Heart failure (HF) is a leading cause of mortality among patients with cardiovascular disease and is often associated with myocardial apoptosis and endoplasmic reticulum stress (ERS). While hydrogen has demonstrated potential in reducing oxidative stress and ERS, recent evidence suggests that magnesium may aid in hydrogen release within the body, further enhancing these protective effects. This study aimed to investigate the cardioprotective effects of magnesium in reducing apoptosis and ERS through hydrogen release in a rat model of isoproterenol (ISO)-induced HF. Magnesium was administered orally to ISO-induced HF rats, which improved cardiac function, reduced myocardial fibrosis and cardiac hypertrophy, and lowered the plasma levels of creatine kinase-MB, cardiac troponin-I, and N-terminal B-type natriuretic peptide precursor in ISO-induced HF rats. It also inhibited cardiomyocyte apoptosis by upregulating B-cell lymphoma-2, downregulating Bcl-2-associated X protein, and suppressing ERS markers (glucose-related protein 78, activating transcription factor 4, and C/EBP-homologous protein). Magnesium also elevated hydrogen levels in blood, plasma, and cardiac tissue, as well as in artificial gastric juice and pure water, where hydrogen release lasted for at least four hours. Additionally, complementary in vitro experiments were conducted using H9C2 cardiomyocyte injury models, with hydrogen-rich culture medium as the intervention. Hydrogen-rich culture medium improved the survival and proliferation of ISO-treated H9C2 cells, reduced the cell surface area, inhibited apoptosis, and downregulated ERS pathway proteins. However, the protective effects of hydrogen were negated by tunicamycin (an inducer of ERS) in H9C2 cells. In conclusion, magnesium exerts significant cardioprotection by mitigating ERS and apoptosis through hydrogen release effects in ISO-induced HF.

The high-sensitivity detection of low-concentration multicomponent biomarkers in the blood of heart failure (HF) patients using surface-enhanced Raman spectroscopy (SERS) remains a significant challenge. In this study, an ultrasensitive biosensor for the detection of multicomponent HF biomarkers was designed. This biosensor utilizes Au@Ag nanoparticles (Au@Ag NPs) functionalized with Raman reporter molecules (RaRs) as SERS probes, and Ag-coated Fe3O4 nanoparticles (Fe3O4-Ag NPs) modified with internal standard (IS) molecules as the capture substrate, offering the dual advantages of magnetic enrichment and SERS enhancement. Additionally, specific aptamers or antibodies were conjugated to the surfaces of Au@Ag NPs and Fe3O4-Ag NPs to specifically recognize target proteins to construct a three-layer composite structure (Fe3O4-Ag/HF biomarkers/Au@Ag). The limit of detection (LOD) of HF markers for cTnI, NT-proBNP, and sST2 is 0.1 pg/mL, 1.0 fg/mL, and 1.0 fg/mL, respectively, surpassing most reported methods. Additionally, the analysis of 45 clinical serum samples revealed no statistically significant differences between the SERS-based results and those obtained by conventional clinical methods, as confirmed by the Shapiro-Wilk test (p > 0.05). In conclusion, this SERS biosensor successfully developed an easy-to-operate accurate diagnosis method capable of simultaneous, quantitative detection of multiple HF biomarkers and provided a new technique for accurate diagnosis of other diseases in clinical testing.

Limited access to echocardiography can delay the diagnosis of suspected heart failure (HF), which in turn postpones the initiation of optimal guideline-directed medical therapy. Although natriuretic peptides like B-type natriuretic peptide (BNP) are valuable biomarkers for diagnosing and managing HF, the utility of combining BNP with other blood-based biomarkers to predict subtypes of new-onset HF remains underexplored.

This study sought to investigate and evaluate the diagnostic significance of adding blood-based biomarkers to BNP for identifying heart failure with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF), with the goal of enhancing diagnostic assays beyond BNP measurements.

We identified candidate blood protein biomarkers using untargeted proteomics workflows from a cohort of individuals recruited to the STOP-HF trial who were at risk of HF and subsequently developed either HFpEF or HFrEF over time ("HF progressors"; n = 40). Candidate biomarkers were verified in an independent cohort (n = 52) from a community-based rapid access HF diagnostic clinic. The biological processes associated with these proteins were assessed, and the diagnostic values of biomarker panels were evaluated using a machine learning approach.

Within HF progressors, we identified 3 proteins associated with HFpEF development: vascular cell adhesion protein 1 (VCAM1), insulin-like growth factor 2 (IGF2), and inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3). Additionally, 4 proteins were linked to HFrEF development: C-reactive protein (CRP), interleukin-6 receptor subunit beta (IL6RB), phosphatidylinositol-glycan-specific phospholipase D (PHLD), and noelin (NOE1). These findings were verified in an independent cohort to distinguish HF subtypes from controls. Moreover, a random forest algorithm demonstrated that combining these candidate biomarkers with BNP measurement significantly improved the prediction of HF subtypes.

We identified candidate proteins linked to HFpEF and HFrEF in a longitudinal HF progressor cohort and validated them in a community-based cohort. Adding these proteins to BNP led to a significant improvement in HF subtype prediction. Study results have clinical implications for blood-based screening of HF subtypes using panels of biomarkers, particularly in resource-limited settings.

