Plasma Concentrations Of NT-proBNP Research Articles

Sex differences related changes in cardiac structure and function after ST-segment elevation myocardial infarction

Abstract Background Sex disparities in presentation, treatment, and outcomes after ST-segment Elevation Myocardial Infarction (STEMI) are well recognized. However, little is known about sex related changes in cardiac structure and function following a STEMI in this contemporary era of early PCI. Purpose To compare sex differences in change of echocardiographic parameters of structure and function following a first-time STEMI. Methods This echocardiographic study involved 380 non-diabetic first-time STEMI patients. Structural and functional parameters were evaluated during initial hospitalization (median 1 day after presentation) and at 4-months. Adverse remodelling was defined as a 20% increase in left ventricular end-diastolic volume (LVEDV) at 4 months compared to the hospitalisation echo. Functional parameters included left ventricular ejection fraction (LVEF) and wall motion score index (WMSI). According to current guidelines, eccentric hypertrophy was defined as left ventricular mass index (LVMI) >95 g/m2 for women and >115 g/m2 for men with a relative wall thickness (RWT) ≤0.42; concentric hypertrophy was defined as LVMI >95 g/m2 for women and >115 g/m2 for men with RWT >0.42. The different patterns in geometry were assessed at 4-months. Results Among 380 patients, comprising 285 males and 95 females, females had a higher prevalence of hypertension (42% vs. 25.6%, p=0.004), lower hemoglobin levels (8.40 mmol/l vs. 9.10, p<0.001), and higher plasma NT-proBNP concentrations upon admission (132 ng/L vs 67, p<0.001) and after 24 hours (1322 ng/l vs 784, p<0.001). During the initial echocardiogram conducted upon hospitalization, as well as during the echocardiogram at 4 months, women had significantly lower LV diameters, LV volumes, LV mass, LAVI and wall thickness compared to man. However, during both evaluations women showed higher E/e’ ratio’s and LVEF. The change in echocardiographic variables between both timepoints did not differ significantly between sexes. Furthermore, no significant difference in LV geometry patterns (eccentric or concentric) were observed between sexes and adverse LV remodelling was similar between both groups at approximately 22-23% (p=0.991). Conclusions Although differences exist between sexes in patient characteristics and individual echocardiographic parameters, no disparity is observed in geometry patterns, adverse LV remodelling, or the change in echocardiographic parameters after STEMI.

Cardiac biomarker profiles in dogs with naturally occurring precapillary pulmonary hypertension

Introduction/ObjectivesThis study evaluated circulating amino-terminal pro-B-type natriuretic peptide (NT-proBNP), amino-terminal pro-A-type natriuretic peptide (NT-proANP), and cardiac troponin I (cTnI) concentrations in dogs with precapillary pulmonary hypertension (Pre-PH) and control dogs with respiratory clinical signs but no Pre-PH. AnimalsTwenty-six dogs (17 affected, and 9 controls) were involved in the study. Materials and MethodsThis was a sub-study of a large prospective single-center observational study. Dogs underwent blood sample collection, physical examination, and echocardiographic evaluation. Pre-PH was diagnosed when a calculated right ventricular-to-right atrial pressure gradient (RV:RA PG) measuring ≥40 mmHg was identified echocardiographically, barring right ventricular outflow obstruction and/or left-sided cardiac disease. ResultsTwo, nine, and six dogs had mild, moderate, and severe Pre-PH, respectively. Plasma concentrations of NT-proBNP, NT-proANP, and cTnI were significantly higher in the affected group than in the control group (P=0.020, P=0.009, P=0.011, respectively). There was a positive correlation between RV:RA PG and NT-proBNP (r = 0.52), NT-proANP (r = 0.54), and cTnI (r = 0.67) concentrations. DiscussionPre-PH should be included in the differential diagnosis list of elevated cardiac biomarker concentrations in dogs with respiratory signs. Study LimitationsStrict selection criteria reduced group sizes. There were rare missing data points. The diagnosis of Pre-PH was obtained from Doppler echocardiographic RV:RA PG. The disease process causing Pre-PH was not evaluated histopathologically. ConclusionsCirculating cardiac biomarker concentrations are increased in dogs with Pre-PH and there is a positive correlation between RV:RA PG and NT-proBNP, NT-proANP, and cTnI concentrations.

