Changes In N-terminal Pro-brain Natriuretic Peptide Research Articles

Improved heart function and cardiac remodelling following sacubitril/valsartan in acute coronary syndrome with HF.

This study sought to assess the effect of treatment of sacubitril/valsartan (S/V) on improving cardiac function and reversing cardiac remodelling in patients with acute coronary syndrome (ACS) complicated with heart failure with reduced ejection fraction after percutaneous coronary intervention (PCI). We enrolled 275 ACS patients with reduced left ventricular ejection fraction after PCI. The patients were divided into the routine and S/V groups according to the treatment drugs. The symptoms, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, echocardiographic parameters [left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI)], major adverse cardiac events (MACEs), and adverse reactions were recorded at baseline and 6months after treatment when a clinical follow-up was performed. The S/V group was further divided into prespecified subgroups including unstable angina (UA) group, non-ST-elevation myocardial infarction (NSTEMI) group, and ST-elevation myocardial infarction (STEMI) group according to the type of ACS. We analysed the changes in LVEF, LVMI, LVEDVI, LVESVI, and NT-proBNP in both groups and evaluated the correlation between the changes in the above variables (ΔLVEF, ΔLVMI, ΔLVEDVI, ΔLVESVI, and ΔNT-proBNP). Cox regression model was used to assess the independent risk factors of MACE. Prespecified subgroup analyses were also conducted. Compared with baseline, LVEF increased significantly (P<0.05), NT-proBNP, LVMI, and LVESVI decreased significantly in both groups after 6months (P<0.05), and LVEDVI decreased significantly in the S/V group (P=0.001). In the S/V group, ΔLVEF (t=-2.745, P=0.006), ΔNT-proBNP (P=0.009), ΔLVEDVI (t=4.203, P=0.001), and ΔLVESVI (t=3.907, P=0.001) were significantly improved than those in the routine group. In the S/V group, ΔLVEF was negatively correlated with ΔNT-proBNP (r=-0.244, P=0.004), ΔLVMI (r=-0.190, P=0.028), ΔLVEDVI (r=-0.173, P=0.045), and ΔLVESVI (r=-0.261, P=0.002). In Cox regression model analysis,ΔLVEF {hazard ratio [HR]=0.87 [95% confidence interval (CI) 0.80-0.95], P=0.003}, ΔLVEDVI [HR=1.04 (95% CI 1.01-1.06), P=0.013], and ΔLVESVI [HR=1.04 (95% CI 1.01-1.08), P=0.026] were independent risk factors for MACE. Subgroup analysis showed that ΔLVEF (t=6.290, P=0.001), ΔLVEDVI (t=2.581, P=0.011), and ΔNT-proBNP (P=0.019) in the NSTEMI group were significantly improved than those in the UA group, ΔLVEDVI in the NSTEMI group was significantly better than that in the STEMI group (t=-3.365, P=0.001), and ΔLVEF in the STEMI group was significantly better than that in the UA group (t=-3.928, P=0.001). There was a significant difference in the survival probability without MACE among the three groups in the analysis of the Kaplan-Meier curve (P=0.042). The incidence of MACE in the UA group was significantly higher than that in the NSTEMI group (32.4% vs. 6.3%, P=0.004). The cardiac function is improved and cardiac remodelling is reversed significantly after treatment of S/V in ACS patients with reduced left ventricular ejection fraction after PCI, and the improvement is more obvious than the routine group. There is a significant negative correlation between the change in LVEF and the changes in NT-proBNP, LVMI, LVEDVI, and LVESVI. The increase of LVEF and the decrease of LVEDVI and LVESVI are protective factors to improve the prognosis. Patients with myocardial infarction and reduced left ventricular ejection fraction might benefit more from the initiation of S/V as first-line heart failure treatment after PCI.

Lipid profile and NT-proBNP changes from pre-clinical to established rheumatoid arthritis: A 12 years follow-up explorative study

