NT-proBNP Values Research Articles

The influence of alcohol dependence on the course of chronic heart failure in patients with HIV infection

Introduction. Alcohol dependence is a condition, the consequences of which are severe in persons with cardiovascular diseases and immunodeficiency. The purpose of the study is to evaluate the influence of alcohol dependence on the course of chronic heart failure (CHF) in persons infected with human immunodeficiency virus (HIV). Materials and methods. A clinical study including 240 HIV-infected patients, 160 of them were diagnosed with CHF, 72 had alcohol dependence. AUDIIT scale was used for diagnostics of alcohol dependence. All patients underwent echocardiography, NT-proBNP concentration was determined in blood plasma, serum - content of SRB, transferrin, ferritin, iron, potassium, sodium, bilirubin, creatinine, urea, uric acid, AST, ALT, GGTP activity. Statistical calculations: Kolmogorov-Smirnov, Mann-Whitney methods, odds ratios and risks. Results. Congestion, lower heart rate prevailed in the group of patients with alcohol dependence. On the background of alcohol dependence in blood serum there was a decrease in the level of total cholesterol, transferrin, potassium, an increase in total bilirubin and GGTP activity, a decrease in the number of platelets. Increase in NT-proBNP concentration was found in blood plasma. Discussion. Alcohol is characterized by cardiotoxic effect, and regular ethanol consumption is associated with the development of non-ischemic dilated cardiomyopathy and CHF. Echocardiographic findings suggest a predominance of right atrial and left ventricular dilatation in the group of patients with alcohol dependence among all patients with CHF infected with HIV due to the formation of cardiomyopathy. Conclusion. Alcohol dependence is a condition aggravating the course of CHF in HIV-infected patients, which is manifested by higher values of blood plasma NT-proBNP, with CHF more often acquiring a congestive character. The course of CHF in HIV-infected patients against the background of alcohol dependence is accompanied by liver dysfunction - 3.5 times increase the chance of cholestasis development, 2.5 times increase the chances of death within 2 months after admission to hospital.

NTproBNP values for diagnosis of congestive heart failure in old patients regarding atrial fibrillation

NTproBNP values for diagnosis of congestive heart failure in old patients regarding atrial fibrillation

Role of Intestinal Inflammation and Permeability in Patients with Acute Heart Failure.

Background and Objectives: Heart failure (HF) represents a major health burden. Although several treatment regimens are available, their effectiveness is often unsatisfactory. Growing evidence suggests a pivotal role of the gut in HF. Our study evaluated the prognostic role of intestinal inflammation and permeability in older patients with acute HF (AHF), and their correlation with the common parameters traditionally used in the diagnostic-therapeutic management of HF. Materials and Methods: In a single-center observational, prospective, longitudinal study, we enrolled 59 patients admitted to the Emergency Department (ED) and then hospitalized with a diagnosis of AHF, from April 2022 to April 2023. Serum routine laboratory parameters and transthoracic echocardiogram were assayed within the first 48 h of ED admission. Fecal calprotectin (FC) and both serum and fecal levels of zonulin were measured, respectively, as markers of intestinal inflammation and intestinal permeability. The combined clinical outcome included rehospitalizations for AHF and/or death within 90 days. Results: Patients with increased FC values (>50 µg/g) showed significantly worse clinical outcomes (p < 0.001) and higher median levels of NT-proBNP (p < 0.05). No significant correlation was found between the values of fecal and serum zonulin and the clinical outcome. Median values of TAPSE were lower in those patients with higher values of fecal calprotectin (p < 0.05). After multivariate analysis, NT-proBNP and FC values > 50 µg/g resulted as independent predictors of a worse clinical outcome. Conclusions: Our preliminary finding supports the hypothesis of a close relationship between the gut and heart, recognizing in a specific marker of intestinal inflammation such as FC, an independent predictive prognostic role in patients admitted for AHF. Further studies are needed to confirm these results, as well as investigate the reliability of new strategies targeted at modulation of the intestinal inflammatory response, and which are able to significantly impact the course of diseases, mainly in older and frail patients.

Significance of Galectin-3 and N-terminal pro b-type natriuretic peptide in the prediction of atrial fibrillation after cardiac surgery.

Post-operative atrial fibrillation (POAF) is a frequent complication after cardiac surgery. It is associated with prolonged hospital stay, increased morbidity, mortality rate and economic costs. The aim of the study was to determine the association between the values of Galectin3 and N-terminal pro-B-type natriuretic peptide (NTproBNP) with POAF after cardiac surgery. A prospective study enrolled patients aged 18-85 years old admitted due to elective coronary artery bypass graft surgery (CABG) or CABG + aortic valve replacement. The plasma Galectin-3 and NT-proBNP levels were measured one day before surgery postoperative days 1 and 7. The study included a total of 103 patients. POAF was registered in 45 patients. The mean age of patients in whom POAF occurred was 68.8 years, while other patients' mean age was 65.5 years (p=0.028). Patients with POAF did not differ from the group without POAF in the values of Galectin-3 and NT-proBNP preoperatively as well as on the first and seventh postoperative days. Changes in Galectin-3 levels on the first postoperative day had statistically significant value for predicting POAF (AUC=0.627 0.509-0.745 , p<0.05). Decrease in Galectin-3 level con centration on the first postoperative day over 17% increases the risk of developing AF. Preoperative values of Galectin-3 and NTproBNP are not associated with POAF development after cardiac surgery.

