N-terminal pro-B-type Natriuretic Peptide Levels Research Articles

Efficacy of omecamtiv mecarbil in heart failure with reduced ejection fraction according to N-terminal pro-B-type natriuretic peptide level: insights from the GALACTIC-HF trial.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT-proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC-HF). The primary outcome was the composite of a worsening heart failure event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT-proBNP (≤ median, > median), excluding individuals with atrial fibrillation/flutter (AF/AFL). Of the 8232 patients analysed, 8206 had an available baseline NT-proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1-Q3) NT-proBNP level was 1675 (812-3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤ median 0.94 (95% confidence interval [CI] 0.80-1.09), > median 0.81 (0.73-0.90) (p-interaction=0.095); for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90-1.15) and > median 0.88 (0.80-0.96) (p-interaction=0.035). There was an interaction between treatment and NT-proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT-proBNP (p-interaction=0.086). In GALACTIC-HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT-proBNP levels, especially in patients without AF/AFL. ClinicalTrials.gov Identifier NCT02929329; EudraCT number, 2016-002299-28.

Metabolomic Signatures Associated With Pulmonary Arterial Hypertension Outcomes.

Pulmonary arterial hypertension (PAH) is a complex disease characterized by progressive right ventricular (RV) failure leading to significant morbidity and mortality. Investigating metabolic features and pathways associated with RV dilation, mortality, and measures of disease severity can provide insight into molecular mechanisms, identify subphenotypes, and suggest potential therapeutic targets. We collected data from a prospective cohort of PAH participants and performed untargeted metabolomic profiling on 1045 metabolites from circulating blood. Analyses were intended to identify metabolomic differences across a range of common metrics in PAH (eg, dilated versus nondilated RV). Partial least squares discriminant analysis was first applied to assess the distinguishability of relevant outcomes. Significantly altered metabolites were then identified using linear regression, and Cox regression models (as appropriate for the specific outcome) with adjustments for age, sex, body mass index, and PAH cause. Models exploring RV maladaptation were further adjusted for pulmonary vascular resistance. Pathway enrichment analysis was performed to identify significantly dysregulated processes. A total of 117 participants with PAH were included. Partial least squares discriminant analysis showed cluster differentiation between participants with dilated versus nondilated RVs, survivors versus nonsurvivors, and across a range of NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, REVEAL 2.0 composite scores, and 6-minute-walk distances. Polyamine and histidine pathways were associated with differences in RV dilation, mortality, NT-proBNP, REVEAL score, and 6-minute walk distance. Acylcarnitine pathways were associated with NT-proBNP, REVEAL score, and 6-minute walk distance. Sphingomyelin pathways were associated with RV dilation and NT-proBNP after adjustment for pulmonary vascular resistance. Distinct plasma metabolomic profiles are associated with RV dilation, mortality, and measures of disease severity in PAH. Polyamine, histidine, and sphingomyelin metabolic pathways represent promising candidates for identifying patients at high risk for poor outcomes and investigation into their roles as markers or mediators of disease progression and RV adaptation.

N-Terminal Pro-Bnp (NT-ProBNP) and High Sensitive Troponin Levels in Patients with Ischemic Dilated Cardiomyopathy and Idiopathic Dilated Cardiomyopathy

Background: The brain-type natriuretic peptides (BNP) and troponins levels can be used for the risk stratification of patients presenting with acute myocardial infarctions. Elevated levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) can be seen in patients with heart failure (HF) and atrial fibrillation. Objectives: The aim is to evaluate the NT-ProBNP levels and high-sensitive troponin-T (Trop T-HS) levels in patients with ischemic and nonischemic HF and to analyze its association with prognosis. Methods: This prospective observational study was conducted in a tertiary Centre over a period of 2 years. We analyzed NT-ProBNP and Trop T-HS levels of patients with HF, who were admitted to our cardiac intensive care unit. Patients with acute coronary syndrome, myocarditis, and renal failure were excluded from the study. The study population consists of 130 patients, of which 90 patients with ischemic dilated cardiomyopathy (ISDCM) and 40 patients with idiopathic dilated cardiomyopathy (IDCM). They belonged to the New York Heart Association functional classes 3 and 4. The diagnosis was made with the help of a coronary angiogram and transthoracic echocardiogram. We analyzed the NT-ProBNP levels and Trop T-HS of both groups of patients. Results: Males were predominant in both groups, i.e., 70 (77.8%) in the ISDCM patients and 26 (65%) in the IDCM patients. The NT-ProBNP levels were significantly higher among patients with ISDCM compared to patients with (IDCM) dilated cardiomyopathy (8648 ± 6207 pg/mL vs. 3100 ± 2906 pg/mL); P = 0.0008. We analyzed the NT-ProBNP levels of the survivors and nonsurvivors in each group separately. We found that there were significant differences in the levels of NT-ProBNP in the survivors and nonsurvivors in the ISDCM group (7061 ± 3663 vs. 18035 ± 4667 pg/mL); P = 0.0004. However, there was no significant difference between the survivors and nonsurvivors of IDCM patients (4701 ± 737 vs. 6821 ± 1212 pg/mL); P = 0.07. Like the previous analysis, higher levels of Trop T-HS levels were found in patients with ISDCM group compared with IDCM group (26.6 ± 8.5 ng/L vs. 16.3 ± 3.4 ng/L); P = 0.0002. There was also a significant raise of Trop T-HS in the nonsurvivors in the ISDCM group compared to the survivors (28.9 ± 16.3 vs. 65.5 ± 17.0 ng/L): P = 0.0003. Conclusion: In this study, we found that HF patients who were admitted with higher levels of NT-ProBNP and Trop T-HS had a poor prognosis.