NT-proBNP is widely measured for the diagnosis of acute heart failure (HF). This study assessed the diagnostic performance of a novel N-terminal pro-B type natriuretic peptide (NT-proBNP) assay in evaluating the dyspneic patient in the acute care setting.

This was a multicenter study of individuals presenting to the emergency department exhibiting clinical symptoms potentially due to acute HF. Blood was drawn for NT-proBNP assessment using the Beckman Coulter Access NT-proBNP assay with results compared to adjudicated diagnoses. Endpoints included negative predictive value and sensitivity of an age-independent cut point of < 300 ng/L to exclude acute HF, and the positive predictive value of the age-dependent cut points of >450, >900, and >1800 ng/L for ages < 50 years, 50-75 years, and >75 years, respectively, for the diagnosis of acute HF.

490 study participants were included, of which 41 % were adjudicated as having acute heart failure. The assay had an area under the receiver-operator characteristic curve (AUC) for the diagnosis of acute HF of 0.87 (P < 0.001), comparable AUC to other commercially available NT-proBNP assays. A rule-out cut point of <300 ng/L had 96 % sensitivity and negative predictive value of 95 %. Age-dependent cut points had sensitivity of 84 %, 90 %, and 87 %, specificity of 81 %, 70 % and 61 %, and positive predictive value of 72 %, 62 %, and 74 %, respectively.

This novel NT-proBNP assay demonstrated high clinical performance in the diagnosis and exclusion of acute HF in the undifferentiated dyspneic patient and performed similarly well to validated assays used in clinical practice.

Clinical trials have established the prognostic benefits of sodium‒glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF) with preserved ejection fraction (HFpEF), although the underlying mechanisms are not clearly understood. The purpose of this study was to determine the effects of the SGLT2 inhibitor empagliflozin on functional capacity, left ventricular (LV) diastolic function/filling pressure, and cardiac reserves in patients with HFpEF and T2DM.

In the present prospective single-center trial, we enrolled 70 diabetic patients with stable HF according to the New York Heart Association functional class II-III criteria, an LV ejection fraction ≥ 50%, and increased LV filling pressure at rest and/or during exercise (determined by echocardiography). The patients were randomly assigned in an open-label fashion to the empagliflozin group (10 mg a day, n = 35) or the control group (n = 35) for 6 months. Echocardiography (at rest and during exercise), the 6-min walk test distance (6MWD), blood levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and the profibrotic biomarker sST2 were analysed at baseline and 6 months after randomization. The primary endpoint was the change in the 6MWD, and the secondary endpoints included the change in the left atrial (LA) volume index, early mitral inflow to mitral annulus relaxation velocity (E/e') ratio both at rest and during exercise, key cardiac reserves and biomarkers in the blood from baseline to 6 months.

After 6 months of empagliflozin therapy, the 6MWTD significantly increased, whereas the LA volume index and the E/e' ratio both at rest and during exercise decreased compared with those of the control group (P < 0.05 for all). LV diastolic, LA reservoir and contractile, and chronotropic reserves also improved in the empagliflozin group compared with those in the control group (P < 0.05 for all). Furthermore, treatment with empagliflozin led to improvements in NT-proBNP and ST2 blood levels compared with those in the control group (P < 0.05 for both).

In diabetic patients with HFpEF, empagliflozin treatment improved exercise capacity, which appeared to be the result of favourable effects on LV diastolic dysfunction and key cardiac reserves: LV diastolic, LA reservoir and contractile, and chronotropic. These haemodynamic mechanisms may underline the benefits of SGLT2 inhibitors in large-scale HFpEF trials.

URL: https://www.

gov . Unique Identifier NCT03753087.

In Portugal, a 15.2% prevalence of heart failure with preserved ejection fraction (HFpEF) was recently identified among those aged ≥50 years. HFpEF represents 90% of Portuguese heart failure patients. HFpEF management in Portugal is challenging due to patient heterogeneity, diagnostic and therapeutic complexity, and organizational constraints on the healthcare system. Considering the above, a panel of Portuguese experts convened to address HFpEF management within the national context. This was done in a two-paper set. This, the second paper, identifies unmet needs and suggests a set of measures to improve the current organization of HFpEF management in Portugal. Our purpose is to create a multidisciplinary integrated care system, ensuring a seamless connection between hospitals and primary care. Additionally, we propose a practical approach to the management of HFpEF, including a roadmap for screening, diagnosis, referral and treatment. The aim is to help clinicians improve HFpEF management throughout the disease trajectory.

This clinical consensus statement revisits the role of left ventricular ejection fraction (LVEF) as a measurement of cardiac function, a prognostic marker and a major criterion to classify patients with heart failure, and gives new advice for clinical practice. Heart failure is traditionally classified on the basis of LVEF thresholds and this has major implications for treatment recommendations. However, the reproducibility of LVEF measurement is poor and its prognostic and diagnostic value lessens when it is above 45%, with no relationship with the severity of either cardiac dysfunction or outcomes at higher values. These limitations dictate the need for a more comprehensive approach to classify and assess heart failure focusing more on the trajectory of LVEF rather than to its absolute value. Furthermore, the assessment of LVEF is not required for the initiation of treatments like sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and diuretics in patients with suspected de novo heart failure and elevated N-terminal pro-B-type natriuretic peptide levels. Future research utilizing advanced imaging techniques and biomarkers which can better characterize myocardial structure, metabolism and performance may facilitate the identification of alternative therapeutic targets and better ways to monitor heart failure therapies across the entire spectrum of LVEF.

