Early Initiation of Sacubitril/Valsartan in Patients With Acute Heart Failure and Renal Dysfunction: An Analysis of the TRANSITION Study.

BACKGROUND: Treatment of patients with heart failure with reduced ejection fraction (HFrEF) and renal dysfunction (RD) is challenging owing to the risk of further deterioration in renal function, especially after acute decompensated HF (ADHF). METHODS AND RESULTS: We assessed the effect of RD (estimated glomerular filtration rate of ≥30 to <60 mL/min/1.73 m2) on initiation, up-titration, and tolerability of sacubitril/valsartan in hemodynamically stabilized patients with HFrEF admitted for ADHF (RD, n = 476; non-RD, n = 483). At week 10, the target dose of sacubitril/valsartan (97/103 mg twice daily) was achieved by 42% patients in RD subgroup vs 54% in non-RD patients (P < .001). Sacubitril/valsartan was associated with greater estimated glomerular filtration rate improvements in RD subgroup than non-RD (change from baseline least squares mean 4.1 mL/min/1.73 m2, 95% confidence interval 2.2-6.1, P < .001). Cardiac biomarkers improved significantly in both subgroups; however, compared with the RD subgroup, the improvement was greater in those without RD (N-terminal pro-brain natriuretic peptide, -28.6% vs -44.8%, high-sensitivity troponin T -20.3% vs -33.9%) (P < .001). Patients in the RD subgroup compared with those without RD experienced higher rates of hyperkalemia (16.3% vs 6.5%, P < .001), investigator-reported cardiac failure (9.7% vs 5.6%, P = .029), and renal impairment (6.4% vs 2.1%, P = .002). CONCLUSIONS: Most patients with HFrEF and concomitant RD hospitalized for ADHF tolerated early initiation of sacubitril/valsartan and showed significant improvements in estimated glomerular filtration rate and cardiac biomarkers. CLINICAL TRIAL REGISTRATION: NCT02661217.

The relative and combined ability of stress hyperglycemia ratio and N-terminal pro-B-type natriuretic peptide to predict all-cause mortality in diabetic patients with multivessel coronary artery disease.

BACKGROUND: Stress hyperglycemia ratio (SHR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased mortality risk in diabetic patients with coronary artery disease (CAD). However, the role of these biomarkers in patients with diabetes and multivessel disease (MVD) remains unknown. The present study aimed to assess the relative and combined abilities of these biomarkers to predict all-cause mortality in patients with diabetes and MVD. METHODS: This study included 1148 diabetic patients with MVD who underwent coronary angiography at Tianjin Chest Hospital between January 2016 and December 2016. The patients were divided into four groups according to their SHR (SHR-L and SHR-H) and NT-proBNP (NT-proBNP-L and NT-proBNP-H) levels. The primary outcome was all-cause mortality. Multivariate Cox regression analyses were performed to evaluate the association of SHR and NT-proBNP levels with all-cause mortality. RESULTS: During a mean 4.2 year follow-up, 138 patients died. Multivariate analysis showed that SHR and NT-proBNP were strong independent predictors of all-cause mortality in diabetic patients with MVD (SHR: HR hazard ratio [2.171; 95%CI 1.566-3.008; P < 0.001; NT-proBNP: HR: 1.005; 95%CI 1.001-1.009; P = 0.009). Compared to patients in the first (SHR-L and NT-proBNP-L) group, patients in the fourth (SHR-H and NT-proBNP-H) group had the highest mortality risk (HR: 12.244; 95%CI 5.828-25.721; P < 0.001). The areas under the curve were 0.615(SHR) and 0.699(NT-proBNP) for all-cause mortality. Adding either marker to the original models significantly improved the C-statistic and integrated discrimination improvement values (all P < 0.05). Moreover, combining SHR and NT-proBNP levels into the original model provided maximal prognostic information. CONCLUSIONS: SHR and NT-proBNP independently and jointly predicted all-cause mortality in diabetic patients with MVD, suggesting that strategies to improve risk stratification in these patients should incorporate SHR and NT-porBNP into risk algorithms.

Serum N-Terminal Pro-B-Type Natriuretic Peptide Level is Negatively Associated with Vascular Reactivity Index by Digital Thermal Monitoring in Patients with Hypertension.