ObjectivesThe aim of the current study was to explore the changes in lipid and NT-proBNP levels in rheumatoid arthritis (RA) patients through different phases of the disease: from the pre-clinical stage and RA onset up to the treatment phase with biological disease-modifying anti-rheumatic drugs (bDMARDS). MethodsThirty-eight consecutive patients, initially with arthralgia and rheumatoid factor and/or anti-citrullinated protein antibodies without arthritis, who later developed RA and eventually started treatment with bDMARDs, were included. Lipid spectrum and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured longitudinally from several months before diagnosis through treatment with bDMARDs. ResultsFrom baseline, C-reactive protein (CPR) initially increased sharply, decreasing with the start of biological treatment. Low-density lipoprotein-cholesterol (LDL-c) remained stable, high-density lipoprotein-cholesterol (HDL-c) increased, apolipoprotein A1 (ApoA1 and lipoprotein (a) (Lp(a)), and total cholesterol (TC)/HDL-c ratio and apolipoprotein B (ApoB) decreased during follow-up. NT-proBNP closely followed progression of CRP. TC, LDL-c, TC/HDL-c ratio, ApoA and ApoB inverse correlated with CRP, while Lp(a) positively correlated. HDL-c and triglycerides showed no correlation. ConclusionChanges in the lipid profile and NT-proBNP in RA patients seem to be related to inflammation, with changes reflecting an increase in CVD risk occurring along with rises in CRP levels. These changes seem to already be present at diagnosis, indicating the need for timely control of inflammation.

Metabolomic Profiling of the Effects of Dapagliflozin in Heart Failure With Reduced Ejection Fraction: DEFINE-HF.

Sodium-glucose cotransporter-2 inhibitors are foundational therapy in patients with heart failure with reduced ejection fraction (HFrEF), but underlying mechanisms of benefit are not well defined. We sought to investigate the relationships between sodium-glucose cotransporter-2 inhibitor treatment, changes in metabolic pathways, and outcomes using targeted metabolomics. DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients With HF With Reduced Ejection Fraction) was a placebo-controlled trial of dapagliflozin in HFrEF. We performed targeted mass spectrometry profiling of 63 metabolites (45 acylcarnitines [markers of fatty acid oxidation], 15 amino acids, and 3 conventional metabolites) in plasma samples at randomization and 12 weeks. Using mixed models, we identified principal components analysis-defined metabolite clusters that changed differentially with treatment and examined the relationship between change in metabolite clusters and change in Kansas City Cardiomyopathy Questionnaire scores and NT-proBNP (N-terminal probrain natriuretic peptide). Models were adjusted for relevant clinical covariates and nominal P<0.05 with false discovery rate-adjusted P<0.10 was used to determine statistical significance. Among the 234 DEFINE-HF participants with targeted metabolomic data, the mean age was 62.0±11.1 years, 25% were women, 38% were Black, and mean ejection fraction was 27±8%. Dapagliflozin increased ketone-related and short-chain acylcarnitine as well as medium-chain acylcarnitine principal components analysis-defined metabolite clusters compared with placebo (nominal P=0.01, false discovery rate-adjusted P=0.08 for both clusters). However, ketosis (β-hydroxybutyrate levels >500 μmol/L) was achieved infrequently (3 [2.5%] in dapagliflozin arm versus 1 [0.9%] in placebo arm) and supraphysiologic levels were not observed. Increases in long-chain acylcarnitine, long-chain dicarboxylacylcarnitine, and aromatic amino acid metabolite clusters were associated with decreases in Kansas City Cardiomyopathy Questionnaire scores (ie, worse quality of life) and increases in NT-proBNP levels, without interaction by treatment group. In this study of targeted metabolomics in a placebo-controlled trial of sodium-glucose cotransporter-2 inhibitors in HFrEF, we observed effects of dapagliflozin on key metabolic pathways, supporting a role for altered ketone and fatty acid biology with sodium-glucose cotransporter-2 inhibitors in patients with HFrEF. Only physiologic levels of ketosis were observed. In addition, we identified several metabolic biomarkers associated with adverse HFrEF outcomes. URL: https://www. gov; Unique identifier: NCT02653482.

NT-proBNP and sRAGE levels in early rheumatoid arthritis

Objective Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment. Method Data from 342 consecutive early RA patients participating in the ‘Parelsnoer’ cohort were used. At baseline and after 6 months’ disease activity, NT-proBNP and sRAGE levels were assessed. Results After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001). Conclusion Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated.

Association of changes in NT-proBNP, hsTnT and uric acid levels with haemodynamic changes after targeted medical therapies in patients with idiopathic pulmonary arterial hypertension.