Ambulatory patients presenting with signs or symptoms of heart failure (HF) should undergo natriuretic peptide testing. Rates of death, HF hospitalization, and healthcare costs were examined in patients thus identified with suspected de novo HF.

This population-based study (REVOLUTION HF) encompassing two large healthcare regions in Sweden examined patients who presented to outpatient care for the first time between 1 January 2015 and 31 December 2020, who had a recorded sign (peripheral oedema) or symptom (dyspnoea) of HF, and whose N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured >300 ng/L within ±30 days of that sign or symptom. Characteristics, outcomes, healthcare patterns, and healthcare costs for these patients were followed for 1 year. Comparisons were made with matched controls without history of HF, its signs, its symptoms, or elevated NT-proBNP.

Overall, 5942 patients (median age 78.7 years; 54% women) presented with suspected de novo HF. Within 1 year, 29% had received a HF diagnosis. Patients with suspected de novo HF had higher rates of all-cause death (11.7 vs. 6.5 events/100 person-years) and HF hospitalizations (12.5 vs. 2.2 events/100 person-years) than matched controls (n = 2048), with the highest event rates in the weeks after presentation. Rates were higher with higher NT-proBNP levels. Although some patients already used HF guideline-directed medical therapies for other indications, initiation of new medications was variable. Healthcare costs were higher in patients with suspected de novo HF than in matched controls, driven mostly by HF and chronic kidney disease.

Patients with suspected HF and elevated NT-proBNP had high mortality and morbidity in the weeks after presentation, and accrued substantial healthcare costs, highlighting an urgent need for prompt identification, evaluation, and treatment of HF.

Migrasomes are newly identified organelles that were first discovered in 2015. Since then, their biological structure, formation process, and physiological functions have been gradually elucidated. Research in recent years has expanded our understanding of these aspects, highlighting their significance in various physiological and pathological processes. Migrasomes have been found to play crucial roles in normal physiological functions, including embryonic development, vascular homeostasis, material transport, and mitochondrial quality control. Additionally, emerging evidence suggests their involvement in various diseases; however, clinical research on their roles remains limited. Current studies indicate that migrasomes may contribute to disease pathogenesis and hold potential for diagnostic and therapeutic applications. This review consolidates existing clinical research on migrasomes, focusing on their role in disease mechanisms and their use in medical applications. By examining their biological structure and function, this review aims to generate insights that encourage further research, ultimately contributing to advancements in disease prevention and treatment.

Background: Suppression of Tumorigenicity 2 (ST2), a member of the interleukin-1 receptor family, plays a crucial role in immune regulation. Elevated sST2 levels are associated with poor prognosis in various inflammatory and cardiovascular diseases, including acute heart failure (AHF), sepsis and transplant rejection. Objectives and methods: This study aimed to evaluate the diagnostic and prognostic accuracy of sST2, along with other biomarkers, such as high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), procalcitonin (PCT) and mid-regional pro-adrenomedullin (MR-proADM), in patients with AHF, sepsis and AHF/sepsis overlap. Results: A cohort of 74 patients was analyzed, and comparison statistics revealed that sST2 levels were significantly higher in the AHF/sepsis group (113.88 ng/mL) compared to the AHF group (42.24 ng/mL, p = 0.024), while no significant difference was observed between sepsis and AHF groups (p = 0.10). Other biomarkers, including hs-CRP and PCT, showed significant differences between the AHF and AHF/sepsis groups. ROC curve analysis identified sST2 as a strong predictor of mortality and readmission, with high AUC values for 30-day readmission (0.821) and mortality (0.87). Conclusions: These findings suggest that combining biomarkers, including sST2, could improve the early diagnosis, risk stratification and management of critically ill patients with overlapping AHF and sepsis. Further studies with larger populations are needed to validate these findings and explore the potential of integrating these biomarkers into clinical practice.

Heart failure (HF) is a major health problem, and preventing the onset of heart failure could have large cost implications for healthcare systems globally. Screening for heart failure and its precursor, left ventricular dysfunction, could allow patients to receive therapies shown to reduce the risk of incident heart failure, such as ACE inhibitors and beta blockers. Using echocardiography to screen patients is costly. Natriuretic peptides could be used to screen populations for asymptomatic left ventricular function. However, natriuretic peptide levels vary by age, sex and presence of comorbidities such as atrial fibrillation and kidney disease. Using one threshold value in a large population may impair the sensitivity and specificity of such an approach, but prior studies in community-based adults suggest that this is a feasible strategy. A higher yield strategy would be to screen high-risk patients, such as those with diabetes mellitus, and current guidelines for the management of diabetes suggest using natriuretic peptides to screen patients for unrecognised heart failure. Natriuretic peptides can also help ascertain the risk of future cardiovascular events and deaths in patients with diabetes. Natriuretic peptides have established themselves as a central part of the definition of heart failure. However, more work needs to be done to determine the optimal age, sex and body weight-based thresholds, as well as thresholds for those with comorbidities like atrial fibrillation and chronic kidney disease. These are needed to determine and optimise the sensitivity and specificity of natriuretic peptides in the diagnosis of heart failure. Clinicians should use guideline-recommended thresholds to diagnose HF with natriuretic peptides but consider factors that influence levels, such as age, kidney function, etc. It is yet unclear if natriuretic peptides can be used to guide the management of patients with heart failure.