Background: B-type natriuretic peptide (BNP) coordinates endothelial homeostasis and remodeling, with endothelial dysfunction associated with cardiovascular mortality in the general population without heart failure. The objective of this study was to investigate the correlation between serum N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels and endothelial dysfunction among patients diagnosed with hypertension. Methods: This cross-sectional, single-center study included 90 patients with hypertension. An electrochemiluminescence immunoassay measured NT-pro-BNP levels, and a digital thermal monitoring device calculated a vascular reactivity index (VRI) as a measurement for endothelial function. In this study, VRI < 1.0 denoted poor vascular reactivity, 1.0 ≤ VRI < 2.0 indicated intermediate vascular reactivity, and a VRI ≥ 2.0 suggested good vascular reactivity. Results: Out of all the hypertensive patients, eight (8.9%) displayed poor vascular reactivity (VRI < 1.0), while 39 (43.3%) exhibited intermediate vascular reactivity (1.0 ≤ VRI < 2.0), leaving the remaining 43 patients demonstrating good vascular reactivity. Older age (p = 0.012) and elevated serum NT-pro-BNP levels (p < 0.001) were found to be associated with poorer vascular reactivity. Older age (r = -0.221, p = 0.036) and log-transformed serum levels of NT-pro-BNP (log-NT-pro-BNP, r = -0.505, p < 0.001) exhibited a negative correlation with VRI values in patients with hypertension. Following a multivariate linear regression test, serum log-NT-pro-BNP level ( ß = -0.505, adjusted R 2 change = 0.246, p < 0.001) emerged as being significantly and independently associated with VRI values among hypertensive patients. Conclusions: In patients with hypertension, there was a negative association observed between serum log-NT-pro-BNP levels and endothelial dysfunction determined by VRI values.

Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study.

AIMS: Different disease processes can combine to cause atrial fibrillation (AF). Their contribution to recurrent AF after ablation in patients is not known. Cardiovascular processes associated with recurrent AF after AF ablation were determined by quantifying biomolecules related to inflammation, metabolism, proliferation, fibrosis, shear stress, atrial pressure, and others in the AXAFA biomolecule study. METHODS AND RESULTS: Twelve circulating cardiovascular biomolecules (ANGPT2, BMP10, CA125, hsCRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NT-proBNP, and hsTnT) were quantified in plasma samples obtained prior to a first AF ablation using high-throughput, high-precision assays. Cox regression was used to identify biomolecules associated with recurrent AF during the first 3 months after AF ablation. In 433 patients (64 years [58, 70]; 33% women), baseline concentrations of ANGPT2, BMP10, hsCRP, FGF23, FABP3, GDF15, and NT-proBNP were elevated in patients with recurrent AF (120/433; 28%). After adjustment for 11 clinical features and randomized treatment, elevated NT-proBNP [hazard ratio (HR) 1.58, 95% confidence interval (1.29, 1.94)], ANGPT2 [HR 1.37, (1.12, 1.67)], and BMP10 [HR 1.24 (1.02, 1.51)] remained associated with recurrent AF. Concentrations of ANGPT2, BMP10, and NT-proBNP decreased in patients who remained arrhythmia free, but not in patients with recurrent AF, highlighting their connection to AF. The other eight biomarkers showed unchanged concentrations. CONCLUSION: Elevated concentrations of ANGPT2, BMP10, and NT-proBNP are associated with recurrent AF after a first AF ablation, suggesting that processes linked to disturbed cardiomyocyte metabolism, altered atrial shear stress, and increased load contribute to AF after AF ablation in patients.

Development of an SI-traceable N-terminal pro-B-type natriuretic peptide certified reference material using structure-based impurity-corrected isotope dilution mass spectrometry approaches.

N-Terminal pro-B-type natriuretic peptide (NT-proBNP) is a pivotal biomarker for the diagnosis and prognosis of heart failure (HF). However, no SI-traceable certified reference material (CRM) or reference measurement procedure (RMP) is available for this biomarker, and so clinical testing results obtained in different laboratories cannot be traced to a higher-order standard, leading to incomparable measurements. Protein hydrolysis and protein cleavage isotope dilution mass spectrometry (AAA-IDMS and PepA-IDMS) were used to develop a CRM. Structurally related impurities were identified by high-resolution mass spectrometry. The quantitative AAA-IDMS results were corrected according to the amino acid compositions of the impurities. Using PepA-IDMS, two peptides from the proteolyzed product were confirmed as signature peptides. To obtain traceable and accurate results, the signature peptides were quantified using impurity-corrected AAA-IDMS. The candidate NT-proBNP solution was denatured and enzymatically digested using the Glu-C endoproteinase. The released signature peptides were measured using an isotopic dilution approach. The homogeneity and stability of the candidate CRM were characterized, and their uncertainties were combined with the value assignment process. The developed CRM can be considered a unique SI-traceable NT-proBNP reference material and is expected to be used as a primary calibrator for matrix NT-proBNP CRM development.

