N-terminal B-type Natriuretic Peptide Research Articles

Association of suPAR, ST2, and galectin-3 with eGFR decline and mortality in patients with advanced heart failure with reduced ejection fraction.

Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of estimated glomerular filtration rate (eGFR) in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants, mean age was 59 years, median eGFR 60 ml/min/1.73 m2, 45 participants died, 33 received VAD, and 25 received orthotopic heart transplantation. Higher baseline serum standardized suPAR (β coefficient = -0.36 √(ml/min/1.73 m2), 95% confidence interval (-0.48 to -0.24), p < 0.001), standardized galectin-3 (-0.14 √(ml/min/1.73 m2) (-0.27 to -0.02), p = 0.02), and log NT-proBNP (-0.23 √(ml/min/1.73 m2) (-0.31 to -0.15), p < 0.001) were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies.

NT-proBNP for Predicting All-Cause Death and Heart Transplant in Children and Adults with Heart Failure.

Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) concentration is a heart failure (HF) biomarker in adults and children. Its prognostic value for HF-related events has been established only in adults. Therefore, weaimed to test the hypothesis that plasma NT-proBNP concentrations predicted the risk of heart transplantation or death in children with HF. We studied the medical records of 109 children with HF enrolled in the IBM Watson Explorys database and from 150 children enrolled in the Pediatric Cardiomyopathy Registry (PCMR). Nonlinear regression was used to assess the relationship between plasma NT-proBNP concentrations and the risk of events in the two cohorts. All children in the PCMR cohort had dilated cardiomyopathy. The Explorys cohort also included children with congenital cardiovascular malformations. Median plasma NT-proBNP concentrations were 1250pg/mL and 184pg/mL in the Explorys and PCMR cohorts, respectively. The percentage of deaths/heart transplantations was 7%/22%, over 2years in the Explorys cohort and 3%/16% over 5years in the PCMR cohort. Mean estimates of plasma NT-proBNP concentration indicative of half-maximum relative risk for events (EC50 values) at 2 and 5years were 3730pg/mL and 4199pg/mL, respectively, values both close to the mean of 3880pg/mL established for adults with HF. The plasma NT-proBNP concentration is suitable for estimating relative risk of mortality and heart transplantation in children with HF, independent of etiology and shows similar relations to clinical outcomes as in adults, indicating its likely value as a surrogate marker both for adult and pediatric HF.ClinicalTrials.gov Identifiers: NCT00005391 (May 26, 2000), NCT01873976 (June 10, 2013).

Potential clinical value of fibrinogen-like protein 1 as a serum biomarker for the identification of diabetic cardiomyopathy

Diabetic individuals with diabetic cardiomyopathy (DbCM) present with abnormal myocardial structure and function. DbCM cannot be accurately diagnosed due to the lack of suitable diagnostic biomarkers. In this study, 171 eligible participants were divided into a healthy control (HC), type 2 diabetes mellitus (T2DM) patients without DbCM (T2DM), or DbCM group. Serum fibrinogen-like protein 1 (FGL-1) and other biochemical parameters were determined for all participants. Serum FGL-1 levels were significantly higher in patients with DbCM compared with those in the T2DM group and HCs. Serum FGL-1 levels were negatively correlated with left ventricular fractional shortening and left ventricular ejection fraction (LVEF) and positively correlated with left ventricular mass index in patients with DbCM after adjusting for age, sex and body mass index. Interaction of serum FGL-1 and triglyceride levels on LVEF was noted in patients with DbCM. A composite marker including serum FGL-1 and triglycerides could differentiate patients with DbCM from those with T2DM and HCs with an area under the curve of 0.773 and 0.789, respectively. Composite marker levels were negatively correlated with N-terminal B-type natriuretic peptide levels in patients with DbCM. Circulating FGL-1 may therefore be a valuable index reflecting cardiac functions in DbCM and to diagnose DbCM.

Feasibility and reproducibility of cardiovascular magnetic resonance-feature tracking for quantitative right atrial function in dilated cardiomyopathy patients.