Preoperative N-terminal pro-B-type natriuretic peptide and myocardial injury after stopping or continuing renin–angiotensin system inhibitors in noncardiac surgery: a prespecified analysis of a phase 2 randomised controlled multicentre trial

BackgroundPatients with elevated preoperative plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP >100 pg ml−1) experience more complications after noncardiac surgery. Individuals prescribed renin–angiotensin system (RAS) inhibitors for cardiometabolic disease are at particular risk of perioperative myocardial injury and complications. We hypothesised that stopping RAS inhibitors before surgery increases the risk of perioperative myocardial injury, depending on preoperative risk stratified by plasma NT-proBNP concentrations. MethodsIn a preplanned analysis of a phase 2a trial in six UK centres, patients ≥60 yr old undergoing elective noncardiac surgery were randomly assigned either to stop or continue RAS inhibitors before surgery. The pharmacokinetic profile of individual RAS inhibitors determined for how long they were stopped before surgery. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury (plasma high-sensitivity troponin-T ≥15 ng L−1 or a ≥5 ng L−1 increase, when preoperative high-sensitivity troponin-T ≥15 ng L−1) within 48 h after surgery. The co-exposures of interest were preoperative plasma NT-proBNP (< or >100 pg ml −1) and stopping or continuing RAS inhibitors. ResultsOf 241 participants, 101 (41.9%; mean age 71 [7] yr; 48% females) had preoperative NT-proBNP >100 pg ml −1 (median 339 [160–833] pg ml−1), of whom 9/101 (8.9%) had a formal diagnosis of cardiac failure. Myocardial injury occurred in 63/101 (62.4%) subjects with NT-proBNP >100 pg ml−1, compared with 45/140 (32.1%) subjects with NT-proBNP <100 pg ml −1 {odds ratio (OR) 3.50 (95% confidence interval [CI] 2.05–5.99); P<0.0001}. For subjects with preoperative NT-proBNP <100 pg ml−1, 30/75 (40%) who stopped RAS inhibitors had myocardial injury, compared with 15/65 (23.1%) who continued RAS inhibitors (OR for stopping 2.22 [95% CI 1.06–4.65]; P=0.03). For preoperative NT-proBNP >100 pg ml−1, myocardial injury rates were similar regardless of stopping (62.2%) or continuing (62.5%) RAS inhibitors (OR for stopping 0.98 [95% CI 0.44–2.22]). ConclusionsStopping renin-angiotensin system inhibitors in lower-risk patients (preoperative NT-proBNP <100 pg ml −1) increased the likelihood of myocardial injury before noncardiac surgery.

Impact of age on the predictive value of NT-proBNP in patients with diabetes mellitus stabilised after an acute coronary syndrome

AimsTo assess the impact of age on the prognostic value of NT-proBNP concentration in patients with type-2 diabetes mellitus (T2DM) stabilised after an Acute Coronary Syndrome (ACS). MethodsThe AleCardio study compared aleglitazar with placebo in 7226 patients with T2DM and recent ACS. Patients with heart failure were excluded. Median follow-up was 104 weeks. Baseline NT-proBNP plasma concentration was measured centrally. Multivariable Cox regression was used to determine the mortality predictive information provided by NT-proBNP across age groups. ResultsMedian age was 61y (IQR 54, 67). NT-proBNP concentration increased by quartile (Q) of age (median 264, 318, 391, and 588 pg/ml). Compared to Q1, patients in Q4 of NT-proBNP had higher (p < 0.001) adjusted HR for all-cause (aHR 6.9; 95 % CI 4.0–12) and cardiovascular (11; 5.4–23) death. Within each age Q, baseline NT-proBNP in patients who died was 3 times higher than in survivors (all p < 0.001). When age and NT-proBNP levels were modeled as continuous variables, their interaction term was nonsignificant. The relative prognostic information provided by NT-proBNP (percent of total X2) increased from 38 % in age Q1 to 75 % in age Q4 for mortality, and from 50 % to 88 % for CV death. ConclusionsAmong patients with T2DM stabilised after an ACS, NT-proBNP level predicts death irrespective of age.

The Relationship of Inflammatory Chemokine, CXCL12, with NT-proBNP: A Marker of Congestive Heart Failure in Rheumatoid Arthritis Patients

Background: Cardiovascular disease (CVD) is the most considerable long-term outcome of rheumatoid arthritis (RA) and the leading cause of premature death in RA patients. The pathogenesis of CVD in RA is largely determined by persistent systemic inflammation and its underlying factors, including chemokines. In this regard, C-X-C motif chemokine ligand 12 (CXCL12) has a crucial role in the CVD and RA pathogenesis. For the first time, plasma CXCL12 was related to conventional CV risk and well-established cardiac biomarkers in RA patients. Methods: This study was conducted on 30 RA patients who have been newly diagnosed, 30 under-treatment RA patients, and 30 healthy subjects. The plasma levels of CXCL12 and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) were measured using the enzyme-linked immunosorbent assay (ELISA) technique. The high sensitivity C-reactive protein (HS-CRP) concentration was evaluated in plasma samples using the ADVIA 1800 Clinical Chemistry System based on the latex-enhanced immunoturbidimetric assay. The CVD risk was measured by calculating the Framingham risk score (FRS) and systematic coronary risk evaluation (SCORE). Results: The mean FRS and plasma concentration of high-density lipid (HDL), NT-proBNP, and HS-CRP were significantly different between the three groups (P = 0.029, P &lt; 0.001, P = 0.016, P &lt; 0.001, respectively). A significant positive correlation was found between CXCL12 with disease activity score-28 (DAS-28) (P = 0.024, r = 0.293) and NT-proBNP (P &lt; 0.0001, r = 0.570) in the patients’ group. Conclusions: Based on the results, there was a significant relationship between the inflammatory mediator CXCL12 and a well-known cardiac biomarker, NT-proBNP.

