BNP level predicts bleeding event in patients with heart failure after percutaneous coronary intervention.

OBJECTIVE: This study aimed to investigate the association between heart failure (HF) severity measured based on brain natriuretic peptide (BNP) levels and future bleeding events after percutaneous coronary intervention (PCI). BACKGROUND: The Academic Research Consortium for High Bleeding Risk presents a bleeding risk assessment for antithrombotic therapy in patients after PCI. HF is a risk factor for bleeding in Japanese patients. METHODS: Using an electronic medical record-based database with seven tertiary hospitals in Japan, this retrospective study included 7160 patients who underwent PCI between April 2014 and March 2020 and who completed a 3-year follow-up and were divided into three groups: no HF, HF with high BNP level and HF with low BNP level. The primary outcome was bleeding events according to the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries classification of moderate and severe bleeding. The secondary outcome was major adverse cardiovascular events (MACE). Furthermore, thrombogenicity was measured using the Total Thrombus-Formation Analysis System (T-TAS) in 536 consecutive patients undergoing PCI between August 2013 and March 2017 at Kumamoto University Hospital. RESULTS: Multivariate Cox regression showed that HF with high BNP level was significantly associated with bleeding events, MACE and all-cause death. In the T-TAS measurement, the thrombogenicity was lower in patients with HF with high BNP levels than in those without HF and with HF with low BNP levels. CONCLUSIONS: HF with high BNP level is associated with future bleeding events, suggesting that bleeding risk might differ depending on HF severity.

Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis.

Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in CORIN, the gene encoding atrial natriuretic peptide (ANP)-converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.

Plasma brain natriuretic peptide, D-Dimer, and serum troponin-I as predictors for in-hospital death in patients with COVID-19.

The severe acute respiratory syndrome coronavirus 2, first appeared in Wuhan, China, in December 2019. Since then, a variety of strains of the virus were spread throughout the world, prompting the World Health Organization to declare a pandemic in March 2020. Additionally, Coronavirus disease 2019 (COVID-19) can cause a variety of symptoms, ranging from fatigue and fever to severe respiratory and cardiovascular complications. This study evaluated the role of brain natriuretic peptide (BNP), troponin-I and D-dimer as biomarkers for death prediction in hospitalized patients with COVID-19. The study included 90 patients with COVID -19 diagnosed with PCR-RNA testing. They were divided into survivors and non-survivors. Also, 20 apparently healthy individuals age and sex matched were included as a control group. Plasma BNP and serum troponin-I were measured by enzyme linked immune-sorbent assay (ELISA) technique. D-dimer was measured by a turbidimetric technique. Patients with COVID-19 had significantly elevated levels of serum Troponin-I and plasma BNP in comparison to controls (p < 0.0001, for both). D-dimer, troponin-I and BNP levels were significantly higher in the non-survivors group when compared to the survivors group. Troponin-1 can predict COVID-19 severity with sensitivity, specificity, and accuracy of 55.1%, 66.7%, and 57.8%, respectively at a cutoff value of 0.075 (ng /ml); and area under the receiver operating characteristic (AUC) curve of 0.670 (95% CI: 0.551 - 0.790, p=0.018). BNP can predict COVID-19 severity with sensitivity, specificity, and accuracy of 98.6%, 71.4%, 92.2%, respectively at a cutoff value of 16.02 (Pg /ml) and AUC of 0.872 (95% CI: 0.778 - 0.965, p < 0.001). Univariate and multivariate logistic regression analysis showed that only BNP level can significantly predict death among COVID-19 infected patients. In conclusion, plasma BNP and serum troponin-I could be used as prognostic biomarkers for determination of the severity of COVID-19 and BNP could predict mortality.

Macitentan in the Young-Mid-term Outcomes of Patients with Pulmonary Hypertensive Vascular Disease treated in a Pediatric Tertiary Care Center.

