NT-proBNP Values Research Articles

Predictive value of NT-proBNP for major adverse cardiovascular events within a 6-month period in patients with acute coronary syndrome.

The role of NT-proBNP as a cardiac biomarker for predicting short-term major adverse cardiovascular events (MACEs) in acute coronary syndrome (ACS) remains unclear. This study investigated the utility of the NT-proBNP level for predicting MACEs within a 6-month period in patients with ACS. This prospective study included 241 consecutively enrolled adults with ACS between September 2023 and February 2024. Demographic data, clinical characteristics, GRACE score, and high-sensitivity cardiac troponin T (hs-cTnT) and NT-proBNP levels were compared between patients who were MACE-positive vs. MACE-negative within a 6-month period. The overall mortality rate was 8.7%, and the incidence of MACEs was 43.2%. The mean serum levels of hs-cTnT and NT-proBNP were significantly higher in the MACE-positive than in the MACE-negative group. Age, concomitant coronary artery disease, NT-proBNP, and GRACE score were independent predictors of MACEs in patients with ACS. An NT-proBNP level of 250pg/mL had a sensitivity of 73.1% and a specificity of 88.3% for predicting MACEs, with an area under the curve of 0.847. The estimated risk of MACEs was 70% and 90% for NT-proBNP values of 600pg/mL and 900pg/mL, respectively. The NT-proBNP level measured at ED admission was strongly associated with short-term MACEs in patients with all ACS subtypes and was an important prognostic biomarker. Therefore, combining the NT-proBNP level with the GRACE score in ACS patients may provide significant benefits in terms of predicting MACEs and obtaining a more accurate risk stratification.

Plasma microRNAs as Biomarkers for Predicting Radiotherapy Treatment-Induced Cardiotoxicity in Lung Cancer.

Background: Lung cancer is the second most common malignancy and stands as a leading cause of cancer-related deaths worldwide. Currently, one of the main treatment options for lung cancer is radiotherapy, but this treatment is associated with complications, such as an increased risk of cardiac-related morbidity and mortality. However, currently available methods for predicting radiation-induced heart disease (RIHD) remain suboptimal. Methods: In this pilot study, using the RT-qPCR method, we analyzed the expression levels of six miRNAs (miRNA-1-3p, miRNA-21-5p, miRNA-24-3p, miRNA-29a-3p, miRNA-34a-5p, and miRNA-222-3p). Results: Fourteen pairs of locally advanced non-small-cell lung cancer patients' plasma samples, taken before and after radiotherapy, were examined. It was observed that miRNA-1-3p, miRNA-21-5p, miRNA-24-3p, miRNA-29a-3p, and miRNA-222-3p were downregulated, while miRNA-34a-5p was upregulated in lung cancer patients' plasma after treatment. Additionally, after definitive radiotherapy, patients with an increased NT-proBNP value displayed a statistically significant difference in miRNA-222-3p levels compared to the normal range of this indicator. The panel of the combined four miRNAs for assessing the risk of cardiac comorbidities demonstrated an AUC of 0.79, sensitivity of 71.43%, and specificity of 100%, with further improved values upon integration with clinical biomarker NT-proBNP. Conclusions: This pilot study shows that the identification of changes in miRNA expression levels in lung cancer patients' plasma before and after radiotherapy could be used for the early diagnosis of RIHD.

High NT pro-BNP levels in children with malignant disorder receiving intensive fluid treatment: a prospective comparative study.

Hematologic malignancies are a well-known risk factor for cardiovascular disease development. Chemotherapeutic protocols commonly include intensive fluid therapy (IFT), which may negatively influence the cardiovascular system and predispose to arterial hypertension. This study aims to evaluate atrial natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and changes in blood pressure in children with hematological malignancies undergoing intensive fluid therapy. This prospective cohort study comprised thirteen children. 24-h ambulatory blood pressure monitoring (ABPM) and concentrations of NT-proBNP and hs-TnT were performed on the first day of IFT and during follow-up. There were no statistically significant differences in 24-h, daytime, night-time systolic (SBP) and diastolic blood pressure (DBP), SBP and DBP dipping, and the number of non-dippers during intensive fluid therapy compared to the control points. The mean NT-proBNP concentration at 24 h was 321.27 ± 318.08 pg/mL and was significantly higher compared with baseline (79.13 ± 105.42 pg/mL) and follow-up (175.92 ± 241.48 pg/mL); p-values 0.005 and p = 0.006 respectively. Troponin T concentration at 24 h was not significantly different compared with baseline and follow-up. These results show no significant influence of intensive fluid therapy on blood pressure profile. In contrast, an increase in NT-proBNP values 24 h after the start of fluid therapy may reflect the impact of fluid overload on the cardiovascular system.

Clinical Value of NT-proBNP and Lactate Parameters in Infants with Congenital Heart Defects

Congenital heart disease (CHD) is one of the most common anomalies worldwide, defined as an anatomical abnormality of the heart and/or great vessels. The aim of review is to find out whether this marker is diagnostically important in detecting and determining the severity of the disease, based on the analysis of NT-proBNP indicators of patients admitted with congenital heart defects under the age of 1 year, and also to check whether there is a correlation between lactate and NT-proBNP among patients with congenital heart defects. In the result NT-proBNP values in 81 critical condition congenital anomaly patients averaged 12811.6±810.7 (445-40163), control group averaged 135.6±14.0 (78-320) among 20 patients, Pf < 0.001 which was reported to be statistically significant. In our study, NT-proBNP indicators of patients diagnosed with CHD were found to be higher in the first 28 days compared to other infant groups (1-6 months and 6-12 months). The results revealed that the difference between the CHD lactate level between the surviving and lethal groups was statistically significant (Pf< 0.001; Pu 0.017). In conclusion, we should state that in our study, blood NT-ProBNP levels in critically ill infants with congenital heart anomalies were found to be approximately 10 times higher than in healthy infants (Pf < 0.001). At the same time, a correlation was established between the blood lactate index and the blood NT-ProBNP level.