The importance of right heart assessment in dilated cardiomyopathy (DCM) is increasingly recognized. The development of cardiovascular magnetic resonance-feature tracking (CMR-FT) has provided a novel approach to quantify myocardial deformation and evaluate cardiac function. In this study, we aimed to evaluate the feasibility and reproducibility of CMR-FT for the quantitative derivation of right atrial (RA) strain and strain rate (SR) in patients with DCM. A total of 68 DCM patients (84% male; aged 50.6±13.2 years) and 58 healthy controls (81% male; aged 48.4±11.2 years) were retrospectively enrolled from September 2018 to August 2022 at the First Affiliated Hospital of Zhejiang Chinese Medical University and Shenzhen Clinical Medical College of Guangzhou University of Chinese Medicine. RA reservoir, conduit, and booster strain (εs, εe, and εa) and peak positive, peak early negative, and peak late negative SR (SRs, SRe, and SRa) were measured using CMR-FT and compared between 2 groups using Student's t-test. Intra- and inter-observer reproducibility was evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plots. Compared to healthy controls, DCM patients showed significantly lower RA strain (εs: 19.7%±9.0% vs. 44.4%±9.7%; εe: 7.9%±5.3% vs. 25.8%±8.6%; εa: 11.8%±6.2% vs. 18.6%±5.1%, all P<0.001) and SR (SRs: 1.17±0.48 vs. 1.92±0.62 s-1; SRe: -0.85±0.56 vs. -1.94±0.63 s-1; SRa: -1.39±0.71 vs. -2.01±0.65 s-1, all P<0.001). There was no significant difference in RA maximum volume index between the 2 groups. Simple linear regression analysis demonstrated a significant correlation between N-terminal B-type natriuretic peptide (NT-proBNP), RA emptying fraction passive (RAEF passive), and RA εe [(NT-proBNP and εe): r=-0.48, P<0.001, 95% confidence interval (CI): -0.64 to -0.26; and (RAEF passive and εe): r=0.41, P=0.001, 95% CI: 0.22 to 0.56, respectively] in DCM patients. Intra- and inter-observer reproducibility was excellent (all ICCs >0.85) for RA deformation measurements. CMR-FT is a promising, noninvasive approach for the quantitative assessment of RA phasic function in patients with DCM. DCM patients exhibit impaired RA reservoir, conduit, and booster pump function prior to visible RA enlargement.

Application Value of NLR, PLR, LMR, HEART score, and POCT in Early Warning and Accurate Graded Diagnosis of High-Risk Chest Pain in Emergency Medicine

Objective: To evaluate the application value of neutrophils/lymphocytes (NLR), platelets/lymphocytes (PLR), lymphocytes/monocytes (LMR), HEART (history, electrocardiogram, age, risk factors, and troponin) score, and point-of-care testing (POCT) in the early warning and precise diagnosis of high-risk chest pain in emergency medicine. Methods: A total of 157 patients with acute chest pain who were admitted to the emergency department and chest pain treatment unit of our hospital between August 2022 and September 2023 were selected. Rapid testing of bedside myocardial markers (ultrasensitive troponin (hs-cTnI), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), D-dimer (D-Dimer), and N-terminal B-type natriuretic peptide precursor (NT-proBNP)) was performed on the patients using a POCT device (ThermoKing BioMQ60proB). A HEART score was used to classify the patients into low (n = 53), intermediate (n = 59), and high-risk (n = 45) groups, and the NLR, PLR, and LMR were calculated. The NLR, PLR, and LMR values were compared among the three groups of patients, and the optimal cutoff values as well as sensitivity and specificity were determined based on receiver operating characteristic (ROC) analysis. Results: The HEART scores of patients in the low-risk, intermediate-risk, and high-risk groups were (2.72 ± 0.24), (4.75 ± 0.56), and (5.32 ± 0.73) respectively, and the differences were statistically significant (P &lt; 0.05). Compared with the low-risk group, the intermediate-risk group and high-risk group had a significantly higher NLR and PLR, and a significantly lower LMR; the high-risk group had higher NLR and PLR and lower values of LMR as compared to the other two groups, and the difference was statistically significant (P &lt; 0.05). The ROC curves suggested that the area under the curve, sensitivity, and specificity of the combined diagnosis of NLR, PLR, LMR, HEART score, and POCT were greater than those of LR, PLR, and LMR with HEART score and POCT alone. Conclusion: The combined application of NLR, PLR, LMR, HEART score, and POCT has significant application value in the early warning and precise diagnosis of emergency high-risk chest pain. It provides a more simple, easy-to-access, and efficient assessment index for the clinical prediction and treatment of emergency high-risk chest pain.