BACKGROUND: Pulmonary hypertension (PH) is a severe hemodynamic condition with high morbidity and mortality. Approved targeted therapies are limited for pediatric subjects, and treatments are widely adopted from adult algorithms. Macitentan is a safe and effective drug used for adult PH, but data on pediatric patients are limited. In this prospective single-center study, we investigated mid- and long-term effects of macitentan in children with advanced pulmonary hypertensive vascular disease. METHODS: Twenty-four patients were enrolled in the study for treatment with macitentan. Efficacy was determined by echo parameters and brain natriuretic peptide levels (BNP) at 3 months and 1 year. For detailed analysis, the entire cohort was subgrouped into patients with congenital heart disease-related PH (CHD-PH) and non-CHD-PH patients, respectively. RESULTS: Mean age of the patients was 10.7 ± 7.6 years; median observation period was 36 months. Twenty of 24 patients were on additional sildenafil and/or prostacyclins. Two of 24 patients discontinued because of peripheral edema. Within the entire cohort, BNP levels and all echo measures such as right ventricular systolic pressure (RVSP), right ventricular end-diastolic diameter (RVED), tricuspid annular plane systolic excursion (TAPSE), pulmonary velocity time integral (VTI), and pulmonary artery acceleration time (PAAT) improved significantly after 3 months (p ≤ 0.01), whereas in the long term significant improvement persisted for BNP levels (-16%), VTI (+14%) and PAAT (+11%) (p < 0.05). By subgroup analysis, non-CHD PH patients showed significant improvements in BNP levels (-57%) and all echo measures (TAPSE +21%, VTI +13%, PAAT +37%, RVSP -24%, RVED -12%) at 3 months (p ≤ 0.01), whereas at 12 months, improvements persisted (p < 0.05) except for RVSP and RVED (nonsignificant). In CHD-PH patients, none of the measures changed (nonsignificant). 6-MWD (distance walked in 6 minutes) slightly increased but was not statistically evaluated. CONCLUSION: Data presented herein account for the largest cohort of severely affected pediatric patients receiving macitentan. Overall, macitentan was safe and associated with significant beneficial effects and sustained positive signals after 1 year, albeit in the long term disease progression remains a major concern. Our data suggest limited efficacy in CHD-related PH, whereas favorable outcomes were mainly driven by improvements in patients with PH not related to CHD. Larger studies are needed to verify these preliminary results and to prove efficacy of this drug in different pediatric PH entities.

Growth Differentiation Factor 15 and Clinical Outcomes in Japanese Patients With Heart Failure.

BACKGROUND: Heart failure (HF) is an increasing health problem associated with a high mortality rate. Growth differentiation factor (GDF) 15, a stress response cytokine belonging to the transforming growth factor-ß superfamily, is associated with poor clinical outcomes in a broad spectrum of cardiovascular diseases. However, the prognostic usefulness of GDF15 in Japanese patients with HF remains unclear.Methods and Results: We measured serum concentrations of GDF15 and B-type natriuretic peptide (BNP) in 1,201 patients with HF. All patients were prospectively followed for a median period of 1,309 days. In all, 319 HF-related events and 187 all-cause deaths occurred during the follow-up period. Kaplan-Meier analysis demonstrated that, among GDF15 tertiles, the highest tertile group had the greatest risk of HF-related events and all-cause mortality. Multivariate Cox proportional hazard regression analysis demonstrated that the serum GDF15 concentration was an independent predictor of HF-related events and all-cause deaths after adjusting for confounding risk factors. Serum GDF15 improved the prediction capacity for all-cause deaths and HF-related events with a significant net reclassification index and integrated discrimination improvement. Subgroup analysis in patients with HF with preserved ejection fraction also showed the prognostic usefulness of GDF15. CONCLUSIONS: Serum GDF15 concentrations were associated with HF severity and clinical outcomes, indicating that GDF15 could provide additional clinical information to track the health status of patients with HF.

Serum pro-B-type natriuretic peptide levels and cardiac index as adjunctive tools of blunt cardiac injury.

BACKGROUND: Blunt cardiac injury (BCI) has a variety of symptoms that may be a potentially life-threatening injury that can lead to death. Depending on the diagnosis of BCI, treatment direction and length of stay may vary. In addition, the utility of other diagnostic tests for cardiac disease as diagnostic tools for BCI remain unclear. The purpose of this study was to investigate the competence of N-terminal pro-B-type natriuretic peptide (NT pro-BNP) and cardiac index (C.I) as adjunctive diagnostic tools for BCI. METHODS: From January 2018 to March 2020, severe trauma patients with sternum fracture who were admitted to the traumatic intensive care unit (TICU) were included this study. Patients with sternum fracture, 18 years of age or older, and with an injury severity score > 16 who required intensive care were included. Invasive measurement for the analysis of the pulse contour for C.I monitoring and intravenous blood sampling for NT pro-BNP measurement were performed. Sampling and 12-lead electrocardiogram were performed at different time points as follows: immediately after TICU admission and at 24 h and 48 h after trauma. RESULTS: Among 103; 33 patients with factors that could affect NT pro-BNP were excluded; therefore, 63 patients were included in this study. According to the American Association for the Surgery of Trauma Cardiac Injury Scale, 33 patients were diagnosed with non-BCI, and 30 patients constituted with BCI. The median ages of the patients were 58 (52-69), and 60 (45-69) years in the non-BCI and BCI groups, respectively (p = 0.77). The median NT pro-BNP values were higher in the BCI group on admission, hospital day (HD) 2, and HD 3, however, no statistical difference was observed (125 (49-245) vs. 130 (47-428) pg/mL, p = 0.08, 124 (68-224) vs. 187 (55-519) pg/mL, p = 0.09, and 121(59-225) vs. 133 (56-600) pg/mL, p = 0.17, respectively). On the contrary, significantly lower values were observed in the median C.I measurement on admission and HD 3 in the BCI group (3.2 (2.8-3.5) vs. 2.6 (2.3-3.5) L/min/m2, p < 0.01 and 3.2 (3.1-3.9) vs. 2.9 (2.4-3.2) L/min/m2, p < 0.01, respectively); however, no significant difference was observed on HD 2 (3.4 (3.0-3.7) vs. 2.6 (2.4-3.4) L/min/m2, p = 0.17), Furthermore, The median lactate levels in the BCI group upon admission, HD 2, and HD 3 were significantly higher than those in the non-BCI group (1.8 (1.1-2.6) vs. 3.1 (2.1-4.4) mmol/L, p < 0.01; 1.3 (0.8-2.3) vs. 3.0 (2.2-4.7) mmol/L, p < 0.01; and 1.5 (0.9-1.5) vs. 2.2 (1.3-3.7) mmol/L, p < 0.01, respectively). CONCLUSION: Consecutive values of NT pro-BNP and C.I show no correlation with ECG-based BCI diagnosis. However, lactate level measurement may help in the early recognition of BCI as an adjunctive tool. It should be noted that this is a hypothesis-generating study for BCI diagnosis. Further studies should be conducted in larger populations with a prospective approach.