Abstract 4136605: Effect Of A Bone Morphogenetic Protein Receptor Type 2 Mutation On The Cardiomyocyte Response To Pressure Overload

Introduction: A mutation in the Bone Morphogenetic Protein Receptor Type 2 ( BMPR2 ) gene is in 70% of hereditary pulmonary arterial hypertension (hPAH) patients the causative mutation of the disease. Previous work demonstrated that right ventricular function is more impaired in hPAH patients with a BMPR2 mutation. However, the underlying mechanism remains elusive. Moreover, natriuretic peptides, such as N-terminal Brain Natriuretic Peptides (NTproBNP) and Mid Regional proAtrial Natriuretic Peptides (MRproANP), are secreted from cardiomyocytes upon stretch as adaptation to increased pressure overload. We hypothesize that the BMPR2 mutation impairs the response to increased pressure overload. For this purpose, we make use of ventricular induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of hPAH patients carrying a BMPR2 mutation and their isogenic controls in which the mutation was corrected. Aim: To study the effect of a BMPR2 mutation on the response to pressure overload in vitro . Methods: iPSCs from 2 hPAH patients and its isogenic controls were used. iPSCs were differentiated into ventricular iPSC-CMs and stretched 10% equiaxially for 24h at 1Hz on the Flexcell FX-6000 system. Natriuretic peptides gene expressions were quantified via RT-PCR. NTproBNP and MRproANP release were measured on cell supernatants throughout specific immunoassays. Normality of the data was checked, and statistics were performed accordingly. Results: No differences were observed on natriuretic peptides gene expression on static and stretched iPSC-CMs. There is a clear correlation between NTproBNP and MRproANP release (R 2 =0.83, p<0.0001, Figure 1A). Interestingly, hPAH iPSC-CMs showed higher baseline values for NTproBNP release compared to isogenic iPSC-CMs (p<0.01, Figure 1B). Furthermore, stretching resulted in increased NTproBNP and MRproANP secretion in both hPAH and isogenic iPSC-CMs (Figure 1B-C). Conclusions: Secretion of NTproBNP and MRproANP was closely correlated in iPSC-CMs. iPSC-CMs of hPAH patients with a BMPR2 mutation showed higher baseline values of NTproBNP. Increased secretion of NTproBNP and MRproANP upon mechanical stimulation was similar between hPAH and isogenic iPSC-CMs. Experiments in atrial iPSC-CMs are currently ongoing to test potential differences in natriuretic peptide secretion between ventricular and atrial cardiomyocytes as the right atrium is also under stretch in PAH.

Abstract 4125300: Prognostic Value of NT-proBNP and the H 2 FPEF Score on Empagliflozin-associated Left Ventricular Remodeling: Insights from the EMPA-HEART and EMPA-HEART 2 CardioLink Trial

Background: NT-proBNP is a prognostic and diagnostic marker for heart failure while the H 2 FPEF score is used to aid in diagnosing heart failure with preserved ejection fraction. Aims: These post hoc analyses of the randomized controlled EMPA-HEART CardioLink-6 and EMPA-HEART 2 CardioLink-7 trials examined how baseline NT-proBNP and the H 2 FPEF score influenced empagliflozin-associated left ventricular (LV) remodeling in people with either type 2 diabetes and coronary artery disease or without diabetes but with cardiovascular risk factors. Methods: A total of 242 participants were assigned to either empagliflozin 10 mg QD (n=118) or placebo (n=124) for 6 months. NT-proBNP was measured and cardiac MRI performed at baseline and end-of-study. Two independent analyses were performed. One divided the participants into those with baseline NT-proBNP < and ≧125 pg/mL and the other into those with H 2 FPEF score ≦2 and ≧3. The relationships between empagliflozin-associated LV mass and functional changes with baseline NT-proBNP and H 2 FPEF scores were assessed with linear models that adjusted for baseline differences (ANCOVA). Results: Mean age of the pooled cohort was 60.6 years; 14.0% were females, 37.2% had type 2 diabetes. Mean (SD) LV ejection fraction (LVEF) was 58.0 (10.2) %; median (IQR) NT-proBNP 77.5 (33, 164) pg/mL; mean (SD) H 2 FPEF score 2.9 (1.4). Empagliflozin (vs placebo) did not significantly alter LV mass index (mean [SD] -1.35 g/m 2 [0.75]; P=0.07) and LV end-systolic volume index (LVESVi; mean [SD] -1.37 mL/m 2 [0.74]; P=0.07) but did improve LVEF (mean [SD] 2.08% [0.82]; P=0.01). The effect of empagliflozin based on the subgroups of baseline NT-proBNP and H 2 FPEF scores are shown in Figures 1 and 2, respectively. Conclusions: These post hoc analyses suggest that lower baseline NT-proBNP levels and H 2 FPEF scores may be associated with more favourable reverse LV remodelling by empagliflozin and should be validated in larger studies.

Predictive Value of NT-proBNP, FGF21, Galectin-3 and Copeptin in Advanced Heart Failure in Patients with Preserved and Mildly Reduced Ejection Fraction and Type 2 Diabetes Mellitus.