Determinants of NT-proBNP Levels in patients with a systemic right ventricle: a new cut-off level for risk stratification?

Abstract Introduction The role of N-terminal natriuretic peptide (NT-proBNP) in the risk prediction of patients with a systemic left ventricle is indisputable. However, its value in patients with a systemic right ventricle (sRV) is not well defined. Method Ninety-eight patients with NT-proBNP values at baseline from the randomized clinical trial SERVE were included. The correlation between baseline NT-proBNP values and parameters of bi-ventricular volumes and function quantified by cardiac magnetic resonance was assessed by means of adjusted linear regression models. The prognostic value of NT-proBNP and other established prognostic markers were assessed by means of adjusted cox proportional hazards model, survival analysis and c-statistic. The primary outcome was defined as the occurrence of either clinically relevant arrhythmia, heart failure or death. Results Median age [interquartile range, IQR] at baseline was 39 years [32,48] and 32% were female. Median NT-proBNP was 238 [137,429] ng/L. Coefficients of determination for the relationship between NT-proBNP levels and right ventricular end-systolic and end-diastolic volume index, and ejection fraction (RVEF) were +0.481, p&amp;lt;0.001; +0.427, p&amp;lt;0.001; and -0.561, p&amp;lt;0.001, respectively. The sex and age adjusted hazard ratio [95% confidence interval, CI] for NT-proBNP values above the 75th percentile (429ng/L) showed an exponential increase (Figure) and there was a significant difference in survival comparing the group above our cut-off value and the group below it (Table). After adjusting for age and sex, the prognostic value of NT-proBNP was comparable to the prognostic value of RVEF and predicted VO2 max (C-statistic: 0.71, 0.72 and 0.71, respectively). Conclusion NT-proBNP levels correlated significantly with right ventricular parameters assessed by means of CMR. Measurement of NT-proBNP is a reliable and convenient tool for the prediction of adverse outcomes in patients with a sRV and using the cut-off value of 429ng/L could assist in the risk stratification for this population.

Impact of sacubitril valsartan initiation in patients with HFrEF and severe mitral regurgitation referred for percutaneous mitral repair

Abstract Background In patients with heart failure with reduced ejection fraction (HFrEF), the severity of functional mitral regurgitation (MR) is a major predictor of worsened symptoms and poor outcomes. Percutaneous MR repair has been shown to improve outcomes in HFrEF with MR. However, because MR is related to abnormal myocardial function and adverse remodeling, the optimization of guideline-directed medical therapy (GDMT) could improve loading conditions, reversal remodelling and left ventricle function and also may reduce MR severity. We sought to evaluated whether the left ventricle reverse remodeling induced by the addition of sacubitril/valsartan may reduce MR severity sufficiently to avoid need for percutaneous MR repair approach. Methods We performed a single-center, prospective assessor-blinded study to determine the reverse remodeling response of sacubitril/valsartan therapy in HFrEF patients (NYHA class II-IV) with MR evaluated for percutaneous MR repair. Echocardiographic images were assessed offline by 2 investigators blinded to both the clinical data and timing of echocardiograms. Doses of sacubitril/valsartan were optimized to individual tolerance. A clinical and echocardiographic 1 year follow-up was performed. Results Thirty-nine HFrEF patients with MR grade 3-4 were included (mean age 63 years old, 69,2% male). Optimal dose of sacubitril/valsartan was reached in 63,2% of patients. After 1-year follow-up, only 1 patient died and, as we show in Table 1, a significant improvement on NYHA functional class and NT-ProBNP values were present. Left ventricle ejection fraction improved (29.7 ± 6.7% vs 41.3 ± 13.2%; P &amp;lt; 0.001) and left ventricular end-diastolic and end-systolic volume indexed to body surface area decreased (123.4 ± 35.7 mL/m2 vs 98.4 ± 39.7 mL/m2; P &amp;lt; 0.001 and 87.7 ± 30.0 mL/m2 vs 61.9 ± 35.3 mL/m2; P &amp;lt; 0.001, respectively). Volumetric remodeling was associated with a reduction in the degree of mitral regurgitation (64.1% grade 3 and 35.9% grade 4 at the beginning to 28.9% grade 1, 36.8% grade 2, 21.5% grade 3 and 13.2% grade 4 after one year of follow-up; [scale from 0-4]). Conclusion The optimization of GDMT with sacubitril/valsartan induced an improvement on functional class and a beneficial reverse cardiac remodelling, with enhancement of left ventricle function and reducing MR severity, enough in 24 patients to avoid need for percutaneous MR repair. In HFrEF patients with grade 3-4 mitral regurgitation, our results reinforce importance of ensuring optimal GDMT before a percutaneous mitral valve repair approach.Table 1.Changes during follow-up.