During pulmonary arterial hypertension (PAH)-targeted therapies for patients with idiopathic pulmonary arterial hypertension (IPAH), regular follow up to evaluate treatment efficacy is essential. Serum biomarkers can reflect various pathobiological processes in IPAH and have the advantages of being non-invasive, simple to carry out and low cost. The aim of our study was to evaluate whether serum biomarkers could serve as non-invasive markers to reflect haemodynamic changes after PAH-targeted therapies in patients with IPAH. A total of 31 eligible patients aged 38.1 ± 12.1 years (25 were female) were included in this study. Changes in haemodynamic parameters and several serum biomarkers (cardiac markers, serum uric acid, high-sensitivity C-reactive protein, hepatic and kidney function markers) were compared before and after at least six months of PAH-targeted therapies. The time interval between the blood assays and right heart catheterisation was within five days. After at least six months of PAH-targeted therapies, the N-terminal pro-brain natriuretic peptide (NT-proBNP) level decreased from 579 (191-905) to 135 pg/ml (60-395) (p < 0.01), high-sensitivity cardiac troponin T (hsTnT) level decreased from 0.009 (0.006-0.012) to 0.007 ng/ml (0.005-0.01) (p < 0.01), and serum uric acid level decreased from 381.5 ± 131.4 to 327.2 ± 110.0 µmol7sol;l (p = 0.011). The change in NT-proBNP level was positively correlated with changes in pulmonary vascular resistance (r = 0.538, p < 0.01) and mean pulmonary arterial pressure (r = 0.440, p = 0.013). The change in hsTnT level was positively correlated with the change in mean right atrium pressure (r = 0.504, p < 0.01). The change in serum uric acid level was negatively correlated with that of cardiac index (r = -0.471, p < 0.01). NT-proBNP, hsTnT and serum uric acid levels can be used as non-invasive tools for evaluating the efficacy of PAH-targeted medications for IPAH patients. The role of these biomarkers in the follow up should be emphasised.

Natriuretic peptide dynamics with remote pulmonary artery pressure monitoring

Abstract Background Real-life clinical practice has confirmed the value of pulmonary artery (PA) pressure-guided therapy in patients with heart failure (HF) and history of repeated HF hospitalizations (HFH), to greater extent to that reported in the pivotal clinical trial CHAMPION-HF. The value of hemodynamic monitoring in a population of patients with HF and elevated natriuretic peptides, but without recent HFH, is unknown. Objective To assess N-terminal-pro-brain natriuretic peptide (NTproBNP) dynamics before and 6 months after PA pressure sensor implantation. Methods Ten patients managed in a multidisciplinary HF clinic implanted with the CardioMEMS PA pressure sensor were consecutively included from June 2019 to July 2020. Mean age was 63.1±23.5 years, 30% were women, 40% had HF with reduced EF (EF &amp;lt;40%). NTproBNP was measured at baseline and six months after sensor implantation. Wilcoxon matched-pairs signed-rank test was used to compare NTproBNP values at baseline and at 6 months. Fractional polynomial fit plot was used to represent changes in mean PA pressure over time. Linear regression was used to predict the change in NTproBNP based on the change in PA pressures. Results Mean daily pressure transmission rate was 92.4±5.1%. During the six-month study period 90% of patients had a change in medication related to PA pressure, with an average of 0.21 [0.17–0.66] changes per patient per month. Mean PA pressure at baseline was 28.5±9.5 mmHg, and decreased by 5.5 mmHg at 6 months (p=0.01) (Figure 1). NTproBNP was also significantly lower six months post CardioMEMS implantation; decreasing from 1696 pg/ml [976–2930] at baseline to 1046 pg/ml [616–2076] after six months (p=0.04) (Figure 2). There was a weak correlation between the change in NTproBNP and the change in mean PA pressure (R2=0.22, p=0.17). Conclusions NTproBNP values were significantly lower 6-months following implantation of a PA pressure sensor to guide HF management. Mean PA pressures were also significantly reduced. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Hospital Universitari Germans Trias i Pujol Figure 1. Change in mean PA pressure over time.Figure 2. Change in NTproBNP after PAP monitoring.

Design of a multifaceted strategy based on automated text messaging in patients with recent heart failure admission.

AimsTo evaluate a telemonitoring strategy based on automated text messaging and telephone support after heart failure (HF) hospitalization.Methods and resultsThe MESSAGE‐HF study is a prospective multicentre, randomized, nationwide trial enrolling patients from 30 clinics in all regions of Brazil. HF patients with reduced left ventricular ejection fraction (<40%) and access to mobile phones are eligible after an acute decompensated HF hospitalization. Patients meeting eligibility criteria undergo an initial feasibility text messaging assessment and are randomized to usual care or telemonitoring intervention. All patients receive a HF booklet with basic information and recommendations about self‐care. Patients in the intervention group receive four daily short text messages (educational and feedback) during the first 30 days of the protocol to optimize self‐care; the feedback text messages from patients could trigger diuretic adjustments or a telephone call from the healthcare team. After 30 days, the frequency of text messages can be adjusted. Patients are followed up after 30, 90, and 180 days, with final status ascertained at 365 days by telephone. Our primary endpoint is the change in N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels after 180 days. Secondary endpoints include changes in NT‐proBNP after 30 days; health‐related quality of life, HF self‐care, and knowledge scales after 30 and 180 days; and a composite outcome of HF hospitalization and cardiovascular death, adjudicated by a blinded and independent committee.ConclusionsThe MESSAGE‐HF trial is evaluating an educational and self‐care promotion strategy involving a simple, intensive, and tailored telemonitoring system. If proven effective, it could be applied to a broader population worldwide.