Background and Objectives: Heart failure (HF) is one of the most common initial presentations of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). There are different cardiac biomarkers related to the pathophysiological mechanisms of HF in T2DM. The current research aims to identify additional biomarkers that could improve the diagnosis and prognosis of HFpEF, which is currently assessed using NT pro-BNP levels. NT pro-BNP is a valuable tool for diagnosing heart failure but may not always correlate with clinical symptom severity or can present normal levels in certain cases, such as obesity. Biomarkers like FGF-21 and galectin-3 could provide greater insight into heart failure severity, especially in diabetic patients. The main objective of the current study is to assess the performance of NT-proBNP, FGF21, Galectin-3 and Copeptin to discriminate between advanced and mild HF. Materials and Methods: A total of 117 patients were enrolled in this study and divided into two groups: 67 patients in NYHA functional class I-II (mild HF) and 50 patients in NYHA III-IV (advanced HF). NT-pro BNP, FGF21, Galectin 3 and Copeptin serum levels were determined with the ELISA method. Receiver operating characteristic (ROC) analysis and binomial logistic regression analysis were used to measure the ability of the studied biomarkers to distinguish between advanced and mild HF patients. Results: In patients with T2DM with advanced HF, serum FGF21 level was significantly positively correlated with eGFR (ρ = 0.35, p = 0.0125) and triglycerides (ρ = 0.28, p = 0.0465) and significantly negatively correlated with serum levels of HDL cholesterol (ρ = -0.29, p = 0.0386) and with RV-RA gradient (ρ = -0.30, p = 0.0358). In patients with mild HF, serum FGF21 level was significantly negatively correlated with NT-proBNP levels (ρ = -0.37, p = 0.0022), E/e' ratio (ρ = -0.29, p = 0.0182), TR velocity (ρ = -0.24, p = 0.0470) and RV-RA gradient (ρ = -0.24, p = 0.0472). FGF21 (AUC = 0.70, 95% CI: 0.60-0.79) and NT-proBNP (AUC = 0.73, 95% CI: 0.63-0.82) demonstrated significant predictive value to discriminate T2DM patients with advanced HF from those with mild HF. Elevated values for FGF21 (≥377.50 ng/mL) or NTproBNP (≥2379 pg/mL) were significantly associated with increased odds of advanced HF after adjusting for demographic and clinical covariates. Conclusions: NTpro-BNP and FGF21 have a similar ability to discriminate T2DM patients with advanced HF from those with mild HF. Univariable and multivariable logistic models showed that, FGF21 and NTproBNP were independent predictors for advanced HF in patients with preserved and mildly reduced ejection fraction and T2DM.

Myocardial work assessment to improve baseline risk stratification in patients with transthyretin amyloidosis

BackgroundCardiac transthyretin (ATTR) amyloidosis is an often underdiagnosed and potentially fatal disorder associated with poor survival. The National Amyloidosis Centre (NAC) staging system, based on NT-proBNP level and eGFR value, discriminates patients according to survival rates. However, NAC stage II involves a heterogenous group of patients with variable prognosis. This retrospective single-center study was set up to explore the potential role of myocardial work (MW) analysis to enhance risk stratification of ATTR patients prior to therapy. Methods and Results37 patients diagnosed with ATTR between March 2021 and August 2023 were included. Baseline NT-proBNP and eGFR values were collected and LVEF, GLS and MW parameters were obtained from stored echocardiographic images. Patients were categorized per NAC stage (16 NAC I, 13 NAC II and 8 NAC III). Whereas the survival rate in NAC II and NAC III was significantly worse than in NAC I (p = 0.031 and p = 0.045 respectively), no significant difference was found between NAC II and III. In the ROC analysis, GCW proved to be the best survival predictor (AUC: 0.7) with optimal cut-off value 1294 mmHg%. Patients from NAC stage II were re-stratified according to GCW cut-off into HIGH RISK together with patients from NAC III or LOW RISK together with patients from NAC I. Patients in the HIGH RISK group exhibited a significantly worse prognosis with only 40 % survival at 2 years follow-up. ConclusionOur results demonstrate the advantages of incorporating MW analysis, particularly the use of a GCW cut-off, in the baseline risk stratification of ATTR patients.

Older patients affected by COVID-19: investigating the existence of biological phenotypes

IntroductionCOVID-19 provides an opportunity to examine biological phenotypes (observable morphological, functional and biological characteristics) in individuals who experience the same acute condition, potentially revealing differences in response to acute external stressors. The aim our study was to investigate biological phenotypes in older patients hospitalized for COVID-19, exploiting a panel of aging biomarkers.MethodsData were gathered from the FRACOVID Project, an observational multicenter study, aimed to evaluate the impact of frailty on health-related outcomes in patients 60 + with COVID-19 in Northern Italy. A hierarchical cluster analysis was run using log-transformed and scaled values of TNF-a, IL-1 beta, IL-6, PAI-1, GDF-15, NT-proBNP, and Cystatin C evaluated at admission.ResultsEighty-one participants (mean age 75.3 years; 60.5% male) were evaluated. Frailty was identified in 42% of the sample and 27.2% were unable to ambulate outdoors. The mean hospital stay was 24.7 days, with an in-hospital mortality rate of 18.5%. Three biological phenotypes were found: (1) ‘inflammatory’, with high inflammatory biomarkers; (2) ‘organ dysfunction’, characterized by elevated cystatin C and NT-proBNP, and lower inflammatory markers; and (3) ‘unspecific’, with lower NT-proBNP and GDF-15 levels, and intermediate concentrations of other biomarkers. The ’organ dysfunction’ phenotype showed the highest mean age and prevalence of frailty, disability, and chronic diseases. The ‘inflammatory‘ phenotype showed the highest burden of respiratory and systemic signs and symptoms of infection.ConclusionBiological phenotypes might be used to identify different clinical and functional phenotypes in individuals affected by COVID-19.

