Plasma B-type Natriuretic Peptide Research Articles

Effect of comorbid heart failure assessed by plasma B-type natriuretic peptide level on the activities of daily living in patients with hospitalization-associated disability after aspiration pneumonia.

We investigated the effects of comorbid heart failure on rehabilitation outcomes in patients with hospitalization-associated disability after aspiration pneumonia(AP). This study included 134 patients with hospitalization-associated disability after AP. Patients were classified into heart failure (B-type natriuretic peptide (BNP) ≧100pg/ml, n = 39) and non-heart failure (BNP < 100pg/ml, n = 95) groups, and the rehabilitation outcomes of both groups were compared. Rehabilitation effectiveness was lower in heart failure group than in non-heart failure group (21.1 ± 22.6% vs 36.2 ± 30.8, p < 0.01). The rate of independent walking at discharge in heart failure group (28.2%) was significantly lower than in non-heart failure group (53.7%). Multiple linear regression analysis revealed that age, male, handgrip strength, quadriceps strength, functional oral intake scale, Mini Nutritional Assessment Short Form, and BNP were significantly associated with rehabilitation effectiveness. Results suggest that comorbid heart failure has a negative impact on rehabilitation outcomes in patients with hospital-associated disability after AP.

Prognostic Implication of Intestinal Wall Edema in Patients with Aortic Stenosis Receiving Trans-Catheter Aortic Valve Replacement.

A recently proposed mechanism, the intestinal-cardiovascular relationship, serves as a framework to elucidate the interplay between these two systems. In our investigation, we assessed the prognostic implications of colon wall thickness, a marker correlated with intestinal congestion and dysfunction, in patients diagnosed with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). Patients diagnosed with severe aortic stenosis who underwent TAVR at our institution during the period spanning 2015 to 2022 were retrospectively enrolled. As part of the institutional protocol, patients underwent abdominal computed tomography upon admission, preceding TAVR. Our analysis aimed to assess the influence of colon wall thickness on the occurrence of either all-cause mortality or readmission due to heart failure within a two-year period. A total of 345 patients were included. The median age was 85 (82, 88) years, and 99 patients were male. Baseline colon wall thickness was distributed widely, with a median value of 2.2 (2.0, 2.5) mm. Patients with thicker colon walls tended to have lower pulmonary artery pulsatility index values, indicating more impaired right ventricular function and more advanced malnutrition. A thicker colon wall was independently associated with 2-year death or heart failure readmission with a hazard ratio of 2.02 (95% confidence interval 1.01-14.07), adjusted for hemoglobin, age, and plasma B-type natriuretic peptide levels (p = 0.049), and significantly stratified the primary endpoint at a cutoff of 2.7 mm (25% versus 10%, p = 0.005). Our initial observation revealed that a thicker baseline colon wall correlated with increased rates of mid-term mortality and readmission due to heart failure subsequent to TAVR. Developing a comprehensive understanding of the underlying causality necessitates further in-depth investigations through subsequent studies.

Rediscover the predictive capacity of B-type natriuretic peptide applied to neonatal supraventricular tachycardia

BackgroundSupraventricular tachycardia (SVT) is one of the most common non-benign arrhythmias in neonates, potentially leading to cardiac decompensation. This study investigated the early risk factors of acute heart failure (AHF) secondary to SVT in neonates, and explored their value in guiding the selection of effective anti-arrhythmic treatment.MethodsA total of 43 newborns diagnosed with and treated for SVT between January 2017 and December 2022 were analyzed. According to the presence of AHF after restoring sinus rhythm in newborns with SVT, they were divided into SVT with AHF group and SVT without AHF group. Clinical data and anti-arrhythmic therapies were analyzed. Risk factors of AHF secondary to SVT in neonates were determined using logistic regression. The cut-off value for predictors of AHF secondary to SVT and demanding of a second-line anti-arrhythmic treatment was determined through receiver operating characteristic (ROC) analysis.ResultsTime to initial control of tachycardia > 24 h, hyperkalemia, anemia, and plasma B-type natriuretic peptide (BNP) were identified as risk factors of AHF secondary to SVT in neonates. BNP exhibited AUC of 0.80 in predicting AHF, and BNP > 2460.5pg/ml (OR 2.28, 95% CI 1.27 ~ 45.39, P = 0.03) was an independent predictor, yielding sensitivity of 70.6% and specificity of 84.6%. Neonates with BNP > 2460.5pg/ml (37.5% versus 7.4%, P = 0.04) had a higher demand for a second line anti-arrhythmic treatment to terminate SVT, with sensitivity and specificity for BNP in predicting at 75.0%, 71.4%, respectively.ConclusionsBNP could be used to predict an incident of AHF secondary to SVT and a demand of second-line anti-arrhythmic treatment to promptly terminate SVT and prevent decompensation in neonates.