Prediction model for developing neuropsychiatric systemic lupus erythematosus in lupus patients.

This study aimed to construct a predictive model for assessing the risk of development of neuropsychiatric systemic lupus erythematosus (NPSLE) among patients with SLE based on clinical, laboratory, and meteorological data. A total of 2232 SLE patients were included and were randomly assigned into training and validation sets. Variables such as clinical and laboratory data and local meteorological data were screened by univariate and least absolute shrinkage and selection operator (LASSO) logistic regression modelling. After 10-fold cross-validation, the predictive model was built by multivariate logistic regression, and a nomogram was constructed to visualize the risk of NPSLE. The efficacy and accuracy of the model were assessed by receiver operating characteristic (ROC) curve and calibration curve analysis. Net clinical benefit was assessed by decision curve analysis. Variables that were included in the predictive model were anti-dsDNA, anti-SSA, lymphocyte count, hematocrit, erythrocyte sedimentation rate, pre-albumin, retinol binding protein, creatine kinase isoenzyme MB, Nterminal brain natriuretic peptide precursor, creatinine, indirect bilirubin, fibrinogen, hypersensitive C-reactive protein, CO, and mild contamination. The nomogram showed a broad prediction spectrum; the area under the curve (AUC) was 0.895 (0.858-0.931) for the training set and 0.849 (0.783-0.916) for the validation set. The model exhibits good predictive performance and will confer clinical benefit in NPSLE risk calculation. Key Points • Clinical, laboratory, and meteorological data were incorporated into a predictive model for neuropsychiatric systemic lupus erythematosus (NPSLE) in SLE patients. • Anti-dsDNA, anti-SSA, LYM, HCT, ESR, hsCRP, IBIL, PA, RBP, CO, Fib, NT-proBNP, Crea, CO, and mild contamination are predictors of the development of NPSLE and may have potential for research. • The nomogram has good predictive performance and clinical value and can be used to guide clinical diagnosis and treatment.

Rapid Homogeneous Fluorescent Enzyme-Linked Immunosorbent Assay (ELISA) for N-Terminal Brain Natriuretic Peptide (NT-proBNP) Combining Magnetic Probes and Ampliflu Red

Heart failure (HF) is the leading cause of death from cardiovascular disease, and early diagnosis using serum markers holds extraordinary significance for the treatment of patients. N-terminal brain natriuretic peptide (NT-proBNP) is the gold standard for HF diagnosis. Herein, a novel, rapid, sensitive, and immune-sensing strategy for NT-proBNP is reported employing an enzyme-linked immunosorbent assay (ELISA) that combines the use of magnetic biological probes and the fluorogenic substrate Ampliflu Red. Functionalized immunomagnetic nanoparticles with large surface areas provide an abundant reaction platform and reduce the analysis time due to their superparamagnetic properties. Ampliflu Red is catalyzed by horseradish peroxidase (HRP) using hydrogen peroxide (H2O2) to produce strong fluorescence and a low background. The reported method achieved a good detection limit of 2.73 ng mL−1 and a wide linear range from 3.13 to 100 ng mL−1. The analysis time was less than 1 h, which is superior to that of traditional ELISA (3–4 h). In addition, the recoveries of spiked human serum were satisfactory, indicating that the proposed strategy has potential applications for the rapid determination of NT-proBNP and other biomarkers in clinical settings.

Efficacy of catheter ablation for atrial fibrillation in heart failure: a meta-analysis of randomized controlled trials.