Predictive value of pre-procedural N-terminal pro-B-type natriuretic peptide level for atrial fibrillation recurrence after radiofrequency catheter ablation.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been demonstrated as a valuable risk marker for mortality and morbidity of cardiovascular disease. Recurrence after atrial fibrillation (AF) radiofrequency catheter ablation remains common. We investigated the predictive value of the pre-procedural level of NT-proBNP to differentiate high-risk patients for post-ablation AF recurrence. 326 individuals with nonvalvular AF and preserved systolic function after enduring an initial radiofrequency catheter ablation (RFCA) between March 2018 and December 2019 were categorized into a recurrent group and a non-AF recurrent group. The serum NT-proBNP levels were examined before the ablation procedure. The researchers used multivariate logistic regression to find the determinants of AF recurrence. During a 14-month (interquartile range (IQR): 12-16) median follow-up, AF recurred in 84 (25.8%) patients. Patients in the recurrence group had considerably greater pre-ablation NT-proBNP levels (389.4 vs. 141.7 pg/ml, p < 0.001 in non-paroxysmal AF and 348.0 vs. 99.4 pg/ml, p < 0.001 in paroxysmal AF) as well as a greater left atrium (40 vs. 36 mm, p = 0.01 in non-paroxysmal AF and 38 vs. 36 mm, p = 0.01 in paroxysmal AF) than the non-AF recurrence group. A cut-off value of NT-proBNP ≥ 168.05 pg/ml identified AF recurrence with a sensitivity of 78.6% and specificity of 53.7% (area under ROC curve 0.68, 95% confidence interval (CI) 0.62-0.74, p < 0.001). Kaplan-Meier examination revealed that the elevated NT-proBNP (≥ 168.05 pg/ml) group presented a considerably shorter period without an occurrence compared to the low-NT-proBNP group (18.4 vs. 22.2 months, log-rank p = 0.001). Multivariate cox regression investigation showed that a level of NT-proBNP ≥ 168.05 pg/ml (hazard ratio (HR): 2.89, 95% CI: 1.71-4.903, p < 0.001) was a reliable predictor of AF recurrence after RFCA. A high pre-ablation NT-proBNP level was associated with AF recurrence, and it was also discovered to be a prognostic factor of recurrence of AF following RFCA.

Comparative Analysis of Different Prognostic Markers in Predicting Outcome in Advanced Heart Failure

Introduction: Heart failure (HF) is a debilitating condition with an adverse outcome, especially during the advanced stage having higher morbidity and mortality rates. Various parameters have been used as prognostic markers in advanced HF. This study highlights about the comparative analysis of different prognostic markers in predicting mortality in advanced HF. Methods: This prospective observational study was conducted in patients of advanced HF admitted to the department of medicine intensive care unit in a rural tertiary care hospital from 2018 to 2020. Advanced HF was diagnosed using the updated HF Association-European Society of Cardiology criteria. The serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), six-minute walk test (6MWT), left ventricular ejection fraction (LVEF), estimated glomerular filtration rate, and glycosylated hemoglobin type A1c levels were measured on admission. Receiver operating characteristic (ROC) curve was also studied for the above-mentioned variables, and the area under ROC curve (AUROC) was also determined. Results: Seventy-five patients with an average age of 60.55 ± 14.04 years were evaluated. Out of 75, 48 (64%) were male and 27 (36%) were female. There was inhospital mortality in 20 (26.67%) patients. The mean NT-proBNP levels among the mortality group was 9826.95 ± 3485.10 pg/mL, while in nonmortality group, it was 6135.40 ± 2342.77 pg/mL (P = 0.001). The cutoff range in this study for on-admission serum NT-proBNP levels was 8990 pg/mL, with AUROC of 0.81, the sensitivity of 70.0%, and specificity of 90.9%. In multiple regression analysis keeping mortality as the dependent variable, it was seen that variables NT-proBNP, 6MWT (&lt;300 m), and LVEF were significantly associated with mortality. Conclusion: Serum NT-proBNP and 6MWT (&lt;300 m) were important predictors of mortality in advanced HF.