A new model for predicting adverse outcomes in arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive disease leading to ventricular arrhythmias and heart failure. Determining optimal time for heart transplantation (HTx) is challenging; therefore, it is necessary to identify risk factors for disease progression. OBJECTIVES: The study aimed to identify predictors of end­stage heart failure and to evaluate the role of biomarkers in predicting adverse outcomes in ARVC. PATIENTS AND METHODS: A total of 91 individuals with ARVC (59 men; mean [SD] age, 47 [16] years) were included. In all patients, information on medical history was collected, electrocardiography and echocardiography were performed, and serum levels of selected biomarkers (soluble form of the ST2 protein [sST2], galectin­3 [Gal­3], extracellular matrix metalloproteinases [MMP­2 and MMP­9], N­terminal pro-B­type natriuretic peptide [NT­proBNP], and high­sensitivity troponin T [hs­TnT]) were measured. Thereafter, the participants were followed for the primary end point of death or HTx, as well as the secondary end point of major arrhythmic events (MAEs), defined as sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter­defibrillator intervention. RESULTS: During the median (interquartile range) follow­up of 36.4 (29.8-41.2) months, 13 patients (14%) reached the primary end point of death or HTx, and 27 (30%) experienced MAEs. The patients who achieved the primary end point had higher levels of sST2, MMP­2, NT­proBNP, and hs­TnT, but not of Gal-3 and MMP-9. Three factors turned out to be independent predictors of death or HTx: higher NT­proBNP concentration (≥890.3 pg/ml), greater right ventricular end­diastolic area (≥39 cm2), and a history of atrial tachycardia. None of the biomarkers predicted MAEs. CONCLUSIONS: An NT­proBNP concentration greater than or equal to 890.3 pg/ml, right ventricular end-diastolic area of 39 cm2 or greater, and a history of atrial tachycardia were identified as risk factors for death or HTx in ARVC. Higher levels of sST2, MMP­2, NT­proBNP, and hs­TnT were associated with reaching the primary end point of death or HTx. The biomarkers had no value in predicting ventricular arrhythmias.

Left atrial appendage dimension predicts elevated brain natriuretic peptide in nonvalvular atrial fibrillation.

INTRODUCTION: BNP elevation in patients with AF is observed in the absence of heart failure; however, prior mechanistic studies have not included direct left atrial pressure measurements. This study sought to understand how emptying function of the left atrial appendage (LAA) and LAA dimension contributes to brain-natriuretic peptide elevations (BNP) in atrial fibrillation (AF) accounting for left atrial pressure (LAP). METHODS: 132 patients referredfor left atrial appendage occlusion (LAAO) were prospectively enrolled in this study. BNP levels and LAP were measured just before LAAO. Statistical analysis considered BNP, rhythm at time of procedure, LAP, LAA morphology, LAA size (ostial diameter, depth, volume), LAA emptying velocity, CHADS2-VASc score, body mass index (BMI), left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), and obstructive sleep apnea (OSA) diagnosis as covariates. RESULTS: Bivariate statistical analysis demonstrated positive associations with age, LAA ostial diameter, depth, and volume, LAP, AF status at time of measurement, OSA, and CHADS2-VASc score. BNP was negatively associated with LVEF, eGFR, LAA emptying velocity and BMI. With multivariate logistic regression including LAP as covariate, significant relationships between BNP and AF/AFL(OR 1.99 [1.03, 3.85]), LAP (OR 1.13 [1.06, 1.20]), LAA diameter (OR 1.14 [1.03, 1.27]), LAA depth (OR 1.14 [1.07, 1.22]), and LAA emptying velocity (OR 0.97 [0.96,0.99]) were observed; however, no significant associations were seen with LAA morphology or CHADS2-VASc score. CONCLUSIONS: BNP elevations in AF are associated with LAA size and function, but not CHADS2-VASc score or appendage morphology after accounting for changes in LAP.

Brain-type natriuretic peptide levels and invasive hemodynamic parameters in dialysis dependent patients.