Role of NT-pro B-type Natriuretic Peptide in Anemic Patients Presenting with High-output Cardiac Failure

ABSTRACT Background: Anemia commonly contributes to cardiovascular alterations, including heart failure (HF). High-output cardiac failure is a less common form of HF, characterized by heart’s inability to provide sufficient blood for the body’s demand. However, anemia sometimes remains undetected because the superficial cardiac function does not precisely reflect the adverse impact of anemia. Plasma B-type natriuretic peptide (BNP) is comes into role in these cases. Material and Method: This cross sectional study was conducted between August 2020 to September 2022 on 40 severe anaemic cases with Hb &lt; 8g/dl according to WHO classification irrespective of etiology with clinical signs of heart failure, age group- above 14 years. Results: Out of total 40 patients, 24 were male and 16 were female. In our study, among the anemic females, 9 (56%) belonged to the age group of &lt;30 years of age. In our study, out of 40 patients, 14 patients presented with high BNP and 26 patients presented with BNP within normal limits. The mean BNP range in patients with high BNP level was 290.6. Conclusion: Understanding the mechanisms of association between anemia and NT-proBNP may improve our understanding of cardiac pathophysiology and help target potential therapies to prevent the development and progression of HF.

Enhancement of Bottle Gourd Oil Activity via Optimized Self-Dispersing Lipid Formulations (SDLFs) to Mitigate Isoproterenol-Evoked Cardiac Toxicity in Rats via Modulating BMP, MMP2, and miRNA-21 and miRNA-23a Genes' Expression.

Bottle gourd (BG) oil (family Cucurbitaceae) has several pharmacological activities including a reduction of the hazard of cardiovascular and atherosclerosis conditions. This work aimed to develop and optimize self-dispersing lipid formulations (SDLFs) of BG oil by applying a full 32 factorial design. The formulation variables (oil concentration and surfactant mixture ratio) showed an obvious impact on the characters of the prepared BG-SDLFs including droplet size (DS), polydispersity index (PDI), emulsification time (ET), and transmission percentage (Tr%). The optimum BG-SDLF composed of 30% oil and Tween 80/Cremophor® RH40 (1:1) showed good emulsification characteristics and a better drug release profile compared with BG oil. In vivo study in isoproterenol-injected rats showed that BG oil and the optimized BG-SDLF improved cardiac function, by elevating the miRNA-23a gene expression level and decreasing miRNA-21 gene expression. They also caused the inhibition of the plasma B-type natriuretic peptide (BNP), N-terminal proatrial natriuretic peptide (NT-pro-BNP), cystatin c, galectin-3, lipoprotein-associated phospholipase A2 (Lp-PLA2), matrix metallopeptidase 2 (MMP2), cardiac troponin I (cTnI), and cardiac troponin T (cTnT). Our study demonstrated that BG oil and the optimized BG-SDLF provided a cardioprotection against isoproterenol-induced cardiac toxicity with better results in groups treated with the optimized BG-SDLF.

Inhibitory action of B-type natriuretic peptide on adrenocorticotropic hormone in patients with acute coronary syndrome.