Heart failure with mildly reduced ejection fraction is not all alike: the importance of disease trajectory

Abstract Background Heart failure with mildly reduced ejection fraction (HFmrEF) is a relatively recent category whose prognosis is described in the literature as intermediate between preserved and reduced ejection fraction (EF). However, this group of patients can be quite heterogeneous, particularly in what concerns their place in HF disease trajectory, since it includes both patients with newly-diagnosed HFmrEF and those who improve from reduced EF to mildly reduced EF. Purpose To compare the phenotype and prognosis of patients with mildly reduced EF at diagnosis and those who initially had reduced EF, which later improved to mildly reduced. Methods We conducted a retrospective study including all consecutive patients assessed in our HF Clinic between 2018 and 2020 who had mildly reduced EF [41-49%]. Participants were divided into two groups: HFmrEF if EF was consistently between 41-49% and imp-HFmrEF if EF had previously been &amp;lt;40%. We compared HF etiology, comorbidities, ECG patterns, blood markers and echocardiogram results between the two groups. The primary endpoint was a composite of death and hospitalizations for HF or ventricular arrhythmias. Results We included 102 patients with a median age of 68 years observed in our HF clinic between 2018 and 2020. The sample was well balanced between HFmrEF (51%) and imp-HFmrEF (49%). Baseline characteristics and comorbidities were similar between the groups, except for a more frequent history of myocardial infarction among HFmrEF patients (45% vs 24%, p = 0.026). For both groups, the most common HF etiology was ischemic heart disease, although tendentially more dominant for HFmrEF patients compared with imp-HFmrEF (56% vs 37%, p = 0.055). On the contrary, a toxic etiology was more frequent among imp-HFmrEF patients (16% vs 2%, p = 0.015). Left ventricular volumes did not differ between the groups, nor did NT-proBNP values. However, as expected, patients with imp-HFmrEF were under more neurohormonal medication compared with HFmrEF. At a median follow-up of 2.3 years, imp-HFmrEF was associated with lower rates of death or hospitalization for HF or ventricular arrhythmias (14% vs 31%; log-rank test: p = 0.037), with a hazard ratio of 0.403 (95% CI 0.166-0.980). Additionally, there was also a tendency towards higher rates of worsening EF to &amp;lt; 40% among HFmrEF patients (16% vs 6%, not reaching statistical significance). Conclusions This study confirms that among HF patients with mildly reduced EF, different phenotypes with differing disease trajectories coexist. It also suggests that clinical prognosis (and, probably, the risk of EF deterioration) of patients diagnosed with HFmrEF is worse, compared with those who improve from reduced EF to mildly reduced EF. Further research with larger groups is required to identify predictors of EF deterioration and assess the potential role of intensification of neurohormonal modulation in preventing it.Table 1ResultsHospitalization-free survival

The impact of microcirculation improvements of coronary artery flow on macrocirculation after coronary intervention

Abstract Background The impact of microcirculation changes of coronary artery after percutaneous coronary intervention (PCI) and its association with macrocirculation remained obscured. Purpose This study aimed to investigate the impact of microcirculation changes of coronary artery flow on macrocirculation after coronary intervention. Methods This prospective study enrolled patients who underwent PCI. Electrical cardiometry was used for hemodynamics measurement before and after PCI. Deidentified data of patients in this study cohort were analyzed. Moreover, peri-procedural deidentified N-terminal-pro-B type natriuretic peptide level (NT-proBNP) values were analyzed. Results There was a total of 40 patients. The mean age was 62.1± 12.1 years, and there was male dominant (82.5%). The index of contractility (ICON) and stroke volume index worsened after PCI but improved on the next day after the procedural day. In addition, systemic vascular resistance index decreased and the improvement of ICON on the next day had remarkable contribution on the overall contractility rather than transient diminution after intervention. Hierarchical Clustering indicated that PCI had benefits for young patients, heart failure population, and patients with moderate to severe Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score. In addition, NT-proBNP values were analyzed, which reported a decreasing trend of level after intervention. Conclusions This study supported that PCI improved coronary flow and myocardial contractility over time after conquering the microvascular impedance. Moreover, microcirculation of coronary flow had impact on macrocirculation improvement, and it was feasible to measure the change by using electrical cardiometry.Figure 1Figure 2

Transtyretin cardiac amyloidosis in the elderly patient: always a wild type?

Abstract Background Transthyretin amyloidosis (ATTR) exists in two forms: a genetic form transmitted by autosomal dominant inheritance (ATTRv) and a wild type form (ATTRwt). Clinically, the hereditary form tends to have an early onset in adulthood and it is characterized by a particular tropism for nervous as well as cardiac tissue. In contrast, the "wild type" form has a later onset with major cardiac involvement and neurological manifestations usually limited to carpal tunnel syndrome (1). Methods and results in our centre, from January to October 2022, 20 patients older than 75 years received a diagnosis of cardiac ATTR (73% male, 27% female, mean age 83±5). In all patients, blood tests showed a significant and stable increase in the values of troponin Ths (0.070± 0.074 ng/mL) and NT-proBNP (1533±1204 pg/ml), with the absence of a monoclonal component in the blood and urine, and miocardial bisphosphonate scintigraphy positive grade 2/3. All patients showed absence of peripheral neuropathy with the presence of carpal tunnel syndrome in 9 cases. Before starting therapy with Tafamidis all patients underwent genetic testing by amplification of exons 2,3 and 4 of the TTR gene with subsequent sequencing. Unexpectedly, in 3 elderly male patients (15%) the genetic test resulted positive with 3 different mutations of pathogenetic significance (Val50Met; Ile88Leu; Val142Ile). First-degree relatives (10 consanguineous, average age 49±12 years) agreed to be subjected to genetic screening; of these 4 (1 male and 3 females, age 47±8 years) were positive for the corresponding mutation and underwent echocardiogram, MRI and myocardial scintigraphy. All of these tests were normal and they were included in an annual follow-up protocol at the to identify an early manifestation of the disease. Conclusions our experience shows that 15% of patients older than 75 years and diagnosed with cardiac ATTR may be affected by a genetic form. Making genetic diagnosis in this context is particularly important for screening family members: current therapies are in fact much more effective if started early before organ damage can occur (2).