The study aims to evaluate whether rhythm control by catheter ablation is superior to medical therapy for the patients with atrial fibrillation (AF) and heart failure (HF). The literatures were searched by using PubMed, Cochrane Library, Embase, and Web of Science databases up to 12 October 2023. The randomized controlled trials (RCTs) comparing rhythm control using catheter ablation vs. medical therapy in AF patients with HF were pooled. The primary outcomes included all-cause mortality, HF re-hospitalization, and stroke, and the secondary outcomes included left ventricular ejection fraction (LVEF), atrial tachyarrythmia recurrence, quality of life (Minnesota Living with Heart Failure Questionnaire score, MLHFQ score), 6min walking distance (6MWD), the level of N-terminal B-type natriuretic peptide precursor (NT-proBNP), and adverse events. Nine RCTs involving in 2293 patients met the inclusion criteria. Compared with medical therapy, catheter ablation reduced all-cause mortality [10.07% (121/1201) vs. 15.26% (175/1147), risk ratio (RR):0.60, 95% confidence interval (CI): 0.48-0.74, P<0.00001, I2=0%] and the rate of HF re-hospitalization (RR: 0.65, P=0.02, 95% CI: 0.45 to 0.94, I2=74%), but had no obvious difference in incidence of stroke (RR: 0.67, P=0.27, 95% CI: 0.32 to 1.38, I2=0%). Catheter ablation enhanced LVEF [mean difference (MD), 6.26%, P<0.00001, I2=89%], reduced AT recurrence (RR: 0.37, P<0.00001, 95% CI: 0.26 to 0.52, I2=89%), improved the quality of life (MLHFQ score) (MD: -6.83, P=0.003, I2=67%), elevated 6MWD (MD: 15.92, P=0.006, I2=76%), and diminished the level NT-proBNP (MD: -44.19, P<0.00001, I2=75%), but had no significant difference in adverse events [25.81% (310/1201) vs. 30.25% (347/1147), RR: 0.81, 95% CI: 0.65-1.01, P=0.06, I2=55%]. Catheter ablation as rhythm control strategy substantially enhances the survival rate, reduces HF re-hospitalization, increases the rate of sinus rhythm maintenance, improves the left ventricular function and the quality of life for AF patients with HF, and has similar safety, compared with medical therapy. The rhythm control by catheter ablation may be a better strategy for the AF patients with HF.

Association of cardiac biomarkers with long-term cardiovascular events in a community cohort

Introduction: We hypothesized that combining biomarkers of atherosclerotic cardiovascular disease (ASCVD) would improve prediction of ASCVD events in a primary prevention cohort. Materials and methods The study assessed major adverse cardiac events (MACE) (myocardial infarction, coronary artery bypass graft, percutaneous intervention, stroke, and death. Cox proportional hazards models assessed apolipoprotein AI (ApoA1), apolipoprotein B (ApoB), ceramide score, cystatin C, galectin-3 (Gal3), LDL-C, Non-HDL-C, total cholesterol (TC), N-terminal B-type natriuretic peptide (NT proBNP), high-sensitivity cardiac troponin (HscTnI) and soluble interleukin 1 receptor-like 1. In adjusted models, Ceramide score was defined by from N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)] and N-lignoceroyl-sphingosine [Cer(24:0)]. Multi-biomarker models were compared with C-statistics and Integrated Discrimination Index (IDI). Results A total of 1131 patients were included. Adjusted NT proBNP per 1 SD resulted in a 31% increased risk of MACE/death (HR = 1.31) and a 31% increased risk for stroke/MI (HR = 1.31). Adjusted Ceramide per 1 SD showed a 13% increased risk of MACE/death (HR = 1.13) and a 29% increased risk for stroke/MI (HR = 1.29). These markers added to clinical factors for both MACE/death (p = 0.003) and stroke/MI (p = 0.034). HscTnI was not a predictor of outcomes when added to the models. Discussion Ceramide score and NT proBNP improve the prediction of MACE and stroke/MI in a community primary prevention cohort.

NATRIURETIC PEPTIDE: DIAGNOSTIC, PROGNOSTIC, AND CLINICAL RELEVANCE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS, ARTERIAL HYPERTENSION AND OBESITY