Exercise Training, Cardiac Biomarkers, and Cardiorespiratory Fitness in Type 2 Diabetes: The HART-D Study

BackgroundHigh-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are cardiac biomarkers commonly detected in adults with type 2 diabetes (T2D) and are associated with heart failure risk. ObjectivesThe purpose of this study was to evaluate the effects of exercise training (ET) on hs-cTnT and NT-proBNP and evaluate the associations of these biomarkers with cardiorespiratory fitness among adults with T2D. MethodsParticipants of the HART-D (Health Benefits of Aerobic and Resistance Training in Individuals with Type 2 Diabetes) trial who were randomly assigned to one of 3 ET groups or a non-exercise control group were included. Cardiac biomarkers and cardiorespiratory fitness (evaluated by peak oxygen uptake [VO2peak]) were assessed at baseline and after 9 months. The effects of ET (3 ET groups pooled) vs non-exercise control on hs-cTnT and NT-proBNP were assessed using separate analysis of covariance models. Multivariable-adjusted linear regression was performed to identify factors associated with follow-up biomarkers and ΔVO2peak. ResultsThe present study included 166 participants randomized to the ET (n = 135) and non-exercise control (n = 31) groups. Compared with the non-exercise control, ET did not significantly change hs-cTnT or NT-proBNP. In adjusted analysis, each ET group and ΔVO2peak were not significantly associated with hs-cTnT or NT-proBNP levels on follow-up. Among individuals in the ET group, baseline hs-cTnT was inversely associated with ΔVO2peak [per 1 SD higher log (hs-cTnT): β = −0.08 (95% CI = −0.15 to −0.01)]. ConclusionsAmong individuals with T2D, ET did not modify cardiac biomarkers. Higher baseline hs-cTnT was associated with blunted cardiorespiratory fitness improvement in response to exercise.

Potential roles of 4HNE-adducted protein in serum extracellular vesicles as an early indicator of oxidative response against doxorubicin-induced cardiomyopathy in rats

Late-onset cardiomyopathy is becoming more common among cancer survivors, particularly those who received doxorubicin (DOXO) treatment. However, few clinically available cardiac biomarkers can predict an unfavorable cardiac outcome before cell death. Extracellular vesicles (EVs) are emerging as biomarkers for cardiovascular diseases and others. This study aimed to measure dynamic 4-hydroxynonenal (4HNE)-adducted protein levels in rats treated chronically with DOXO and examine their link with oxidative stress, antioxidant gene expression in cardiac tissues, and cardiac function. Twenty-two male Wistar rats were randomly assigned to receive intraperitoneal injection of normal saline (n = 8) or DOXO (3 mg/kg, 6 doses, n = 14). Before and after therapy, serum EVs and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were determined. Tunable resistive pulse sensing was used to measure EV size and concentration. ELISA was used to assess 4HNE-adducted protein in EVs and cardiac tissues. Differential-display reverse transcription-PCR was used to quantitate cardiac Cat and Gpx1 gene expression. Potential correlations between 4HNE-adducted protein levels in EVs, cardiac oxidative stress, antioxidant gene expression, and cardiac function were determined. DOXO-treated rats showed more serum EV 4HNE-adducted protein than NSS-treated rats at day 9 and later endpoints, whereas NT-proBNP levels were not different between groups. Moreover, on day 9, surviving rats' EVs had higher levels of 4HNE-adducted protein, and these correlated positively with concentrations of heart tissue 4HNE adduction and copy numbers of Cat and Gpx1, while at endpoint correlated negatively with cardiac functions. Therefore, 4HNE-adducted protein in serum EVs could be an early, minimally invasive biomarker of the oxidative response and cardiac function in DOXO-induced cardiomyopathy.

Serum N-terminal pro-B-type natriuretic peptide and cystatin C for acute kidney injury detection in critically ill adults in China: a prospective, observational study

ObjectiveSerum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cystatin C (sCysC) are available clinically and beneficial in diagnosing acute kidney injury (AKI). Our purpose is to identify the performance of their...

The effects of qishen granules for patients with chronic heart failure: A multicenter randomized double-blind placebo-controlled trial.