In addition to the classical actions of hemodynamic regulation, natriuretic peptides (NPs) interact with various neurohumoral factors that are deeply involved in the pathophysiology of cardiovascular diseases. However, their effects on the hypothalamic-pituitary-adrenal (HPA) axis, which is activated under acute high-stress conditions in acute coronary syndrome (ACS), remain largely unknown. We investigated the impact of plasma B-type NP (BNP) on plasma adrenocorticotropic hormone (ACTH)-cortisol levels during the acute phase of ACS ischemic attacks. The study population included 436 consecutive patients with ACS for whom data were collected during emergency cardiac catheterization. Among them, biochemical data after acute-phase treatment were available in 320 cases, defined as the ACS-remission phase (ACS-rem). Multiple regression analyses revealed that plasma BNP levels were significantly negatively associated with plasma ACTH levels only during ACS attacks (P < 0.001), but not in ACS-rem, whereas plasma BNP levels were not significantly associated with plasma cortisol levels at any point. Accordingly, covariance structure analyses were performed to clarify the direct contribution of BNP to ACTH by excluding other confounding factors, confirming that BNP level was negatively correlated with ACTH level only during ACS attacks (β = -0.152, P = 0.002), whereas BNP did not significantly affect ACTH in ACS-rem. In conclusion, despite the lack of a significant direct association with cortisol levels, BNP negatively regulated ACTH levels during the acute phase of an ACS attack in which the HPA axis ought to be activated. NP may alleviate the acute stress response induced by severe ischemic attacks in patients with ACS.NEW & NOTEWORTHY BNP negatively regulates ACTH during a severe ischemic attack of ACS in which hypothalamic-pituitary-adrenal axis ought to be activated, indicating an important role of natriuretic peptides as a mechanism of adaptation to acute critical stress conditions in humans.

Feasibility and Efficacy of Exercise Training Concomitant with Re-Assessment of Medical Therapy in Patients with Heart Failure Receiving Intravenous Inotropes.

Exercise training in addition to re-assessment of medical treatments is recommended for patients with advanced heart failure. However, the feasibility and efficacy of exercise training in patients with heart failure receiving intravenous inotropes remains uncertain.Clinical data were analyzed from consecutive patients with stabilized hemodynamics receiving intravenous inotropes for more than 1 week and undergoing cardiac rehabilitation at our institute between February 2020 and May 2022. All patients received re-assessment of guideline-directed medical therapy and non-pharmacological treatment, in addition to the exercise therapy. The intensity of exercise training was determined based on the results of cardiopulmonary exercise testing.A total of 10 patients receiving intravenous inotropes (median age 60 years, left ventricular ejection fraction 23%) were included. All patients received low-dose dobutamine and 4 patients received concomitant milrinone. Exercise training was continued for 112 days on median without any critical complications. Intravenous inotropes were continued for 41 days on median and weaned off in all patients. Plasma B-type natriuretic peptide decreased slightly from 291 (129, 526) to 177 (54, 278) pg/mL (P = 0.070) and peak oxygen consumption increased from 10.0 (8.3, 15.3) to 15.2 (10.9, 17.2) mL/kg/minute (P = 0.142) during the 6-month observational period following the initiation of exercise intervention.Exercise training might be feasible and effective in patients with advanced heart failure receiving low-dose intravenous inotrope support concomitant with re-assessment of medical treatment.

Inhibition of protein arginine deiminase 4 prevents inflammation-mediated heart failure in arthritis.

Rheumatoid arthritis is a prototypic inflammatory condition with affected patients being at greater risk of incident heart failure (HF). Targeting innate immune cell function in the pathogenesis of HF bears the potential to guide the development of future therapies. A collagen-induced arthritis (CIA) model in DBA/1 J mice was used to generate arthritis. Mice with CIA developed concentric hypertrophic myocardial remodeling, left ventricular (LV) diastolic dysfunction, and HF with elevated plasma B-type natriuretic peptide levels but preserved LV ejection fraction. Key features of HF in CIA were increased infiltration of activated neutrophils, deposition of neutrophil extracellular traps in the myocardium, and increased tissue levels of the proinflammatory cytokine IL-1β. Specific inhibition of protein arginine deiminase 4 (PAD4) by an orally available inhibitor (JBI-589), administered after the onset of clinical arthritis, prevented HF with reduced neutrophil infiltration. We identify PAD4-mediated neutrophil activation and recruitment as the key thromboinflammatory pathway driving HF development in arthritis. Targeting PAD4 may be a viable therapeutic approach for the prevention of HF secondary to chronic inflammation.

Initial Experience of Vericiguat Treatment in Patients with Heart Failure and Reduced Ejection Fraction.

