains unknown. This study aimed to answer this question by sorting patients with heart failure based on the presence of LGE and LVRR and comparing their prognoses. Another aim was to identify useful factors for predicting LVRR.All patients were followed-up for 24 months. LVRR was defined as a ≥ 10% increase at the last follow-up at 12 ± 6 months from baseline, on echocardiography. The primary endpoint was a composite of cardiovascular death and hospitalization due to worsening heart failure within 18 ± 6 months. Baseline data and data from each outpatient visit were collected and analyzed. We enrolled 80 consecutive patients with heart failure and reduced left ventricular ejection fraction (< 50%) who underwent CMR.LGE was positive in 40 patients (50.0%) and LVRR was observed in 50 patients (63%). The incidence of the primary endpoint was significantly lower in the group that achieved LVRR, regardless of LGE status (LGE-positive group, P = 0.01; LGE-negative group, P = 0.02). In the multivariate analysis, the percentage change in NT-pro BNP levels at 3 months, NT-pro BNP levels at 6 months, and age were independent predictors of LVRR.LGE-positive patients may have a better prognosis if they achieve LVRR. Serial NT-pro BNP testing may be a valuable predictor of LVRR.

Abstract 16990: Empagliflozin Therapy is Associated With Improved Left Ventricular Diastolic Function in Patients With Transthyretin Amyloid Cardiomyopathy

Introduction: Although SGLT-2 inhibitors demonstrated beneficial clinical effects in patients with heart failure with preserved ejection fraction, their role in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains undefined. Hypothesis: We investigated the effects of empagliflozin on myocardial function in patients with ATTR-CM. Methods: In a prospective single-center non-randomized cohort study we enrolled 15 consecutive patients with ATT-CM receiving tafamidis 61 mg qd and standard heart failure therapy for at least six months prior to enrolment. At the time of inclusion, all patients started receiving empagliflozin 10 mg qd. Biochemical and echocardiographic parameters were evaluated at baseline and again at 6-months. Results: At the time of inclusion, the average age of patients was 74.8±5.7 years, 14 (93%) were male, and 14 (93%) had NYHA class II symptoms; 10 (67%) patients were receiving ARNI/ACEI/ARB, 5 (33%) were treated with beta blockers, and 3 (20%) were receiving mineralocorticoid receptor antagonists. At 6-months follow-up we found no change in NT-proBNP levels (1694±1237 ng/L at baseline vs. 1549±1203 ng/L at follow up; P=0.78), hs-Troponin I levels (33±19 ng/L vs. 39±26 ng/L; P=0.50), or eGFR (65.9±14.4 mL/min vs. 64.9±14.8 mL/min; P=0.87). Furthermore, we observed no changes in LVEDV (84±19 mL vs. 88±17 mL; P=0.61), LVEF (57±8% vs. 57±7%; P=0.94), LV mass (265±74 g vs. 279±88 g; P=0.67), or RVIDd (39±8 mm vs. 36±7 mm; P=0.39). However, at 6 months we found a significant decrease in E/e’ (19.2±5.1 vs. 14.9±5.4; P=0.05). When stratifying patients according to the baseline E/e’ value we found a significant improvement of right ventricular FAC (44.1±6.2% vs. 31.9±8.9%; P=0.04) and TR pressure gradient (26.0±5.7 mmHg vs. 39.7±5.2 mmHg; P=0.04) in patients with E/e’ below median compared to patients with E/e’ above median value. Conclusion: In patients with ATTR-CM, empagliflozin therapy appears to reduce left ventricular filling pressures and may be associated with improved right ventricular systolic function in a subset of this patient population.

POS-368 DOES NT-PROBNP VARIABILITY PREDICT RENAL AND CARDIOVASCULAR ADVERSE EVENTS IN PATIENTS WITH CKD STAGE G4-5?