Chronic kidney disease in patients with chronic heart failure infected with human immunodeficiency virus

Chronic kidney disease (CKD) is the most common manifestation of target organ damage in chronic heart failure (CHF). The aim of the study was to determine the risk factors associated with the course of CKD in patients with CHF infected with the human immunodeficiency virus (HIV). According to the results obtained, the prevalence of CKD among HIV-infected patients with CHF is 58.82%, which is 4 times more common than in patients with HIV infection without CHF. The dependence of glomerular filtration rate (GFR) on three main factors that reflect damage to the heart muscle – blood plasma NT-proBNP concentration, left ventricular ejection fraction (LVEF%) and left ventricular myocardial mass index (LVMI) was proved, which together, being included in the regression model, determine 42.2% of the variance of GFR values and are decisive in the development of CKD in patients with CHF on the background of HIV infection. The concentration of NT-proBNP in the blood plasma of patients with CHF equal to or greater than 683.65 pg/ml can be considered as a diagnostic criterion for the development of CKD in HIV-infected people with a sensitivity of the method of 75.0% and a specificity of 75.4%, respectively. In addition, risk factors for the development of CKD in patients with CHF and HIV infection are smoking, alcohol and drug use, a history of chronic and acute forms of coronary artery disease, atrial fibrillation, ventricular arrhythmias, diabetes mellitus, chronic viral hepatitis C, anemia and thrombocytopenia. Patients with CHF and CKD have a more rigid arterial wall – there is a significant excess of the stiffness indices of the aorta and peripheral arteries. Long-term use of antiplatelet agents, NRTIs, NNRTIs, and protease PIs may aggravate the course of CHF in HIV-infected people with CKD manifestations.

Long-term outcome of patients with transposition of the great arteries and a systemic right ventricle: A systematic review and meta-analysis

BackgroundPatients with a transposition of the great arteries (TGA) and a systemic right ventricle are at risk of heart failure (HF) development, arrhythmia and early mortality. Prognostic evaluations in clinical studies are hampered by small sample sizes and single-centred approaches. We aimed to investigate yearly rate of outcome and factors affecting it. MethodsA systematic literature search of four electronic databases (PubMed, EMBASE, Web of Science and Scopus) was conducted from inception to June 2022. Studies reporting the association of a systemic right ventricle with mortality with a minimal follow-up of 2 years during adulthood were selected. Incidence of HF hospitalization and/or arrhythmia were captured as additional endpoints. For each outcome, a summary effect estimate was calculated. ResultsFrom a total of 3891 identified records, 56 studies met the selection criteria. These studies described the follow-up (on average 7.27 years) of 5358 systemic right ventricle patients. The mortality incidence was 1.3 (1–1.7) per 100 patients/year. The incidence of HF hospitalization was 2.6 (1.9–3.7) per 100 patients/year. Predictors of poor outcome were a lower left ventricular (LV) and right ventricular ejection fraction (RVEF) (standardized mean differences (SMD) of −0.43 (−0.77 to −0.09) and − 0.85 (−1.35 to −0.35), respectively), higher plasma concentrations of NT-proBNP (SMD of 1.24 (0.49–1.99)), and NYHA class ≥2 (risk ratio of 2.17 (1.40–3.35)). ConclusionsTGA patients with a systemic right ventricle have increased incidence of mortality and HF hospitalization. A lower LVEF and RVEF, higher levels of NT-proBNP and NYHA class ≥2 are associated with poor outcome.

Efficacy of pulmonary artery pressure monitoring in patients with chronic heart failure: a meta-analysis of three randomized controlled trials.

Adjustment of treatment based on remote monitoring of pulmonary artery (PA) pressure may reduce the risk of hospital admission for heart failure (HF). We have conducted a meta-analysis of large randomized trials investigating this question. A systematic literature search was performed for randomized clinical trials with PA pressure monitoring devices in patients with HF. The primary outcome of interest was the total number of HF hospitalizations. Other outcomes assessed were urgent visits leading to treatment with intravenous diuretics, all-cause mortality, and composites. Treatment effects are expressed as hazard ratios, and pooled effect estimates were obtained applying random effects meta-analyses. Three eligible randomized clinical trials were identified that included 1898 outpatients in New York Heart Association functional classes II-IV, either hospitalized for HF in the prior 12 months or with elevated plasma NT-proBNP concentrations. The mean follow-up was 14.7 months, 67.8% of the patients were men, and 65.8% had an ejection fraction ≤40%. Compared to patients in the control group, the hazard ratio (95% confidence interval) for total HF hospitalizations in those randomized to PA pressure monitoring was 0.70 (0.58-0.86) (P = .0005). The corresponding hazard ratio for the composite of total HF hospitalizations, urgent visits and all-cause mortality was 0.75 (0.61-0.91; P = .0037) and for all-cause mortality 0.92 (0.73-1.16). Subgroup analyses, including ejection fraction phenotype, revealed no evidence of heterogeneity in the treatment effect. The use of remote PA pressure monitoring to guide treatment of patients with HF reduces episodes of worsening HF and subsequent hospitalizations.