Socioeconomic position is associated with N-terminal pro-brain natriuretic peptide (NT-proBNP)-Results of the population-based Heinz Nixdorf Recall study.

N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) is a diagnostic marker for heart failure and a prognostic factor for cardiovascular disease (CVD). The aim of this study was to examine the association of socioeconomic position (SEP) with NT-proBNP while assessing sex-differences and the impact of CVD risk factors and prevalent CVD on the association. Baseline data of 4598 participants aged 45-75 years of the Heinz Nixdorf Recall Study were used. Income and education were used as SEP indicators. Age- and sex-adjusted linear regression models were fitted to calculate effect size estimates and 95% confidence intervals (95%-CIs) for the total effect of SEP indicators on NT-proBNP, while potential mediation was assessed by additionally accounting for traditional CVD risk factors (i.e., systolic blood pressure, HDL cholesterol, LDL cholesterol, diabetes, anti-hypertensive medication, lipid-lowering medication, BMI, current smoking). Education and income were included separately in the models. With an age- and sex-adjusted average change in NT-proBNP of -6.47% (95%-CI: -9.91; -2.91) per 1000€, the association between income and NT-proBNP was more pronounced compared to using education as a SEP indicator (-0.80% [95%-CI: -1.92; 0.32] per year of education). Sex-stratified results indicated stronger associations in men (-8.43% [95%-CI: -13.21; -3.38] per 1000€; -1.63% [95%-CI: -3.23; -0.001] per year of education) compared to women (-5.10% [95%-CI: -9.82; -0.01] per 1000€; -1.04% [95%-CI: -2.59; 0.50] per year of education). After adjusting for CVD risk factors some of the observed effect size estimates were attenuated, while the overall association between SEP indicators and NT-proBNP was still indicated. The exclusion of participants with prevalent coronary heart disease or stroke did not lead to a substantial change in the observed associations. In the present study associations of education and income with NT-proBNP were observed in a population-based study sample. Only parts of the association were explained by traditional CVD risk factors, while there were substantial sex-differences in the strength of the observed association. Overt coronary heart disease or stroke did not seem to trigger the associations.

Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial

Backgrounds/AimSodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD).MethodsThe study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration.ResultsIn an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV.ConclusionsOur data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug.Trial registration University Medical Information Network Clinical Trial Registry, number 000024502

Six-year changes in N-terminal pro-brain natriuretic peptide and changes in weight and risk of obesity.

The aim of this study was to study the prospective association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and changes in weight and obesity risk in a community-based population. Data from 9,681 participants from the Atherosclerosis Risk in Communities Study were analyzed at two time points 6 years apart. Among people without obesity at baseline, multivariable logistic regression models were used to examine the association between baseline levels of NT-proBNP and incident obesity. A multivariable linear regression model was used to examine the association between changes in NT-proBNP (visit 2 serum and visit 4 plasma samples) and changes in weight. The prevalence of obesity increased from 28% to 35% in the 6-year follow-up period. Compared with individuals in the highest NT-proBNP quartile, those in the lowest were more likely to have obesity at baseline (odds ratio 1.25; 95% CI: 1.08-1.45) and, among people who did not have obesity at baseline, were more likely to develop obesity at follow-up (odds ratio 1.35; 95% CI: 1.07-1.69). Changes in NT-proBNP were inversely associated with weight change. In this prospective study, lower levels of NT-proBNP were associated with higher risk of obesity, and changes in NT-proBNP were inversely associated with changes in weight. This suggests that natriuretic peptides or their pathways may be potential targets in the treatment of obesity.

Changes in extracellular water and left ventricular mass in peritoneal dialysis patients.