Brain natriuretic peptide as a predictive marker of mortality in sepsis: an updated systematic review and meta-analysis.

INTRODUCTION: Early identification of patients with sepsis at high risk of death remains a challenge, and whether brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a prognostic effect on patients with sepsis is controversial. Here, we clarified the prognostic value of BNP and NT-proBNP and sought to establish suitable cutoff values and intervals. METHODS: We searched five databases to identify studies that met the inclusion criteria. The primary outcomes were the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and corresponding 95% credible interval (95% CI) of BNP and NT-proBNP. The secondary outcomes were the sensitivity and specificity of BNP or NT-proBNP in subgroup analyses. RESULTS: Forty-seven studies were included in our meta-analysis. The pooled sensitivity of NT-proBNP (0.77 [0.68, 0.84]) was weaker than that of BNP (0.82 [0.76, 0.87]), the pooled specificity of NT-proBNP (0.70 [0.60, 0.77]) was less than that of BNP (0.77 [0.71, 0.82]), and the AUC of BNP (0.87 [0.83-0.89]) was greater than that of NT-proBNP (0.80 (0.76-0.83]). The results of the subgroup analysis showed that the cutoff range of 400-800 pg/mL for BNP had high sensitivity (0.86 [0.74-0.98]) and specificity (0.87 [0.81-0.93]) and was probably the most appropriate cutoff range. CONCLUSIONS: Elevated levels of BNP and NT-proBNP were significantly related to the mortality of patients with sepsis and had a moderate prognostic value in predicting the mortality of patients with sepsis. In addition, our meta-analysis preliminarily established appropriate cutoff values for BNP and NT-proBNP.

A non-invasive nomogram for predicting heart failure with preserved ejection fraction in taiwanese outpatients with unexplained dyspnea and fatigue.

BACKGROUND: While Reddy proposed the H2FPEF diagnostic algorithm to aid in diagnosing heart failure with preserved ejection fraction (HFpEF), certain parameters like age and obesity are not suitable for Asian population, especially given the increasing incidence of HFpEF in younger individuals. Therefore, this study aimed to develop an easy-to-use nomogram with non-invasive indices that can be used in outpatient clinics in Taiwan to quickly estimate the probability of HFpEF and help decide whether further invasive cardiopulmonary exercise test (CPET) is needed. METHODS: Outpatients with unexplained dyspnea and fatigue were recruited divided into HFpEF (n = 64) and non-HFpEF (n = 34) groups based on invasive CPET and echocardiography. Multivariate logistic regression analyses identified independent noninvasive variables for developing an HFpEF nomogram. The nomogram's performance was assessed and validated using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS: Multivariate logistic regression analyses identified five independent noninvasive variables for developing an HFpEF nomogram, including dyslipidemia (OR = 5.264, p = 0.010), diabetes (OR = 3.929, p = 0.050), left atrial area (OR = 1.130, p = 0.046), hemoglobin <13 g/dL (OR = 5.372, p = 0.010), and NT-proBNP ≥245 pg/mL (OR = 5.108, p = 0.027). The nomogram showed good discriminatory ability (C-index = 0.842) and calibration performance (p = 0.873) and high net benefit (0.1-0.95). Notably, the HFpEF nomogram showed better diagnostic accuracy than the H2FPEF score model in predicting Taiwanese HFpEF patients (AUC: 0.873 vs. 0.608, p = 0.0006). CONCLUSION: The noninvasive HFpEF nomogram provides a preliminary estimation of the probability of HFpEF in Taiwanese outpatients with unexplained dyspnea and fatigue, which may help the decision-making on further invasive CPET.

Carcinoid Heart Disease Management: A Multi-Disciplinary Collaboration.

Carcinoid heart disease (CaHD) is an important complication among patients with metastatic neuroendocrine tumors and carcinoid syndrome (CS). CS patients (25%-65%) eventually develop CaHD; these patients face a significantly increased risk of morbidity and mortality. Guidance papers (eg, clinical practice guidelines, consensus guidelines, and expert statements) have been established by major organizations across the disciplines of cardiology and oncology; however, these recommendations are not routinely implemented. The aim of this article is to encourage the integration of current recommendations from national societies into clinical practice. Early screening upon recognition of CS and prior to the development of CaHD symptoms is paramount, as no existing therapies are approved to reverse the fibrotic damage to the heart once it occurs. Valvular replacement is the only definitive treatment for CaHD once it has developed. When patients are noted to have urinary 5-hydroxyindoleacetic acid (5-HIAA) levels ≥300 µmol/24 h and/or serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels >260 pg/mL, echocardiography is recommended. Systemic approaches to control tumor growth and hormonal secretion include somatostatin analogs (SSAs), followed by options including peptide receptor radiotherapy (PRRT), everolimus and liver embolization. Telotristat is the primary choice for control of diarrhea refractory to SSA. Diuretics are the mainstay of heart failure symptom management for patients who develop CaHD. Considerations for future research are discussed, including the ongoing TELEHEART (TELotristat Ethyl in a HEART biomarker study) trial involving telotristat and not yet activated CHARRT (Carcinoid Heart disease And peptide Receptor Radiotargetted Therapy) study involving PRRT with lutetium 177 (177Lu) dotatate.