Prognostic utility and cutoff differences of NT-proBNP level across subgroups in heart failure with preserved ejection fraction: Insights from the PURSUIT-HFpEF Registry

ObjectivesN-terminal pro brain natriuretic peptide (NT-proBNP) is a biomarker for myocardial stress used in diagnosing and prognosticating heart failure (HF). However, its interpretation is complicated by clinical factors. This study aims to clarify the prognostic value of NT-proBNP in patients with heart failure with preserved ejection fraction (HFpEF), and risk-prediction cutoffs considering various clinical factors. MethodsThe study utilized data of prospective multicenter observational Asian HFpEF registry. Patients with acute decompensated HF and left ventricular ejection fraction ≥ 50% were included. NT-proBNP levels were measured at discharge. The primary endpoint was a composite of all-cause death and hospitalization for HF within 1 year after discharge. ResultsA total of 1,231 patients (83 [77, 87] years, 551 (45%) male) were enrolled, with 916 eligible patients analyzed. The median NT-proBNP level was 1,060 pg/m. In multivariable logistic regression model, NT-proBNP was significantly associated with the primary endpoint (adjusted OR for log-transformed NT-proBNP:2.71, 95%CI:1.78-4.18, p<0.001). Subgroup analysis revealed varying NT-proBNP distributions and differential safety cutoffs (329-929 pg/mL) at sensitivity of 0.8 based on factors like atrial fibrillation and chronic kidney disease, maintaining its discriminatory performance (Area under the curve: 0.587-0.734). ConclusionsNT-proBNP at discharge is a significant prognostic marker for HFpEF. Although NT-proBNP showed different distributions in various subgroups and cutoff values were distinctive for each, the prognostic utility was found to be equivalent in almost all subgroups with similar moderate discriminative performance. The study highlights the necessity of personalized NT-proBNP cutoffs for better management and prognostication of HFpEF.

Associação entre peptídeos natriuréticos e gravidade clínica em pacientes internados por insuficiência cardíaca descompensada

This study aims to associate the values of natriuretic peptides (NP), BNP, and NT-proBNP, with the severity of clinical presentation in patients hospitalized with decompensated heart failure (HF). METHODS: This is a historical cohort study where data was collected from the medical records of patients admitted to a private hospital with decompensated heart failure between 2016 and 2023. RESULTS: The most common comorbidities included systemic arterial hypertension in 79 out of 96 patients (82.2%), previous HF in 46 (47.9%), dyslipidemia in 41 (42.7%), and diabetes mellitus in 38 (39.5%). The data revealed that patients who died of cardiac causes during hospitalization had higher NP values compared to those who did not experience the same outcome. Among these deaths, 57.14% of patients exhibited hemodynamic instability on hospital admission (p=0.017). Additionally, two patients were readmitted within 6 months of discharge due to a new episode of decompensated HF, both presenting hemodynamic instability on admission (p=0.03), and eventually progressed to cardiac death. Cardiac and non-cardiac deaths were associated with higher NT-proBNP values (p=0.043). CONCLUSION: The findings indicate that higher NP levels in patients hospitalized with decompensated HF correlate with greater initial severity and long-term, including an increased likelihood of hemodynamic instability and a higher risk of readmission, respectively. Elevated NT-proBNP values are also linked to a higher mortality rate.

Multiparametric assessment of decongestion in patients admitted with acute heart failure: dynamic changes and correlation with natriuresis

Abstract Background Heart Failure (HF) is a major public health problem, expected to increase in the next few decades. The vast majority of acute HF (AHF) episodes are precipitated by congestion with volume overload and/or fluid redistribution. Current Guidelines stress on the importance of relieving congestion before discharge, recommending anyway only daily assessment of signs and symptoms. Lung ultrasound (LUS) B-lines and other ultrasound markers of congestion has emerged as valuable tools to improve diagnostic accuracy and help clinicians in fluid management. Purpose To assess the dynamic changes of B-lines and other markers of congestion and their relationship with the clinical evaluation, chest X-ray (CXR) and natriuretic peptides in patients admitted for AHF. Methods Fifty-eight patients (age 72±11 ys, 35% women) admitted with acute HF were enrolled. Patients underwent clinical evaluation (Clinical Congestion Score, CCS, including rales, pathological S3 heart sound, pedal oedema, jugular vein distension; range 0-4), and CXR (CXR score, including enlargement and loss of definition of hilar structures, peribronchial and perivascular cuffing, cardiomegaly, pleural effusion; range 0-4). An integrated multiorgan ultrasound exam including LUS B-lines, echocardiography, and venous excess ultrasound (VExUS) score was performed at admission (T0), between 24 and 48 hours from T0 (T1), and at discharge (T2). Follow-up data at 30 days were collected. Results Mean CCS was 1.52±0.99 at T0, with a reduction at T1 (0.86±0.66; p&amp;lt;0.01), and at T2 (0.34±0.66; p&amp;lt;0.01). Sixteen percent of patients with a CCS=0 at T0 showed, however, persistent B-lines on LUS (mean B-lines 19±6). The mean number of B-lines was 26±12 at T0 with a reduction at T1 (17±11; p&amp;lt;0.001), and at T2 (13±11; p&amp;lt;0.001). Other echocardiographic non-invasive hemodynamic parameters, such as pulmonary artery systolic pressure (PASP) and E/e’ showed a reduction only at T2, but not at T1 (figure). The number of B-lines correlated at all time points with CCS, CXR score, VExUS score, and NT-proBNP values (all p&amp;lt;0.05). We divided patients into two groups: "responders" (with ≥15 reduction of B-lines between T0 and T2) and "non-responders" (with &amp;lt;15 reduction of B-lines between T0 and T2). Responders had higher chlorine and sodium urinary excretion at T1 compared to non-responders. The number of B-lines at all time points was associated to 30-days cardiovascular mortality at univariable analysis. Neither CCS nor CXR score were associated with 30-day events. Conclusions In patients with acute HF, B-lines quantification is related to standard congestion assessment based on clinical evaluation, CXR and NT-proBNP, showing, however, a more dynamic behaviour in the assessment of decongestion. B-lines variations are also related to diuresis and chlorine urinary output, a recognized predictor of diuretic response. Persistent congestion is related to an increased risk of hospitalization and death.