Vericiguat, a novel oral soluble guanylate cyclase stimulator, decreased the incidence of cardiovascular death and heart failure hospitalization in the cohort receiving triple therapy for heart failure with reduced ejection fraction. However, efficacy and optimal patient selection in real-world practice in the era of "quadruple therapy" remains unknown. Consecutive patients who received vericiguat between September 2021 and December 2022 were retrospectively evaluated. A total of 28 patients (median age 66 years, median left ventricular ejection fraction 33%) were included. Of them, 21 patients (75%) received quadruple therapy, and the dose of sacubitril/valsartan was 100 mg in the median. Three patients receiving dobutamine infusion discontinued vericiguat due to symptomatic hypotension. One patient with a high N-terminal pro-B-type natriuretic peptide of 4848 pg/mL at the baseline underwent unexpected heart failure hospitalization. Efficacy was evaluated in 21 patients who continued vericiguat for more than 4 months. The plasma B-type natriuretic peptide concentration tended to increase during the six-month pre-treatment period from 104 pg/mL to 179 pg/mL on median (p = 0.665) but remained unchanged after six-month vericiguat treatment to 170 pg/mL on median (p = 0.188). Vericiguat therapy might be feasible and effective upon quadruple therapy for those with heart failure, although further investigation is warranted to validate our findings.

Postoperative Atrial Fibrillation Following Off-Pump Coronary Artery Bypass Graft Surgery: Elderly Versus Young Patients.

Background Atrial fibrillation (AF) is one of the common rhythm disturbances that occur after coronary artery bypass graft (CABG) surgery. Postoperative atrial fibrillation (POAF) can lead to thromboembolic events, hemodynamic instability, and prolonged hospital stay, affecting morbidity and influencing short and long-term outcomes after CABG. Methodology This prospective comparative study was conducted between May 2018 and April 2020. This study aimed to compare the prevalence of POAF following off-pump coronary artery bypass graft surgery (OPCAB) between elderly and young patients. Additionally, we aimed to determine the risk factors associated with POAF following OPCAB in the elderly compared to young patients. Patients aged ≥65 years were considered elderly, and those aged <65 years were considered young. A total of 120 patients (60 in the elderly group and 60 in the young group) were included in this study and evaluated to correlate the preoperative and intraoperative risk factors with postoperative outcomes during the hospital stay. Results The prevalence of POAF following OPCAB in the elderly was significantly higher compared to young patients (48.3% vs. 20%,p = 0.002). The elderly group also had a significantly longer intensive care unit stay (p = 0.001) and hospital stay (p = 0.001). In an unadjusted logistic regression model, age (odds ratio (OR) = 3.74, 95% confidence interval (CI) = 1.66-8.41, p = 0.001), preoperative plasma B-type natriuretic peptide (OR = 1.01, 95% CI = 1.00-1.01, p = 0.001), and left atrial diameter (OR = 1.10, 95% CI = 1.03-1.17, p = 0.001) were significantly associated with POAF. However, in an adjusted logistic regression model, age was found to be an independent predictor (OR = 1.31, 95% CI = 1.14-1.52, p < 0.0001) of POAF following OPCAB. Although stroke developed in the elderly (p >0.05), no mortality was observed postoperatively. Conclusions The prevalence of POAF following OPCAB in the elderly is higher than in young patients. Advancing age is an independent predictor of POAF following OPCAB.

Scientific evidence of sodium-glucose cotransporter-2 inhibitors for heart failure with preserved ejection fraction: an umbrella review of systematic reviews and meta-analyses.

It remains controversial whether sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are effective in treating heart failure with preserved ejection fraction (HFpEF). The objective of this umbrella review is to provide a summary of the available evidence regarding the efficacy and safety of SGLT-2is for the treatment of HFpEF. We extracted pertinent systematic reviews and meta-analyses (SRs/MAs) from PubMed, EMBASE, and the Cochrane Library that were published between the inception of the database and December 31, 2022. Two independent investigators assessed the methodological quality, risk of bias, report quality, and evidence quality of the included SRs/MAs in randomized controlled trials (RCTs). We further evaluated the overlap of the included RCTs by calculating the corrected covered area (CCA) and assessed the reliability of the effect size by performing excess significance tests. Additionally, the effect sizes of the outcomes were repooled to obtain objective and updated conclusions. Egger's test and sensitivity analysis were used to clarify the stability and reliability of the updated conclusion. This umbrella review included 15 SRs/MAs, and their methodological quality, risk of bias, report quality, and evidence quality were unsatisfactory. The total CCA for 15 SRs/MAs was 23.53%, indicating a very high level of overlap. The excess significance tests did not reveal any significant results. Our updated MA demonstrated that the incidence of the composite of hospitalization for heart failure (HHF) or cardiovascular death (CVD), first HHF, total HHF, and adverse events as well as the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and 6 min-walk distance (6MWD) were all substantially improved in the SGLT-2i intervention group compared to the control group. However, there was limited evidence that SGLT-2is could improve CVD, all-cause death, plasma B-type natriuretic peptide (BNP) level, or plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level. Egger's test and sensitivity analysis proved that the conclusion was stable and reliable. SGLT-2 is a potential treatment for HFpEF with favourable safety. Given the dubious methodological quality, reporting quality, evidence quality, and high risk of bias for certain included SRs/MAs, this conclusion must be drawn with caution. https://inplasy.com/, doi: 10.37766/inplasy2022.12.0083, identifier INPLASY2022120083.