Relationship between the circulating N-terminal pro B-type natriuretic peptide and the risk of carotid artery plaque in different glucose metabolic states in patients with coronary heart disease: a CSCD-TCM plus study in China.

OBJECTIVE: Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) is a marker for heart failure in patients with coronary heart disease (CHD) and associated with glycemic abnormalities. Studies on the association and diagnostic value of NT-proBNP in carotid plaques (CAP) in patients with CHD are limited. METHODS: The relationships between NT-proBNP and the risk of CAP in different glucose metabolic states, sexes, and age categories were also examined using 5,093 patients diagnosed with CHD. The NT-proBNP tertiles were used to divide patients into three groups in which the NT-proBNP levels, blood glucose levels, the occurrence of CAP, and the number and nature of CAP were measured using normoglycemic (NG), prediabetes (Pre-DM), and diabetes mellitus (DM) glucose metabolic statuses. Logistic regression analyses were used to compare the relationship between NT-proBNP and the risk of CAP occurrence and the number and nature of CAP. The diagnostic value of NT-proBNP for CAP risk was measured using receiver operating characteristic (ROC) curves. RESULTS: We found a 37% relative increase in the correlation between changes in NT-proBNP per standard deviation (SD) and the incidence of CAP. After adjusting for potential confounders, NT-proBNP at the T3 level was found to be associated with an increased CAP odds ratio (OR) when T1 was used as the reference. This relationship was also present in males, patients aged > 60 years, or both pre-DM and DM states. NT-proBNP was more likely to present as hypoechoic plaques at T1 and as mixed plaques at T3. We also measured the diagnostic accuracy of CAP for NT-proBNP in patients with CHD, with an AUC value of 0.627(95% CI 0.592-0.631), sensitivity of 50.7%, and specificity of 68.0%. CONCLUSION: An increase in NT-proBNP was significantly associated with the risk of CAP in patients with CHD, especially in males and patients aged > 60 years, and exhibited specific characteristics under different glucose metabolism states. Trial registration The study was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (Approval number TJUTCM-EC20210007) and certified by the Chinese Clinical Trials Registry on April 4, 2022 (Registration number ChiCTR2200058296) and March 25, 2022 by ClinicalTrials.gov (registration number NCT05309343).

Risk prediction of atrial fibrillation and its complications in the community using hs troponin I.

AIMS: Atrial fibrillation (AF) is becoming increasingly common. Traditional cardiovascular risk factors (CVRF) do not explain all AF cases. Blood-based biomarkers reflecting cardiac injury such as high-sensitivity troponin I (hsTnI) may help close this gap. METHODS: We investigated the predictive ability of hsTnI for incident AF in 45,298 participants (median age 51.4 years, 45.0% men) across European community cohorts in comparison to CVRF and established biomarkers (C-reactive protein, N-terminal pro B-type natriuretic peptide). RESULTS: During a median follow-up of 7.7 years, 1734 (3.8%) participants developed AF. Those in the highest hsTnI quarter (≥4.2 ng/L) had a 3.91-fold (95% confidence interval (CI) 3.30, 4.63; p < .01) risk for developing AF compared to the lowest quarter (<1.4 ng/L). In multivariable-adjusted Cox proportional hazards models a statistically significant association was seen between hsTnI and AF (hazard ratio (HR) per 1 standard deviation (SD) increase in log10(hsTnI) 1.08; 95% CI 1.01, 1.16; p = .03). Inclusion of hsTnI did improve model discrimination (C-index CVRF 0.811 vs. C-index CVRF and hsTnI 0.813; p < .01). Higher hsTnI concentrations were associated with heart failure (HR per SD 1.37; 95% CI 1.12, 1.68; p < .01) and overall mortality (HR per SD 1.24; 95% CI 1.09, 1.41; p < .01). CONCLUSION: hsTnI as a biomarker of myocardial injury does not improve prediction of AF incidence beyond classical CVRF and NT-proBNP. However, it is associated with the AF-related disease heart failure and mortality likely reflecting underlying subclinical cardiovascular impairment.