Effect of disabling biventricular pacing in patients with left ventricular assist device and cardiac resynchronization therapy

Abstract Introduction Taking into account the mechanism of the left ventricular assist device (LVAD) function, the cardiac resynchronization therapy (CRT) seems to be unnecessary and, according to the current reports, the left ventricular lead (LVL) should be disabled. However, observation of the patients suggests that deactivation of the left ventricle (LV) pacing leads to deterioration of the patients condition and progression of the heart failure (HF) symptoms. Purpose The study aimed to determine differences in survival of the patients with LVAD and maintained or disabled CRT, including patients subjected to heart transplantation, as well differences in left and right ventricle function, kidneys and liver condition, NTproBNP value, subjective exercise tolerance and frequency of HF exacerbation before and after CRT deactivation. Methods The study group involved 55 patients with LVAD and CRT devices, including 11 patients with disabled LV pacing. The statistical analysis concerned the comparison of groups with and without biventricular stimulation as well results within the group with disabled LVL before and after its deactivation. Analyzed data included laboratory results, echocardiographic parameters, number of HF exacerbation episodes and exercise tolerance by NYHA classification. Results Total CRT period did not differ in group with maintained and disabled CRT [24 (12-36)months vs. 30 IQR(12-48)months respectively; p=0,74]. The median period of CRT deactivation was 30 IQR(12-48) months after LVAD implantation. Time from LVAD implantation to heart transplantation differed significantly between patients with and without CRT [20 IQR(9-32)months vs. 49,5 IQR(46,5-62)months respectively; p=0,003]. LV disabling was connected with a significant increase of NTproBNP [3072 IQR(2287-6636) pg/ml vs. 2133 IQR(1618-3437) pg/ml before LVL deactivation; p=0,009), without an aggravation of the exercise intolerance by NYHA classification (p=0,11) or total number of HF exacerbation episodes (p=0,72). Lack of LV pacing was not related to change of concentration of creatinine (p=0,13), AST (p=0,89, ALT (p=0,5), bilirubin (p=0,06) and albumin (p=0,69) before and after LV deactivation. Comparison of echocardiographic parameters with and without CRT did not demonstrate significant differences in LV ejection fraction (p=0,37), LV end-diastolic diameter (p=0,33), TAPSE (p=0,72) and tricuspid regurgitation degree (p=0,39). Death-free survival from LVAD implantation has not differed in patients with and without CRT(p=0,08), similarly like death-free survival from heart transplantation (p=0,56), however with tendency to better outcome of patients with CRT till 12 months after the heart transplant. Conclusion CRT does not improve general health condition as well death-free survival in LVAD recipients, including patients subjected to heart transplantation, however with tendency to better outcome of patients with CRT till 12 months after the heart transplant.Death-free surival after LVADDeath-free survival after transplant

Prognostic value of alveolar surfactant type-B in acute heart failure: a long-term comparative analysis vs NT-proBNP

Abstract Background In heart failure (HF) biomarkers are an integral component of prognostic assessment. Natriuretic peptides are the gold standard, but they do not directly reflect lung vascular injury. Surfactant type B (Surf-B) is released by type 2 alveolar cells under pressure induced trauma, with few reports just addressing its plasmatic levels in stable chronic HF (CHF). Information on acute HF (AHF) is lacking. Purpose To clarify the prognostic value of Surf-B changes vs NT-proBNP levels after decongestion therapy and to compare their prognostic ability at 1-year follow-up. Methods Patients with acute pulmonary edema (APE) underwent a combined evaluation of Surf-B and NT-proBNP serum levels with quantification of B-lines at hospital admission (time 0), discharge (time 1) and at 1 year (time 2). Results 54 patients (mean age 72.1 ± 11 years; mean LVEF 36% ± 13%; 65% men) were enrolled. At time 1, the average Surf-B, NT-proBNP and B-lines were significantly reduced compared to time 0 (p&amp;lt;0.0001). No correlation between Surf-B and NT-proBNP was observed either at time 0 (r=-0.21; p=0.12) or at time 1 (r=0.05; p=0.71). Despite the significant decrease in Surf-B levels from time 0 to time 1, 18.5% of patients behaved as non-responders exhibiting no changes in Surf-B; conversely, only 5.5% did not show significant reduction in NT-proBNP, despite significant decongestion. 38 patients were followed up to time 2: of these, 13 (34%) reached the composite endpoint of death or hospitalization for HF. Surf-B measured at time 1 was a strong predictor of adverse outcome. Patients with Surf-B above median at discharge displayed a worse survival-free from HF hospitalization compared to the remainders (Log rank p=0.012) (Figure). Also, patients with Surf-B above median at discharge had a more than 4-fold increased risk of the composite endpoint (HR 4.5, 95%CI 1.4-20.2, p=0.023). Conversely, NT-proBNP at discharge was not significantly associated with HF-free survival (Log rank p=0.26) (Figure) and was not a significant predictor of the composite outcome (HR 1.9, 95%CI 0.6-9.3, p=0.25). At ROC analysis, discharge Surf-B levels showed a higher area under the curve (AUC=0.763, p=0.011) than NT-proBNP values (AUC=0.69, p=0.063). Conclusions These data suggest that Surf-B, an organ specific biomarker of lung injury, is highly sensitive to the effectiveness of decongestion therapy, outperforming NT-proBNP. Given the high rate of patients who do not improve their Surf-B levels over time, the reparative processes of alveolar break damage may dissociate from mere decongestion and cardiac healing in AHF.Figure:1yr Kaplan-Meier survival curves