This clinical consensus statement revisits the role of left ventricular ejection fraction (LVEF) as a measurement of cardiac function, a prognostic marker and a major criterion to classify patients with heart failure, and gives new advice for clinical practice. Heart failure is traditionally classified on the basis of LVEF thresholds and this has major implications for treatment recommendations. However, the reproducibility of LVEF measurement is poor and its prognostic and diagnostic value lessens when it is above 45%, with no relationship with the severity of either cardiac dysfunction or outcomes at higher values. These limitations dictate the need for a more comprehensive approach to classify and assess heart failure focusing more on the trajectory of LVEF rather than to its absolute value. Furthermore, the assessment of LVEF is not required for the initiation of treatments like sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and diuretics in patients with suspected de novo heart failure and elevated N-terminal pro-B-type natriuretic peptide levels. Future research utilizing advanced imaging techniques and biomarkers which can better characterize myocardial structure, metabolism and performance may facilitate the identification of alternative therapeutic targets and better ways to monitor heart failure therapies across the entire spectrum of LVEF.

Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) is commonly used to diagnose heart failure with preserved ejection fraction (HFpEF), but its diagnostic performance in the ambulatory/outpatient setting is unknown because previous studies lacked objective reference standards.

Among patients with chronic dyspnea, diagnosis of HFpEF or noncardiac dyspnea was determined conclusively by exercise catheterization in a derivation cohort (n=414), multicenter validation cohort 1 (n=560), validation cohort 2 (n=207), and a nonobese Japanese validation cohort 3 (n=77). Optimal NT-proBNP cut points for HFpEF rule out (optimizing sensitivity) and rule in (optimizing specificity) were derived and tested, stratified by obesity and atrial fibrillation. Derived cut points were tested in 3 additional validation cohorts (cohorts 4-6) in whom HFpEF was diagnosed by resting catheterization only (n=260), previous hospitalization for heart failure (n=447), or exercise echocardiography (n=517), respectively.

Current recommended rule-out NT-proBNP threshold <125 pg/mL had 82% sensitivity (95% CI, 77%-88%) with a body mass index (BMI) <35 kg/m2, decreasing to 67% (95% CI, 58%-77%) with a BMI ≥35 kg/m2. A lower rule-out NT-proBNP threshold <50 pg/mL displayed good sensitivity with a BMI <35 kg/m2 (97% [95% CI, 95%-99%]), with a modest decline in sensitivity with a BMI ≥35 kg/m2 (86% [95% CI, 79%-93%]); diagnostic thresholds were confirmed in validation cohorts 1 and 2 (91% [95% CI, 88%-95%] and 86% [95% CI, 80%-93%] with a BMI <35 kg/m2; 80% [95% CI, 74%-87%] and 84% [95% CI, 74%-93%] with a BMI ≥35 kg/m2). Current consensus age- and BMI-stratified rule-in thresholds demonstrated only 65% specificity (95% CI, 57%-72%). Rule-in NT-proBNP threshold ≥500 pg/mL had 85% specificity (95% CI, 78%-91%) with a BMI <35 kg/m2 (87% [95% CI, 80%-94%] and 90% [95% CI, 81%-99%] in validation cohorts), with 100% specificity at a BMI ≥35 kg/m2 (93% [95% CI, 81%-100%] and 100% in validation cohorts). With a BMI ≥35 kg/m2, lower rule-in thresholds (≥220 pg/mL) provided good specificity (88% [95% CI, 73%-100%]; 93% [95% CI, 81%-100%] and 100% in validation cohorts). Findings were consistent in validation cohorts 3 through 6 (sensitivity of <50 pg/mL, 93%-98%; specificity of ≥500 pg/mL, 82%-89%). NT-proBNP provided no incremental discrimination among patients with history of AF; ≥98% of patients with AF and dyspnea were found to have HFpEF in our cohorts.

In patients with chronic unexplained dyspnea, current rule-in and rule-out NT-proBNP diagnostic thresholds lead to unacceptably high error rates, with important interactions by obesity and AF status. In our study, NT-proBNP provided little value in those with AF and dyspnea because the presence of AF is by itself a robust biomarker of HFpEF. Use of separate rule-in and rule-out diagnostic thresholds stratified by BMI reduces miscategorization and can guide more appropriate use of exercise testing for possible HFpEF.

Given the close relationship between cardiovascular disease (CVD) and malnutrition, we examined whether higher concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), which indicate CVD risk in the general population, were prospectively associated with malnutrition incidence in community-dwelling older adults without CVD.

We used data from 1490 individuals ≥65 years from the Seniors-ENRICA-2 cohort followed up for 2.2 years. Malnutrition was evaluated by the screening Mini Nutritional Assessment-Short Form (MNA-SF) score, which consists of a short questionnaire, and a complete nutritional assessment according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. Associations were summarized with odds ratios (OR) and their 95% confidence interval (CI), obtained from logistic regression and adjusted for the main confounders.

NT-proBNP was associated with higher malnutrition incidence assessed by the MNA-SF score and the GLIM criteria, with OR (95% CI) of 1.51 (1.09-2.09) and 1.43 (1.04-1.96) per one logarithmic-unit increment, respectively. Malnutrition incidence according to the GLIM criteria was also higher in participants who had elevated NT-proBNP (heart stress age-specific rule-in cutoffs) vs those who did not, with OR (95% CI) of 1.84 (1.05-3.22). hs-cTnT was not associated with higher malnutrition incidence.