Relationship of NT-proBNP to All-Cause Death and Heart Transplant in Children with Ventricular Dysfunction and Compared to Adults with Heart Failure

<h3>Purpose</h3> Plasma NT-proBNP concentration is a widely used diagnostic biomarker for heart failure (HF) in adults and children. We sought to determine whether NT-proBNP concentrations predicted the risk of heart transplantation or death in pediatric HF patients. <h3>Methods</h3> We studied medical records from 109 children with HF in the IBM Watson Explorys database and from 150 children in the Cardiac Biomarkers in Pediatric Cardiomyopathy (PCMR) study. Nonlinear regression with an Emax function was used to model the relationship between NT-proBNP concentrations and the number of events in the two cohorts and with adult patients from Explorys. <h3>Results</h3> All children in the PCMR cohort had dilated cardiomyopathy, whereas the Explorys cohort also included children with congenital heart diseases (Table). Mean age at diagnosis was 3 years in the Explorys cohort and 1.4 years in the PCMR cohort; median NT-proBNP concentrations were 1250 pg/mL and 183.5 pg/mL, respectively. The percentage of deaths and transplantations was higher in the Explorys cohort (7% and 22%, respectively, over 2 years) than in the PCMR cohort (3% and 16%, respectively, over 5 years). Mean estimates of NT-proBNP concentration indicative of half-maximum risk for events (EC50 values) at 2 and 5 years were 3730 pg/mL and 4199 pg/mL, values both close to the mean of 3880 pg/mL established for adults with HF (Figure). <h3>Conclusion</h3> NT-proBNP concentration is suitable for estimating the risk of mortality and morbidity in children with HF, independent of age, and is a candidate surrogate marker for clinical outcome both in adults and children with HF.

ASA Status, NPPA/NPPB Haplotype and Coronary Artery Disease Have an Impact on BNP/NT-proBNP Plasma Levels.

Plasma concentrations of natriuretic peptides (NP) contribute to risk stratification and management of patients undergoing non-cardiac surgery. However, genetically determined variability in the levels of these biomarkers has been described previously. In the perioperative setting, genetic contribution to NP plasma level variability has not yet been determined. A cohort of 427 patients presenting for non-cardiac surgery was genotyped for single-nucleotide polymorphisms (SNPs) from the NPPA/NPPB locus. Haplotype population frequencies were estimated and adjusted haplotype trait associations for brain natriuretic peptide (BNP) and amino-terminal pro natriuretic peptide (NT-proBNP) were calculated. Five SNPs were included in the analysis. Compared to the reference haplotype TATAT (rs198358, rs5068, rs632793, rs198389, rs6676300), haplotype CACGC, with an estimated frequency of 4%, showed elevated BNP and NT-proBNP plasma concentrations by 44% and 94%, respectively. Haplotype CGCGC, with an estimated frequency of 9%, lowered NT-proBNP concentrations by 28%. ASA classification status III and IV, as well as coronary artery disease, were the strongest predictors of increased NP plasma levels. Inclusion of genetic information might improve perioperative risk stratification of patients based on adjusted thresholds of NP plasma levels.

Effects of dexmedetomidine and its reversal with atipamezole on echocardiographic measurements and circulating cardiac biomarker concentrations in normal cats.

To investigate the effects of dexmedetomidine (DXM) and its subsequent reversal with atipamezole (APM) on the echocardiogram and circulating concentrations of cardiac biomarkers in cats. 14 healthy cats. Cats underwent echocardiography and measurements of circulating cTn-I and NT-proBNP concentrations before (PRE) and during (INTRA) DXM sedation (40 µg/kg IM) and 2 to 4 (2H POST) and 24 (24H POST) hours after reversal with APM. Administering DXM significantly decreased heart rate, right ventricular and left ventricular (LV) outflow tract velocities, and M-mode-derived LV free-wall thickness; increased LV end systolic diameter and volume; and caused valvar regurgitation. While sedative effects resolved within 25 minutes of APM reversal, the evolution of echocardiographic changes was mixed: LV ejection fraction and mitral valvar regurgitation score were different at 2H POST than at both INTRA and PRE (partial return toward baseline), LV end-diastolic volume was different PRE to INTRA and INTRA to 2H POST but not different PRE to 2H POST (full return toward baseline), and M-mode-derived LV free-wall thickness was significantly different from PRE to INTRA and PRE to 2H POST (no return toward baseline). Serum cTn-I and plasma NT-proBNP concentrations increased significantly with DXM, which remained significant 2H POST. Administration of DXM and APM reversal produced changes in echocardiographic results and in circulating cTn-I and NT-proBNP concentrations. Understanding these changes could help veterinarians differentiate drug effects from cardiac disease.