B-Type Natriuretic Peptide Can Distinguish Ischemic Stroke Subtypes Better than Other Cardiac Biomarkers.

BACKGROUND The primary benefit to patients of being able to distinguish among subtypes of ischemic stroke (IS) is creation of a better treatment decision-making process. Current classification methods are complex and time-consuming, requiring hours to days. Blood-based cardiac biomarker measurements have the potential to improve mechanism classification of ischemic stroke. MATERIAL AND METHODS In this study, 223 patients with IS were selected as the case group and 75 healthy people who underwent physical examination at the same time were selected as the control group. The chemiluminescent immunoassay (CLIA) method established in this study was used to quantitatively detect plasma B-type natriuretic peptide (BNP) levels in subjects. All subjects were assessed for serum creatine kinase isoenzyme-MB (CK-MB), cardiac troponin I (cTnI), and myoglobin (MYO) after admission. We investigated the effectiveness of BNP and other cardiac biomarkers in the diagnosis of different subtypes of IS. RESULTS The levels of the 4 cardiac biomarkers were increased in IS patients. BNP could better diagnose different types of IS compared to other cardiac biomarkers, and BNP combined with other cardiac biomarkers was better than a single indicator in diagnosing IS. CONCLUSIONS Compared with other cardiac biomarkers, BNP is a better marker for the diagnosis of different subtypes of ischemic stroke. Routine screening for BNP in IS patients is recommended to improve the treatment decision-making process and minimize the time to thrombosis, thereby providing a more precise treatment for patients with different subtypes of stroke.

Time-Dependent Changes in N-Terminal Pro-Brain Natriuretic Peptide and B-Type Natriuretic Peptide Ratio During Hospitalization for Acute Heart Failure.

The time-dependent changes in the simultaneous evaluation of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels during hospitalization for acute heart failure (AHF) remain obscure.A total of 356 AHF patients were analyzed. Blood samples were collected within 15 minutes of admission (Day 1), 48-120 hours (Day 2-5) and between days 7 and 21 (Before-discharge). Plasma BNP and serum NT-proBNP were significantly decreased on Days 2-5 and Before-discharge in comparison to Day 1, but the NT-proBNP/BNP ratio was not changed. Patients were divided into 2 groups according to the median NT-proBNP/BNP (N/B) ratio on Day 2-5 (Low-N/B versus High-N/B). A multivariate logistic regression model showed that age (per 1-year increase), serum creatinine (per 1.0-mg/dL increase), and serum albumin (per 1.0-mg/dL decrease) were independently associated with High-N/B (odds ratio [OR]: 1.071, 95%confidence interval [CI]: 1.036-1.108, OR: 1.190, 95%CI: 1.121-1.264 and OR: 2.410, 95%CI: 1.121-5.155, respectively). Kaplan-Meier curve analysis showed that the High-N/B group had a significantly poorer prognosis than the Low-N/B group, and a multivariate Cox regression model revealed that High-N/B was an independent predictor of 365-day mortality (hazard ratio [HR]: 1.796, 95%CI: 1.041-3.100) and HF events (HR: 1.509, 95%CI: 1.007-2.263). The same trend in prognostic impact was significantly observed in both low and high delta-BNP cohorts (< 55% and ≥ 55% BNP value on the start date/BNP value at 2-5-days).A high NT-proBNP/BNP ratio on Day 2-5 was associated with non-cardiac conditions and was associated with adverse outcomes even if BNP was adequately decreased by the treatment of AHF.