BackgroundIncreasing number of peritoneal dialysis (PD) patients are reported to have increased left ventricular hypertrophy (LVH), a major risk factor for cardiovascular mortality. We wished to determine which factors were most associated with changes in left ventricular mass index (LVMI).MethodsWe reviewed patient and treatment factors in prevalent PD patients with repeat echocardiograms 18 to 24 months apart, with corresponding bioimpedance measurements of extracellular water (ECW) and serum N-terminal pro-brain natriuretic peptide (NT-proBNP).ResultsWe studied 60 patients (34 males, 35 with diabetes) who were treated with PD for a median of 14 months (2.5–26.3 months). All but one had LVH; on repeat echocardiography, there was no overall change in LVMI (106 [84–127] g/m2 vs. 108 [91–122] g/m2) despite a loss of residual renal function. Left ventricular mass increased in 34 (56.7%), and the percent change in LVMI was associated with percent change in NT-proBNP (r = 0.51, p = 0.017) and ECW/height (r = 0.32, p = 0.029), but not with ECW/total body water or changes in systolic or mean arterial pressure, urine output, 24-hour PD ultrafiltration, or net sodium balance. Only ECW/height remained independently associated with the percent change in LVMI in a multivariable model (odds ratio, 1.25; 95% confidence interval, 1.08–1.36; p = 0.007). ConclusionIn this observational longitudinal report, a reduction in ECW/height was associated with regression of LVMI, whereas an increased ECW/height was associated with increased LVMI. As there was no corresponding association with systolic or mean arterial pressure, then volume expansion would appear to be a more significant factor in determining LVH than blood pressure.

Mortal Interaction Between Hemophagocytic Syndrome and Newly Developed Heart Failure.

ResumoFundamento:A síndrome hemofagocítica (SHF) é uma síndrome hiperinflamatória debilitante. O status da insuficiência cardíaca (IC) com fração de ejeção preservada (ICFEP) está intimamente relacionado ao aumento da inflamação sistêmica e intramiocárdica.Objetivos:este estudo pretende determinar os preditores de mortalidade e os parâmetros de monitoramento confiáveis nos casos de SHF que desenvolveram a ICFEP durante seu curso clínico.Métodos:Trinta e nove pacientes, diagnosticados com SHF de acordo com os critérios diagnósticos do estudo HLH 2004 com Hscore ≥169, e com aspiração ou biópsia de medula óssea comprovada, foram recrutados retrospectivamente. Foram investigados retrospectivamente os fatores de risco tradicionais, como proteína C reativa sérica, níveis de albumina e ferritina com contagens de linfócitos e plaquetas, e fatores não tradicionais, como relação neutrófilolinfócito (NLR), relação linfócito-monócito (MLR), volume plaquetário médio (MPV) e pró-peptídeo natriurético cerebral N-terminal (NTproBNP). Analisou-se a relação entre os valores laboratoriais alterados ao longo do tempo entre si e com a mortalidade. O nível de significância geral foi de 5%.Resultados:Foi demonstrado que a alteração temporal dos níveis de índice cardiotorácico (ICT), NTproBNP sérico, ferritina, PCR e albumina foram detectados como sendo preditores de mortalidade (p<0,05, para todos) em análise univariada. As contagens de linfócitos e plaquetas com valores de NLR e MPV também foram significativos (p<0,05). A relação entre NT-proBNP e o aumento dos marcadores inflamatórios sistêmicos também foi considerada significativa. Além de fatores de risco tradicionais, os níveis de ferritina sérica, e os níveis de NLR, MLR e MPV foram considerados significativamente correlacionados entre si.Conclusão:Acompanhado de parâmetros de monitoramento confiáveis, o diagnóstico rápido e o tratamento antiinflamatório agressivo com controle rígido de volume podem salvar vidas de pacientes com SHF que sofrem de complicações por ICFEP. O monitoramento rígido da inflamação pode prever o resultado do paciente que sofre de ICFEP.

Changes of NT-proBNP and sST2 levels for predicting isolated episodes of ventricular tachyarrhythmias and electrical storm in patients with systolic heart failure and various implanted devices

Aim . To study the changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth stimulation gene-2 (sST2) to predict isolated episodes of ventricular tachyarrhythmias (VTA) and electrical storm (ES) in patients with systolic heart failure and implanted cardioverter-defibrillators, cardiac resynchronization therapy (CRT) defibrillators, as well as cardiac contractility modulation (CCM) devices. Material and methods . The study included 69 patients (mean, 59; women, 10; mean age, 59±13 years) with class I-III systolic HF and ischemic (n=36) or nonischemic (n=33) cardiomyopathy. The survey was carried out at baseline, as well as 1, 3, 6 and 12 months after device implantation. This included data collection, physical examination, determination of NT-proBNP and sST2, 6-minute walk test, electrocardiography (ECG), 24-hour Holter monitoring, echocardiography, assessment of device performance. Predictors of isolated VTA and ES were identified using ROC and multivariate analyzes. Results . According to the follow-up (median, 28 months) results, 3 groups of patients were formed: group 1 — without VTA (n=45); group 2 — isolated VTA (n=15); group 3 — ES (n=9). According to multivariate analysis, predictors of isolated VTA were as follows: 1) baseline NT-proBNP &gt;3200 pg/ml; 2) minimum NTproBNP &gt;1100 pg/ml during 12-month follow-up; 3) sST2 &gt;26 ng/ml 3 months after device implantation; 4) presence of old myocardial infarction; 5) no echocardiographic signs of response to CRT or CCM therapy. There were following predictors of ES: 1) left ventricular end-systolic dimension &gt;7,0 cm; 2) presence of VTA runs according to 24-hour Holter monitoring; 3) no echocardiographic signs of response to CRT or CCM therapy. Conclusion . The results obtained indicate that NT-proBNP and sST2 assessment in patients with systolic heart failure is promising for predicting isolated VTA, but not ES. Cardiac reverse remodeling as a result of effective CRT or CCM therapy is associated with a significant risk reduction for isolated VTA and ES.

Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE)

Abstract Background Little is known about the impacts of sodium glucose co-transporter 2 inhibitors on cardiac functional parameters, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). Purpose To compare the effect of canagliflozin with glimepiride, based on changes in N-terminal pro-brain natriuretic peptide (NT-proBNP), in that patient population. Methods This trial was an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint trial at 34 centers in Japan. Patients with T2D and clinically stable CHF excluding NYHA class IV, randomized to receive canagliflozin 100 mg or glimepiride (starting dose: 0.5 mg), were examined using the primary endpoint of non-inferiority of canagliflozin versus glimepiride, defined as a margin of 1.1 in the upper-limit of the 2-sided 95% confidence interval (95% CI) for the group ratio of percentage change in NT-proBNP at 24 weeks. Results Data analysis of 233 patients (mean age 68.6±10.1 yrs; 75% male) showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6±14.6%, with 71% of patients having a preserved LVEF (≥50%). The ratio of NT-proBNP percentage change was 0.48 (95% CI, −0.13 to 1.59, P=0.226), and therefore did not meet the prespecified non-inferiority margin. However, data stratified according to baseline NT-proBNP levels showed a trend that canagliflozin treatment reduced NT-proBNP levels to a greater extent than in subgroups with elevated levels of NT-proBNP (Figure A). Furthermore, NT-proBNP levels in the canagliflozin group did show a nonsignificant trend lower in the subgroup with preserved LVEF (Figure B), but not in the subgroup with reduced LVEF (Figure C). Additionally, the changes in the NYHA class were comparable between groups (P=0.061) in the overall cohort, whereas in the subgroup with a preserved LVEF canagliflozin caused a significant improvement in NYHA classes compared to that found for glimepiride treatment (P=0.027). Conclusions This trial did not meet the predefined primary endpoint of changes in NT-proBNP levels, with 24 weeks of treatment with canagliflozin relative to glimepiride which together with other recent studies would question the value of continuing to monitor NT-proBNP levels after the initial diagnosis of heart failure. Nevertheless, in a subgroup with preserved LVEF, there was a non-significant trend for canagliflozin treatment to reduce NT-proBNP levels and improve symptoms even in stable HF patients. Further research is therefore warranted to determine whether patients with preserved LVEF, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors. Changes in NT-proBNP Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Mitsubishi Tanabe Pharma Corporation

Serial measurement of biomarkers and the risk of stroke or systemic embolism and bleeding in patients with atrial fibrillation in ENGAGE AF-TIMI 48