Prognostic value of NT-proBNP and cardiac troponin levels in ambulatory patients with congestive heart failure - Insight from NHANES

Abstract Background Recently there has been increased interest in the utility of cardiac troponin and NT-proBNP to predict the prognosis in patients with CHF. The aim of this study was to investigate the prognostic significance of NT-proBNP and cardiac troponin in CHF patients in ambulatory settings. Methods The NHANES, conducted by the National Center for Health Statistics, collects nationally representative data on the health and nutritional status of the non-institutionalized US population. We included heart failure patients aged ≥ 40 years with valid entries for NT-proBNP and cardiac troponin. We used data collected during the period 1999 -2004. The primary endpoint was all-cause mortality. Vital status (dead or alive) was determined by linkage to a record match of the National Death Index, conducted by the National Center for Health Statistics through December 31, 2020. Follow up period was from the examination date to either the date of death or December 31, 2020, whichever came first. NT-proBNP and cardiac troponin levels were stratified into tertiles, and mortality was assessed using cox proportional hazard mortality multivariate logistic regression models. K-M survival curves were used to display mortality over time. All analyses were done using STATA version 17, with p-values less than 0.05 considered statistically significant. Results In all, there were 551 persons, corresponding to 4.4 million, with a diagnosis of CHF. Of this, 379, corresponding to 4.1 million persons, were retained for analyses. Hypertension (61.6%), diabetes (34.26%), CKD (32.7%), nicotine use (65.45%), and cardiovascular diseases (CVD) were the most prevalent comorbidities. On the multivariate analysis, compared to lower tertile for elevated NT-proBNP, being in the middle tertile increased the risk of all-cause mortality up to 54% (HR 1.54, CI 1.03 – 2.3, P = 0.035) and up to 2 fold for being in upper tertile (HR 1.95, CI 1.29 – 2.96, P = 0.002)(Figure 1). Similarly, compared to the lower tertile for elevated troponin, being in the upper tertile increased the risk of all-cause mortality up to threefold (HR 2.84, CI 1.82- 4.44, P = 0.000) while being in the middle tertile could not achieve statistical significance for predicting the outcome (HR 1.44, CI 0.95 - 2.17, P = 0.082)(Figure 2). Among other predictors included in the analysis, CKD and history of smoking were associated with overall worse survival (HR 1.68, CI 1.25- 2.23, P = 0.000) and (HR 1.5, CI 1.099-2.076, P = 0.011), respectively. Conclusion CHF patients in the middle and upper tertile for NT-proBNP and cardiac troponin compared to the lower tertile showed an overall poor prognosis on follow up in the ambulatory settings. Our findings suggest that monitoring NT-proBNP and cardiac troponin levels can be useful tools for predicting prognosis. Further studies are needed for the clinical implications of this strategy.K-M survival estimates for NT-proBNPK-M survival estimates for troponin

Prevalence and risk factors of left ventricular diastolic dysfunction in systemic sclerosis patients: insights from new echocardiographic parameters

Abstract Background Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by excessive extracellular matrix deposition and fibrosis that can affect the skin, blood vessels, and internal organs, including the heart. Primary heart involvement in SSc refers to the presence of cardiac fibrosis, inflammation, and dysfunction in the absence of pulmonary hypertension (PH). Although PH is usually considered the major risk factor for death in SSc patients, diastolic dysfunction has been proposed as an independent predictor of mortality, which may be more robust than PH. Purpose Early identification and management of heart complications in SSc patients are crucial to prevent further deterioration and improve treatment outcomes. However, myocardial damage caused by SSc is often poorly understood, and the long-term effects and prognosis remain unknown. Methods We conducted a cross-sectional study of 69 patients (p) with SSc diagnosis evaluated between February 2022 and February 2023. We analyzed the prevalence of left ventricular diastolic dysfunction (LVDD) as recommended by the 2016 ASE/EACVI guidelines. We compared the presence of risk factors associated with LVDD and its association with other echocardiographic findings. Of the 69p, 24 (34.8%) had LVDD, 41 (59.4%) had normal diastolic function, and 4 (5.8%) had undetermined diastolic dysfunction. Older age (mean age 69.7 ± 11.2 vs 57 ± 12.8; p &amp;lt; 0.01), arterial hypertension (50% vs 22%; p = 0.02), higher body mass index (28.3 ± 8 vs 24.6 ± 4.5; p = 0.02), and higher NTproBNP levels (131 [64-403] vs 97 [45-163]; p = 0.047) were significantly associated with LVDD. The absence of antitopoisomerase (scl70 0% vs 22.2%; p = 0.021) and the presence of anticentromere (CENP-A 81% vs 55.6%; p = 0.05) and (CENP-B 85.7% vs 55.6%; p = 0.02) antibodies were also significantly associated with LVDD. Additionally, classical parameters of ventricular function, such as left ventricular ejection fraction (LVEF 63.5 ± 4.2 vs 63.4 ± 3.7; p = 0.9) or tricuspid annular plane systolic excursion (TAPSE 20.6 ± 2.3mm vs 21.2 ± 2.4mm; p = 0.32), were not associated with LVDD. However, impairment of the right ventricular free wall strain (-23.8 ± 4 vs -27 ± 2.8; p = 0.017), and lower left atrial strain reservoir function (27.7 ± 10 vs 38.4 ± 12.7; p = 0.05) were significantly associated with LVDD. Conclusion LVDD is highly prevalent in patients with systemic sclerosis, particularly in elderly patients with a higher body mass index and those affected by arterial hypertension. These patientes have higher values of NTproBNP. Futhermore, antitopoisomerases antibodies are less likely to be expressed and anticetromere antibodies are more likely to be expressed . These findings highlight the importance of regular cardiovascular monitoring in SSc patients and the potential value of using new echocardiographic parameters to identify those at risk for LVDD.