Relationship between 3D and 2D global longitudinal strain in patients with acute myocardial infarction after percutaneous revascularization

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This research was funded by “Iuliu Haţieganu” University of Medicine and Pharmacy, Dept. of Cardiology, Cluj-Napoca, Romania. This paper was published under the frame of European Social Found, Human Capital Operational Programme 2014-2020, project no. POCU/380/6/13/125171 Introduction Impaired longitudinal strain (GLS) is associated with increased wall stress following acute myocardial infarction (MI). However, little is known about the relationship between three-dimensional (3D)-GLS and two-dimensional (2D)-GLS. The aim of this study was to evaluate the relationship between 3D-GLS and 2D-GLS and also the association of 3D-GLS with specific biomarkers (NT-proBNP and Troponin) in patients with acute MI following percutaneous revascularization (PCI). Methods We included 100 patients with acute MI after successful PCI with a left ventricular ejection fraction (LVEF) &amp;gt;40%. 2D-GLS and 3D-GLS were assessed using speckle-tracking echocardiography and plasma concentrations of NT-proBNP and high sensitive troponin were analyzed. Results The patients had a mean age of 67.1 ± 13.1 years. 69 patients were diagnosed with ST-elevation MI (STEMI). Mean 3D-GLS was of -9.44 ± 4.35% and mean 2D-GLSwas of -10.1 ± 3.9%. 3D-GLS showed a strong correlation with 2D-GLS (r=-0.57, p &amp;lt; 0.001) and LVEF (r=-0.58,p &amp;lt; 0.001), a moderate correlation with NT-proBNP (r = 0.22), but no correlation with Troponin (r = 0.19). There was no difference (paired t-test) between 3D-GLS and 2D-GLS (p = 0.56, mean of differences of 0.65), but the limits of agreement were wide (-6.8% and 8.11%). Conclusion 3D-GLS showed small bias compared to 2D-GLS, but wide limits of agreement. The correlation between 3D-GLS and NT-proBNP was only moderate in acute MI. 3D-GLS might offer additional advantages in patients with complex geometry after acute MI due to faster data acquisition and lack of geometric assumption,but future studies are needed to confirm its role. Abstract Figure. Relationship between 3D and 2D GLS Abstract Figure. Corresponding Bland-Altman plots

Assessment of global longitudinal strain and plasma natriuretic peptide in patients with asymptomatic left ventricular dysfunction.

Objective The purpose of this study was to investigate the association between global longitudinal strain (GLS) and plasma NT-proBNP for predicting left ventricular (LV) performance in asymptomatic patients after acute myocardial infarction (AMI).Material and methods We prospectively included patients with diagnosis of AMI without clinical signs and symptoms of heart failure (HF) and followed these patients for 6 mos. Baseline echocardiography was performed at admission, and follow-up echocardiography was performed after 6 mos. A normal GLS was defined as having an absolute value of ≥16 %. According to the baseline GLS, participants were divided into two groups and compared. In all participants, blood samples of plasma NT-proBNP were obtained at admission, before discharge, and 6 mo after discharge.Results The study population was consisted of 98 participants, of which 80 (81.6 %) were males, and the mean age was 56.0±9.3 years. Baseline echocardiography showed that most of the participants (60, 61.2 %) had abnormal GLS&lt;16 %, whereas 38 (38.8 %) participants had normal or borderline GLS ≥16 %. Compared with the normal GLS group, participants with abnormal GLS had higher GRACE score, higher troponin I concentration, lower systolic blood pressure, lower mean LV ejection fraction, and decreased LV diastolic function. At 6‑mo follow-up, only LV systolic function remained significantly different between the two groups. Compared to baseline, there was a significant improvement of GLS in the abnormal GLS group at 6‑mo follow-up (p=0.04). Prevalence of complications after AMI was significantly higher in this group. There were significant differences between baseline and discharge NT-proBNP concentrations between the two groups (p&lt;0.05). In the abnormal GLS group, there were significant correlations between baseline and discharge NT-proBNP concentrations with baseline LV systolic function. Discharge NT-proBNP concentration also correlated significantly with 6‑mo follow-up GLS. For determining the effect of baseline GLS abnormality, the areas under the ROC curve for baseline and discharge NT-proBNP concentrations were 0.73 (95 % CI 0.60-0.85, p=0.001) and 0.77 (95 % CI 0.66-0.87, p&lt;0.001), respectively. Regarding early prediction of follow-up GLS abnormality, the area under the ROC curve for discharge NT-proBNP concentration was significantly higher 0.70 (95 % CI 0.55-0.84, p=0.016). The optimum cut-off value of discharge NT-pro-BNP was 688.5 pg / ml, with 72.4 % sensitivity and 65.4 % specificity to predict 6‑mon GLS abnormality following acute myocardial infarction.Conclusion The main finding of this study is that impaired LV GLS is associated with elevated plasma concentrations of NT-proBNP in post-AMI patients. Pre-discharge NT-proBNP concentration combined with impaired initial GLS could predict worsening LV systolic function over time in asymptomatic post-AMI patients.