BACKGROUND: Pulmonary hypertension (PH) is associated with increased mortality in patients with end-stage renal disease (ESRD). The prevalence of PH within ESRD as measured by right heart catheterization (RHC) is poorly described, and the correlation of BNP to pulmonary artery pressure (PAP) is unknown. METHODS: The renal transplant database at our center was used to identify adult ESRD patients from July 2013 to July 2015 who had a plasma BNP level measurement and invasive hemodynamic assessment by RHC within a 1-month period. Pulmonary hypertension was defined as a mean pulmonary artery pressure (PAP) ≥ 25 mmHg. Multivariate linear regression analysis was used to identify correlations between BNP and RHC parameters. To estimate the utility of BNP in the screening of PH, a receiver-operating characteristic (ROC) curve was generated. RESULTS: Eighty-eight patients were included in the study of which 43 had PH. Compared to patients without PH, BNP was significantly higher within the PH cohort (1619 ± 2602 pg/ml vs. 352 ± 491 pg/ml). A statistically significant association (r [86] = 0.60, p<0.001) between plasma BNP and mean PAP was identified. ROC curve indicated an acceptable predictive value of BNP in PH with a c-statistic of 0.800 (95% CI 0.708 - 0.892). CONCLUSIONS: In ESRD patients being considered for renal transplantation, PH is highly prevalent and BNP levels are elevated and significantly correlated with higher PAP. BNP may be a useful non-invasive marker of PH in these patients.

Prognostic Value of Combined Biomarkers in Patients With Heart Failure: The Heartmarker Score.

Background: Heart failure (HF) biomarkers have prognostic value. The aim of this study was to combine HF biomarkers into an objective classification system for risk stratification of patients with HF. Methods: HF biomarkers were analyzed in a population of HF outpatients and expressed relative to their cut-off values (N-terminal pro-B-type natriuretic peptide [NT-proBNP] >1,000 pg/mL, soluble suppression of tumorigenesis-2 [ST2] >35 ng/mL, growth differentiation factor-15 [GDF-15] >2,000 pg/mL, and fibroblast growth factor-23 [FGF-23] >95.4 pg/mL). Biomarkers that remained significant in multivariable analysis were combined to devise the Heartmarker score. The performance of the Heartmarker score was compared to the widely used New York Heart Association (NYHA) classification based on symptoms during ordinary activity. Results: HF biomarkers of 245 patients were analyzed, 45 (18%) of whom experienced the composite endpoint of HF hospitalization, appropriate implantable cardioverter-defibrillator shock, or death. HF biomarkers were elevated more often in patients that reached the composite endpoint than in patients that did not reach the endpoint. NT-proBNP, ST2, and GDF-15 were independent predictors of the composite endpoint and were thus combined as the Heartmarker score. The event-free survival and distance covered in 6 minutes of walking decreased with an increasing Heartmarker score. Compared with the NYHA classification, the Heartmarker score was better at discriminating between different risk classes and had a comparable relationship to functional capacity. Conclusions: The Heartmarker score is a reproducible and intuitive model for risk stratification of outpatients with HF, using routine biomarker measurements.

Predictive value of serum initial brain natriuretic peptide and troponin on functional prognosis in noncardiogenic patients with anterior and posterior circulation cerebral infarction.

BACKGROUND: Brain natriuretic peptide (BNP) and troponin have a close relationship with cardiogenic cerebral embolism (CCE), but their relationship with noncardiogenic patients with anterior circulation ischemia (ACI) and posterior circulation ischemia (PCI) is not clear. OBJECTIVE: To explore the predictive value of serum initial BNP and troponin on the functional prognosis of patients with noncardiogenic ACI and PCI. METHODS: Consecutive patients with first-episode cerebral infarction within 12 hours of symptom onset were enrolled in the present 1-year prospective cohort study. Serum levels of BNP and troponin were collected within 12 hours of onset. Infarction location was classified as ACI and PCI by magnetic resonance imaging (MRI). According to the modified Rankin Scale (mRS) score at 90 days after onset, ACI and PCI cases were respectively divided into a good prognosis group (mRS score between 0 and 2) and a poor prognosis group (mRS score between 3 and 6). The general state of health and results of laboratory examinations and other auxiliary examinations of all patients were recorded. Single-factor analysis and multivariate logistic regression analysis were used to assess the relationship between serum levels of BNP, troponin, and functional outcome. RESULTS: The multivariate logistic regression found that higher levels of initial BNP (odds ratio [OR] = 1.024; 95% confidence interval [CI]: 1.006-1.041; p = 0.007) and C-reactive protein (CRP) (OR = 1.184; 95%CI: 1.024-1.369; p = 0.022) were independent predictors of poor functional prognosis of noncardiogenic PCI at 90 days after onset after adjusting for age, gender, ethnicity, history of hypertension and of diabetes. CONCLUSIONS: The levels of initial BNP and CRP were related to poor functional outcomes in noncardiogenic PCI patients at 3 months, independent of troponin.