Prognostic impact of improvement in quality of life after discharge in patients with ADHF with preserved ejection fraction regardless of the course of HF -PURSUIT-HFpEF registry

Abstract Background Lower quality of life (QOL) is associated with poor clinical outcome in patients with heart failure (HF). However, there is not fully clarified whether the changes in QOL could have prognostic value in patients with HF with preserved ejection fraction (HFpEF). Purpose The purpose of this study is to investigate the prognostic impact of changes in QOL in patients with HFpEF in relation to the changes in condition of heart failure. Methods We prospectively studied 435 patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF) without the poor outcome within 1 year after the discharge. The patients’ QOL was evaluated at discharge and 1 year after the discharge using EuroQol 5 dimensions 5-level (EQ-5D-5L) and the difference in the EQ-5D-5L index at these two time points was used to assess the change in QOL. The primary outcome was all-cause death. Results The median EQ-5D-5L index were 0.753 (0.562-0.875) at discharge and 0.784 (0.646-0.895) at 1 year after the discharge. During a mean follow-up period of 1.6±1.2 years, primary outcome occurred in 92 patients. Patients with improved QOL (defined as equal to or greater than the EQ-5D-5L index at discharge) were significantly younger, had lower volume load on echocardiography and higher level of hemoglobin and serum sodium than those without improved QOL. Both the improved QOL and the improvement of HF (defined as more than -0.035 in the difference in Log NTproBNP value within 1 year after discharge by ROC analysis: AUC 0.570 [0.506-0.635]) were associated with primary outcome at univariate Cox proportional hazard analysis and the improved QOL was significantly independently associated with primary outcome after multivariable adjustment. Kaplan-Meier analysis revealed that patients with improved QOL had significantly lower risk for primary outcome than those without improved QOL not only in the whole study patients (14% vs 27%, p=0.0007) but also both in the group with improving HF (11% vs 22% p=0.0129) and in those with worsening HF (17% vs 31% p=0.0468). Conclusion(s) The improvement in QOL had the prognostic impact in patients with ADHF-HFpEF regardless of the course of heart failure.

Role of NTproBNP and donor-derived cell-free DNA in the diagnosis of acute rejection in heart transplant recipients: a prospective study

Abstract Background Donor-derived cell-free DNA (dd-cfDNA) has shown a good ability to rule out rejection in heart transplant (HT) recipients, but there is scarce information on the utility of NTproBNP (and the combination of both biomarkers) in this setting. Methods We prospectively obtained levels of both biomarkers in all patients included in the FreeDNA-CAR study (NCT 04973943), just before performing surveillance endomyocardial biopsies (EMB) at 0.5, 1, 2, 3, 4, 6 and 12 months post-HT. Primary end-point was the correlation between dd-cfDNA and NTproBNP levels. Results A total of 206 HT patients from 12 different centers were included (mean age 54±12 years, 74% male), with a median of 5.6 EBM per patient. After excluding visits with missing data, 883 pairs of EBM-both biomarkers were available for analysis. ACR, defined as grade ≥2R, was present in 37 EMB (4.2%), and AMR ≥1 in 16 EMB (1.8%). Median (IQR) NTproBNP values for each ACR group were: 0R 1067 pg/ml (454-2563), 1R 1300 pg/ml (562-3298) and 2R-3R 1780 pg/ml (943-4880) and median dd-cfDNA values: 0R 0.08% (0.038-0.178), 1R 0.105% (0.04-0.34), 2R-3R 0.22% (0.058-0.7). Regarding AMR, median NTproBNP in pAMR0 was 1200 pg/ml (504-2840) and in pAMR≥1 2230 pg/ml (806-4256) (Figures 1A and 1B). Using a GEE (generalized estimating equation) approach to account for repeated measures in each individual, a statistically significant correlation between both biomarkers was found, with a coefficient of 0.001 (CI95% 0.0006-0.002), meaning that for every increase of 100 units of NTproBNP, %dd-cfDNA increased in 0.001, p &amp;lt;0.001 (Figure 2). Moreover, in a multivariable analysis, both biomarkers were associated with the risk of acute rejection, with an OR 1.48 (CI95% 1.04-2.11), p=0.03 for dd-cfDNA, and OR 1.007 (IC95% 1.001-1-013) p=0.017 for each additional 100 pg/ml of NTproBNP. Conclusion In a cohort of HT patients in their first post-transplant year, dd-cfDNA and NT-proBNP levels were associated with acute rejection and showed a good correlation between them. Further studies are needed in order to determine if the combination of both biomarkers could improve individual performance and increase the number of EMB that could be safely eliminated.Median (IQR) NTproBNP levels (pg/ml)Linear prediction of dd-cfDNA