In this cohort of older adults without CVD, NT-proBNP was associated with higher malnutrition incidence. Further research is needed to validate our findings, uncover the underlying biological mechanisms, and assess whether preventive interventions can reduce NT-proBNP concentrations and, consequently, reduce the risk of malnutrition.

Natriuretic peptide-based pre-heart failure screening has been proposed in recent guidelines. However, an effective strategy to identify screening targets from the general population, more than half of which are at risk for heart failure or pre-heart failure, has not been well established. This study evaluated the performance of machine learning prediction models for predicting elevated N terminal pro brain natriuretic peptide (NT-proBNP) levels in the US general population.

Individuals aged 20-79 years without cardiovascular disease from the nationally representative National Health and Nutrition Examination Survey 1999-2004 were included. Six prediction models (two conventional regression models and four machine learning models) were trained with the 1999-2002 cohort to predict elevated NT-proBNP levels (>125 pg/mL) using demographic, lifestyle, and commonly measured biochemical data. The model performance was tested using the 2003-2004 cohort. Of the 10 237 individuals, 1510 (14.8%) had NT-proBNP levels >125 pg/mL. The highest area under the receiver operating characteristic curve (AUC) was observed in SuperLearner (AUC [95% CI] = 0.862 [0.847-0.878], P < 0.001 compared with the logistic regression model). The logistic regression model with splines showed a comparable performance (AUC [95% CI] = 0.857 [0.841-0.874], P = 0.08). Age, albumin level, haemoglobin level, sex, estimated glomerular filtration rate, and systolic blood pressure were the most important predictors. We found a similar prediction performance even after excluding socio-economic information (marital status, family income, and education status) from the prediction models. When we used different thresholds for elevated NT-proBNP, the AUC (95% CI) in the SuperLearner models 0.846 (0.830-0.861) for NT-proBNP > 100 pg/mL and 0.866 (0.849-0.884) for NT-proBNP > 150 pg/mL.

Using nationally representative data from the United States, both logistic regression and machine learning models well predicted elevated NT-proBNP. The predictive performance remained consistent even when the models incorporated only commonly available variables in daily clinical practice. Prediction models using regularly measured information would serve as a potentially useful tools for clinicians to effectively identify targets of natriuretic-peptide screening.

Physicians' adherence to guideline-recommended heart failure (HF) treatment remains suboptimal, especially regarding the target doses. In particular, there is evidence that non-cardiologists are less compliant with HF guideline recommendations. This is likely to have a detrimental impact on patients' survival, readmissions and quality of life. Thus, the present document aims to address the reasons underlying low implementation and under-dosing of guideline-directed medical therapy in HF and to update a guidance for the initiation and rapid titration of HF drugs. In particular, aim of this document is to provide practical indications for drug implementation, to be applied not only by cardiologists but also by GPs and internal medicine doctors.

Heart failure (HF) remains a major cause of morbidity and mortality worldwide and represents a major challenge for diagnosis, prognosis and treatment due to its heterogeneity. Traditional biomarkers such as BNP and NT-proBNP are valuable but insufficient to capture the complexity of HF, especially phenotypes such as HF with preserved ejection fraction (HFpEF). Recent advances in multi-omics technology and novel biomarkers such as cell-free DNA (cfDNA), microRNAs (miRNAs), ST2 and galectin-3 offer transformative potential for HF management. This review explores the integration of these innovative biomarkers into clinical practice and highlights their benefits, such as improved diagnostic accuracy, enhanced risk stratification and non-invasive monitoring capabilities. By leveraging multi-omics approaches, including lipidomics and metabolomics, clinicians can uncover new pathways, refine the classification of HF phenotypes, and develop personalized therapeutic strategies tailored to individual patient profiles. Remarkable advances in proteomics and metabolomics have identified biomarkers associated with key HF mechanisms such as mitochondrial dysfunction, inflammation and fibrosis, paving the way for targeted therapies and early interventions. Despite the promising results, significant challenges remain in translating these findings into routine care, including high costs, technical limitations and the need for large-scale validation studies. This report argues for an integrative, multi-omics-based model to overcome these obstacles and emphasizes the importance of collaboration between researchers, clinicians and policy makers. By linking innovative science with practical applications, multi-omics approaches have the potential to redefine HF management and lead to better patient outcomes and more sustainable healthcare systems.

In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article.

This survey investigates natriuretic peptide (NP) testing in community and hospital settings, assessing awareness, accessibility, and utilization.

This investigator-initiated survey, conceived within the HFA of the European Society of Cardiology, comprised 14 questions. It underwent validation and pilot testing to ensure question readability and online system functionality. The survey was accessible for 87 days, from 5 April 2023 to 1 July 2023 via a web platform. There were 751 healthcare professionals across 99 countries who responded. Of them, 92.5% had access to NPs testing in hospital whereas 34.3% had no access to NTproBNP in community settings. Access to point of care NP testing was uncommon (9.6%). Public insurance fully covered NPs testing in 31.0% of cases, with private insurance providing coverage in 37.9%. The majority (84.0%) of participants believed that the medical evidence supporting NPs testing was strong, and 54.7% considered it cost-effective. Also, 35.8% found access, awareness, and adoption to be in favour of NPs testing both in hospital and community settings. Strategies to optimize NP testing involved regular guideline updates (57.9%), prioritizing NPs testing for dyspnoea assessment (36.4%), and introducing clinician feedback mechanisms (21.2%). Notably, 40% lacked a community-based HF diagnostic pathway for referring high-NP patients for echocardiography and cardiology evaluation.