NT-proBNP levels correlate with fluid overload and cardiac dysfunction in CKD patients. While baseline NT-proBNP levels are associated with adverse renal and cardiovascular (CV) events, whether the variability of this biomarker over time influences risk prediction in patients with advanced CKD remains to be determined. We thus aimed to characterise the association between NT-proBNP variability and major adverse events. We measured NT-proBNP in patients with CKD G4-5 at two consecutive advanced kidney care clinic appointments and followed them for a minimum of one year. Participants were categorised according to whether a change in NT-proBNP levels occurred between baseline and the follow-up visit (Group 1, decrease ≥10%; Group 2, stable levels; Group 3, increase ≥10%). The primary outcome was a composite of renal (≥40% estimated glomerular filtration rate decline, need for replacement therapy or death from renal causes) and CV (myocardial infarction, hospitalisation for heart failure, stroke or CV death) events, starting from the date of the second NT-proBNP measurement. Cox proportional hazard regressions adjusted for baseline NT-proBNP level were used. We included 127 participants with CKD G4-5 and a median follow-up of 11.1 (IQR 6.8-12.5) months (or 101 patient-years). The median baseline eGFR and NT-proBNP level were 19 (15-23) mL/min/1.73m2 and 1125 (IQR 398-3217) ng/L, respectively. Baseline characteristics were similar across the tree exposure groups. Major adverse events occurred in 20 (51%) of the 39 patients in Group 1 (decreasing levels), 7 (29%) of the 24 in Group 2 (stable levels) and 23 (36%)of the 64 in Group 3 (increasing levels). Compared to patients in Group 2, those in Groups 1 and 3 had similar risks of adverse events [HR 2.02 (95% CI 0.85-4.82), p=0.11 and HR 1.50 (95% CI 0.61-3.69), p=0.38, respectively]. In patients with CKD stage G4-5, variability in NT-proBNP levels was not associated with an increased risk of renal or cardiovascular adverse events. albeit this study may not have sufficient power to detect such a difference. Whether NT-proBNP levels monitoring can improve the management of advanced CKD remains to be determined.

Vitamin B12 Supplementation and NT-proBNP Levels in COPD Patients: A Secondary Analysis of a Randomized and Controlled Study in Rehabilitation.

PurposeThere is evidence of complex interaction between vitamin B12 (vB12) level, hyperhomocysteinemia (HyCy), and natriuretic peptide secretion. Exercise training could also modulate such interaction. In this secondary analysis of a Randomized Clinical Trial performed in a chronic obstructive pulmonary disease (COPD) rehabilitation setting, our primary objective was to investigate the interaction between vB12 supplementation, exercise training, and changes in NT-proBNP levels after 8 weeks of intervention. Secondary objectives were to explore the correlations between acute changes in NT-proBNP levels with (i) acute exercise and (ii) oxygen uptake (V’O2) kinetics during rest-to-exercise transition.MethodsThirty-two subjects with COPD were randomized into four groups: Rehabilitation+vB12 (n = 8), Rehabilitation (n = 8), vB12 (n = 8), or Maltodextrin(n = 8). They were evaluated at baseline and after 8 weeks, during resting and immediately after maximal exercise constant work-rate tests (CWTs, Tlim), for NT-proBNP plasmatic levels.ResultsAfter interaction analysis, the supplementation with vB12 significantly changed the time course of NT-proBNP responses during treatment (p = 0.048). However, the final analysis could not support a significant change in NT-proBNP levels owing to high-intensity constant work-rate exercise (p-value > 0.05). There was a statistically significant correlation between V’O2 time constant and ΔNT-proBNP values (Tlim – rest) at baseline (p = 0.049) and 2 months later (p = 0.015), considering all subjects (n = 32).ConclusionWe conclude that vB12 supplementation could modulate NT-proBNP secretion. Moreover, possibly, the slower the initial V’O2 adjustments toward a steady-state during rest-to-exercise transitions, the more severe the ventricular chamber volume/pressure stress recruitment, expressed through higher NT-proBNP secretion in subjects with larger V’O2 time constants, despite unchanged final acute exercise-induced neurohormone secretion.