Abstract Background Patients with atrial fibrillation (AF) have progressive cardiac structural changes that may be manifest by biomarkers of myocardial injury and hemodynamic stress. Baseline values of hsTnT (high-sensitivity troponin T), and NT-proBNP (N-terminal pro-brain natriuretic peptide) are associated with stroke risk and GDF-15 (growth differentiation factor-15) is associated with bleeding risk in patients with AF. However, the variability of these biomarkers over time and their associations with stroke or systemic embolism events (S/SEE) and bleeding in patients with AF remain unclear. Purpose We examined whether patients with AF demonstrate detectable changes in these biomarkers over 12 months and whether such changes from baseline to 12 months are associated with the subsequent risk of S/SEE (hsTnT, NT-proBNP) and bleeding (GDF-15). Methods ENGAGE AF-TIMI 48 was a multinational randomized trial of the oral factor Xa inhibitor edoxaban in patients with atrial fibrillation and a CHADS2 score ≥2. We performed a nested prospective biomarker study in 6062 patients, analyzing hsTnT, NT-proBNP, and GDF-15 at baseline and 12 months. Event rates were estimated and displayed with annualized event rates after 12 months. Results Of 6062 patients, hsTnT was dynamic in 46.9% (≥2 ng/L change), NT-proBNP in 51.9% (≥200 pg/L change), GDF-15 in 45.6% (≥300 pg/L change) between baseline and 12 months. In addition, 7.7% in hsTnT shifted from low-&amp;gt;high categories, 9.4% in NT-proBNP from low-&amp;gt;high, 10.6% in GDF-15 from low-&amp;gt;high over 12 months (Figure). Elevated hsTnT (≥14 ng/L) and NT-proBNP (≥900 pg/L) either at baseline or at 12 months were independently associated with higher rates of subsequent S/SEE, and elevated GDF-15 (≥1800 pg/L) either at baseline or at 12 months were independently associated with higher rates of subsequent bleeding (P&amp;lt;0.001 for each). In a Cox regression model, the absolute changes in log2-transformed hsTnT and NT-proBNP were associated with increased risk of S/SEE (adj-HR, 1.75; 95% CI, 1.38–2.23; p&amp;lt;0.001, and adj-HR, 1.31; 95% CI, 1.11–1.55; p=0.002, respectively) and log2-transformed GDF-15 with bleeding (adj-HR, 1.42; 95% CI, 1.04–1.92; p=0.025). Analyzed in a categorical manner (Figure), patients who increased hsTnT or NT-proBNP between baseline and 12 months or had high hsTnT or NT-proBNP at both timepoints were at higher risk for S/SEE (adj-HR 1.87 and 1.50 for hsTnT; adj-HR 1.80 and 2.59 for NT-proBNP, respectively). Patients with persistently elevated GDF-15 appeared to be at higher risk for bleeding (adj-HR,1.35) (Figure). Conclusions Serial assessment of hsTnT, NT-proBNP, and GDF-15 revealed a substantial proportion of patients with AF had dynamic values. Patients with either persistently elevated or dynamic values were at higher risk of adverse clinical outcomes. Those biomarkers may play a role in personalizing preventive strategies in patients with AF based on risk. Change in biomarkers and event rate Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Pharma Development

Effect of growth hormone treatment on circulating levels of NT-proBNP in patients with ischemic heart failure

AimsGrowth hormone (GH) therapy in heart failure (HF) is controversial. We investigated the cardiovascular effects of GH in patients with chronic HF due to ischemic heart disease. MethodsIn a double-blind, placebo-controlled trial, we randomly assigned 37 patients (mean age 66 years; 95% male) with ischemic HF (ejection fraction [EF] < 40%) to a 9-month treatment with either recombinant human GH (1.4 mg every other day) or placebo, with subsequent 3-month treatment-free follow-up. The primary outcome was change in left ventricular (LV) end-systolic volume measured by cardiac magnetic resonance (CMR). Secondary outcomes comprised changes in cardiac structure and EF. Prespecified tertiary outcomes included changes in New York Heat Association (NYHA) functional class and quality of life (QoL), as well as levels of insulin-like growth factor-1 (IGF-1) and N-terminal pro-brain natriuretic peptide (NT-proBNP). ResultsNo changes in cardiac structure or systolic function were identified in either treatment group; nor did GH treatment affect QoL or functional class. In the GH group, circulating levels of IGF-1 doubled from baseline (+105%; p < 0.001) and NT-proBNP levels halved (−48%; p < 0.001) during the treatment period, with subsequently a partial return of both towards baseline levels. No changes in IGF-1 or NT-proBNP were observed in the placebo group at any time during the study. ConclusionIn patients with chronic ischemic HF, nine months of GH treatment was associated with significant increases in levels of IGF-1 and reductions in levels of NT-proBNP, but did not affect cardiac structure, systolic function or functional capacity.

Pregnancy in a healthy population: dynamics of NTproBNP and hs-cTroponin T

ObjectiveTo describe the intraindividual changes of heart biomarker levels during and after pregnancy and to evaluate existing cut-off levels for heart failure or myocardial ischaemia in pregnant women.MethodA total of...

Brain-Heart Axis and Biomarkers of Cardiac Damage and Dysfunction after Stroke: A Systematic Review and Meta-Analysis.