Post-processing measurement of left ventricular ejection fraction compared to direct measurement in patients with heart failure with reduced ejection fraction

Abstract Introduction Left ventricular ejection fraction (LVEF) derived from transthoracic echocardiography (TTE) is routinely used to guide therapeutic decisions in patients with heart failure with reduced ejection fraction (HFrEF). However, TTE-based quantification of LVEF is limited by low diagnostic accuracy and poor agreement with gold-standard methods which may be improved by application of post-processing (pp) analysis tools. In our study, we aimed to compare different methods of LVEF quantification, using direct and pp techniques, and their correlations to NT-proBNP plasma concentrations in patients with a previous diagnosis of HFrEF. Methods A total of 205 clinically stable patients with HFrEF were enrolled in a prospective cohort study. They underwent a standardized TTE examination performed by two experienced investigators. Biplane LVEF according to Simpson's method was evaluated directly during the examination. Pp evaluation of biplane and triplane LVEF (pp LVEF) using a vendor-independent software on digitally saved echo loops was performed by a blinded investigator who underwent comprehensive training in pp analysis but was otherwise unexperienced in TTE. For correlation analyses patients were subdivided according to the underlying etiology into ischemic and non-ischemic HF. Results Pp analysis was feasible in 164 patients. Mean direct biplane LVEF was 36.0±9.1%, mean pp biplane LVEF was 35.8±8.2%, mean pp triplane LVEF was 34.2±8.8%, and median NT-proBNP was 978 [IQR 332–2279] pg/mL. All LVEF parameters had strong and comparable correlations to NT-proBNP (direct biplane r=−0.352; pp biplane r=−0.412; pp triplane r=−0.426; p&amp;lt;0.01 for each). Bland Altman Plot revealed a high variability between direct and pp biplane LVEF, with a mean difference of 0.15±6.2%. Linear regression analysis indicated proportional bias across all LVEF ranges (β=0.154, p=0.049). Among 83 patients with direct biplane LVEF &amp;gt;35%, 16 had a pp biplane LVEF ≤35% (mean pp biplane 43.3±4.5 vs 32.0±2.3%, p&amp;lt;0.001; median NT-proBNP 511 [179–1421] vs 1205 [457–3706] pg/mL, p=0.055). On the other hand, out of 81 patients with direct biplane LVEF ≤35%, 16 patients had pp biplane LVEF &amp;gt;35% (mean pp biplane 28.2±4.8 vs 39.2±3.4%, p&amp;lt;0.001; median NT-proBNP 1644 [711–3113] vs 543 [297–3015] pg/mL, p=0.1). Furthermore, the correlation between biplane LVEF and NT-proBNP was more pronounced in patients with ischemic HF (n=65) using pp than direct measurement (pp r=−0.443, p&amp;lt;0.001; direct r=−0.314, p=0.01). We did not observe such a signal in patients with non-ischemic HF (n=99). Conclusion Direct biplane LVEF shows low agreement with pp biplane LVEF in patients with HFrEF. Moreover, application of pp analyses leads to a reclassification from LVEF &amp;gt;35 to ≤35% in one out of five patients. In conclusion, pp biplane LVEF analysis appears to provide more accurate values and should be preferred in examinations with therapeutic implication, particularly in patients with HFrEF of ischemic origin. Funding Acknowledgement Type of funding sources: None.

Circulating adrenomedullin and B-type natriuretic peptide do not predict blood pressure fluctuations during pheochromocytoma resection: a cross-sectional study.

Despite adequate presurgical management, blood pressure fluctuations are common during resection of pheochromocytoma or sympathetic paraganglioma (PPGL). To a large extent, the variability in blood pressure control during PPGL resection remains unexplained. Adrenomedullin and B-type natriuretic peptide, measured as MR-proADM and NT-proBNP, respectively, are circulating biomarkers of cardiovascular dysfunction. We investigated whether plasma levels of MR-proADM and NT-proBNP are associated with blood pressure fluctuations during PPGL resection. Study subjects participated in PRESCRIPT, a randomized controlled trial in patients undergoing PPGL resection. MR-proADM and NT-proBNP were determined in a single plasma sample drawn before surgery. Multivariable linear and logistic regression analyses were used to explore associations between these biomarkers and blood pressure fluctuations, use of vasoconstrictive agents during surgery as well as the occurrence of perioperative cardiovascular events. A total of 126 PPGL patients were included. Median plasma concentrations of MR-proADM and NT-proBNP were 0.51 (0.41-0.63) nmol/L and 68.7 (27.9-150.4) ng/L, respectively. Neither MR-proADM nor NT-proBNP were associated with blood pressure fluctuations. There was a positive correlation between MR-proADM concentration and the cumulative dose of vasoconstrictive agents (03B2 0.44, P =0.001). Both MR-proADM and NT-proBNP were significantly associated with perioperative cardiovascular events (OR: 5.46, P =0.013 and OR: 1.54, P =0.017, respectively). plasma MR-proADM or NT-proBNP should not be considered as biomarkers for the presurgical risk assessment of blood pressure fluctuations during PPGL resection. Future studies are needed to explore the potential influence of these biomarkers on the intraoperative requirement of vasoconstrictive agents and the perioperative cardiovascular risk.