Candidacy and predicted efficacy of vericiguat in contemporary heart failure outpatient clinics

Abstract Background Vericiguat is a novel drug class (soluble guanylate cyclase stimulator) approved for the treatment of symptomatic heart failure with reduced ejection fraction (HFrEF) patients who are stable after recent decompensation. Its safety and efficacy in high-risk HFrEF patients (ejection fraction &amp;lt;45%) with recent hospitalisation was demonstrated in the VICTORIA trial, along with advantages: lesser impact on blood pressure, sustained efficacy up to eGFR 15 mL/min/1.73m2. Subgroup analyses have shown variability in heart failure hospitalisation (HFH) and cardiovascular death (CVD) reduction according to NT-proBNP levels. While real-world candidacy for Vericiguat have been described in hospitalised patients, data on Vericiguat eligibility within contemporary heart failure outpatient (HF OPD) clinics is limited. Purpose We describe the proportion of HFrEF patients reviewed in HF OPD clinics eligible for vericiguat (according to the VICTORIA trial criteria) and likely to benefit from therapy based on NT-proBNP levels. Methods A retrospective review was performed on HFrEF patients reviewed in HF OPD services in 2022. Hospital records were assessed to identify community managed HFrEF patients experiencing HFH in 2022 and the VICTORIA trial's selection criteria was applied to determine Vericiguat eligibility. Predicted efficacy (reduction in HFH and/or CVD) in Vericiguat eligible patients was based on NT-proBNP level cut-off: &amp;gt;8000 ng/L: no benefit; ≤8000 ng/L: net benefit; ≤5314 ng/L: strong benefit. Stable NT-proBNP value was taken as the peak value within 30 days of discharge of the HFH event. Results 333 HFrEF patients were reviewed in HF OPD services in 2022. 94 (28.2%) patients experienced HFH in 2022, of which 33 (9.9%) occurred after guideline directed medical therapy (GDMT) was optimized in HF OPD review. Pharmacotherapy patterns of patients with HFH were identified at HF OPD review: 24 (33.8%) quadruple GDMT, 18 (25.4%) triple GDMT, 21 (40.8%) dual or single GDMT. 71 (21.3%) patients with HFH met the VICTORIA trial criteria and were eligible for Vericiguat. When subdivided according to NT-proBNP level cut-off, the following predicted efficacy were identified: 52 (15.6%) net benefit, 42 (12.6%) strong benefit, and 19 (5.7%) no benefit. Conclusions In HF OPD services, 28.2% of HFrEF patients may experience HFH within 1 year with 9.9% occurring despite GDMT optimization. 40.8% of community managed HFrEF patients were still only on dual or single GDMT. The proportion of community managed HFrEF patients eligible for Vericiguat is 21.3%. Based on NT-proBNP levels, the proportion likely to experience net and strong beneficial effects from Vericiguat were 15.6% and 12.6% respectively. Considering Vericiguat has advantages over the traditional barriers (hypotension, renal function) of conventional HFrEF pharmacotherapy agents, our findings provide insight into the potential real-world use of Vericiguat within contemporary HF OPD clinics.Figure 1Table 1

Abstract 13038: Predictive Value of Cardiac Function Parameters and NT-proBNP in Patients With Pulmonary Arterial Hypertension (PAH) Treated With Sotatercept in the STELLAR Trial

Background: Sotatercept is an activin signaling inhibitor under investigation for PAH. Goal: Evaluate the prognostic utility of hemodynamic and cardiac function parameters in PAH patients receiving sotatercept vs placebo. Methods: Participants in STELLAR, a phase 3 trial (NCT04576988), were randomized 1:1 to sotatercept (0.3 up to 0.7 mg/kg once every 3 weeks) or placebo added to background therapies. Eligible participants had WHO functional class II-III, pulmonary vascular resistance ≥400 dyn·s·cm -5 , and 6-minute walk distance 150-550 m. This post-hoc analysis assessed clinical worsening events at last measurement by baseline echocardiography (ECHO), right heart catheterization (RHC), and NT-proBNP parameters. Clinical worsening events were assessed up to week 60. Uni-/multivariate-adjusted Cox models identified baseline parameters significantly (p&lt;0.05) associated with events. Parameters with p-values &lt;0.10 were carried forward to multivariate model. Receiver operating characteristic curves assessed discriminatory utility of cutoff values. Results: Of the significant univariate predictors, only study treatment and log2 NT-proBNP were significant independent predictors of clinical worsening in multivariate model (Table). Each unit increase in log2 NT-proBNP at baseline was associated with a 61% increase in risk (HR 1.61, 95% CI 1.39, 1.88; p&lt;0.001). The AUC for log2 NT-proBNP (0.76 [95% CI 0.67, 0.85]) showed good performance. The optimal NT-proBNP cutoff value was 322 pg/mL. Sotatercept treatment was associated with an 81% reduction in risk vs placebo (HR 0.19, 95% CI 0.10 to 0.38; p&lt;0.001), even after adjusting for NT-proBNP. Conclusions: This post-hoc analysis demonstrated that NT-proBNP is a strong predictor of clinical worsening events in PAH patients. Sotatercept treatment offered protection beyond that achieved with standard therapies alone, even after adjusting for the impact of NT-proBNP.