Intravenous lipid emulsion for the treatment of acute lipid-soluble anesthetic drug toxicity in pediatric patients

Clinical studies on the use of lipid emulsions for the treatment of lipid-soluble anesthetic drug intoxication in children are relatively absent. Since children are not shrinking versions of adults, the therapeutic efficacy of lipid emulsions for the treatment of lipid-soluble anesthetic drug intoxication in pediatric patients is uncertain. This paper investigates the therapeutic efficacy and therapeutic mechanism of intravenous lipid emulsion for reversing acute narcotic drug intoxication in pediatric patients based on clinical data from west China Hospital of Sichuan University. The clinical data of 106 pediatric patients with acute lipid-soluble drug intoxication admitted to an inpatient center in the past 3 years were retrospectively analyzed and randomly divided into an observation group and a control group. The cardiac function indexes and blood gas indexes of patients in both groups were compared before and after treatment. After treatment, the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD) values and plasma B-type natriuretic peptide (BNP) in the observation group were lower than control group, and the left heart ejection fraction (LVEF) was higher than those in the control group, with statistically significant differences (P&lt;0.05). The arterial oxygen saturation (), partial pressure of oxygen () and acid-base (pH) values were higher in the observation group than in the control group, and the partial pressure of carbon dioxide () values were lower than in the control group. And these differences were statistically significant (P&lt;0.05). Therefore, intravenous lipid emulsion has a positive effect in reversing acute fat-soluble anesthetic drug intoxication in pediatric patients, and is effective in promoting recovery of cardiac function, reversing respiratory failure, and improving blood gas indexes. The results of the study demonstrated the effectiveness of intravenous lipid emulsion in reversing pediatric lipid-soluble anesthetic drug intoxication and enrich the clinical research on this issue.

Glucagon-Like Peptide-1 Receptor Agonist Protects Against Diabetic Cardiomyopathy by Modulating microRNA-29b-3p/SLMAP.

Our aims were to investigate the pathogenesis of diabetic cardiomyopathy (DCM) and to explore the protective effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) on DCM. After 12 weeks of treatment with exenatide-loaded microspheres, a long-acting GLP-1RA, in DCM mice, cardiac structure and function were evaluated by plasma B-type natriuretic peptide (BNP), echocardiography, H&E, oil red and Sirius staining. The expression of glucagon-like peptide-1 receptor in mouse heart tissue was determined by immunofluorescence staining. The label-free proteomic analysis of cardiac proteins was conducted among control, DCM and DM+GLP-1RA groups. Then, quantitative real-time PCR, Western blotting and dual-luciferase reporter assay were performed to verify the regulation of target protein by the upstream microRNA (miRNA). GLP-1RA treatment obviously improved serum BNP, myocardial fibrosis, lipid deposition of the myocardium and echocardiography parameters in DCM mice. Sarcolemmal membrane-associated protein (SLMAP) was one of 61 differentially expressed cardiac proteins found in three groups by proteomic analysis. Up-regulation of microRNA-29b-3p (miR-29b-3p) and down-regulation of SLMAP were found in the ventricular myocardium of GLP-1RA-treated DCM mice. SLMAP was a target of miR-29b-3p, while GLP-1RA regulated SLMAP expression through miR-29b-3p. Furthermore, inhibition of glucagon-like peptide-1 receptor (GLP-1R) in cardiomyocytes reversed the effects of GLP-1RA on miR-29b/SLMAP. SLMAP may play roles in the pathogenesis of DCM and may be a target of GLP-1RA in protecting against DCM. After binding to myocardial GLP-1R, GLP-1RA can regulate the expression of myocardial SLMAP through miR-29b-3p.

Insights and perspectives into clinical biomarker discovery in pediatric heart failure and congenital heart disease-a narrative review.