Abstract P415: Weight Variation and Change in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)

Introduction: Natriuretic peptides (NPs) are biochemical markers of cardiac function and NTproBNP strongly predicts heart failure. NPs also have a role in the adipose tissue, stimulating lipolysis, mitochondrial biogenesis and browning of adipocytes. Cross-sectional studies have demonstrated that diabetes and higher levels of adiposity are paradoxically associated with lower levels of BNP and NT-proBNP, suggesting that NPs may protect against metabolic dysregulation. Methods: We hypothesized that increases in NT-proBNP over time would be associated with decreases in weight and a lower risk of obesity in a community-based population. We analyzed data from 10,093 participants from the Atherosclerosis Risk in Communities (ARIC) Study with measurements of NT-proBNP at two time points 6-years apart (visit 2, 1990-92 and visit 4, 1996-98). Multivariable regression models were used, and sensitivity analysis excluding patients with heart failure was performed. Results: Mean age at baseline (1990-1992) was 57 years (SD 6), 57% were women and 78% were white. The prevalence of obesity increased from 28% to 35% in the 6-year follow up period. Higher baseline levels of NT-proBNP were associated with reduced risk of obesity after adjustment for other risk factors ( Table ). There was an inverse association between change in NT-proBNP levels between the visits and weight change ( Figure ). Results were similar after excluding cases of heart failure. Conclusions: We found inverse associations of NT-proBNP levels with weight change and incidence of obesity. Our results suggest that NPs or their pathways may be potential targets in the treatment of obesity. Nonetheless, the molecular networks involving the natriuretic system are complex and additional work, especially intervention studies, are needed to address the clinical relevance of this finding.

The Effect of High Lactate Level on Mortality in Acute Heart Failure Patients With Reduced Ejection Fraction Without Cardiogenic Shock.

We aimed to determine the effect of blood lactate levels on cardiovascular (CV) death and hospitalization for heart failure (HF) in acute HF patients with reduced left ventricular ejection fraction (EF). Eighty-five acute HF patients with reduced ejection fraction were divided into two groups according to admission blood lactate levels. 48 of them had low blood lactate levels (< 2mmol/l) and 37 of them had high blood lactate levels (≥ 2mmol/l). Patients with acute coronary syndrome, cardiogenic shock, sepsis and low blood pressure at admission were excluded from the study. Primary endpoint is the composite of cardiovascular (CV) death and hospitalization for heart failure (HHF) in 6-month follow-up. Secondary endpoint is the change in NT-proBNP levels from admission to 72h. Baseline characteristics of patients were similar in two groups. On baseline echocardiographic evaluation; patients with high lactate revealed a higher mitral E/A ratio (2.34 [0.43-3.31], p = 0.008) and a lower TAPSE ratio (14 [10-27], p = 0.008) than patients with low lactate levels. Over a median follow-up period of 6months, the primary end point occurred in 28 (75.7%) of 37 patients assigned to high lactate group and in 20 (41.7%) of 48 patients assigned to low lactate group (p = 0.006). High lactate levels significantly increased the risk of CV death and HHF at 6months by nearly 5.35-fold in acute HF patients with reduced EF. The change in NT-proBNP levels at 72nd hour after admission were similar between two groups. Higher lactate levels at admission related with higher HHF at 6months and may be related with higher risk of CV death in acute HF patients with reduced EF.

Angiotensin receptor neprilysin inhibitor in heart failure with reduced ejection fraction: Real-world experience from a safety perspective

Background: Angiotensin receptor neprilysin inhibitor (ARNI) reduces morbidity and mortality in patients of heart failure with reduced ejection fraction (HFrEF). However, the use of ARNI in real-world practice is limited by safety issues, especially in acute decompensated heart failure (ADHF) patients. Methods and Results: Forty-seven hospitalized ADHF inpatients and 53 chronic compensated heart failure (CCHF) outpatients were enrolled in the study. ARNI was initiated and aimed to be up-titrated to a target dose of 97 mg of sacubitril with 103 mg of valsartan twice daily. Efficacy endpoints were New York Heart Association functional class, 6-min walk distance (6MWD), change in N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels and left ventricular ejection fraction (LVEF) from baseline with follow-up at 1 month, 6 months, and 2 years. Safety endpoints were the rates of worsening serum creatinine, hyperkalemia, symptomatic hypotension, angioedema, and need for drug discontinuation. Cumulative adverse drug effect was observed in 42.6% and 13.2% patients of ADHF and CCHF groups, respectively. The most common side-effect was symptomatic hypotension that occurred in 10 (21.3%) patients of ADHF group and 3 (5.7%) patients of CCHF group. Drug discontinuation rate was 19.1% in ADHF group and 3.8% in CCHF group. Significant improvement was seen in both the groups with respect to 6 MWD, functional class, change in NT-pro BNP levels and LVEF. At 2-year follow-up, 3 (6.4%) deaths occurred in ADHF group while none was reported from CCHF group. Conclusion: ARNI results in a significant clinical, biochemical, and functional improvement in HFrEF patients but at the cost of worsening renal function and hypotension especially in ADHF setting.