Predictive Value of N-Terminal Pro B-Type Natriuretic Peptide for Contrast-Induced Nephropathy Non-Recovery and Poor Outcomes Among Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Contrast-induced nephropathy (CIN) is a frequent complication in patients undergoing percutaneous coronary intervention (PCI). The degree of recovery of renal function from CIN may affect long-term prognosis. N-terminal pro B-type natriuretic peptide (NT-proBNP) is a simple but useful biomarker for predicting CIN. However, the predictive value of preprocedural NT-proBNP for CIN non-recovery and long-term outcomes in patients undergoing PCI remains unclear.Methods and Results: This study prospectively enrolled 550 patients with CIN after PCI between January 2012 and December 2018. CIN non-recovery was defined as persistent serum creatinine >25% or 0.5 mg/dL over baseline from 1 week to 12 months after PCI in patients who developed CIN. CIN non-recovery was observed in 40 (7.3%) patients. Receiver operating characteristic analysis indicated that the best NT-proBNP cut-off value for detecting CIN non-recovery was 876.1 pg/mL (area under the curve 0.768; 95% confidence interval [CI] 0.731-0.803). After adjusting for potential confounders, multivariable analysis indicated that NT-proBNP >876.1 pg/mL was an independent predictor of CIN non-recovery (odds ratio 1.94; 95% CI 1.03-3.75; P=0.0042). Kaplan-Meier curves showed higher rates of long-term mortality among patients with CIN non-recovery than those with CIN recovery (Chi-squared=14.183, log-rank P=0.0002). CONCLUSIONS: Preprocedural NT-proBNP was associated with CIN non-recovery among patients undergoing PCI. The optimal cut-off value for NT-proBNP to predict CIN non-recovery was 876.1 pg/mL.

Cardiac Troponin T and NT-proBNP for Prediction of 30-Day Readmission or Death in Patients with Acute Dyspnea: Data from the Akershus Cardiac Examination 2 Study.

INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) measurements are recommended in patients with acute dyspnea. We aimed to assess the prognostic merit of cTnT compared to NT-proBNP for 30-day readmission or death in patients hospitalized with acute dyspnea. METHODS: We measured cTnT and NT-proBNP within 24 h in 314 patients hospitalized with acute dyspnea and adjudicated the cause of the index admission. Time to first event of readmission or death ≤30 days after hospital discharge was recorded, and cTnT and NT-proBNP measurements were compared head-to-head. RESULTS: Patients who died (12/314) or were readmitted (71/314) within 30 days had higher cTnT concentrations (median: 32.6, Q1-Q3: 18.4-74.2 ng/L vs. median: 19.4, Q1-Q3: 8.4-36.1 ng/L; p for comparison <0.001) and NT-proBNP concentrations (median: 1,753.6, Q1-Q3: 464.2-6,862.0 ng/L vs. median 984, Q1-Q3 201-3,600 ng/L; for comparison p = 0.027) compared to patients who survived and were not readmitted. cTnT concentrations were associated with readmission or death within 30 days after discharge both in the total cohort (adjusted hazard ratio [aHR]: 1.64, 95% confidence interval [CI]: 1.30-2.05) and in patients with heart failure (HF) (aHR: 1.58, 95% CI: 1.14-2.18). In contrast, NT-proBNP concentrations were not associated with short-term events, neither in the total cohort (aHR: 1.10, 95% CI: 0.94-1.30) nor in patients with adjudicated HF (aHR: 1.06, 95% CI: 0.80-1.40). CONCLUSION: cTnT concentrations are associated with 30-day readmission or death in patients hospitalized with acute dyspnea, as well as in patients adjudicated HF.

The efficacy and safety of sacubitril/valsartan in heart failure with reduced ejection fraction patients with hypotension.

Despite previous studies showing that patients with low systolic blood pressure (sBP) in heart failure with reduced ejection fraction (HFrEF) has a poor prognosis, it has few treatment options. This study aimed to investigate the efficacy and safety of sacubitril/valsartan (S/V) in HFrEF patients with hypotension. We included 43 consecutive HFrEF patients with sBP < 100 mmHg despite guideline-directed medical therapy for at least 3 months and who received S/V between September 2020 and July 2021. Patients admitted for acute heart failure were excluded and 29 patients were evaluated for safety endpoints. Furthermore, patients who performed non-pharmacological therapy or died within 1 month were excluded, finally, 25 patients were evaluated for efficacy endpoints. The mean initial S/V dose was 53.0 ± 20.5 mg/day and the mean dosage was increased to 84.0 ± 34.5 mg/day in 1 month. Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values significantly decreased from 2200 [interquartile range (IQR): 1462-3666] pg/ml to 1409 (IQR: 964-2451) pg/ml. (p < 0.0001). No significant change in sBP occurred (pre-sBP: 93.2 ± 4.9 mmHg, post-sBP: 93.4 ± 9.6 mmHg, p = 0.91), and no patients discontinued the S/V due to symptomatic hypotension in 1 month after S/V initiation. S/V can be safely introduced in HFrEF patients with hypotension to reduce serum NT-proBNP values. Thus, S/V may be useful for the treatment of HFrEF patients with hypotension.