Heart failure (HF) in the pediatric population is a multi-factorial process with a wide spectrum of etiologies and clinical manifestations, that are distinct from the adult HF population, with congenital heart disease (CHD) as the most common cause. CHD has high morbidity/mortality with nearly 60% developing HF during the first 12 months of life. Hence, early discovery and diagnosis of CHD in neonates is pivotal. Plasma B-type natriuretic peptide (BNP) is an increasingly popular clinical marker in pediatric HF, however, in contrast to adult HF, it is not yet included in pediatric HF guidelines and there is no standardized reference cut-off value. We explore the current trends and prospects of biomarkers in pediatric HF, including CHD that can aid in diagnosis and management. As a narrative review, we will analyze biomarkers with respect to diagnosis and monitoring in specific anatomical types of CHD in the pediatric population considering all English PubMed publications till June 2022. We present a concise description of our own experience in applying plasma BNP as a clinical biomarker in pediatric HF and CHD (tetralogy of fallot vs. ventricular septal defect) in the context of surgical correction, as well as untargeted metabolomics analyses. In the current age of Information Technology and large data sets we also explored new biomarker discovery using Text Mining of 33M manuscripts currently on PubMed. (Multi) Omics studies from patient samples as well as Data Mining can be considered for the discovery of potential pediatric HF biomarkers useful in clinical care. Future research should focus on validation and defining evidence-based value limits and reference ranges for specific indications using the most up-to-date assays in parallel to commonly used studies.

Deterioration of Phosphate Homeostasis Is a Trigger for Cardiac Afterload - Clinical Importance of Fibroblast Growth Factor 23 for Accelerated Aging.

Background: After the discovery of the Klotho gene, phosphate came into focus as a pathogenetic aging agent. Phosphate homeostasis is controlled by phosphate-regulating hormones: fibroblast growth factor 23 (FGF23), vitamin D3, and parathyroid hormone. This study investigated the relationship between the deterioration in phosphate homeostasis and arterial stiffness by measuring serum FGF23 concentrations. Methods and Results: The study subjects comprised 82 hospitalized patients (31 males, 51 females; mean [±SD] age 78.6±10.5 years). All patients underwent chest computed tomography, measurement of central blood pressure (BP), and blood chemistry tests. Arterial calcification and/or stiffness was evaluated using the Agatston calcification score (ACS) and pulse wave velocity (PWV). PWV was significantly correlated with age (t=23.47, P<0.0001), estimated glomerular filtration rate (eGFR; t=-4.40, P<0.0001), and ACS (t=4.36, P<0.0001). Serum FGF23 concentrations were significantly correlated with age (t=2.52, P=0.014), eGFR (t=-3.37, P<0.001), serum inorganic phosphorus concentrations (t=3.49, P<0.001), serum vitamin D3 concentrations (t=-4.57, P<0.001), ACS (t=2.30, P=0.025), augmentation pressure (t=2.48, P=0.015), central systolic BP (t=2.00, P=0.049), plasma B-type natriuretic peptide (BNP) concentrations (t=3.48, P<0.001), and PWV (t=2.99, P=0.004). PWV was positively related to augmentation pressure (t=4.09, P<0.001), central systolic BP (t=3.13, P=0.002), and plasma BNP concentrations (t=3.54, P<0.001). Conclusions: This study shows that the increase in serum FGF23 concentrations reflects deterioration of phosphate homeostasis and is an important predictor for arterial stiffness, which intensifies cardiac afterload.

Coronary microcirculation dysfunction evaluated by myocardial contrast echocardiography predicts poor prognosis in patients with ST-segment elevation myocardial infarction after percutaneous coronary intervention

BackgroundThe mortality rate of acute ST-segment elevation myocardial infarction (STEMI) remains substantial, despite advances in treatment strategies. Coronary microcirculation dysfunction (CMD) persists after percutaneous coronary intervention (PCI) in a substantial proportion of STEMI patients. The association between CMD assessed using myocardial contrast echocardiography (MCE) and prognosis requires further elucidation. This study aimed to evaluate the impact of CMD after successful PCI on the prognosis of patients with STEMI.MethodsWe enrolled 167 patients with STEMI after PCI who underwent MCE during hospitalization between January 2018 and March 2022. Patients were classified into the CMD and non-CMD groups according to the results of MCE. The clinical data and MCE results of both groups were analyzed. Follow-up was conducted for major adverse cardiac events.ResultsMCE detected CMD in 105 patients (62.9%). The CMD group contained fewer hypertensive patients (55.2% versus 74.2%, P = 0.015). Patients with CMD exhibited significantly higher levels of plasma troponin I (TnI) [73.2 (23.0–124.0) versus 28.9 (12.7–80.2) ng/mL, P = 0.004], higher levels of plasma B-type natriuretic peptide [255 (99–641) versus 193 (59–389) pg/mL, P = 0.004], poorer Killip classification (P = 0.038), and different culprit vessels (P < 0.001) compared to the non-CMD group. Patients with CMD exhibited lower left ventricular ejection fraction [50 (43–58) versus 61 (54–67) %, P < 0.001], poorer wall motion score index values (1.68 ± 0.4 versus 1.31 ± 0.26, P < 0.001) and poorer left ventricular global longitudinal strain [–11.2 (–8.7 to –14.1) versus –13.9 (–11.0 to –17.2) %, P < 0.001] compared to the non-CMD group. Patients underwent follow-up for 13 (7–20) months. After adjusting for hypertension, peak TnI level, culprit vessel, and Killip classification, CMD was an independent predictor of total major adverse cardiac events at 13 months’ follow-up [adjusted odds ratio (OR), 2.457; 95% confidence interval (CI), 1.042–5.790; P = 0.040], and patients with CMD had a higher risk of hospitalization for heart failure (adjusted OR, 5.184; 95% CI, 1.044–25.747; P = 0.044) and repeat myocardial infarction (adjusted OR, 2.896; 95% CI, 1.109–7.565; P = 0.030).ConclusionsMCE is a safe and effective method for detecting CMD in patients with STEMI. CMD detected by MCE after successful PCI in patients with STEMI is a common occurrence, which is associated with a significantly worse prognosis, especially hospitalization for heart failure and repeat myocardial infarction.