ANTECEDENTES: O peptídeo natriurético cerebral (BNP, na sigla em inglês) e a troponina estão intimamente relacionados com a embolia cerebral cardiogênica (CCE, na sigla em inglês), mas a relação com pacientes não cardioembólicos com isquemia de circulação anterior (ICA) e isquemia de circulação posterior (ICP) não é clara. OBJETIVO: Investigar o valor preditivo dos níveis séricos iniciais do BNP e da troponina no prognóstico de pacientes com AVC isquêmico não cardiogênico. MéTODOS: Os níveis séricos de BNP e de troponina foram recolhidos de pacientes com primeiro episódio de acidente vascular cerebral (AVC) isquêmico dentro de 12 horas após o início dos sintomas, com localização classificada como ICA e ICP de acordo com exame de ressonância magnética (RM). De acordo com a pontuação modificada da escala de Rankin (mRS), aos 90 dias após o início dos sintomas, ICA e ICP foram divididas respectivamente em um grupo de bom prognóstico (mRS entre 0 e2) e em um grupo de mau prognóstico (mRS entre 3 e 6). Foram registrados exames laboratoriais e outros exames complementares de todos os pacientes. Foram utilizadas análise fatorial única e análise de regressão logística multivariada para investigar a relação entre os níveis séricos de BNP e de troponina e o resultado funcional. RESULTADOS: A regressão logística multivariada evidenciou que os níveis mais altos de BNP inicial (odds ratio [OR] = 1,024, intervalo de confiança [IC] de 95%: 1,006­1,041; p = 0,007) e proteína C reativa (CRP, na sigla em inglês) (OR = 1,184; 95%CI: 1,024­1,369; p = 0,022) foram preditores independentes de mau prognóstico funcional da ICP não cardiogênica aos 90 dias após o início dos sintomas. CONCLUSõES: Os níveis iniciais de BNP e CRP se associaram a maus resultados funcionais em pacientes com ICP não cardiogênica aos três meses, independentemente da troponina.

Association between B-type natriuretic peptide and long-term mortality in patients with acute severe hypertension visiting the emergency department.

B-type natriuretic peptide (BNP) is a well-established prognostic factor for cardiovascular disorders. However, the association between BNP levels and mortality in patients with acute severe hypertension remains unclear. This study aimed to investigate the association between BNP levels and long-term mortality in patients with acute severe hypertension visiting the emergency department (ED). This retrospective study included patients aged ≥ 18 years who were admitted to the ED between 2016 and 2019 with acute severe hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg). Patients were categorized into tertiles according to BNP levels upon admission to the ED. Of the 3099 patients with acute severe hypertension, 6.4% in the first (lowest) tertile, 24.8% in the second tertile, and 44.4% in the third (highest) tertile of BNP died within 3-years. After adjusting for clinically relevant variables, patients in the second tertile of BNP (adjusted hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.96-3.55), and patients in the third tertile of BNP (adjusted HR 4.18; 95% CI, 3.09-5.64) had a significantly higher risk of 3-year all-cause mortality than those in the first tertile of BNP. Therefore, BNP may be valuable for the initial assessment to identify high-risk patients among those with acute severe hypertension.

BNP on Admission Combined with Imaging Markers of Multimodal CT to Predict the Risk of Cardioembolic Stroke.

Background: The aim of the study was to find the potential roles of B-type natriuretic peptide (BNP) and imaging markers on distinguishing cardioembolic (CE) stroke from non-CE stroke, so as to provide useful information for making individualized endovascular treatment (EVT) plan for the patients with acute ischemic stroke (AIS). Methods: The patients with unilateral anterior circulation large vessel occlusion who underwent EVT between March 2016 and December 2021 were analyzed in this study, retrospectively. The risk factors, laboratory test indicators, imaging parameters, and other factors were compared between the CE group and non-CE group. Logistic regression was used to analyze the risk factors of CE stroke. ROC curves were used to assess the values of different parameters on distinguishing CE stroke from non-CE stroke. The relationships between BNP and imaging parameters were assessed using the Spearman correlation analysis. Results: 160 patients were enrolled in the study and divided into the CE group (n = 66) and non-CE group (n = 94). BNP (odds ratio (OR) = 1.004; 95% CI, 1.001-1.009; p = 0.038), MMR (OR = 0.736; 95% CI, 0.573-0.945; p = 0.016), NIHSS (OR = 1.150; 95% CI, 1.022-1.294; p = 0.020), and AF (OR = 556.968; 95% CI, 51.739-5995.765; p < 0.001) were the independent predictive factors of CE stroke. The area under the curve (AUC) of BNP and mismatch ratio (MMR) were 0.846 (95% CI (0.780-0.898), p < 0.001) and 0.636 (95% CI (0.633-0.779), p < 0.001), respectively. The cut-off value of BNP was 249.23 pg/mL with the sensitivity of 74.24% and the specificity of 82.98%. BNP combined with MMR improved the predictive value for CE stroke. The AUC of the combination was 0.858 with the sensitivity of 84.85% and the specificity of 73.40%. BNP was correlated with 4D CTA collateral score, MMR, clot burden score, final infarct volume, infarct core volume, and ischemic penumbra volume (all, p < 0.05). Conclusion: BNP on admission combined with MMR is valuable for the risk prediction of CE stroke, which will promote the further screening of the high-risk patients with CE stroke and provide more diagnostic information for clinicians.