This survey reveals NP awareness, access, and adoption across several countries. Highlighting the importance of community-based early heart failure diagnosis and optimizing HF diagnostic pathways remains a crucial, unmet opportunity to improve patient outcomes.

Blood-biomarkers have the potential to aid clinicians in pediatric emergency departments (PED) in managing children with mild traumatic brain injury (mTBI) acutely. However, studies focusing on pediatric populations remain limited. We aim to assess the performances of two routinely used biomarkers in other fields: the neurofilament light chain protein (NfL), and the N-terminal prohormone of brain natriuretic peptide (NTproBNP), to safely discharge children without intracranial injuries (ICIs).

A prospective multicenter cohort study was conducted, enrolling children suffering from mTBI, both with and without imaging during their acute management in the PED. A blood sample was collected within 24 h post-trauma for biomarker analysis. Inclusion criteria followed the PECARN (Pediatric Emergency Care Applied Research Network) guidelines for the diagnosis of mTBI and for ICI on CT as the primary outcome (CT+).

A total of 302 mTBI patients were analyzed comparing children with ICI (18 CT+) versus all the other children without ICI (54 CT- and 230 in-hospital-observation patients without CT). NfL and NTproBNP were increased in the CT+ group and their performances to safely rule-out patient without ICI reached up to 30% specificity with 100% sensitivity. Equivalent performances were observed whether selecting patients with blood collection within 6 h or 24 h post-trauma.

NfL and NTproBNP were described for the first time in children suffering mTBI. Their performances were comparable to well-known biomarkers, such as S100b, GFAP, or HFABP, with the benefit of already being used in routine tests for other diseases. Further large-scale studies are necessary to verify and validate these results.

Background/Objectives: Soluble αKlotho (sαKlotho) and fibroblast growth factor 23 (FGF-23) are increased in acute heart failure (AHF). This study aimed to assess changes in serum sαKlotho and FGF-23 concentrations during an episode of AHF as well as the usefulness of both biomarkers for predicting long-term prognosis. Methods: The study included 104 consecutive patients hospitalized in t he intensive cardiac care unit due to AHF (mean age, 65.8 ± 14.6 years; mean ejection fraction, 31.4% ± 14). New-onset AHF was reported in 43.3% of the population. Blood samples were measured at entry and on discharge from hospital. The main clinical outcomes assessed in this study were all-cause mortality or rehospitalization due to HF during a 3-year follow-up. Results: At admission sαKlotho, FGF-23, and NT-pro BNP levels, compared with discharge, were significantly higher at p < 0.001, p < 0.001, and p < 0.001 respectively. The 3-year Kaplan-Meier analysis, based on tertiles, revealed, for sαKlotho levels from Tertile 1 on admission and at discharge, a 2-fold higher rate of all-cause mortality or rehospitalization for HF compared with Tertile 3 (p = 0.006 and p = 0.028, respectively). One-third of patients showed an increase in FGF-23 and sαKlotho levels during hospitalization. Patients with the highest percentage increase in the levels of both biomarkers had an elevated risk of all-cause morality or hospitalization for HF (hazard ratio, 2.75; confidence interval, 1.19-6.35; p = 0.02). Conclusions: sαKlotho and FGF-23 levels are elevated during an episode of AHF. Low sαKlotho levels are associated with an increased risk of all-cause mortality or rehospitalization for HF. Increases in sαKlotho and FGF-23 values during hospitalization identify patients with poor prognosis.

Epidemiological studies indicate that heart failure (HF) prevalence and associated mortality are significantly higher among Eastern European countries as compared to their Western European counterparts. The significant financial burden on the healthcare system matches these sobering data. Thus, efficient programs for patients with HF have been called for. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) represents a widely used, cost-effective, and readily available test that can be used to evaluate HF risk. However, it should not be used as a universal assessment, given the existing variability in proposed cut-off scores for various subgroups of patients. Thus, the clinical context needs to always be considered, and alternative diagnoses need to be ruled out. Based upon evidence from the literature for the above assumptions, the advantages and limitations of using NT-proBNP in primary care settings, along with other HF diagnostic modalities, are discussed in this paper. Also, this paper argues that an effective primary care network, in collaboration with specialist providers, may avoid a delay in HF diagnoses, may help provide on-time treatments, and may ultimately cut unnecessary healthcare expenditures associated with HF hospitalizations. Therefore, the present paper proposes an algorithm for diagnosing HF in primary care settings and discusses specific knowledge and skills that family physicians should be well equipped with in order to successfully respond to the needs of their patients with HF.