Biomarkers for monitoring patients with cardiac amyloidosis during transthyretin-stabilizer therapy

Abstract Introduction Cardiac amyloidosis is characterized by deposition of amyloid fibrils in the heart, leading to structural abnormalities and functional impairments resulting in heart failure. Amyloid transthyretin amyloidosis cardiomyopathy (ATTR-CM) is the most common form with increasing incidence due to growing awareness and improved diagnosis. The ATTR stabilizer tafamidis serves as the first specific therapy approved for ATTR-CM, and many promising substances are in late-stage clinical trials. With growing numbers of patients receiving stabilizer therapy, valid tools for monitoring treatment response and detecting disease progression are currently lacking. Here, we aim to assess systemic and cardiac biomarkers in patients receiving stabilizer therapy. Method All individuals diagnosed with ATTR-CM at our university hospital, were systematically assessed for eligibility in this study. We enrolled patients who were undergoing therapy with tafamidis. Biomarkers including Hemoglobin (Hb), Creatinine, estimated glomerular filtration rate (eGFR), International Normalized Ratio (INR), C-reactive protein (CRP), Troponin and NT-proBNP were examined at baseline and during 6 and 12 months follow-up. Wilcoxon signed rank test was used for statistical analysis. The study was approved by the local ethics committee (23-11500-BO). Results 194 patients were included in the analysis with median age of 80 (76-83) years (86,6% male). Results showed an impaired renal function at baseline (all mean ± SD) with creatinine 1.24 ± 0.46 mg/dl and eGFR 58.64 ± 18.24 ml/min/kg with statistically significant increase after 6 months in creatinine (1.31 ± 0.51 mg/dl, p&amp;lt;0.001) and eGFR (55.06 ± 17.65 ml/min/kg, p&amp;lt;0.001) and after 12 months (creatinine 1.35 ± 0.54 mg/dl, p&amp;lt;0.001, eGFR 53.27 ± 17.68 ml/min/kg, p&amp;lt;0.001). Hb showed a significant increase after 6 (13.61 ± 1.78 g/dl, p&amp;lt;0.001) and 12 months (13.6 ± 1.79 g/dl, p&amp;lt;0.001), compared to baseline (13.41 ± 1.71 g/dl, p&amp;lt;0.001). Comparison of baseline values for CRP (0.08 ± 1.18 mg/dl), Troponin (86.33 ± 190.6 ng/l), NT-pro BNP (4703 ± 4385 pg/ml) and INR (1.25 ± 0.46) after 6 (CRP p=0.28, Troponin p=0.7, NT-pro BNP p=0.97, INR p=0.91) and 12 months (CRP p=0.12, Troponin p=0.59, NT-pro BNP p=0.78, INR p=0.28) showed no significant changes. Conclusion Although troponin and BNP are routinely used and recommended as biomarker for monitoring patients with ATTR-CM, the diagnostic value may be insufficient to assess therapy response. Results emphasize the need to identify new biomarkers to adequately reflect the specific aspects of ATTR-CM disease progression. This study reveals significant alterations in creatinine and eGFR due to a worsening of kidney function, but an increase of Hb, suggesting a potential indicator for treatment response. Future research should explore innovative approaches like proteomic analysis as promising approach for both diagnostic and prognostic biomarkers.

Cardiac autonomic changes after stroke

Abstract Introduction There is a highly complex and clinically important relationship between the cardiac and the nervous system, called the heart-brain axis [1]. Therefore, acute brain damage may lead to alterations in cardiac function due to changes in the autonomic nervous system[2,3]. Novel computerised biosignal analysis techniques and advanced biosignal assessment could provide a valuable tool to sensitively analyse cardiac autonomic function (CAF). CAF can be characterized by two complementary digital biomarkers, periodic repolariation dynamics (PRD) and deceleration capacity (DC). The aim of this study was to determine CAF by means of PRD and DC in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and to analyze them according to their relationship with specific cardiac (high-sensitive Troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP)) and stroke (location, type, severity) characteristics. Methoden / Methods Between February 22, 2021, and May 5, 2023, 282 patients after an AIS or TIA were enrolled in the study. During the inpatient stay, all relevant parameters were recorded and stored in a database. To assess CAF, a 30-minute biosignal measurement was performed with a high resolution (1kHz) electrocardiogram (ECG). Cardiac autonomic biomarkers, PRD and DC, were calculated semiautomatically afterwards from patients. Results Fifteen ECGs were excluded due to poor recording quality. Consequently, data from 261 AIS and 21 TIA patients were analyzed. A total of 105 patients (37.2 %) had pathological PRD (≥ 5.75 deg2) and/or DC (≤ 2.5 ms), 78 patients (27.7 %) had pathological PRD, and 57 patients (20.2 %) had pathological DC. The median PRD was 3.13 deg2 and the median DC was 5.30 ms (see Figure). There were no significant differences in the distribution of PRD and DC between male and female patients (PRD p = 0.38, DC p = 0.30), and between AIS and TIA patients (PRD p = 0.13, DC p = 0.66). Patients with middle cerebral artery (MCA) infarction had significantly higher median PRD values (3.56 deg2 [IQR 1.51 - 6.59 ] vs. 2.81 deg2 [IQR 1.15 - 5.99], p = 0.047) and lower median DC values (4.66 ms [IQR 2.65 – 7.76] vs. 6.11 ms [IQR 3.15 – 10.61], p = 0.011) than patients with stroke located in another cerebral regions (see Figure). Patients with pathological PRD or DC had significantly higher hsTnT (13.50 ng/l [IQR 9.7 – 24.1] vs. 11.05 ng/l [ IQR 7.13 – 16.23], p &amp;lt; 0.001) and NT-pro BNP (269.00 ng/l [IQR 117.50 – 687.00] vs. 125.50 ng/l [IQR 57.00 – 288.25], p &amp;lt; 0.001) values. Conclusions The study showed that a considerable proportion, more than one third of all patients, had evidence of cardiac autonomic dysfunction after acute cerebral ischaemia. Of particular interest, PRD was higher and DC was lower in patients with MCA ischaemia, reflecting a potentially higher cardiac risk profile. Cardiac autonomic dysfunction was also associated with increased hsTnT and NT-proBNP levels.