Effects of Very Low (12/13mg) and Low Dose (24/26mg) Sacubitril/Valsartan on N-Terminal Pro-B-Type Natriuretic Peptide

Introduction Sacubitril/valsartan (S/V) has been shown to decrease N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels. Reduction of NT-proBNP is associated with lower morbidity and mortality rates. However, there is very little data with the effects of low dose S/V on NT-proBNP. Methodology This was a retrospective study conducted between October 2015 and January 2018 of patients who received either low dose or very low dose S/V. Patients were divided into 3 groups based on S/V dosing. Group 1 patients received very low dose, group 2 patients received very low dose titrated to low dose, and group 3 patients received low dose. The primary endpoint was the change in NT-proBNP levels between baseline and the most recent obtained value. Results A total of 293 patients were reviewed and 45 patients met inclusion criteria. Across all S/V dosing groups, there was a statistically significant reduction in NT-proBNP levels. The average days of therapy between NT-proBNP values were 108, 149, and 196 in group 1, 2, and 3, respectively. 71% of patients were on loop diuretics prior to S/V with an average furosemide equivalent dose of 73mg which decreased by 27% to 53mg after receiving S/V. Conclusion Low doses of S/V, including half of the lowest dose clinically available, appears to have substantial benefit in terms of NT-proBNP which can be seen within 3 to 6 months. Despite a reduction in loop diuretic dose, there was still a significant reduction in NT-proBNP which may be attributed to the natriuretic effect of S/V. Although reductions in NT-proBNP levels are associated with improvements in survival, these data cannot be used to infer that a similar reduction in mortality would be expected. However, they do suggest that very low doses of S/V appear to have a biochemical effect and perhaps should be studied in future trials since not all patients can be titrated to the maximum dose of S/V. While patients should be titrated to guideline recommended doses, low doses seem to be beneficial in terms of reducing NT-proBNP levels.

22 The effects of apelin on serum NT-proBNP levels in pulmonary hypertension patients

Background Pulmonary Hypertension has a poor prognosis and therapy is limited to symptomatic relief. Apelin, a new therapy, has the potential to provide both symptomatic relief and address the underlying pathology. Disease severity, in pulmonary hypertension, is measured using NT-proBNP. This study investigated the effects of apelin on serum NT-proBNP levels in groups of pulmonary hypertension patients and controls. Methods Serum samples from patients recruited for a haemodynamic investigation of apelin were used. The groups studied were controls, pulmonary arterial hypertension and pulmonary hypertension due to left heart failure. In the haemodynamic study each patient was given an apelin and placebo infusion separately, over a period of several minutes. Serum samples were taken pre and post infusions. NT-proBNP concentration in the samples was determined using the ABNOVA ELISA kit. Results Across all groups there was no significant change in NT-proBNP levels due to apelin infusion (P = 0.830). There was no significant difference in pre-infusion levels between groups (P = 0.287). Conclusions Apelin infusion, over a period of several minutes, has no effect on NT-proBNP levels in serum. This is consistent amongst control and pulmonary hypertension patients. Despite the lack of change in NT-proBNP seen in this study, the haemodynamic results for apelin were positive. These haemodynamic results have been associated with a decrease in NT-proBNP in other drug studies. The main difference in these studies was a longer time period. As a result, investigation of therapy over a longer time period is required to assess if apelin has any effect on NT-proBNP levels.