Hypertension is a major risk factor of various cardiac complications, including hypertensive heart disease (HHD). This condition can lead to a number of structural and functional changes in the heart, such as left ventricular hypertrophy, diastolic dysfunction, and, eventually, systolic dysfunction. In the management of hypertensive heart disease, early diagnosis and appropriate treatment are crucial for preventing the progression to congestive heart failure. One potential diagnostic marker that has gained attention in recent years is the N-terminal pro-brain natriuretic peptide (NT-proBNP). The natriuretic peptides, including the brain natriuretic peptide (BNP) and its inactive N-terminal fragment, are secreted by the myocardium in response to increased wall stress and volume overload. In patients with hypertensive heart disease, increased NT-proBNP levels may reflect the structural and functional changes occurring in the myocardium as a result of chronic pressure overload. Several studies have investigated the diagnostic utility of NT-proBNP in hypertensive heart disease. NT-proBNP levels can be a useful adjunct in the diagnosis of hypertensive heart disease, particularly in the assessment of diastolic dysfunction and left ventricular hypertrophy. This review paper explores the role of NT-proBNP levels in the diagnosis of hypertensive heart disease.

This study assessed the achievement rates of metabolic risk factor targets and their association with clinical characteristics and comorbidities among individuals with type 2 diabetes (T2D) treated in the primary care in Austria.

A countrywide cross-sectional study, the AUSTRO-PROFIT, was conducted in Austria from 2021 to 2023 on 635 individuals with T2D. Metabolic risk factor targets were defined as the percentage of people achieving low-density lipoprotein cholesterol (LDL-C) <70 mg/dL (or < 55 mg/dL if cardiovascular or microvascular disease was present), glycated haemoglobin (HbA1c) <7% (53 mmol/mol) and blood pressure < 140/90 mmHg.

The mean age of the participants was 65.7 ± 11.2 years; the median duration of T2D was 8 (4-14) years; and 58.7% of the participants were male. The percentages of participants achieving LDL-C, HbA1c, blood pressure and all targets were 44%, 53%, 57% and 13%, respectively. Older age, longer T2D duration, cardiovascular disease and microvascular complications were associated with suboptimal achievement of metabolic risk factor targets.

The AUSTRO-PROFIT study revealed notable variations in metabolic targets achievement with respect to clinical characteristics and comorbidities. These findings underscore the importance of establishing national diabetes registries and implementing multifactorial targeted and individualized interventions to further improve the quality of T2D care in primary care settings in Austria.

When considering whether a patient is fit for surgery, a comprehensive patient assessment represents the first step for an anaesthetist to evaluate the risks associated with the procedure and the patient's underlying diseases, and to optimise (whenever possible) the perioperative surgical journey. These guidelines from the European Society of Anaesthesiology and Intensive Care Medicine (ESAIC) update previous guidelines to provide new evidence on existing and emerging topics that consider the different aspects of the patient's surgical path.

A comprehensive literature review focused on organisation, clinical facets, optimisation and planning. The methodological quality of the studies included was evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. A Delphi process agreed on the wording of recommendations, and clinical practice statements (CPS) supported by minimal evidence. A draft version of the guidelines was published on the ESAIC website for 4 weeks, and the link was distributed to all ESAIC members, both individual and national, encompassing most European national anaesthesia societies. Feedback was gathered and incorporated into the guidelines accordingly. Following the finalisation of the draft, the Guidelines Committee and ESAIC Board officially approved the guidelines.

In the first phase of the guidelines update, 17 668 titles were initially identified. After removing duplicates and restricting the search period from 1 January 2018 to 3 May 2023, the number of titles was reduced to 16 774, which were then screened, yielding 414 abstracts. Among these, 267 relevant abstracts were identified from which 204 appropriate titles were selected for a comprehensive GRADE analysis. Additionally, the study considered 4 reviews, 16 meta-analyses, 9 previously published guidelines, 58 prospective cohort studies and 83 retrospective studies. The guideline provides 55 evidence-based recommendations that were voted on by a Delphi process, reaching a solid consensus (>90% agreement).

This update of the previous guidelines has covered new organisational and clinical aspects of the preoperative anaesthesia assessment to provide a more objective evaluation of patients with a high risk of postoperative complications requiring intensive care. Telemedicine and more predictive preoperative scores and biomarkers should guide the anaesthetist in selecting the appropriate preoperative blood tests, x-rays, and so forth for each patient, allowing the anaesthetist to assess the risks and suggest the most appropriate anaesthetic plan.

Each patient should have a tailored assessment of their fitness to undergo procedures requiring the involvement of an anaesthetist. The anaesthetist's role is essential in this phase to obtain a broad vision of the patient's clinical conditions, to coordinate care and to help the patient reach an informed decision.

Diabetes mellitus is a significant risk factor for the development of heart disease (HD), with heart failure (HF) being one of the early manifestations of the disease in this population. The diagnostic process is challenging and contributes to a significant number of undiagnosed cases of HD among individuals with diabetes. This is largely due to the non-specific nature of symptoms and signs in the initial stages of disease, making early detection elusive. Timely identification and prevention of HD in patients with diabetes have the potential to significantly improve patient prognosis and alleviate the growing burden of this population on the national healthcare system. Natriuretic peptides (BNP and NT-proBNP) have been recognized as reliable, cost-effective biomarkers for detecting HD and can be further used as risk assessment biomarkers in asymptomatic patients. Despite being recommended in several European and American guidelines to rule-out and rule-in HF, the routine use of these biomarkers for the diagnosis of HDs in patients with diabetes has only recently been proposed by the American Diabetes Association (ADA) and has not yet been implemented in Portugal. Therefore, a multidisciplinary panel of experts from four medical societies, the Portuguese Society of Endocrinology, Diabetes and Metabolism, the Portuguese Society of Cardiology, the Diabetes Study Group from the Portuguese Society of Internal Medicine and the Portuguese Association of Family Medicine were convened to discuss and establish consensus recommendations for natriuretic peptide screening in patients with diabetes and its integration into routine diabetes management protocols. This manuscript draws on the consensus recommendations from four Portuguese medical societies, offering clear guidance on natriuretic peptides use tailored to Portuguese clinical practice. Accordingly, this consensus advises the use of NT-proBNP analysis for all patients with diabetes aged 50 years and older, or under 50 if they have risk factors and/or comorbidities. Adjusted rule-out and rule-in values for age, sex and risk factors are provided. NT-proBNP levels above 125 pg/mL should prompt additional testing and cardiovascular investigation. Routine evaluation every two to three years for low-risk patients and annually for high-risk patients is proposed when NT-proBNP is below 125 pg/mL and in the absence of suspected heart disease.