[Predictive value of plasma TMAO combined with NT-proBNP on the prognosis and length of hospitalization of patients with ischemic heart failure].

Objective: To explore the value of the assessment of plasma trimethylamine N-oxide (TMAO) combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) on predicting the all-cause mortality, length of hospitalization, and hospital cost in ischemic heart failure (IHF) patients. Methods: This prospective cohort study included 189 patients (157 males, mean age (64.0±10.5) years) with a left ventricular ejection fraction<45% caused by coronary artery disease, who hospitalized in our department from March 2016 to December 2020. Baseline data, including demographics, comorbid conditions and laboratory examination, were analyzed. The cumulative rate of all-cause mortality was evaluated using the Kaplan-Meier method and compared between the groups according to the log-rank test. Relative risks were reported as hazard ratios (HR) and 95% confidence interval (95%CI) calculated using the Cox proportional-hazards analysis, with stepwise adjustment for covariables. Spearman correlation analysis was then performed to determine the relationship between TMAO combined with NT-proBNP and length of hospitalization and hospital cost. Results: There were 50 patients in the low TMAO+low NT-proBNP group, 89 patients in high TMAO or high NT-proBNP group, 50 patients in high TMAO+high NT-proBNP group. The mean follow-up period was 3.0 years. Death occurred in 70 patients (37.0%), 27 patients (54.0%) in high TMAO+high NT-proBNP group, 29 patients (32.6%) in high TMAO or high NT-proBNP group and 14 patients (28.0%) in low TMAO+low NT-proBNP group. TMAO, in combination with NT-proBNP, improved all-cause mortality prediction in IHF patients when stratified as none, one or both biomarker(s) elevation, with the highest risk of all-cause mortality in high TMAO+high NT-proBNP group (HR=3.62, 95%CI 1.89-6.96, P<0.001). ROC curve analysis further confirmed that TMAO combined with NT-proBNP strengthened the prediction performance on the risk of all-cause death (AUC=0.727(95%CI 0.640-0.813), sensitivity 55.0%, characteristic 83.1%). Spearman correlation analysis showed that IHF patients with high TMAO and high NT-proBNP were positively associated with longer duration of hospitalization (r=0.191,P=0.009), but not associated with higher hospital cost (r=0.030, P=0.686). Conclusions: TMAO combined with NT-proBNP are valuable prediction tool on risk stratification of patients with IHF, and those with two biomarkers elevation face the highest risk of mortality during follow-up period, and are associated with the longer hospital stay.

Risk stratification of patients with cardiac sarcoidosis: the ILLUMINATE-CS registry.

AIMS: This study evaluated the prognosis and prognostic factors of patients with cardiac sarcoidosis (CS), an underdiagnosed disease. METHODS AND RESULTS: Patients from a retrospective multicentre registry, diagnosed with CS between 2001 and 2017 based on the 2016 Japanese Circulation Society or 2014 Heart Rhythm Society criteria, were included. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, and documented fatal ventricular arrhythmia events (FVAE), each constituting exploratory endpoints. Among 512 registered patients, 148 combined events (56 heart failure hospitalizations, 99 documented FVAE, and 49 all-cause deaths) were observed during a median follow-up of 1042 (interquartile range: 518-1917) days. The 10-year estimated event rates for the primary endpoint, all-cause death, heart failure hospitalizations, and FVAE were 48.1, 18.0, 21.1, and 31.9%, respectively. On multivariable Cox regression, a history of ventricular tachycardia (VT) or fibrillation [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.59-4.00, P < 0.001], log-transformed brain natriuretic peptide (BNP) levels (HR 1.28, 95% CI 1.07-1.53, P = 0.008), left ventricular ejection fraction (LVEF) (HR 0.94 per 5% increase, 95% CI 0.88-1.00, P = 0.046), and post-diagnosis radiofrequency ablation for VT (HR 2.65, 95% CI 1.02-6.86, P = 0.045) independently predicted the primary endpoint. CONCLUSION: Although mortality is relatively low in CS, adverse events are common, mainly due to FVAE. Patients with low LVEF, with high BNP levels, with VT/fibrillation history, and requiring ablation to treat VT are at high risk.

Study of the Role of Plasma NT-proBNP in the Diagnosis of Heart Failure.