Natriuretic peptides are one of the main biomarkers of chronic heart failure (CHF). The level of NT-proBNP makes it possible to evaluate the negative prognosis in patients with CHF, as well as to monitor the sensitivity of patients with left ventricular dysfunction to the appointment of treatment. The purpose of the study: to study the NT-proBNP biomarker in comorbid patients with hypertension, obesity, type 2 diabetes and determine the relationship with a number of hormonal and biochemical indicators. Materials and methods: all patients were divided into 4 groups depending on the presence of comorbid pathology in them: patients with hypertension – 1 group – 22 people; patients with hypertension combined with obesity – group 2 – 30 people; Hypertension in combination with type 2 diabetes – group 3 – 31 people; patients with hypertension, type 2 diabetes and obesity – group 4 – 28 people. Determination of the content of N-terminal brain natriuretic peptide (NT-proBNP) in the blood serum of patients was carried out by the immunoenzymatic method on the analyzer "Labline-90" (Austria) using a commercial test system manufactured by the company "Elabscience" (ELISA, China) according to the instructions, which was part of the set. Conclusions. It was established that in patients with hypertension, hypertension in combination with obesity, hypertension in combination with type 2 diabetes, as well as hypertension in combination with type 2 diabetes and obesity, there is a significant increase in NT-proBNP compared to the indicator of the control group (p&lt;0.05). It has been proven that NT-proBNP has a direct correlation with creatinine (p=0.045), urea (p=0.038), triglyceride level (p=0.027) and cholesterol (p=0.031); direct correlation with the level of HbA1c (r=0.202; p=0.0038). The level of NT-proBNP has a significant predictive value for the risk of developing cardiovascular complications in patients with hypertension.

Fibroblast growth factor 23 during septic shock and myocardial injury in ICU patients

ObjectiveFibroblast growth factor 23 (FGF23) has been recognized as an important biomarker of cardiovascular disease and is closely related to inflammation over the past decade. This study aimed to assess the relationship between FGF23 and myocardial injury in patients with sepsis. MethodsWe sequentially measured serum FGF23, Klotho, biomarkers of inflammation (CRP, IL-6 and WBC), myocardial injury (cTnI and N-terminal B-type natriuretic peptide) and sepsis (procalcitonin) at peak of intercurrent septic shock and after complete resolution or before death in a series of 29 patients with septic shock. 29 healthy adults without infections were used as controls. ResultsThere was a difference in serum FGF23 level between patients with septic shock and healthy adults (p < 0.0001), and the peak level of FGF23 in septic shock in the survivor group was higher than that after complete remission (p < 0.0001). No statistical difference was found in the level of FGF23 before and after treatment in the death group (p = 0.0947). At the peak of septic shock, FGF23 was significantly correlated with inflammatory markers, CRP (r = 0.8063, p < 0.0001), PCT (r = 0.6091, p = 0.0005) and WBC (r = 0.8312, p < 0.0001), while the correlation with IL-6 was not statistically significant (r = 0.0098, p = 0.9598). At the same time, it was found that FGF23 was significantly correlated with myocardial injury markers, cTNI (r = 0.8475, p < 0.0001) and NTproBNP (r = 0.8505, p < 0.0001). Nevertheless, FGF23 and klotho are not correlated (r = 0.2609, p = 0.1717). ConclusionIn conclusion, in patients with septic shock and myocardial injury, the exacerbation of inflammation in the septic process was accompanied by a abnormal increase of circulating FGF23 level. FGF23 also subsided after the improvement of inflammation, and the opposite was true for patients who did not survive. The up-regulation of FGF23 may be involved in the response of patients to septic shocks, and it is also speculated that FGF23 is involved in the myocardial injury of septic shock.

Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort study

Assessment of cardiovascular risk is critical for patients with cancer. Previous retrospective studies suggest potential cardiotoxicity of CAR T cell therapies. We aimed to prospectively assess cardiotoxicity and the predictive value of cardiac biomarkers and classical risk factors (age, cardiac function, diabetes, arterial hypertension, smoking) for cardiac events and all-cause mortality (ACM). In this prospective cohort study, all patients treated with CAR T cell constructs (axi-cel, tisa-cel, brexu-cel, ide-cel, or the 3rd generation CAR HD-CAR-1) from Oct 1, 2018, to Sept 30, 2022at the University Hospital Heidelberg were included. Surveillance included cardiac assessment with biomarkers (high-sensitive Troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP)), 12-lead-ECG, and 2D echocardiography. ACM was defined as the primary study endpoint, while cardiotoxicity, defined by clinical syndromes of heart failure or decline in ejection fraction, served as a secondary endpoint. Overall, 137 patients (median age 60, range 20-83, IQR 16), were included in the study. 46 patients died during the follow up period (median 0.75 years, range 0.02-4.33, IQR 0.89) 57 month, with a median survival of 0.57 years (range 0.03-2.38 years, IQR 0.79). A septal wall thickness above 11mm (HR 2.48, 95%-CI=1.10-5.67, p=0.029) was associated with an increased risk of ACM, with a trend seen for reduced left ventricular ejection fraction prior to therapy (LVEF <40%; HR 9.17, 95%-CI=1.30-183.11, p=0.051). Secondary endpoint was reached by 93 patients while no baseline parameter was able to predict an elevated risk. However, hs-cTnT change from baseline of 50% or more during the first 14 days after CAR infusion predicted ACM (HR 3.81, 95%-CI=1.58-9.45; p=0.003). None of the baseline characteristics was able to predict the incidence of cardiac events. Reduced pre-lymphodepletion ejection fraction and early post-infusion biomarker kinetics may be associated with increased ACM and cardiotoxicity events. These findings may help to identify patients who could benefit from intensified cardio-oncological surveillance. The German Center for Cardiovascular Research, German Research Foundation, and the Federal Ministry of Education and Research.

Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT study).

Liver dysfunction contributes to worse clinical outcomes in heart failure (HF) patients. However, studies exploring temporal evolutions of liver function parameters in chronic HF (CHF) pa- tients, and their associations with clinical outcome, are scarce. Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction. Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models. Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). Serial levels of ALP and GGTP, and slopes of the temporal evolutions of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP. Changes in serum levels of TBIL, ALP, GGTP, and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in heart failure with reduced ejection fraction patients in clinical practice.

Treatment of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review and meta-analysis

The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of randomized controlled trials (RCTs). Thus, we performed a meta-analysis of RCTs that reported outcomes for CTD-PAH. PubMed and EMBASE were searched for CTD-PAH treatment. The selected outcomes were functional class (FC) change, survival rates, 6-min walk distance (6-MWD), clinical worsening (CW), N-terminal prohormone BNP (NT-proBNP), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), right atrial pressure (RAP), and cardiac index (CI). The meta-analysis was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42020153560). Twelve RCTs conducted with 1837 patients were included. The diagnoses were systemic sclerosis in 59%, SLE in 20%, and other CTDs in 21%. The pharmacological interventions were epoprostenol, treprostinil, sildenafil, tadalafil, bosentan, macitentan, ambrisentan, riociguat, and selexipag. There was a significant difference between interventions and placebo in FC, 6MWD, CW, PVR, RAP, and CI that favored intervention. Our analysis showed a 39% reduction in the CW risk with PAH treatment. The short-term survival rates and mean serum NT-proBNP changes were similar between the study and control groups. Treatment for CTD-PAH had favorable effects on clinical and hemodynamic outcomes but not on survival and NT-proBNP levels. Different from the previous meta-analyses that focused on 6-MWD, time to clinical worsening, and CW as outcomes, this meta-analysis additionally reports the pooled analysis of change in FC, hemodynamic measurements (RAP, PVR, CI), and NT-proBNP, some of which have prognostic value for PAH.

Hemodynamic changes with serial balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension

Objective: To monitor hemodynamic changes during serial balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Methods: General clinical data of CTEPH patients diagnosed from October 2017 to January 2022 in Beijing Chaoyang Hospital were collected, and 83 patients who underwent at least 1 BPA treatment were included to analyze their 6 min walking distance, WHO functional class, N-terminal B-type natriuretic peptide precursor (NT-proBNP), troponin I (cTnI) and haemodynamic indices. Baseline and follow-up after the final BPA clinical data and hemodynamics, functional status and serial hemodynamics before each series of BPA were collected to evaluate the efficacy of BPA for CTEPH patients. Complications and managements were documented to confirm the safety of BPA for CTEPH patients. Results: Three hundred and forty BPA procedures were performed in 83 CTEPH patients. The median number of BPA procedures was 4.0 and a total of 2104 vessels were dilated. In general, mPAP [from 50.0(42.0-55.25) mmHg(1 mmHg=0.133 kPa) to 32.0(27.0-42.0) mmHg, P<0.001], PVR[from (806.6±323.2) dyn·s·cm-5 to 420.0(295.0-613.5) dyn·s·cm-5, P<0.001] were significantly improved compared with baseline, but not CO and CI. Functional parameters including WHO functional class Ⅰ/Ⅱ/Ⅲ/Ⅳ (from 0/35/34/14 to 43/32/7/1, P<0.001), 6MWD [from 364.5(300.0-429.5)m to 461.0(409.0-501.0)m, P<0.001], NT-proBNP [from 1 357.0(232.0-2 715.0) ng/L to 141.0(57.0-627.8) ng/L,P<0.001] were significantly improved compared with baseline. A cumulative (compared to baseline) and serial (compared to preceding BPA session) analysis of the sequential BPA session confirmed that a major hemodynamic improvement in PVR and mPAP occurred in the first 3 serial BPA treatments. There was a dose-response relationship: the more segments that were treated, the greater were the subsequent reduction in PVR and mPAP. There were 32.0 complications (9.4%) associated with BPA procedures, and the most common complication was pulmonary hemorrhage caused by catheter-related vascular injury. Conclusions: BPA is an effective and safe alternative for technically non-operable CTEPH patients. The hemodynamic benefits of BPA in CTEPH patients were cumulative and correlated with the total number of vessels successfully dilated.