Background: Despite advancements in chronic heart failure (CHF) treatment, the effect often remains unsatisfactory and unstable. More effective therapies are needed. Qishen granules (QSG) are a novel Chinese botanical drug effective in treating CHF in animal models, but clinical evidence remains inadequate. Objective: This study aims to evaluate the effects of QSG on patients with CHF. Methods: We enrolled CHF patients in this 12-week, randomized, double-blind, placebo-controlled trial and randomly assigned them to the QSG (twice a day, 6.8g granules at once) or placebo group. The primary endpoint was a change in the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level after treatment. The secondary outcome consists of the New York Heart Association (NYHA) functional classification, 6-min walking distance (6MWD), TCM syndrome integral scale, quality of life, and echocardiographic index. Results: A total of 191 patients completed the 12-week follow-up period, with 94 in the QSG group and 97 in the placebo group. The Qishen granules group demonstrated a considerably greater reduction in NT-proBNP than the placebo group (50% vs 32% for QSG vs placebo, respectively; p = 0.011). Patients who received QSG performed better in the NYHA functional rank, 6MWD, TCM syndrome integral scale, and quality of life (p < 0.05). The QSG group performed better in HFrEF patients regarding the efficiency of NT-proBNP. There was no statistical significance in the change in evaluated safety parameters, such as blood routine and biochemistry. Conclusion: Based on standard treatment, Qishen granules further reduced the levels of NT-proBNP when compared with placebo. Together with other outcomes, our findings suggest that QSG could be used in combination therapy for CHF. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT03027375. Registered 9 October 2017.

Effect of Intensive Blood Pressure Control on Troponin and Natriuretic Peptide Levels: Findings From SPRINT.

Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP. hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or <50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models. Randomization to intensive SBP lowering (versus standard SBP management) resulted in a 3% increase in hs-cTnT levels over 1-year follow-up (geometric mean ratio, 1.03 [95% CI, 1.01-1.04]) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47 [95% CI, 1.13, 1.90]). In contrast, randomization to intensive SBP lowering led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90 [95% CI, 0.87-0.93]) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57 [95% CI, 0.46-0.72]). The association of randomized treatment assignment on change in hs-cTnT was completely attenuated after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was completely attenuated after adjusting for change in SBP. Increases in hs-cTnT and NT-proBNP from baseline to 1 year were associated with higher risk for heart failure and death, with no significant interactions by treatment assignment. Intensive SBP lowering increased hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering decreased NT-proBNP, a finding that was explained by the decrease in SBP. These findings highlight the importance of noncardiac factors influencing variation in cardiac biomarkers and raise questions about the potential role of hs-cTnT as a surrogate marker for heart failure or death in SBP-lowering studies.

The Role of Neutrophil Gelatinase-Associated Lipocalin and N-Terminal Pro B-Type Natriuretic Peptide in the Prediction of Heart Failure in Patients with Acute Coronary Syndrome

BACKGROUND: Heart failure, where the heart cannot pump blood effectively, significantly affects patient quality of life and impacts national health-care services. Acute coronary syndrome is a common underlying cause of acute heart failure. Neutrophil gelatinase-binding lipocalin (NGAL) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are biomarkers released during myocardial injury. Thus, the measured levels of these chemicals may be associated with heart failure events in patients with acute coronary syndrome. AIM: The present study determined the serum levels and measured increases in NGAL and NT-proBNP, as well as recorded heart failure events in patients with acute coronary syndrome in Vietnam. METHODS: A descriptive cross-sectional method was used to recruit 58 patients with acute coronary syndrome and assess the degree to which the two markers could predict ejection fraction (EF). RESULTS: The median values of NGAL and NT-proBNP concentrations in the group with EF ≥40% (7.14 ng/mL and 952.00 pg/mL) were significantly lower than those with EF &lt;40% (166.10 ng/mL and 27,498.00 pg/mL). NGAL was used to predict heart failure events at a threshold of 94.86 ng/mL with a sensitivity of 83.3%, a specificity of 90.4%, and an area under the curve (AUC) of 0.83. Similarly, NT-proBNP predicted heart failure events at a threshold of 8660.5 pg/mL with a sensitivity of 83.3%, a specificity of 84.6%, and an AUC of 0.79. CONCLUSIONS: Serum NGAL and NT-proBNP levels can be used as reliable biomarkers for predicting heart failure events in patients with acute coronary syndrome.