Abstract 12519: Biomarker Characterisation of Heart Failure Subtypes: A Population-Based Bioresource Linked Study

Background: Deep learning (DL)-based interpretation of echocardiographic images can help create pragmatic cohort studies to validate novel biomarkers. In this study, we have characterised biomarkers implicated in heart failure (HF) pathophysiology across the ejection fraction (EF) range in a DL-supported pragmatic cohort study. Methods: We used electronic health record data from Tayside, representing 20% of the Scottish population, between 1993 and 2021. Utilising record linkage to DL automated reading of echocardiographic DICOM images, we identified patients with HFrEF or HFpEF and patients without HF. We then linked identified patients to available plasma samples from the Go-SHARE BioBank. We analysed multi-panel biomarkers, such as NT-proBNP, high-sensitivity cardiac troponin-T (hs-cTnT), growth differentiation factor-15 (GDF-15), insulin-like growth factor-binding protein-7 (IGFBP-7), bone morphogenetic protein-10 (BMP-10), Dickkopf WNT Signaling Pathway Inhibitor-3 (DKK-3), fibroblast growth factor-23 (FGF-23), angiopoietin-2 (Ang2), and fatty acid-binding protein-3 (FABP-3), all with electrochemiluminescence immunoassays (Roche Diagnostics, Germany). Results: We identified 236 patients with HFpEF, 156 with HFrEF, and 185 patients without HF with available plasma samples from 3680 patient records linked to echocardiographic DICOMs and blood samples. Patients with HFrEF and HFpEF had significantly higher median values of hs-cTnT, GDF-15, NT-proBNP, IGFBP-7, DKK-3, and FGF-23 than controls. The diagnostic accuracy (AUC) of NT-proBNP, hs-cTnT, GDF-15, IGFBP-7, and FABP-3 was &gt;0.8 for identifying patients with HFrEF or HFpEF from controls. DL-algorithm-based interpretation of DICOM images provided further coverage of echocardiographic parameters relevant for diagnosis of HF subtypes. All biomarkers were associated with all-cause mortality and HF-related hospitalisation during a median follow-up of 1089 days. Conclusions: In this population-based study, we demonstrated a novel approach utilising a bioresource linked to a DL-supported pragmatic study to explore biomarkers in HF and demonstrated that multiple biomarkers to have diagnostic and prognostic significance for patients with HFrEF and HFpEF.

Abstract 18673: Lack of Influence of Comorbidities on NT Pro-BNP/BNP Ratio in ATTR-CA: A Prospective, Single Sample, Paired Data Analysis

Introduction: Scores to stage amyloidosis include laboratory values of NT pro-BNP and BNP. However, no prior data on the correlation between the two markers is available for the same sample in ATTR patients with a spectrum of co-morbidities. While established staging systems for cardiac amyloidosis use NT-pro BNP, many centers routinely measure BNP. To facilitate universal staging, we explored the relationship between NT-pro BNP and BNP measured from a single blood sample in ATTR patients with a spectrum of co-morbidities. Hypothesis: The ratio of NT pro-BNP to BNP is influenced by atrial fibrillation, BMI, left ventricular and renal function. Methods: ATTR-CA patients had serial NT pro-BNP and BNP measured from a SINGLE blood sample. Ratios were compared in patients stratified by co-morbidities. A regression equation to derive BNP from NT pro- BNP was created. Results: Among 101 patients, (85% men, 84% Caucasian), co-morbidities were prevalent (atrial fibrillation: 56%, LVEF &lt; 50%: 46%, GFR &lt;60 mL/min/1.73 m 2 : 51%, BMI ≥ 27: 51%); 4% were on ARNI. A strong correlation (r = 0.83) and a ratio of the log transformed data of 1.32 (95% CI: 1.29 - 1.34) was found between NT-pro BNP and BNP levels, which was not different among patients stratified according to co-morbidities. The relationship between NT pro-BNP and BNP was defined by ln(BNP) = 0.59 + 0.69 ln(NT pro-BNP). Conclusions: Our study suggests a robust correlation between NT-pro BNP and BNP in ATTR-CA patients and a constant ratio among patients with different co-morbidities. A regression equation may facilitate deriving BNP levels from NT- pro BNP and must be validated independently.