Use of Preoperative Natriuretic Peptide in Predicting Mortality After Coronary Artery Bypass Grafting: A Systematic Review and Meta-analysis.

The objective of this systematic review was to evaluate the current evidence on the utility of preoperative B-type natriuretic peptide (BNP) and N-terminal-pro B-type natriuretic peptide (NT-proBNP) in predicting short-term and long-term mortality after coronary artery bypass grafting (CABG). OVID MEDLINE, EMBASE, SCOPUS, and PUBMED were searched from 1946 to August 2022 using the following terms: "coronary artery bypass grafting" and "BNP" and "outcomes." Eligible studies included observational studies reporting the association between preoperative BNP and NT-proBNP levels and short- and long-term mortality after CABG. Articles were selected systematically, assessed for bias, and, when possible, meta-analyzed using a random effect model. After retrieving 53 articles, 11 were included for qualitative synthesis and 4 for quantitative meta-analysis. Studies included in this review showed that elevated preoperative natriuretic peptide levels, despite variable cut-offs, have been consistently shown to be associated with short- and long-term mortality after CABG. The median BNP cut-off value was 145.5 pg/mL (25th-75th percentile 95-324.25 pg/mL), and the mean NT-proBNP value was 765 ± 372 pg/mL. Compared to patients with normal natriuretic peptide levels, patients with elevated BNP and NT-proBNP presented higher mortality rates after CABG (odds ratio 3.96, 95% confidence interval 2.41-6.52; p < 0.00001). Preoperative BNP level is a powerful predictor of mortality in patients undergoing CABG. The measurement of BNP can add significant value to these patients' risk stratification and therapeutic decision-making.

Can biomarkers predict myocardial iron overload in children with thalassemia major?

AIM: Beta-thalassemia major requires regular blood transfusions throughout life, which in turn leads to iron accumulation in the body. While cardiac T2* MRI is the gold standard in determining cardiac iron accumulation, it is not always feasible, which has led to the search for new biomarkers. Herein, the value of growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide in predicting cardiac iron accumulation is investigated in asymptomatic children with beta-thalassemia major. MATERIALS AND METHOD: Forty-one patients aged 11-21 years and 41 age-, gender-, body mass index-matched healthy controls were included. Serum growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were compared between the patients and controls. Additionally, the relations of these biomarkers with cardiac and liver T2 * MRI were investigated in the patients. RESULTS: In the patients, growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were higher than healthy controls (p < 0.001, p = 0.025, p < 0.001, respectively). There were no significant correlations of growth differentiation factor-15 and N-terminal pro-B-type natriuretic peptide levels with both cardiac and liver T2 * MRI measurements. While there was no significant correlation of serum galectin-3 with cardiac T2 * MRI measurements, a negative correlation was found with liver T2 * MRI measurements (p = 0.040, rho = -0.325). CONCLUSION: All three biomarkers investigated in this study failed to predict myocardial iron accumulation in asymptomatic children with beta-thalassemia major. However, a weak relation between serum galectin-3 level and hepatic iron accumulation was demonstrated.

Is COPD the Determinant Factor for Myocardial Injury and Cardiac Wall Stress in OSA Patients?