Background: Cardiac complications after a stroke are the second leading cause of death worldwide, affecting the treatment and outcomes of stroke patients. Cardiac biomarkers such as cardiac troponin (cTn), brain natriuretic peptide (BNP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) have been frequently reported in patients undergoing a stroke. The aim of the present study is to meta-analyze the relationship between changes in such cardiac biomarkers and stroke and to present a systematic review of the previous literature, so as to explore the brain–heart axis. Methods: We searched four online databases pertinent to the literature, including PubMed, Embase, the Cochrane Library, and the Web of Science. Then, we performed a meta-analysis to investigate changes in cTn, BNP, and NT-proBNP associated with different types of stroke. Results and Conclusions: A significant increase in cTnI concentration was found in patients exhibiting a brain hemorrhage. BNP increased in cases of brain infarction, while the NT-proBNP concentration was significantly elevated in patients suffering an acute ischemic stroke and brain hemorrhage, indicating cardiac damage and dysfunction after a stroke. Our analysis suggests that several potential mechanisms may be involved in the brain–heart axis. Finally, clinicians should pay careful attention to monitoring cardiac function in the treatment of cerebrovascular diseases in order to provide a timely and more accurate treatment.

N-terminal Pro-B-Type Natriuretic Peptide and Malnutrition in Patients on Hemodialysis.

Natriuretic peptides, brain natriuretic peptide (BNP), and N-terminal probrain natriuretic peptide (NT-proBNP) are mainly known as diagnostic markers for heart failure with high diagnostic and prognostic values in the general population. In patients who are undergoing hemodialysis (HD), changes in NT-proBNP can be related to noncardiac problems such as fluid overload, inflammation, or malnutrition and can also be influenced by the dialysis characteristics. The current review aimed to summarize findings from studies on the association between NT-proBNP and malnutrition in HD patients. Articles published after 2009 and over a ten-year period were considered for inclusion. We first briefly discuss the traditional functions of NT-proBNP, and after, we describe the functions of this prohormone by focusing on its relation with protein energy wasting (PEW) in HD patients. Mechanisms that could explain these relationships were also discussed. Overall, 7 studies in which the investigation of the relations between NT-proBNP and nutritional status in HD patients were among the main objects were taken into account. NT-proBNP levels correlated with several factors described in the 4 categories of markers indicative of PEW (body mass and composition, muscle mass, biochemical criteria, and dietary intakes) and/or were associated with PEW. Interactions between several parameters could be involved in the association between NT-proBNP and malnutrition with a strong role of weight status. NT-proBNP is elevated in HD patients and is associated with malnutrition. Nevertheless, the prognostic value of NT-proBNP on nutritional status should be evaluated.

Diagnostic Utility of N-terminal pro-Brain Natriuretic Peptide and C-reactive Protein in Diagnosing Heart Failure in Patients with Acute Hypoxemic Respiratory Failure.

IntroductionShortness of breath is a leading cause of intensive care unit (ICU) admissions and is multifactorial. Acute hypoxemic respiratory failure due to heart failure is one of the leading causes of ICU admissions. N-terminal pro-brain natriuretic peptide (NT-proBNP) is secreted by ventricles and carries a negative predictive value for heart failure (2). NT-proBNP can also be raised in sepsis (4). Changes in NT-proBNP strongly correlated with changes in C-reactive protein (CRP) and leukocytes levels (8).ObjectiveThis study was conducted to explore the diagnostic utility of NT-proBNP and CRP to diagnose heart failure in patients presenting with acute hypoxemic respiratory failure.Materials and methodsAfter informed consent and approval from the institutional review board (IRB), patients of acute hypoxemic respiratory failure were included in the study. History and physical examination were done by a medical resident and recorded in the patients' files. Data were transferred to a structured proforma by the researcher. All tests were conducted within three hours of presentation. The diagnosis of heart failure was made by a panel of experts, including the consultant cardiologist and consultant intensivist in charge. The chest X-ray was reported by the radiologist. The cost of the test was afforded by the institution.Data were analyzed by SPSS version 15 (SPSS Inc., Chicago, Illinois). Analysis of variance (ANOVA), Pearson correlation and linear regression were applied to find out the relation between variables and significance.ResultsWe studied 137 patients. Out of them, 72.9% were diagnosed as heart failure. Heart failure was more common in females (43.7%) as compared to males (29%). NT-proBNP was raised in 111 (81%) patients and out of them, 88 patients (79%) had heart failure. Sensitivity and specificity of NT-proBNP were found to be (95.56%) and (46.81%), respectively. Similarly, CRP was 90% sensitive and 25.53% specific for heart failure. The most common findings in chest X-rays of patients with heart failure were upper lobe diversion and enlarged cardiothoracic ratio (71%).ConclusionWe concluded our study as NT-proBNP is a highly sensitive test to diagnose heart failure in settings of acute hypoxemic respiratory failure. CRP is also significantly raised in heart failure. Upper lobe diversion and an increased cardiothoracic ratio is a strong predictor of heart failure.