Abstract 13706: Determinants of Right Ventricular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial Experience

Introduction: Right ventricular dysfunction (RVD) is a major prognostic factor in patients with heart failure with preserved ejection fraction (HFpEF), however determinants of RVD in HFpEF are not well described. Although sex-specific mechanisms have been incriminated in the development of HFpEF, it is unclear whether this is also true for RVD. Goals: (1) Assess the prevalence of RVD (defined as a tricuspid annular plane systolic excursion [TAPSE] &lt;1.7 cm, a fractional area change [FAC] &lt;35% or a RV free wall longitudinal strain [RVFWLS] &lt;20%, absolute value) in patients with HFpEF; (2) identify determinants of RVD, overall and according to sex, in patients with HFpEF. Methods: We used data from patients enrolled in the echocardiographic sub-study of the PARAGON-HF trial with adequate image quality (N=809, 53% women, mean age 74±8 years). Determinants of RVD, in the whole study population and according to sex, were identified using a multivariable logistic regression model. Results: There were 461 patients (57%) with RVD. After multivariable adjustment, RVD was cross-sectionally associated with a history of atrial fibrillation of flutter (AFF), older age, higher heart rate, greater LV mean wall thickness and higher NT-proBNP values. Systolic blood pressure and LV global longitudinal strain (absolute value) showed an inverse association ( Figure ). These results were consistent between men and women, except for AFF and LV mean wall thickness, which were associated with a greater likelihood of RVD in men (OR 2.46, 95%CI 1.33-4.56, OR 1.61, 95%CI 1.18-2.21 respectively) but not in women (OR 0.99, 95%CI 0.58-1.68, OR 0.90 95%CI 0.69-1.17 respectively, p-values for interaction=0.028 and 0.006). Conclusions: RVD was highly prevalent in our study population. Determinants of RVD included AFF, LV remodeling and systolic impairment, and increased NT-proBNP levels. Differences between men and women suggest gender-specific mechanisms in the development of RVD in HFpEF.

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

BackgroundThe 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). MethodsPeripheral 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. ResultsThe mean value of NT-proBNP was 160 ± 137 pg/ml, and sST2 was 29 ± 13, ng/ml in the entire population. 58 % had an elevated NT-proBNP, while sST2 was abnormal in 40 %. Mean NT-proBNP was significantly higher in patients with severe PR (169 ± 150 vs145 ± 118, pg/ml, p < 0.001), while similar sST2 levels were observed in both groups (29 ± 14 vs30 ± 12, ng/ml, p > 0.05). NT-proBNP and sST2 levels were higher in patients with transannular patch when compared to other RVOT intervention (174 ± 145 vs 107 ± 100, pg/ml, p < 0.001); (31 ± 13 vs 29 ± 15, ng/ml, p < 0.05). Both biomarkers were significantly associated with exercise capacity, but NT-proBNP (r = −0.60, p < 0.001) was stronger. The optimal cut-off of 90 pg/ml for NT-proBNP had a sensitivity of 74 % and specificity of 63 % for detection of impaired exercise capacity. ConclusionsSerum 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 repair. Incorporating both markers in these patients increased the ability to detect impairment in exercise capacity.

Prognostic and diagnostic significance of the cardiac biomarker NT-proBNP in the perioperative period of vascular surgery procedures

The objective was to study the dynamics of NT-proBNP blood level during the perioperative period of vascular surgery and to study the association of this biomarker level at the stages of treatment with developed cardiovascular complications (CVC).Materials and Methods. The study involved 129 patients aged 66 [61–70] years who underwent elective vascular surgery. NT-proBNP blood level was determined at stages: I – before surgery, II – 24 hours after surgery, III – before discharge from the hospital. Correlation analysis, logistic regression and ROC-analysis were used for data processing.Results. Median NT-proBNP (pg/ml) at stage I was 54[42–215], stage II – 149[63–298] (p1–2 = 0.0001) and stage III – 78[48–288] (p1–3 = 0.037). NT-proBNP blood level at stage I correlated with the biomarker level at stages II (rho = 0.558, p &lt; 0.0001) and III (rho = 0.689, p &lt; 0.0001). The biomarker was associated with CVC at all stages: I – OR 1.0048, 95% CI 1.0021–1.0074, p &lt; 0.0001, AUC 0.825; II – OR 1.0040, 95% CI 1.0020–1.0060, p &lt; 0.0001, AUC 0.820; III – OR 1.0026, 95% CI 1.006–1.0046, p = 0.015, AUC 0.687. At stage I, NT-proBNP &gt; 218 pg/ml was a CVC predictor (sensitivity 82%, specificity 85%), this biomarker level was registered in 30 (23.2%) patients; at stage II, NT-proBNP &gt; 281 pg/ml was associated with CVR (sensitivity 81%, specificity 80%), at stage III NT-proBNP &gt; 158 pg/ml was associated with CCC (sensitivity 79%, specificity 65%).Conclusions. After vascular surgery, the median NT-proBNP value increases significantly, remaining within the reference limits, and does not de[1]crease until the patients discharge from the hospital. The perioperative NT-proBNP dynamics may differ in patients with different initial biomarker levels. In 23.2% of vascular surgical patients, the preoperative NT-proBNP blood level increased to a level of more than 218 pg/ml, indicating CVC risk (very good quality predictor model). After surgery, the level of NT-proBNP associated with CVC (very good quality model) exceeds 281 pg/ml. Prior to discharge of patients from the hospital, the association of NT-proBNP with CVC is characterized by a moderate quality model (AUC 0.687). The prognostic significance of the biomarker at this stage of surgical treatment needs further research.