Background and Objectives: Evidence shows that COPD-OSA overlap syndrome (OS) is more frequently accompanied by cardiovascular disease (CVD) in comparison to either disease alone. The aim of the study was to explore whether patients with OS have a higher burden of subclinical myocardial injury and wall stress compared with OSA patients. Materials and Methods: Consecutive patients, without established CVD, underwent polysomnography and pulmonary function testing, due to suspected sleep-disordered breathing. An equal number of patients with OS (n = 53, with an apnea hypopnea index (AHI) > 5/h and FEV1/FVC < 0.7) and patients with OSA (n = 53, AHI > 5/h and FEV1/FVC > 0.7) were included in the study. The detection of asymptomatic myocardial injury and wall stress was performed via the assessment of serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), respectively. Results: OS patients were older (p < 0.001) and had worse hypoxemic parameters, namely average oxyhemoglobin saturation (SpO2) (p = 0.002) and time spent with SpO2 < 90% (p = 0.003) during sleep as well as daytime pO2 (p < 0.001), than patients with OSA. No difference was observed between groups in terms of Epworth Sleepiness Scale (p = 0.432) and AHI (p = 0.587). Both levels of hs-cTnT (14.2 (9.1-20.2) vs. 6.5 (5.6-8.7) pg/mL, p < 0.001) and NT-proBNP (93.1 (37.9-182.5) vs. 19.2 (8.3-35.4) pg/mL, p < 0.001) were increased in OS compared to OSA patients. Upon multivariate linear regression analysis, levels of NT-proBNP and hs-cTnT correlated with age and average SpO2 during sleep. Conclusions: Our study demonstrated higher levels of hs-cTnT and NT-proBNP in OS patients, indicating an increased probability of subclinical myocardial injury and wall stress, compared with OSA individuals.

The Ratio of Urine N-Terminal Pro B-Type Natriuretic Peptide to Cyclic Guanosine Monophosphate Predicts Emergency Department Visits for Heart Failure.

INTRODUCTION: Emergency department (ED) visits for decompensated heart failure (HF) are frequent and associated with poor long-term outcomes. Plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) and cyclic guanosine monophosphate (cGMP) are used in diagnosis and prognosis of HF patients, while clinical values of urine NT-proBNP/cGMP ratio have been rarely explored. This study aims to compare the predictive values of urine NT-proBNP/cGMP ratio versus plasma NT-proBNP for ED visits for decompensated HF. METHODS: This prospective study included 126 HF patients with reduced left ventricular ejection fraction (<50%) and without chronic kidney disease. Baseline data included demographics, co-morbidities, and co-medications. Medical records were used to determine the incidence of ED visits for decompensated HF during the 3 months following the last visit. RESULTS: Patients with subsequent ED visits had significantly higher levels of plasma and urine NT-proBNP and urine cGMP in than those without. Multivariate Cox regression analysis disclosed that Lg10urine NT-proBNP/cGMP was an independent risk factor for subsequent ED visits (OR = 3.267; 95% CI: 1.105-9.663; p = 0.032). ROC analysis revealed an Lg10urine NT-proBNP/cGMP ratio optimal cut-off value of 0.1706 (AUC, 0.700; 95% CI: 0.543-0.857; p = 0.036) for predicting subsequent HF-related ED visits. CONCLUSION: A single measurement of urinary NT-proBNP/cGMP ratio is predictive of subsequent ED visits for decompensated HF. This noninvasive and easy measurement may be a clinically useful tool for identifying a subset of patients at higher risk of ED visits.

Subclinical cardiovascular disease and frailty risk: the atherosclerosis risk in communities study.

BACKGROUND: Cardiovascular disease (CVD) is associated with a greater frailty risk, but it remains unknown if pathways that contribute to CVD are associated with the frailty risk. Thus, we aimed to investigate whether elevations in high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for those without known CVD at baseline are associated with a higher frailty risk. METHODS: This study used data from the Atherosclerosis Risk in Communities study. Cardiac biomarkers were measured from stored plasma samples collected at Visit 2 (1991-1993). Frailty was recorded at Visit 5 (2011-2013). Cox regression models were used to determine the association of cardiac biomarkers with frailty risk. RESULTS: Overall, 360/5199 (6.9%) participants aged 55.1 ± 5.1 years developed frailty during a median follow-up of 21.7 years. The incidence of frailty was significantly higher in participants with hs-cTnT ≥14 ng/L (vs. < 14 ng/L: 17.9% vs. 6.7%) or NT-proBNP ≥300 pg/ml (vs. < 300 pg/ml: 19.7% vs. 6.8%) (all P < 0.001). Comparing higher vs. lower cut-off levels of either hs-cTnT (14 ng/l) or NT-proBNP (300 pg/ml) demonstrated a greater than two-fold higher frailty risk, with hazard ratios (HRs) of 2.13 (95% confidence interval (CI): 1.130-4.01, P = 0.020) and 2.61 (95% CI: 1.28-5.33, P = 0.008), respectively. Individuals with both elevated hs-cTnT and NT-proBNP had a higher frailty risk than those without it (HR: 4.15; 95% CI: 1.50-11.48, P = 0.006). CONCLUSIONS: High hs-cTnT and NT-proBNP levels are strongly associated with incident frailty in the community-dwelling population without known CVD. Subclinical cardiac damage (hs-cTnT) and/or wall strain (NT-proBNP) may be the key pathway of CVD patients developing frailty. Detection of hs-cTnT and NT-proBNP may help for early screening of high-risk frailty and providing individualised intervention. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT00005131 .