Improving the prediction of major adverse cardiovascular events in patients with hypertrophic cardiomyopathy by adding plasma SVEP1 to conventional clinical model including NT-proBNP

Abstract Background Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease with a prevalence between 1 in 200 to 500 [1]. HCM can lead to major adverse cardiovascular events (MACE) such as heart failure (HF) hospitalization and cardiac death [2,3]. A protein named "sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1" (SVEP1) is a large extracellular matrix protein whose activity can be measured in plasma [4,5]. SVEP1 promotes inflammation and atherosclerosis [4,5]. SVEP1 is associated with risk of HF hospitalization and cardiac death in patients with HF with reduced ejection fraction [6]. However, no prior study has assessed the prognostic value of SVEP1 in patients with HCM. Purpose To test the hypothesis that the addition of SVEP1 improves the predictive performance of the conventional model based on clinical risk factors plus NT-proBNP for future MACE in patients with HCM. Methods We performed a multicenter prospective cohort study of patients with HCM [7]. The outcome was MACE, defined as a composite of HF hospitalization or cardiac death [6]. After dividing the cohort into four groups using the median values of SVEP1 and NT-proBNP, we compared the risk of the outcome event using the Cox proportional hazards model adjusting for 15 clinical risk factors known to be associated with MACE in HCM (Figure 1) [8-11]. We also developed the Lasso-regularized Cox proportional hazards model to predict the time to first MACE by adding SVEP1 to the 15 clinical risk factors with or without NT-proBNP in the training cohort (randomly selected 75% of the cohort). We then compared the predictive performance in the test cohort (25% of the cohort) using the C-statistic of each model. Results During a median follow-up of 1.9 (25 percentile-75 percentile, 0.7-4.3) years, the outcome event occurred in 63 (10%) of 610 patients. The four groups stratified by the median of SVEP1 and NT-proBNP levels had different risks of the outcome event (log-rank p&amp;lt;0.001: Figure 1). Even in the groups with lower-than-median NT-proBNP levels, the high-SVEP1 group had higher risks of MACE compared with the low-SVEP1 group (adjusted hazard ratio 4.52, p=0.042: Figure 1). In the prediction of time to first MACE, the addition of SVEP1 improved the C-statistic of the clinical model (p&amp;lt;0.001) and that of the clinical plus NT-proBNP model (p=0.01: Figure 2). The clinical plus SVEP1 model also outperformed the clinical plus NT-proBNP model (p=0.005: Figure 2). Conclusions In the present multicenter prospective cohort study of 610 patients with HCM, SVEP1 improved MACE risk stratification when added to the conventional model consisting of clinical risk factors plus NT-proBNP. SVEP1 also exhibited a superior predictive ability than NT-proBNP to predict MACE in patients with HCM. These data collectively indicate that SVEP1 provides additional risk stratification and may be a better biomarker than NT-proBNP for the prognostication of patients with HCM.Figure 1.Kaplan-Meier curves for MACEFigure 2.Time-dependent AUROC curves

Enhancing primary prevention: the incremental predictive value of NTproBNP beyond ASCVD risk assessment

Abstract Background Atherosclerotic cardiovascular disease (ASCVD) is a global health challenge, prompting widespread use of conventional risk assessment tools (SCORE2 in Europe and the ASCVD Risk calculator in the United States) to guide preventive strategies. Emerging evidence indicates that NTproBNP may help refine risk stratification. We investigate whether measuring NTproBNP in primary prevention correlates with mortality and enhances prediction compared to conventional risk score stratification. Methods Utilizing National Health and Nutrition Examination Survey (NHANES) data (1999 to 2004) linked to the National Death Index, our cohort included individuals without a history of CVD at baseline and suitable for assessment of the ASCVD ACC/AHA risk score. Individuals were grouped based on computed 10-year risk (low: &amp;lt;5%; borderline: 5-7.5%; intermediate: 7.5-20%; high: ≥ 20%). NTproBNP levels were measured (Roche assay, cut-off &amp;gt; 125pg/mL considered as positive). Cox regression estimated the association between ASCVD risk categories, with or without NTproBNP, and all-cause and cardiovascular mortality. Results Among 5257 adults, 47% male, mean age 54 ± 9.1 years, the mean 10-year ASCVD risk was 8.17 ± 8.2%, grouped as: low: 53.3%; borderline: 11.5%; intermediate: 23.9%; and high: 11.3%. NTproBNP &amp;gt; 125pg/mL was measured in 12.2%, 16%, 23.2% and 48.6% individuals, respectively (p &amp;lt; 0.001). Over 16.2 ± 3.4 years, all-cause and cardiovascular death was 22.3% and 5.6%, respectively. Compared to low-risk, the hazard ratio (HR) for all-cause death increased to 2.85 (2.2-3.7), 5.6 (4.2-7.5), and 15.3 (11.7-19.9) for borderline, intermediate, and high-risk, respectively. A significant interaction with NTproBNP was observed (low: HR 1.96 (1.33-2.9); borderline: HR 2.5 (1.6-3.9); intermediate: HR 2 (1.6-2.6), high: HR 1.7 (1.4-2.2), p&amp;lt;0.01 for all interactions, see Fig. 1). For cardiovascular death, a significant interaction also occurred across the groups, but of higher magnitude in low and borderline groups (low: HR 3.2 (1.4-7.3); borderline: HR 5.5 (2.5-12.4), p &amp;lt; 0.001 for both). Conclusion Our findings suggest that NTproBNP provides incremental predictive value, approximately doubling the hazard of all-cause death across all risk categories, and more than tripling the hazard of CV death in low/borderline risk groups, compared to ASCVD risk alone. The integration of NTproBNP measurements into risk assessment strategies could refine primary prevention approaches.