Preeclampsia (PE) is thought to be the consequence of impaired placental perfusion leading to placental hypoxia. While it has been demonstrated that PE may be a consequence of maternal cardiovascular maladaptation, the exact role of maternal cardiac function remains to be determined. This study sought to assess cardiac characteristics in pregnant women diagnosed with PE and to determine the possible relationship between PE, maternal cardiac changes/function, and NT-proBNP levels.

This was a retrospective analysis of 65 pregnant women diagnosed with PE who had an echocardiographic examination during pregnancy. Where available, NT-proBNP levels were analyzed. All patients underwent a comprehensive echocardiographic examination based on a standardized examination protocol.

Left ventricular size was within the normal range, and there was normal radial left ventricular function. Longitudinal contractility was impaired with a global longitudinal strain of -17.8% (quartiles -20.2 to -15.4). The cardiac index was in the normal range with a median of 3.2 ml/min/m2 (quartiles 2.6-4.0). The left atrium was of borderline size in longitudinal diameter [50 (44.8-54.3) mm], but within the normal range in volumetric index [27.3 (22.9-37.3) ml/m2]. Furthermore, mild left ventricular hypertrophy [septal thickness 12 (10-13) mm] and at least borderline elevated filling pressures with an E/e' ratio of 10.6 (8.5-12.9) were found. Maximal tricuspid regurgitation velocity [2.9 (2.5-3.3) m/s] and derived systolic pulmonary pressure [38 (29.5-44.5) mmHg] were borderline elevated. Regarding NT-proBNP levels, an increase in NT-proBNP levels correlated with a decrease in gestational age at delivery (p < 0.0002) and maternal cardiac changes. Obstetric characteristics showed a preterm rate of 71.43%, mostly due to maternal aggravation of PE or because of fetal signs of deprivation based on placental insufficiency. Neonatal deaths occurred in five cases (7.69%).

Changes in cardiac function in the context of hypertensive pregnancy diseases can be observed with regard to various echocardiographic parameters. Furthermore, there is a significant association between NT-proBNP levels and a decrease in gestational age at delivery in women with PE, which thus might be useful as a prognostic factor for the management of women with preeclampsia and changes in maternal cardiac function during pregnancy.

The objective of this study was to evaluate the feasibility of point-of-care testing (POCT) devices for N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement in prehospital settings, with the aim of improving the speed and accuracy of stroke diagnosis, thereby facilitating quicker and more effective patient care.

Prehospital blood samples were collected from suspected stroke patients, and NT-proBNP levels were measured using a POCT device in ambulances and hospitals. Results from the NT-proBNP POCT and smartphone images were analyzed. Plasma samples underwent Elecsys proBNP II immunoassay after storage at -80ºC.

A total of 121 suspected stroke patients were included in the study. The correlation between POCT measured by the POCT and immunoassay for NT-proBNP was strong (R = 0.926). Smartphone images also strongly correlated with POCT values at 10 min (R²=0.9716) and 15 min (R²=0.9405). Stability analysis of samples showed consistent NT-proBNP results and a high correlation (R = 0.907) was observed between plasma and whole blood samples for NT-proBNP POCT.

This study highlights the potential of NT-proBNP POCT devices in ambulances to expedite stroke diagnosis and management within 10 min. Smartphone integration further enhances efficiency, adding advancement in prehospital stroke management.

NT-proBNP levels with a wide range at admission play both a diagnostic and a prognostic role in patients with HF. The differences regarding the clinical profiles and demography in decompensated HF patients according to NT-proBNP levels at admission are not clear.

This study aimed to analyze and compare clinical profiles and demographics in patients hospitalized for decompensated heart failure according to levels of NT-proBNP at admission. The study included 302 patients hospitalized for decompensated HF who were divided into three groups based on admission NT-proBNP levels: group A (n = 46, with NT-proBNP level < 3000 pg/mL), group B (n = 130, NT-proBNP level between 3000-10,000 pg/mL), and group C (n = 126, NT-proBNP level > 10,000 pg/mL).

Patients hospitalized with decompensated HF and very high levels of NTproBNP, above 10,000 pg/mL at admission, are older, have a lower LVEF, higher NYHA class, more renal dysfunction, and longer hospital stay, resulting in a more severe clinical profile.

The presence of very high levels of NT-proBNP may identify a category of patients with a more severe prognosis that requires more aggressive management and closer follow-up.