BACKGROUND: The diagnosis of heart failure (HF) remains essentially clinical-Based. However, the history, physical examination, and chest radiograph findings are often inadequate in the diagnosis because multiple other conditions that affect the cardiopulmonary system mimic the symptoms of HF. N-terminal pro-BNP (NT-proBNP) has long been used for diagnosing HF. N-terminal pro-BNP values vary with different patient parameters. There is a scarcity of Indian studies on this topic. Especially with the use of newer drugs like angiotensin receptor neprilysin inhibitor (ARNI), it is important to have data from our own population on the same. AIMS AND OBJECTIVES: (i) To assess the role of NT-proBNP in the diagnosis of HF. (ii) Achieve diagnostic clarity in cases having cardiorespiratory symptoms and signs like acute onset dyspnea, pedal edema, and basal crepitations. (iii) To study the effect of various factors like age, body mass index (BMI), and creatinine on NT-proBNP. (iv) Establish a relation between NT-proBNP levels and left ventricular ejection fraction (LVEF), disease severity, and etiology of HF. MATERIALS AND METHODS: An observational prospective study of 50 patients presenting with acute onset breathlessness was carried out, fulfilling inclusion and exclusion criteria over a period of 10 months. Detailed history and examination of the patients were obtained. Venous sample for the measurement of NT-proBNP was collected within 24 hours of onset of symptoms. Other relevant blood and radiographic investigations were obtained. The NT-proBNP "cut-offs" set forth by the American Heart Association (AHA)/American College of Cardiology (ACC) were used to "rule in" or "rule out" HF. Two-dimensional echocardiography (2D Echo) was used to confirm the diagnosis. The correlation between NT-proBNP and various parameters like age, BMI, creatinine, and LVEF was obtained. Sensitivity and specificity tests were applied as well. RESULTS: Out of the 50 patients presenting with acute onset dyspnea, the most common cause was ischemic heart disease (IHD) (44%) followed by dilated cardiomyopathy (DCM) (32%), chronic obstructive pulmonary disease (COPD) (10%), anemia (4%), followed by other causes. The median NT-proBNP value was the highest for IHD patients (9485 pg/mL), followed by DCM (8969 pg/mL), followed by COPD (2846 pg/mL), and followed by anemia (850 pg/mL). There is a significant positive correlation between NT-proBNP and age (coefficient of correlation r = 0.4007, significance level p = 0.0389, and class interval = 0.137-0.61). There is a significant negative correlation between creatinine clearance and NT-proBNP (coefficient of correlation r = -0.372, significance level p = 0.007, and class interval = -0.58 to -0.105). There was significant negative correlation between LVEF and NT-proBNP (coefficient of correlation r = -0.36, significance level p = 0.009, and class interval = -0.58 to -0.09). Higher LVEF is associated with lower NT-proBNP values. There is marked heterogeneity in the values though. CONCLUSION: It is seen that the values of NT-proBNP vary with factors like age, BMI, and creatinine clearance in addition to LVEF. This may lead to falsely positive or falsely negative diagnosis of HF. With the above observations in mind, it can be concluded that NT-proBNP can help diagnose HF but only in addition to clinical findings.

[Troponin-T and n-terminal pro-brain type natriuretic peptide plasma levels and its relationship with mortality in COVID-19]. / Niveles plasmáticos de troponina T y de la fracción aminoterminal del propéptido natriurético cerebral y su relación con mortalidad en COVID-19.

INTRODUCTION: Cardiovascular compromise in coronavirus disease 2019 (COVID-19) does not necessarily present with the classic symptoms described in myocarditis. There is growing evidence demonstrating subclinical cardiovascular compromise in the context of the intense inflammation unleashed, the cytokine storm involved, the baseline prothrombotic state, and the consequent endothelial dysfunction. We set out to analyse whether Troponin-T (TT) and the amino-terminal fraction of pro-brain natriuretic peptide (NT-proBNP) determined at hospital admission, are related to mortality during the hospitalization of these patients. MATERIAL AND METHODS: Analytical, observational, retrospective cohort and cross-sectional study. It included subjects with COVID-19 hospitalized for moderate-severe illness, from 20/03/20 to 15/11/20. The TT and NT-proBNP obtained in the first 24 hours from admission were analysed. Altered TT was considered if ≥.014 ng/dl and altered NT-proBNP if ≥300 pg/ml. RESULTS: One hundred and eight subjects were included, 63.2% men, age 51.5 years (59-43), 28% were admitted to the Critical Unit and 25% died. The group with elevated TT presented higher mortality (OR = 3.1; 95%CI = 1.10-8.85; p = .02). The group with elevated NT-proBNP also show higher mortality (OR = 3.47; 95%CI = 1.21-9.97; p = .01). On multivariate analysis, only NT-proBNP ≥300 pg/ml remained an independent risk factor. CONCLUSIONS: NT-proBNP levels ≥300 pg/ml at admission in patients with moderate-severe COVID-19 were associated with higher mortality.