NT-proBNP in young healthy adults undergoing non-cardiac surgery

ObjectivesN-terminal pro-brain natriuretic peptide (NT-proBNP), a standard marker for diagnosis and treatment guidance of heart failure, has previously been investigated in high-risk patients undergoing cardiac and non-cardiac surgery. However, the kinetics of NT-proBNP in healthy patients undergoing non-cardiac surgery are unknown. Design & methodsA secondary analysis of a prospective cohort study was conducted. NT-proBNP plasma concentrations were measured preoperatively, 2–6 h, and 18–30 h after surgery in 120 patients, 18–35 years, undergoing elective non-cardiac surgery. Reasons for non-inclusion: history or symptoms of cardiac disease, kidney disease, pulmonary embolism, thrombosis, stroke, diabetes, head or chest trauma, pregnancy, incomplete panel of perioperative NT-proBNP plasma samples.Absolute and relative change of NT-proBNP plasma concentration were calculated. Changes between preoperative, 2–6 h, and 18–30 h (POD 1) NT-proBNP values, and of within-patient change in NT-proBNP were analyzed. ResultsIn 95 patients, NT-proBNP plasma concentrations (median [IQR]) were 8 [5–26] pg/mL at baseline, 17 [5–53] pg/mL 2–6 h, and 42 [11–86] pg/mL 18–30 h after surgery. Absolute and relative NT-proBNP increase after surgery was 32 [5–74] pg/mL and 196% [61 – 592%] compared to baseline. NT-proBNP elevation above the age- and sex-specific reference range was observed in 6/95 (6%) patients prior to surgery and in 39/95 (41%) patients after surgery. ConclusionsEven after uncomplicated surgery and postoperative period, NT-proBNP concentrations markedly increase in otherwise healthy adult patients. The aetiology of postoperative NT-proBNP increase is currently unknown and may be multifactorial.

Population Pharmacokinetics and Pharmacodynamics of Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.

BackgroundVericiguat, a stimulator of soluble guanylate cyclase, has been developed as a first-in-class therapy for worsening chronic heart failure in adults with left ventricular ejection fraction < 45%.ObjectiveThe objective of this article was to characterize the pharmacokinetics and pharmacokinetic variability of vericiguat combined with guideline-directed medical therapy (standard of care), and identify exposure–response relationships for safety (hemodynamics) and pharmacodynamic markers of efficacy (N-terminal pro-B-type natriuretic peptide concentration [NT-proBNP]) in patients with heart failure and left ventricular ejection fraction < 45% in the SOCRATES-REDUCED study (NCT01951625).MethodsVericiguat and NT-proBNP plasma concentrations in 454 and 432 patients in SOCRATES-REDUCED, respectively, were analyzed using nonlinear mixed-effects modeling.ResultsVericiguat pharmacokinetics were well described by a one-compartment model with apparent clearance, apparent volume of distribution, and absorption rate constant. Age, bodyweight, plasma bilirubin, and creatinine clearance were identified as significant covariates on apparent clearance; sex and bodyweight on apparent volume of distribution; and bodyweight and plasma albumin level on absorption rate constant. Pharmacokinetic/pharmacodynamic analysis showed initial minor and transient effects of vericiguat on blood pressure with low clinical impact. There were no changes in heart rate following initial or repeated vericiguat administration. An exposure-dependent and time-dependent turnover pharmacokinetic/pharmacodynamic model for NT-proBNP described production and elimination rates and an demonstrated exposure-dependent reduction in [NT-proBNP] by vericiguat plus standard of care compared with placebo plus standard of care. This effect was dependent on baseline [NT-proBNP].ConclusionsVericiguat has predictable pharmacokinetics, with no long-term effects on blood pressure in patients with heart failure and left ventricular ejection fraction < 45%. A pharmacokinetic/pharmacodynamic model described a vericiguat exposure-dependent reduction of NT-proBNP.Clinical Trial IdentifierNCT01951625.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01024-y.