Correlation Between Plasma B-Type Natriuretic Peptide Levels and Remote Dielectric Sensing in Patients with Heart Failure.

Plasma B-type natriuretic peptide (BNP) is a practical tool with which to estimate hemodynamic status including intra-cardiac pressure in patients with heart failure (HF). However, plasma BNP levels cannot be measured immediately in an outpatient private clinic. We investigated the value of remote dielectric sensing (ReDS), a novel non-invasive electromagnetic energy-based tool to quantify lung fluid amount immediately, to predict plasma BNP levels.Successive measurements of ReDS values and plasma BNP levels were performed in patients hospitalized to treat HF in a prospective manner. Correlations between ReDS values and plasma BNP levels were assessed.A total of 117 datasets for HF patients were obtained in this prospective study. The median ReDS value was 28% (interquartile range: 25%, 34%) and the median plasma BNP level was 205 (86, 469) pg/mL, both of which had a slight correlation (r = 0.234, P = 0.011). Their correlation improved when those with a body mass index less than 18.5 (n = 23) were excluded (r = 0.278, P = 0.007).ReDS might be a practical tool for estimating plasma BNP levels, particularly in outpatient private clinics where the immediate measurement of plasma BNP levels is not available.

Abstract 12648: Comparison of Transthyretin Amyloid Cardiomyopathy Patients Taking Tafamidis and Those Not Taking Tafamidis Using Two-Dimensional Speckle Tracking Echocardiography

Objectives: Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), this study investigated the effect of tafamidis on left heart function in ATTR-CM patients by using two-dimensional speckle tracking echocardiography. Methods and Results: We evaluated 222 consecutive patients with ATTR-CM who were diagnosed at our department between January 2002 and February 2022 retrospectively. Eighty patients taking tafamidis had a history of echocardiography before and 12 months after treatment, and thirty-four untreated patients had a history of echocardiography after diagnosis and 12 months later. Serum high-sensitivity cardiac troponin T (hs-cTnT) significantly decreased in the treatment group (hs-cTnT :0.067±0.037 vs. 0.056±0.031, p&lt;0.01) but didn’t change significantly in the untreated group (hs-cTnT :0.085±0.110 vs. 0.084±0.070, p=0.98). Plasma B-type natriuretic peptide did not change significantly in each group. Creatinine increased significantly in the treatment group (creatinine:1.12±0.31 vs. 1.19±0.50, p=0.03) and did not change in the untreated group (creatinine:1.40±0.91 vs. 1.48±0.90, p=0.17). Left ventricular global longitudinal strain (LVGLS) and left atrial strain rate during atrial contraction (LASRa) didn’t change significantly in the treatment group (LVGLS: -8.4±2.9 vs. -8.3±2.9, p=0.30 LASRa: -0.24±0.21 vs. -0.23±0.18, p=0.49) but increased significantly in the untreated group (LVGLS: -10.9±3.3 vs. -7.8±5.2, p&lt;0.01, LASRa: -0.44±0.39 vs. -0.29±0.24, p=0.01). Conclusion: Tafamidis may be effective in maintaining left heart function in ATTR-CM patients.