NT-proBNP Levels Following IVIG Treatment of Multisystem Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: N-terminal of probrain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels are often elevated in multisystem inflammatory syndrome in children (MIS-C) secondary to inflammation, myocardial dysfunction, or increased wall tension. Intravenous immunoglobulin (IVIG), accepted treatment of MIS-C, may transiently increase myocardial tension and contribute to an increase in NT-proBNP. We sought to study the association between pre- and post-IVIG levels of NT-proBNP and CRP and their clinical significance. METHODS: This single-center, retrospective, cohort study included consecutive children, aged ≤21 years, with diagnosis of MIS-C who received IVIG from April 2020 to October 2021. Data collection included clinical characteristics, laboratory tests, management, and outcomes. Study cohort consisted of patients who received IVIG and had NT-proBNP levels available pre- and post-IVIG. RESULTS: Among 35 patients with MIS-C, 30 met inclusion criteria. Twenty-four, 80%, showed elevation in NT-proBNP post-IVIG. The median NT-proBNP level pre-IVIG was 1921 pg/mL (interquartile range 548-3956), significantly lower than the post-IVIG median of 3756 pg/mL (interquartile range 1342-7634)) (P = .0010). The median pre-IVIG CRP level was significantly higher than the post-IVIG level (12 mg/dL vs 8 mg/dL, P = .0006). All but 1 recovered before discharge, and none had signs of worsening cardiac function post-IVIG. In those who recovered, NT-proBNP had normalized by discharge or 1-week follow-up. CONCLUSIONS: Our study shows that NT-proBNP levels often transiently increase immediately after IVIG therapy without signs of worsening myocardial function. These values should be interpreted in the context of CRP levels and clinical recovery.

Circulating Biomarkers Predict Symptomatic but Not Asymptomatic Carotid Artery Stenosis.

BACKGROUND: Subjects exposed to risk factors such as age, gender, hypertension, diabetes mellitus, and smoking are prone to atherosclerotic events. AIMS: The main aim of this longitudinal cohort study was to determine whether the role of novel plasma biomarkers for atherosclerotic carotid artery disease is different in subjects developing symptomatic carotid artery stenosis (CAS), as opposed to those with incident asymptomatic CAS. METHODS: The following biomarkers were measured in 5,550 middle-aged subjects in a population-based cohort study: C-reactive protein (CRP), lipoprotein-associated phospholipase A2 mass and activity, proneurotensin, midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT pro-BNP), copeptin, and cystatin C. After exclusion of those with prevalent CAS, subjects were thereafter followed in national patient registers for 23.4 (interquartile range 19.5-24.3) years regarding incident symptomatic and asymptomatic CAS. RESULTS: Among 110 patients with confirmed incident CAS, 56 were symptomatic and 54 were asymptomatic. When including conventional risk markers in a Cox regression analysis, NT pro-BNP (hazard ratio [HR] 1.59; 95% confidence interval [CI]: 1.20-2.11), MR-proADM (HR 1.40; CI: 1.13-1.73), cystatin C (HR 1.21; CI: 1.02-1.43), and CRP (HR 1.53; CI: 1.13-1.73) were independently associated with incident symptomatic CAS, whereas no plasma biomarker was associated with incident asymptomatic CAS. CONCLUSION: Plasma biomarkers NT pro-BNP, MR-proADM, cystatin C, and CRP were independently associated with incident symptomatic CAS, whereas no such association could be demonstrated with incident asymptomatic CAS. As these biomarkers indicate future development of clinically relevant atherosclerotic CAS, their potential utility in relation to intensified preventive measures and selection of potential candidates for carotid surgery should be further evaluated.

Relationship Between Serum Brain-Type Natriuretic Peptide and Biomarkers of Growth in Infants With Shunt-Dependent Single Cardiac Ventricle.

For infants with shunt-dependent or ductal-dependent single ventricle heart disease, poor growth is common and associated with morbidity and impaired neurodevelopmental outcomes. Although attention has focused on nutrition to promote weight gain, little is known about the relation between heart failure and growth factors. A prospective observational pilot study was performed to assess the relation between heart failure, assessed by brain natriuretic peptide (BNP), and growth factors (insulin-like growth factor 1 [IGF-1] and insulin-like growth factor-binding protein 3) at 3 visits: (1) before discharge from neonatal intervention with the establishment of stable pulmonary blood flow, (2) immediately before superior cavopulmonary connection, and (3) before discharge after superior cavopulmonary connection operation. The relation between BNP and growth factors was analyzed using Spearman pairwise correlations at each visit and modeled over time with a linear mixed-effects model. Correlations were considered worthy of further exploration using a p <0.10, given the exploratory nature of the study. The study included 38 infants (66% male, 68% hypoplastic left heart syndrome). Median BNP was elevated at visit 1 and decreased over time (287 pg/dl [interquartile range 147 to 794], 85 pg/dl [52 to 183], and 90 pg/dl [70 to 138]). Median IGF-1 Z score was <0 at each visit but increased over time (-0.9 [interquartile range -1.1 to 0.1], -0.7 [-1.2 to 0.1], and -0.5 [-1.2 to 0]). Inverse correlations were found between BNP and IGF-1 at visit 1 (r = -0.40, p = 0.097), BNP and IGF-1 and insulin-like growth factor-binding protein 3 at visit 2 (r = -0.33, p = 0.080 and r = -0.33, p = 0.085, respectively) and BNP and IGF-1 Z score at visit 3 (r = -0.42, p = 0.049). Significant relations were likewise found between the change in BNP and the change in IGF-1 between visits 1 and 3 (p = 0.046) and between visits 2 and 3 (p = 0.048). In conclusion, this pilot study demonstrates an inverse correlation between BNP and growth factors, suggesting that the heart failure state associated with this physiology may play a mechanistic role in impaired growth.