Prevalence of amyloidosis among patients with mild to severe aortic stenosis. Validation of screening parameters

Abstract Background Cardiac amyloidosis (CA) is an increasingly recognized cause of human heart failure. Up to 16% of patients with severe aortic stenosis (AS) undergoing transcatheter valve replacement have been reported to suffer concomitant transthyretin CA (ATTR). Since the diagnosis of CA implies distinct therapies with prognostic relevance, early diagnosis of CA is crucial. Different parameters have been described to improve screening accuracy for detection of CA, but it is unknown whether these parameters are valid, and the prevalence of CA is stable throughout the spectrum of AS. Purpose To validate screening parameters for the detection of CA in mild, moderate and severe AS. Methods Patient 65 years and above undergoing echocardiography with mild to severe AS, defined as calculated valve orifice area &amp;lt;2 cm2 by velocity-time-integral, and an intraventricular septum thickness &amp;gt; 11mm, fulfilling at least one of two additional criteria (Sokolow-Lyon-Index to left ventricular mass index ratio &amp;lt; 1.5 or stroke volume index &amp;lt; 35 ml/m2) were prospectively included and screened for CA using bone scintigraphy and immunofixation in blood and urine. Results 57 patients were included and completed the diagnostic work-up. Mean age was 83 ± 0.7 years and 71% were male. Overall, 15 (26%) of patients were diagnosed with CA (12 with ATTR and 3 with light-chain CA, Figure1A). 17 patients had mild, 21 had moderate and 19 patients were diagnosed with severe AS. Among patients with mild AS 41% were diagnosed with CA, whereas only 24% of patients with moderate and 16% of patients with severe AS suffered CA (Figure 1B), these results did not show statistically significant differences (p= 0.2, by Chi-Square Quadrat test). Patients with CA were less likely to have NYHA classes I or II (20 vs. 57%, p= 0.03), had higher values of NT-proBNP (4572 [2323; 6044] vs. 817 [589; 2571], p&amp;lt; 0.001) and high-sensitive troponin (66 [47; 103.5] vs. 22.5 [17; 33.6], p&amp;lt; 0.001) and were more likely to have an atrioventricular block of any degree (60 vs. 26%, p=0.04). Conclusion Prevalence of CA among patients fulfilling the criteria of this screening algorithm seems to be high independent of AS severity. Clinicians should not only focus on patients with severe AS to detect CA early. Further research is needed to estimate the prevalence of CA among all patients with AS. Figure 1 A: Among patients with an age &amp;gt;65 years, IVS &amp;gt;11mm, AS and SLI/LVMMI &amp;gt;1.5 or SVI &amp;lt;35 ml/m2 26% (red area) of patients were diagnosed with CA (n= 57). B: In patients with mild AS 41% were diagnosed with CA, whereas in patients with moderate AS only 24% and in patients with severe AS 16% had CA. These differences did not show statistical significance (p= 0.2). IVS: intraventricular septum, AS: aortic stenosis, SLI: Skolow-Lyon-Index, LVMM= left ventricular myocardial mass index, SVI: stroke volume index, CA: cardiac-amyloidosis. (Statistics performed by chi-square test using GraphPad Prism 9.0).

Blood biomarkers to detect functional impairment in adult patients with repaired Tetralogy of Fallot

Abstract Background The relationship between plasma brain natriuretic peptide (NT-proBNP) and soluble suppression of tumorigenicity-2 (sST2) with structural adaptions and exercise capacity remains incompletely described in patients with repaired Tetralogy of Fallot (rTOF). Methods Peripheral venous blood samples were drawn for 99 patients with repaired TOF, 59 patients with severe pulmonary regurgitation (PR) and 40 patients with no or mild PR. NT-proBNP was measured using enzyme-linked immunosorbent assays (Roche Diagnostics, Indianapolis, IN). Soluble ST2 levels were assessed on Aspect-plus ST2 quantitative rapid test. Results The mean value of NT-proBNP was 160±137 pg/ml, and sST2 was 29±13, ng/ml in the entire population. Mean NT-proBNP was significantly higher in patients with severe PR (169±150 vs145±118, pg/ml, p&amp;lt;0.001), while similar sST2 levels were observed in both groups (29±14 vs30±12, ng/ml, p&amp;gt;0.05). NT-proBNP and sST2 levels were higher in patients with transannular patch when compared to other RVOT intervention. Both biomarkers were significantly associated with exercise capacity, but NT-proBNP (r=-.60, p&amp;lt;0.001) was stronger. The optimal cut-off of 90pg/ml for NT-proBNP had a sensitivity of 74% and specificity of 63% for detection of impaired exercise capacity. Conclusions Serum levels of sST2 and NT-proBNP are elevated in patients with repaired TOF, with higher values observed in those with severe PR, but also in patients undergoing transannular patch. Incorporating both markers in these patients increased the ability to detect impairment in exercise capacity.