Preoperative NT-proBNP and LVEF for the prediction of acute kidney injury after noncardiac surgery: a single-centre retrospective study.

BACKGROUND: Acute kidney injury (AKI) is one of the most common postoperative complications in noncardiac surgical patients, has an important impact on prognosis and is difficult to predict. Whether preoperative N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations and left ventricular ejection fraction (LVEF) levels can predict postoperative AKI in noncardiac surgical patients is unclear. METHODS: We included 3,314 patients who underwent noncardiac surgery and had measurements of preoperative NT-proBNP concentrations and LVEF levels at a tertiary academic hospital in China between 2008 and 2018. Multiple logistic regression analysis was used to construct a postoperative AKI risk prediction model for this cohort. Then, NT-proBNP concentrations and LVEF levels were included in the abovementioned model as independent variables, and the predictive ability of these two models was compared. RESULTS: Postoperative AKI occurred in 223 (6.72%) patients within 1 week after surgery. Preoperative NT-proBNP concentrations and LVEF levels were independent predictors of AKI after adjustment for clinical variables. The area under the receiver operating characteristic curve (AUROC) of the AKI risk predictive model established with clinical baseline variables was 0.767 (95% CI: 0.732, 0.802). When NT-proBNP concentrations and LVEF levels were added to the base model, the AUROC was 0.811 (95% CI: 0.779, 0.843). The addition of NT-proBNP concentrations and LVEF levels improved reclassification by 22.9% (95% CI 10.5-34.4%) for patients who developed postoperative AKI and by 36.3% (95% CI 29.5-43.9%) for those who did not, resulting in a significant overall improvement in net reclassification (NRI: 0.591, 95% CI 0.437-0.752, P < 0.000). The integral discrimination improvement was 0.100 (95% CI: 0.075, 0.125, P < 0.000).The final postoperative AKI prediction model was constructed, and had a good discriminative ability and fitted to the dataset. CONCLUSIONS: Preoperative NT-proBNP concentrations and LVEF levels were independently associated with the risk of AKI after noncardiac surgery, and they could improve the predictive ability of logistic regression models based on conventional clinical risk factors. TRIAL REGISTRATION: The protocol was preregistered in the Chinese Clinical Trial Registry ( ChiCTR1900024056 ).

Urine N-terminal pro-B-type natriuretic peptide and plasma proenkephalin are promising biomarkers for early diagnosis of cardiorenal syndrome type 1 in acute decompensated heart failure: a prospective, double-center, observational study in real-world.

BACKGROUND: Patients with acute decompensated heart failure (ADHF) show cardiorenal syndrome type 1 (CRS-1) are more likely to have a poor outcome. However, the current criteria often lead to delayed CRS-1 diagnosis. Therefore, we evaluated the predictive value of plasma proenkephalin (pPENK) and urine NT-proBNP (uNT-proBNP) for early diagnosis of CRS-1 and vulnerable-phase prognosis in ADHF patients. METHODS: The plasma NT-proBNP (pNT-proBNP), pPENK, and uNT-proBNP were measured in 121 ADHF patients on admission. The plasma neutrophil gelatinase-associated lipocalin (pNGAL) was chosen as the reference. Logistic regression was used to determine the predictors of CRS-1. The area under the receiver operating curves (ROCs) was calculated to assess the early diagnostic value of pNGAL, pPENK, and uNT-proBNP/uCr for CRS-1. To evaluate the prognostic risk of factors for the 90-d outcomes of all ADHF patients, the Cox regression was performed and the cumulative risk curve was plotted. RESULTS: We found that pPENK [OR 1.093 (95% CI 1.022-1.169), p = 0.010; AUROC = 0.899 (95% CI 0.831-0.946)] and uNT-proBNP/uCr ratio [OR 1.015 (95% CI 1.003-1.028), p = 0.012; AUROC = 0.934 (95% CI 0.874-0.971)] could independently predict the occurrence of CRS-1 in hospitalized patients with ADHF. The pPENK [HR 1.014 (95% CI 1.000-1.042), p = 0.044] and uNT-proBNP/uCr ration [HR 0.998 (95% CI 0.997-1.000), p = 0.045] were also independent predictors of the risk of HF readmission or all-cause death 90 d after discharge in ADHF patients. CONCLUSIONS: The newly found pPENK and noninvasive test of uNT-proBNP/uCr ratio (pg/nmol) on admission may be two promising novel predictive biomarkers for early diagnosis of CRS-1 occurrence and vulnerable-phase outcomes in ADHF patients.