CHANGES IN THE LEVEL OF NT-proBNP AND MEAN PULMONARY ARTERY PRESSURE FOLLOWING BRONCHOPLASTIC LOBECTOMY OR PNEUMONECTOMY AS MARKERS OF RIGHT VENTRICULAR DYSFUNCTION

Background There are scanty data of right ventricular dysfunction markers after major pulmonary resection.Objective To study the changes of plasma level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and its association with pulmonary artery pressure (PAP) as markers of right ventricular dysfunction in patients who underwent bronchoplastic lobectomy or pneumonectomy.Material and Methods The study population consisted of 36 patients aged 40–65 who underwent major pulmonary resection for lung cancer in 2016–2018. Patients were stratified into two groups according to the type of surgical procedure: bronchoplastic lobectomy, the main group (n = 19), and pneumonectomy, control group (n = 17). They were then analyzed for plasma NT-proBNP concentration, operative time, blood loss, intraoperative fluid administration, intraoperative urine output, and mean PAP level before and after an operation.Results The mean PAP level correlated positively with the plasma NT-proBNP concentration in the pneumonectomy group (Pearson r = 0.916754; p &lt; 0.001). This correlation was no evident in the subset of patients undergoing bronchoplastic lobectomy at the same determination point (Pearson r = 0.234741; p = 0.330).Conclusion The mean PAP increased significantly after pneumonectomy and is closely correlated with plasma NTproBNP concentration. These findings support the conclusion that bronchoplasty is preferable over pneumonectomy for lung cancer patients.

Evaluation of plasmatic levels of CK-MB and C-Reactive Protein in brachicephalic dogs who have narin stenosis before and after diode laser rhinoplasty

To evaluate the protective effect of rhinoplasty with diode laser on the cardiovascular system and in the reduction of the inflammatory state, CK-MB and PCR measurements were performed before and 30 days after the surgical procedure. Rhinoplasty using the diode laser promoted a significant reduction in plasma CK-MB and PCR levels, 30 days after its completion. No association was found between the pre-surgical plasma concentration of CK-MB and CRP and the degree of stenosis of the nostrils, race, age, sex and weight of the animals. A significant reduction in CK-MB was observed in dogs with severe stenosis, French Bulldog, one year old and over four years old, male and between 10 and 20 kg. Animals with severe stenosis, of the Pug breed, weighing less than 10 kg and three years of age exhibited a significant decrease in serum CRP values ​​after surgery. As a result, the degree of stenosis of the nostrils, the breed, age, sex and weight of the animals did not influence the plasma concentration of NTpro-BNP, CK-MB and PCR in brachycephalic dogs. Rhinoplasty with diode laser has been shown to be effective in reducing the plasma concentration of the natriuretic peptide CK-MB and CRP in dogs with brachycephalic syndrome, showing that the procedure has a protective effect on the cardiovascular function of these animals and is also effective in reducing inflammatory biomarkers.

Abstract 16095: Plasma NT-proBNP Concentrations are Two-fold Lower in Pacific versus European Population Samples: Evidence for Glycosylation Impacting Assay Detection and/or ProBNP Processing

Introduction: Pacific Islanders in New Zealand (NZ) have high rates of cardiovascular and metabolic disorders. The Pasifika Heart Study (PHS) recorded ethnic-specific clinical and biomarker data to inform clinical management in community care. Methods: For the PHS, Pacific adults (n=200) aged 20-64 years were selected from patients of a Pacific-led health centre in Christchurch, NZ, and screened for existing cardio-metabolic disorders and risk factors. Circulating concentrations of NT-proBNP (Roche Cobas NT-proBNP II), total proBNP and proBNP not glycosylated at Threonine 71 (T71) residue (both by in-house Luminex assays) were measured. Assay data were compared with European participants in the INSPIRE study (n=103 healthy volunteers, 20-70 years). Results: PHS participants had a mean age (SD) of 41.7 (11.5) years, 48% were male, mostly of Samoan and Tongan ethnicities (44% and 32% respectively). INSPIRE European participants had a mean age of 46.8 (15.0) years, 46% were male. NTproBNP concentrations measured by Cobas were two-fold lower in the PHS (median = 18.4 ng/L, IQR = [7.3, 35.8]) compared with INSPIRE (40.0 ng/L [19.8, 70.2]) (p&lt;0.001). Moreover, consistently lower concentrations were observedin PHS across a spectrum of either age or BMI (see Figure). In contrast, total proBNP concentrations exhibited a broad range in both cohorts, but did not differ between PHS (192.8 [35.7, 414.2] ng/L) and INSPIRE (36.1 [36.1, 225.1] ng/L, p&lt;0=0.278). This suggests that in the PHS, either the Cobas assay underestimates NT-proBNP due to glycosylation of antibody-binding sites and / or proBNP is not processed to NTproBNP due to glycosylation at the T71 cleavage site. As evidence for the latter, only 8% of PHS had proBNP not glycosylated at T71 versus 31% of INSPIRE (p&lt;0.001). Conclusions: Use of NT-proBNP thresholds based on European reference ranges to assess cardiovascular risk in community care may lead to under-diagnosis of evolving heart failure in Pacific Islanders.