Clinical characteristics, diagnosis and management of nivolumab-induced myocarditis.

Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment.

Soluble urokinase plasminogen activator receptor and cardiotoxicity in doxorubicin-treated breast cancer patients: a prospective exploratory study

BackgroundSoluble urokinase plasminogen activator receptor is an inflammatory biomarker that may prognosticate cardiovascular outcomes. We sought to determine the associations between soluble urokinase plasminogen activator receptor and established markers of cardiotoxicity in breast cancer patients receiving doxorubicin.MethodsWe conducted a prospective cohort study of women with newly diagnosed breast cancer receiving standard-dose doxorubicin (240 mg/m2) at Rush University Medical Center and Rush Oak Park Hospital (Chicago, IL) between January 2017 and May 2019. Left ventricular ejection fraction, global longitudinal strain, and cardiac biomarkers (N-terminal prohormone B-type natriuretic peptide, troponin-I, and high-sensitivity C-reactive protein) were measured at baseline and at intervals up to 12-month follow-up after end of treatment. The associations between soluble urokinase plasminogen activator receptor and these endpoints were evaluated using multivariable mixed effects linear regression.ResultsOur study included 37 women (mean age 47.0 ± 9.3 years, 60% white) with a median baseline soluble urokinase plasminogen activator receptor level of 2.83 ng/dL. No participant developed cardiomyopathy based on serial echocardiography by one-year follow-up. The median percent change in left ventricular strain was -4.3% at 6-month follow-up and absolute changes in cardiac biomarkers were clinically insignificant. There were no significant associations between soluble urokinase plasminogen activator receptor and these markers of cardiotoxicity (all p > 0.05).ConclusionsIn this breast cancer cohort, doxorubicin treatment was associated with a very low risk for cardiotoxicity. Across this narrow range of clinical endpoints, soluble urokinase plasminogen activator receptor was not associated with markers of subclinical cardiotoxicity. Further studies are needed to clarify the prognostic utility of soluble urokinase plasminogen activator receptor in doxorubicin-associated cardiomyopathy and should include a larger cohort of leukemia and lymphoma patients who receive higher doses of doxorubicin.

Biomarkers in Peripartum Cardiomyopathy-What We Know and What Is Still to Be Found.

Peripartum cardiomyopathy (PPCM) is a form of heart failure, often severe, that occurs in previously healthy women at the end of their pregnancy or in the first few months after delivery. In PPCM, the recovery of heart function reaches 45-50%. However, the all-cause mortality in long-term observation remains high, reaching 20% irrespective of recovery status. The incidence of PPCM is increasing globally; therefore, effort is required to clarify the pathophysiological background of the disease, as well as to discover specific diagnostic and prognostic biomarkers. The etiology of the disease remains unclear, including oxidative stress; inflammation; hormonal disturbances; endothelial, microcirculatory, cardiomyocyte and extracellular matrix dysfunction; fibrosis; and genetic mutations. Currently, antiangiogenic 16-kDa prolactin (PRL), cleaved from standard 23-kDa PRL in the case of unbalanced oxidative stress, is recognized as the main trigger of the disease. In addition, 16-kDa PRL causes damage to cardiomyocytes, acting via microRNA-146a secreted from endothelial cells as a cause of the NF-κβ pathway. Bromocriptine, which inhibits the secretion of PRL from the pituitary gland, is now the only specific treatment for PPCM. Many different phenotypes of the disease, as well as cases of non-responders to bromocriptine treatment, indicate other pathophysiological pathways that need further investigation. Biomarkers in PPCM are not well established. There is a deficiency in specific diagnostic biomarkers. Pro-brain-type natriuretic peptide (BNP) and N-terminal BNP are the best, however unspecific, diagnostic biomarkers of heart failure at the moment. Therefore, more efforts should be engaged in investigating more specific biomolecules of a diagnostic and prognostic manner such as 16-kDa PRL, galectin-3, myeloperoxidase, or soluble Fms-like tyrosine kinase-1/placental growth factor ratio. In this review, we present the current state of knowledge and future directions of exploring PPCM pathophysiology, including microRNA and heat shock proteins, which may improve diagnosis, treatment monitoring, and the development of specific treatment strategies, and consequently improve patients' prognosis and outcome.