733 NT-PROBNP CONCENTRATIONS ACROSS PULMONARY HYPERTENSION GROUPS

Abstract Background Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are found in both pre-capillary pulmonary hypertension (PH), including pulmonary arterial hypertension, PH associated with hypoxia/lung disease and chronic thromboembolic pulmonary hypertension, and post-capillary PH associated with left heart disease. We asked the question of whether NT-proBNP concentrations differ among these PH subtypes. Methods Based on right heart catheterization (RHC) data collected at our institution between Jan. 2019 and Dec. 2021, 146 patients were classified as no PH, pre-capillary PH, isolated post-capillary PH (iPC-PH) or combined pre- and post-capillary PH (cPC-PH) according to the 2022 ESC/ERS guidelines (GL). NT-proBNP values were compared across PH groups by Kruskal-Wallis test with Bonferroni correction. The characteristics of subjects with pre-capillary PH and NT-proBNP ≤ or &amp;gt;1.100 pg/mL, a cut-off for severity proposed by the 2022 GL, were compared by chi-square test, T-test, or Mann-Whitney test, as appropriate. We also applied the hemodynamic definitions of the 2018 6th World Symposium on PH (6WSPH) and of the 2015 GL, examined the differences in the distribution of PH groups with the McNemar test, and reassessed NT-proBNP concentrations. Results 44 (30%) of patients did not have PH, 38 (26%) had pre-capillary PH, 18 (12%) had iPC-PH, and 46 (32%) had cPC-PH. NT-proBNP levels were progressively higher from pre-capillary PH to iPC-PH to cPC-PH (Figure). Interestingly, the 25th percentile of the cPC-PH group was 1.138 pg/mL, close to the 1.100 pg/mL cut-off. Compared with patients with pre-capillary PH and NT-proBNP ≤1.100 pg/mL, those with &amp;gt;1.100 pg/mL NT-proBNP had larger right ventricle basal diameter [50 (43-53) vs 43 (36-45) mm; p=0.02], lower TAPSE/sPAP ratio [0.21 (0.15-0.25) vs 0.35 (0.25-0.43), p=0.01], more often massive tricuspid regurgitation (83% vs 20%, p&amp;lt;0.001), higher pulmonary vascular resistance [9.5 (7.6-15.1) vs 5.7 (2.7-7.8) WU; p=0.004], and lower stroke volume index [28 (17-32) vs 36 (32-50) mL/m2; p=0.002]. The proportion of no PH decreased and the one of cPC-PH increased when the 6WSPH or the 2015 GL criteria were used (p for trend &amp;lt;0.001). Nonetheless, the trend of NT-proBNP remained similar to that observed with the 2022 GL definitions (Figure). Conclusions A gradient of NT-proBNP exists across PH groups, with the highest values being in cPC-PH. The concentrations of NT-proBNP in severe pre-capillary PH overlap with those in cPC-PH, indirectly confirming the validity of this biomarker to discriminate the severity of pre-capillary PH.

Correlation of NT-proBNP and Echocardiographic Parameters in Patients with Heart Failure with Preserved Left Ventricular Systolic Function

OBJECTIVE: Natriuretic peptides are increasingly used in clinical practice to diagnose myocardial dysfunction in heart failure (HF) with preserved ejection fraction (HFpEF). Recent studies indicate that plasma brain natriuretic peptide (BNP) may have a role in the diagnosis and management of HF. However, there is marked heterogeneity in BNP levels among subjects with HFpEF, which is only partially explained by differences in left ventricular (LV) dimensions or systolic function. This study aims to investigate if N-terminal proBNP (NT-proBNP) can be a useful tool to guide management in patients with HFpEF when echocardiography is not easily accessible. MATERIALS AND METHODS: N-terminal proBNP in patients admitted in Chong Hua Hospital from July 2019 to July 2020 was collected from the hospital laboratory. Data of patients with HF symptoms with preserved LV systolic function and other echocardiographic parameters were collected from the hospital records. The correlation between the different echocardiographic parameters and NT-proBNP was determined. RESULTS: The NT-proBNP levels increased significantly in HFpEF as the values of left atrial volume index (P &lt;0.001), E/A ratio (P = 0.042), E/e′ (P &lt;0.001), and tricuspid regurgitation velocity (P &lt;0.001) increased. The mean NT-proBNP level was 5588 pg/mL. Highest levels were seen predominantly in diastolic dysfunction grade II. CONCLUSION: Our findings indicate that NT-proBNP is positively correlated to echocardiographic parameters, namely, left atrial volume index, E/A ratio, E/e′, and tricuspid regurgitation velocity in patients with preserved LV systolic function.

Cardiovascular complications among hematopoietic cell transplantation survivors - the role of cardiomarkers.

Allogeneic hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for numerous malignant and nonmalignant diseases. The number of survivors and length of follow-up after successful HSCT is continually increasing. HSCT can induce damage of various organs and tissues - from minimal potentially progressive subclinical changes to life-threatening conditions. The aim of this thesis was to assess the prognostic value of high sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing and early identification of patients at high risk of a cardiac event after allogeneic HSCT. Sixty-three patients with the median age of 37 years at the time of allogeneic HSCT for hematologic diseases were studied. Cardiac bio-markers were serially measured before conditioning regimen and at days 1, 14 and 30 after HSCT. Cardiac systolic and diastolic functions were assessed before the conditioning regimen and 1 month after HSCT by echocardiography. The differences in plasma NT-proBNP and hs-cTnT concentrations during the 30 days following HSCT were statistically significant (P &lt; 0.001 vs. P = 0.02). Seven of 63 patients (11.1 %) developed a cardiac event defined as cardiovascular dys-rhythmias, pericarditis with cardiac tamponade and heart failure. By multivariate analysis, the strongest prognostic factor of cardiac event was an increased level of hs-cTnT and NT-proBNP persisted for a period of 14 days after HSCT (P &lt; 0.0001). The area under the curve from hs-cTnT testing plus NT-proBNP testing together (AUC = 0.95) was superior to each dia-gnostic modality alone. Measurements of plasma NT-proBNP and hs-cTnT concentrations might be a useful tool for identification of high-risk patients requiring further cardiological follow up. Measurement of hs-cTnT plus NT-proBNP together was superior to hs-cTnT and NT-proBNP measurements alone.