THE COURSE OF NT-PROBNP IN REAL-LIFE PATIENTS UNDERGOING TRANSFEMORAL AORTIC VALVE IMPLANTATION

NT-proBNP has been reported as predictor of survival in severe aortic stenosis (AS). Aim of this study was to examine the change in NT-proBNP levels over time and its value as predictor of outcome after treatment with transfemoral aortic valve implantation (TAVI). From May 2007 until June 2013, 142

Relative Change in NT-proBNP Level: An Important Risk Predictor of Cardiovascular Congestion in Haemodialysis Patients

Background: Cross-sectional studies have shown that B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are predictive of cardiovascular death in haemodialysis (HD) patients. In the present study, we tested the hypothesis that monitoring NT-proBNP measurements adds further prognostic information, i.e. predicts congestive heart failure (CHF) events. Methods: In a prospective cohort of 236 HD patients, NT-proBNP levels were measured monthly during 18 months. Patients were divided according to the occurrence of CHF events. In a nested case-control study, we assessed the evolution of NT-proBNP levels. Results: On average, the 236 HD patients were followed up for 12.5 months, a period during which 44 patients developed a CHF event (half requiring hospitalisation). At baseline, patients who developed a CHF event had significantly more dilated cardiomyopathy and/or altered left ventricular ejection fraction and higher NT-proBNP levels compared with patients who did not develop a CHF event. During follow-up, we observed a significant increase in NT-proBNP levels preceding the CHF event. At a 20% relative increase of NT-proBNP, the sensitivity of NT-proBNP as a predictor of CHF events was 0.57 and the specificity 0.77. Conclusion: The relative change in NT-proBNP levels is a significant risk predictor of a CHF event.

Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension

The aims of this study were to evaluate the diagnostic value and to explore the prognostic value of N-terminal brain natriuretic peptide (N-TproBNP) in patients with systemic sclerosis (SSc) both with and without pulmonary arterial hypertension (PAH). N-TproBNP, six-minute walk distance (SMWD), haemodynamics (at right heart catheterization) or tricuspid gradient (by echocardiography), and survival were assessed in 109 patients with SSc. The study population included 68 individuals with PAH [mean pulmonary artery pressure (PAP) >25 mmHg and pulmonary capillary wedge pressure <15 mmHg] and 41 individuals without PAH. In patients with PAH, the prognostic value of baseline and change in WHO functional class, N-TproBNP levels, and SMWD were compared using Kaplan-Meier survival curves and Cox proportional hazard analysis. The mean duration of follow-up was 10 months (range 1-18 months). One year survival in patients with normal PAP was 100% when compared with 83.5% in those with SSc-PAH (P < 0.05). The patients without PAH had a mean N-TproBNP level of 139 pg/mL (SD 151); those with SSc-PAH had a significantly higher mean N-TproBNP level of 1474 pg/mL (SD 2642) (P = 0.0002). Among patients with PAH for every order of magnitude increase in N-TproBNP level there was a four-fold increased risk of death (P = 0.002 for baseline level and P = 0.006 for follow-up level). Baseline N-TproBNP levels were correlated positively with mean PAP (r = 0.62; P < 0.0001), pulmonary vascular resistance (PVR) (r = 0.81; P < 0.0001), and inversely with SMWD (r = -0.46; P < 0.0001). Among patients with SSc-PAH, 13 patients (19%) were in WHO functional classes II and had mean N-TproBNP levels of 325 pg/mL (SD 388). Fifty-three patients (78%) were in WHO classes III and IV and had significantly higher mean N-TproBNP levels of 1677 pg/mL (SD 2835) (P = 0.02). At an N-TproBNP level of 395 pg/mL, the sensitivity and specificity for predicting the presence of SSc-PAH were 56 and 95% respectively. Raised N-TproBNP levels are directly related to the severity of PAH. In screening programs, SSc patients with an N-TproBNP in excess of 395 pg/mL have a very high probability of having pulmonary hypertension. Baseline and serial changes in N-TproBNP levels are highly predictive of survival. A 10-fold increase in N-TproBNP level on therapy is associated with a greater than three-fold increase in mortality, and may indicate therapeutic failure.