Factors Associated With Fatigue in Persons With Atrial Fibrillation in the Atherosclerosis Risk in Communities (ARIC) Study.

Atrial fibrillation (AF) is a common cardiac arrhythmia affecting over 6 million people in the U.S. Fatigue is a frequent symptom of AF, yet no underlying biological mechanisms have been identified in AF-related fatigue as in other chronic conditions such as cancer or HIV fatigue (inflammation, tissue injury). We aimed to identify biomarkers and correlates of AF-fatigue in ARIC participants. Participants with AF from ARIC visit 5 (2011-2013) were included in the study. Multiple linear regression was used to estimate the association of high sensitivity troponin (hs-TnT), N-terminal fragment B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) levels with self-reported fatigue (SF-12 and PROMIS Fatigue Scale), depressive symptoms (Center for Epidemiological Studies Depression survey), and physical functioning (Short Physical Performance Battery) scores. All biomarkers underwent natural-log transformation. There were 446 participants (mean age: 78y ± 5; 44% women). In adjusted analyses, NT-proBNP was associated with AF-fatigue (β: 0.11, 95% CI: 0.03, 0.19), increased depressive symptoms (β: 0.44, 95% CI: 0.19, 0.70), and decreased physical function (β: -0.48, 95% CI: -0.72, -0.23). Hs-TnT was also associated with elevated AF-fatigue (β: 0.24, 95% CI: 0.09, 0.39) along with decreased physical function (β: -1.19, 95% CI: -1.64, -0.75). No significant associations were found with hsCRP and fatigue. Increased levels of cardiac injury biomarkers, depressive symptoms, and decreased physical function were associated with AF-fatigue. Inflammation was not associated with AF-fatigue; other physiological pathways, such as cardiac overload or myocardial injury may be more relevant in AF-fatigue.

Utility of bioelectrical phase angle for cardiovascular risk assessment among individuals with and without diabetes mellitus.

Low values of bioimpedance-derived phase angle (PA) have been associated with various adverse outcomes. We investigated the association of PA with cardiovascular markers in individuals with and without diabetes mellitus (DM). PA was measured in 452 adults (without DM n = 153, T1DM n = 67, T2DM n = 232). Carotid intima-media thickness (IMT), renal resistive index (RRI), ankle-brachial index (ABI) and carotid-femoral Pulse Wave Velocity (cfPWV) were estimated. Furthermore, the levels of high-sensitive Troponin-T [hsTnT], N-terminal brain natriuretic peptide [NT-pro-BNP]) were measured. PA values were lower in DM independently of age, gender, and BMI (estimated marginal means 6.21, 5.83, 5.95 for controls, T1DM, T2DM p < .05), a finding which persisted after propensity score matching. PA correlated negatively with IMT (r = -0.181), RRI (r = -0.374), cfPWV (r = -0.358), hsTnT (r = -0.238) and NT-pro-BNP (r = -0.318) (all p < .001). In multivariable analysis, the associations with RRI, cfPWV, hsTnT and NT-pro-BNP remained unchanged. PA values 6.0-6.5° for males and 5.2-5.8° for females were predictive of commonly used cutoffs. The combination of ΑCC/AHA ASCVD Score with PA outperformed either factor in predicting cfPWV, RRI for males and hsTnT, BNP for both genders. PA exhibits independent correlations with various parameters pertinent to cardiovascular risk and may be useful for cardiovascular assessment.