ECG and Biomarker Profile in Patients with Acute Heart Failure: A Pilot Study.

Biomarkers, electrocardiogram (ECG) and Holter ECG are basic, accessible and feasible cardiac investigations. The combination of their results may lead to a more complex predictive model that may improve the clinical approach in acute heart failure (AHF). The main objective was to investigate which ECG parameters are correlated with the usual cardiac biomarkers (prohormone N-terminal proBNP, high-sensitive cardiac troponin I) in patients with acute heart failure, in a population from Romania. The relationship between certain ECG parameters and cardiac biomarkers may support future research on their combined prognostic value. In this prospective case-control study were included 49 patients with acute heart failure and 31 participants in the control group. For all patients we measured levels of prohormone N-terminal proBNP (NT-proBNP), high-sensitive cardiac troponin I (hs-cTnI) and MB isoenzyme of creatine phosphokinase (CK-MB) and evaluated the 12-lead ECG and 24 h Holter monitoring. Complete clinical and paraclinical evaluation was performed. NT-proBNP level was significantly higher in patients with AHF (p &lt; 0.001). In patients with AHF, NT-proBNP correlated with cQTi (p = 0.027), pathological Q wave (p = 0.029), complex premature ventricular contractions (PVCs) (p = 0.034) and ventricular tachycardia (p = 0.048). Hs-cTnI and CK-MB were correlated with ST-segment modification (p = 0.038; p = 0.018) and hs-cTnI alone with complex PVCs (p = 0.031). The statistical relationships found between cardiac biomarkers and ECG patterns support the added value of ECG in the diagnosis of AHF. We emphasize the importance of proper ECG analysis of more subtle parameters that can easily be missed. As a non-invasive technique, ECG can be used in the outpatient setting as a warning signal, announcing the acute decompensation of HF. In addition, the information provided by the ECG complements the biomarker results, supporting the diagnosis of AHF in cases of dyspnea of uncertain etiology. Further studies are needed to confirm long-term prognosis in a multi-marker approach.

Carbohydrate antigen 125 combined with N-terminal pro-B-type natriuretic peptide in the prediction of acute heart failure following ST-elevation myocardial infarction.

The value of serum carbohydrate antigen 125 (CA125) combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the evaluation of acute heart failure (AHF) after ST-segment elevation myocardial infarction (STEMI) remains unclear. The aim of this study was to evaluate the efficacy of CA125 combined with NT-proBNP in predicting AHF following STEMI. A total of 233 patients with STEMI were evaluated, including 39 patients with Killip II-IV and 194 patients with Killip I. The optimal cutoff point for predicting AHF was determined by receiver operating characteristic (ROC) curve, and the independent predictors of AHF were evaluated by multiple logistic regression. According to the cutoff value, it was divided into three groups: C1 = CA125 < 13.20 and NT-proBNP < 2300 (n = 138); C2 = CA125 ≥ 13.20 or NT-proBNP ≥ 2300 (n = 59); C3 = CA125 ≥ 13.20 and NT-proBNP ≥ 2300 (n = 36). Differences between groups were compared by odds ratio (OR). The levels of CA125 and NT-proBNP in AHF group were higher than those in non-AHF group (19.90 vs 10.00, P < .001; 2980.00 vs 1029.50, P < .001, respectively). The optimal cutoff values of CA125 and NT-proBNP for predicting AHF were 13.20 and 2300, both of which were independent predictors of AHF. The incidence of AHF during hospitalization was highest in C3 (69.44%), middle in C2 (20.34%) and lowest in C1 (1.45%). After adjustment for clinical confounding variables, compared with C1: C2 (OR = 6.41, 95% CI: 1.22-33.84, P = .029), C3 (OR = 19.27, 95% CI: 3.12-118.92, P = .001). Elevated CA125 and NT-proBNP are independent predictors of AHF in STEMI patients, and their combination can improve the recognition efficiency.

Rhabdomyolysis following Nuss Procedure: A Prospective Study in Children.

Postoperative rhabdomyolysis (RML) has been documented after several surgical procedures in adults. Musculoskeletal remodeling after Nuss procedure for pectus excavatum (PE) could cause RML. We evaluated the incidence of RML after Nuss procedure in children. This study was a prospective study from 2018 to 2021. We enrolled all otherwise healthy patients who underwent PE correction with only one bar. Studied variables included demographic and clinical data, duration of surgery, complications, and length of hospitalization. The patients included underwent serial measurements of serum creatine kinase (CK), troponin I, N terminal pro B-type natriuretic peptide (NT-proBNP), serum creatinine, urea, and glomerular filtration rate at 6 and 48 hours postoperatively, and hospital discharge. Forty-six patients met criteria (40 males/6 females), with a mean age of 15.1 ± 1.4 years. Mean duration of surgery was 74 ± 28 minutes, and length of hospitalization was 4.6 ± 1.6 days. RML was diagnosed in 30.4% of patients at 6 hours, 91.3% at 48 hours, and 21.7% at hospital discharge. Mean preoperative CK value was 181.1 ± 141.6 IU/L, and postoperative values were 863.3 ± 302.6 IU/L at 6 hours, 1,675.2 ± 561 IU/L at 48 hours, and 850 ± 683.7 IU/L at hospital discharge, with statistically significant differences (p = 0.001). High-sensitivity troponin I and NT-proBNP levels increased significantly during the postoperative time (p = 0.001). Renal function remained stable (p = 0.55). Nuss technique produces RML without kidney injury in healthy patients. This knowledge should be considered for patients at increased risk of developing acute kidney injury and other complications.

Effect of Voxelotor on Cerebral Perfusion and Cerebral Oxygen Metabolism in Adult Patients with Sickle Cell Disease; Preliminary Results of the Coverage Study

Background: Sickle cell disease (SCD) is characterized by hemolytic anemia and a hyperdynamic circulation resulting in impaired cerebral hemodynamics and perfusion, culminating in ischemic damage of the brain. SCD is strongly associated with overt strokes or silent cerebral infarctions (SCI) which have been related to elevated flow in the median cerebral artery in children measured by transcranial Doppler. Patients with SCD have an increased cerebral blood flow (CBF) to maintain adequate oxygen delivery (OD). Previously, we and others have demonstrated with special MRI techniques that despite the maintained OD, cerebral metabolic rate of oxygen (CMRO2) is reduced in SCD due to reduced oxygen extraction fraction (OEF), which in turn is strongly related to CBF and hemoglobin (Hb) level. Voxelotor is a small molecule that reversibly binds to Hb and increases its oxygen affinity, thereby decreasing Hb polymerization and sickling. The resulting decreased hemolytic anemia can potentially ameliorate cerebral hemodynamics and perfusion, the increased oxygen affinity may reduce the offloading of oxygen. The aim of our study is to assess the effects of voxelotor on markers of cerebral perfusion and oxygen metabolism. In addition, the effect of voxelotor on the hyperdynamic cardiac function was assessed. Methods: This single-arm, interventional trial is being conducted in a tertiary hospital in Amsterdam, The Netherlands. Adult SCD patients with the severe genotypes of HbSS and HbSβ0-thalassemia were eligible for inclusion. Other major inclusion criteria were: Hb ≤ 10.5 g/dL and in case of hydroxyurea use, a stable dose for at least 90 days. Major exclusion criteria were: regular transfusions or a transfusion within 90 days prior to inclusion, hospitalization for vaso-occlusive crisis ≤ 14 days before inclusion. At baseline and after 3 months of voxelotor treatment (1500 mg pd), MRI scans, echocardiography and laboratory assessments were performed. Time-encoded arterial spin labeling was performed to obtain CBF measurements, gray matter CBF was derived by using white matter and gray matter masks. T2 relaxation under spin tagging was performed in order to calculate OEF. Oxygen delivery and CMRO2 were calculated: formula, CBF x OD, with the OD calculated from OEF and oxygen content. Maximal tricuspid regurgitation velocity (TRVmax) was assessed by trans-thoracic echocardiography as a marker of hyperdynamic circulation. N-Terminal pro-B-type natriuretic peptide (NT-proBNP) was measured as a marker of cardiac stress/dilatation. Parametric data are presented with mean and SD and analyzed by a paired T-test and non-parametric data with median and IQR, and analyzed by a Wilcoxon signed-rank test. Results: Preliminary results of 15 patients (HbSS/HbSβ0-thalassemia, 11/4, mean age 38 years (SD 10), 4 female) who completed their 3 month follow-up are presented here. Upon 3 months of voxelotor treatment, Hb levels significantly increased, 7.6 g/dL, (IQR 6.9 - 8.2) compared to 10.0 g/dL (IQR; p < 0.001), and hemolysis significantly reduced, represented by reticulocyte count, bilirubin and LDH levels (p = < 0.05; Table 1). After 3 months of treatment also a significant increase in oxygen delivery from 6.4 to 8.2 ml O2/100g/min (p = 0.006) was observed, which was primarily due to the increased Hb levels. However, CBF and CMRO2 did not change significantly after 3 months of voxelotor treatment (Table 2) while OEF decreased significantly at 3 months as compared to baseline (from 28.9% to 23.2%, p = 0.002) (Table 2). No significant changes in NT-proBNP levels and TRVmax were observed (Table 1) although a significant decrease was observed in patients with NT-proBNP-levels >160 at baseline (213 (IQR 161 - 254) ng/L vs 152 (IQR 50 -163) ng/L; p = 0.028)). Conclusion: In this preliminary study, no changes in cerebral hemodynamics (CBF) and oxygen metabolic rate (CMRO2) were observed, despite an increased cerebral oxygen delivery due to improvement of Hb levels. CMRO2 remained unchanged as a result of diminished OEF, based on the calibration according to the Li-Bush model, most likely due to the increased oxygen affinity attributed to voxelotor. With respect to the cardiac measures of the circulatory state, no effect on NT-proBNP levels and TRVmax was observed although a significant decrease in NT-proBNP-levels was observed in a post-hoc analysis of patients with elevated NTproBNP levels at baseline. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Sex and N-terminal pro B-type natriuretic peptide: The potential mediating role of iron biomarkers.

Levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), a marker of heart failure and cardiovascular risk, are generally higher in women than men. We explored whether iron biomarkers mediate sex differences in NT-proBNP levels. We included 5,343 community-dwelling individuals from the Prevention of Renal and Vascular Endstage Disease study. With linear regression analyses, we investigated the association of sex and iron biomarkers with NT-proBNP levels, independent of adjustment for potential confounders. The assessed iron biomarkers included ferritin, transferrin saturation (TSAT), hepcidin, and soluble transferrin receptor (sTfR). Next, we performed mediation analyses to investigate to which extent iron biomarkers influence the association between sex and NT-proBNP. Of the included 5,343 participants, the mean standard deviation age was 52.2 ± 11.6 years and 52% were females. After adjustment for potential confounders, women compared to men, had higher NT-proBNP (β = 0.31; 95%CI = 0.29, 0.34), but lower ferritin (β = -0.37; 95%CI = -0.39, -0.35), hepcidin (β = -0.22, 95%CI = -0.24, -0.20), and TSAT (β = -0.07, 95% CI = -0.08, -0.06). Lower ferritin (β = -0.05, 95%CI = -0.08, -0.02), lower hepcidin (β = -0.04, 95%CI = -0.07, -0.006), and higher TSAT (β = 0.07; 95%CI = 0.01, 0.13) were associated with higher NT-proBNP. In mediation analyses, ferritin and hepcidin explained 6.5 and 3.1% of the association between sex and NT-proBNP, respectively, while TSAT minimally suppressed (1.9%) this association. Our findings suggest that iron biomarkers marginally explain sex differences in levels of NT-proBNP. Future studies are needed to explore causality and potential mechanisms underlying these pathways.

Abstract 9543: Cilostazol Improves Symptom Scores and Lowers NT-proBNP in HFpEF Preliminary Results From the CLIP-HFpEF N-of-1 Study

Introduction: Although heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly common, targeted HFpEF therapies remain limited. Current evidence-based treatment options are modestly effective and provide limited symptom relief. Hypothesis: Cilostazol, a generic and oral phosphodiesterase type 3 (PDE-3) inhibitor, rapidly improves HF symptoms and serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in HFpEF patients with an ejection fraction of 50% or higher. Methods: A prospective, double-blind, n-of-1 study with three crossovers with unblinding at the 1-month endpoint was designed. Stable outpatients with HFpEF received either placebo twice daily or Cilostazol 100mg twice daily for one week followed by three weekly crossovers. HF symptoms were assessed each week using the Kansas City Heart Failure Questionnaire (KCCQ-12) and NT-proBNP levels were measured at the end of weeks one and four. Results: Preliminary data from the initial 11 participants are presented (six men and five women, mean age 67±13 years). The mean KCCQ-12 score was eight points higher with Cilostazol than placebo (47±12 vs. 39±12; p&lt;0.05) (Figure 1A). Median NT-proBNP levels were lowered by 22% with Cilostazol compared to placebo (412 [293-1066] pg/dL vs. 659 [323-897] pg/dL; p&lt;0.05) (Figure 1B). Conclusions: In this preliminary analysis of CLIP-HFpEF, treatment with Cilostazol led to a rapid alleviation of HF symptoms and a decline in NT-proBNP levels when compared to placebo. The results of CLIP-HFpEF suggest a marked benefit of Cilostazol in HFpEF patients. Further studies are needed to elucidate the mechanism and long-term clinical benefits of Cilostazol in patients with HFpEF.