Heart failure (HF) is a growing health problem and around two percent are affected in the general population. Accurate diagnostic markers that have the potential for early diagnosis of HF are lacking. This study aimed to compare the expression levels of microRNA-210-3p with biomarkers NT-proBNP, sST2, and galectin-3, in heart failure patients with preserved and reduced ejection fractions.

The cross-sectional study was conducted on 270 hypertensive heart failure patients in the age group of 30 to 75 years of both genders. The participants with evidence of HF were recruited from the Department of Cardiology in a tertiary care hospital in Chennai, India. MicroRNA-210-3p was analyzed by qRT-PCR in a stratified sample of 80 HF patients and 20 apparently healthy individuals. Biomarkers were analyzed by ELISA. Institutional ethics committee approval and written informed consent were obtained. Statistical analysis was performed using R software (4.2.1). Based on the type of distribution of data, appropriate statistical tools were used. p-value ≤  0.05 was considered to be statistically significant.

All the biomarkers including microRNA-210-3p were significantly higher in HFrEF than in HFpEF. MAGGIC score showed a positive correlation with all the biomarkers. The cut-off of microRNA-210-3p was 5.03.

All the biomarkers were significantly elevated in HFrEF compared to HFpEF. However, microRNA-210-3p could be an early marker in the diagnosis of heart failure. The strategy of employing a multi-marker approach could help in the early diagnosis as well as in stratifying the HF patients.

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 patients with atrial fibrillation (AF) who have undergone catheter ablation, the comparative effectiveness of sacubitril-valsartan (SV) versus ACE inhibitors (ACEi) or angiotensin-receptor blockers (ARB) in preventing AF recurrence remains unclear. The purpose of the present systematic review and meta-analysis is to determine whether SV offers superior outcomes in this clinical setting.

This study systematically reviewed PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) and propensity-matched cohorts (PMC), evaluating SV's efficacy in preventing AF recurrence after catheter ablation. Outcomes included AF recurrence and structural remodeling assessed via left ventricular ejection fraction (LVEF) and left atrial volume index (LAVi), with statistical analyses performed using Review Manager 5.1.7 and heterogeneity assessed via I2 statistics.

The analysis comprised 642 patients from three RCTs and one PMC (319 SV-treated). SV significantly reduced AF recurrence [risk ratios (RR) 0.54; 95% confidence intervals (CI) 0.41-0.70; p < 0.00001; I2 = 0%), a trend also observed when considering RCTs exclusively (RR 0.58; 95% CI 0.41-0.84; p = 0.004; I2 = 0%). Moreover, SV demonstrated a notable reduction in LAVi [mean deviation (MD) -5.34 mL/m2; 95% CI -8.77 to -1.91; p = 0.002; I2 = 57%] compared with ARB, alongside a significant improvement in LVEF (MD 1.83%; 95% CI 1.35-2.32; p < 0.00001; I2 = 0%). Subgroup analyses among patients with hypertension and LVEF < 50% also indicated lower AF recurrence with SV.

SV therapy exhibited superior efficacy in reducing AF recurrence compared with ACEi or ARB and demonstrated superior outcomes in attenuating atrial structural remodeling after catheter ablation. These findings underscore the potential of SV as a therapeutic option for patients with AF undergoing catheter ablation, highlighting its efficacy in mitigating AF recurrence and structural remodeling.

PROSPERO identifier number CRD42024497958.

Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), shows promising result in treating resistant hypertension (RH) but lacks comprehensive evaluation. We performed a systematic review to assess and compare the efficacy of ARNI in managing RH.

We conducted a systematic search on multiple databases such as Cochrane, ProQuest, PubMed, and Google Scholar. Studies comparing the effects of ARNI on blood pressure in adult RH patients were included in the review. Data extraction and synthesis followed PRISMA guidelines, and the risk of bias was assessed using Cochrane tools. The primary outcome is to determine the effect of ARNI on blood pressure in RH patients, and the secondary outcome was to assess the safety of ARNI in RH patients.

Four studies involving 915 RH patients were included in the systematic review. The sacubitril/valsartan dose used ranged between 100 and 400 mg/day. All studies reported a statistically significant reduction in blood pressure, with 24-h blood pressure reduction ranging from 15.8/6.5 to 16.6/9.3 mmHg and office systolic blood pressure reduction ranging from 24.7 to 10.3 mmHg. Additionally, two studies reported improvements in cardiac remodeling and left ventricular function associated with sacubitril/valsartan. The most common adverse events were hypotension and elevated serum potassium levels, though these were minimal and did not require discontinuation of ARNI therapy.

Sacubitril/valsartan is a promising alternative to ARB or ACEi in managing RH, offering superior blood pressure reductions and potential benefits in reversing cardiac remodeling, while maintaining a favorable safety profile with minimal risk of serious adverse events.

Angiotensin receptor-neprilysin inhibitor (ARNI) and angiotensin II receptor blockers (ARB) are antihypertension medications that improve cardiac remodeling and protect the heart. However, at the early stage of hypertension, it is still unclear how these two drugs affect the transcriptomic profile of multiple organs in hypertensive rats and the transcriptomic differences between them. We performed RNA sequencing to define the RNA expressing profiles of the eight tissues (atrium, ventricle, aorta, kidney, brain, lung, white fat, and brown fat) in spontaneously hypertensive rats (SHRs) and SHRs treated with ARNI or ARB. Acquired data was processed and analyzed by computational analyses (i.e., clustering, DEG, functional association, WGCNA, and protein-protein interaction (PPI) network analysis). We discovered that various tissues produced significant transcriptomic changes at the early stage of hypertension. The transcriptomic differences are notably in brown fat, kidney, lung, and brain tissues between ARNI and ARB treatment. Meanwhile, ARNI or ARB treatment can reverse the dysregulated expression genes related to the metabolism process, especially in brown fat, lung, and kidney tissues under hypertension. The current study has presented a comprehensive rat RNA-Seq transcriptomic landscape in SHRs and compared the transcriptome differences between ARNI and ARB treatment as a biomedical research resource for further study.

Diabetes Mellitus (DM) is a metabolic disorder characterized by persistent hyperglycemia and/or insulin resistance. If left uncontrolled, it can lead to a combination of cardiac and renal alterations known as cardiorenal syndrome. Additionally, oxidative stress and inflammation contribute to tissue damage, thereby reducing the life expectancy of individuals with diabetes.

The aim of this study was to identify early molecular markers associated with cardiorenal syndrome, oxidative stress, and inflammation, and to investigate their correlation with the duration of exposure to DM.

An experimental DM model was employed using Wistar rats. The rats were divided into four groups: diabetic rats at 7 days (DM7), diabetic rats at 30 days (DM30), control sham at 7 days (CS7), and control sham at 30 days (CS30). Blood and brain tissue from the brainstem region were collected at 7 and 30 days after confirming DM induction. Gene expression analysis of Bnp, Anp, Cat, Gpx, Sod, Tnf-α, and Il-6 was performed.

The analysis revealed lower expression values of Cat in the brainstem tissue of the DM7 group compared to the NDS7 group. Moreover, diabetic animals exhibited statistically lower levels of Tnf-α in their peripheral blood compared to the control animals.

This study concluded that DM alters the oxidative balance in the brainstem after 7 days of DM induction, resulting in lower Cat expression levels. Although some genes did not show statistical differences after 30 days of DM induction, other genes exhibited no expression values, indicating possible gene silencing. The study identified an imbalance in the studied pathways and concluded that the organism undergoes a compensatory state in response to the initial metabolic alterations caused by DM.

Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has demonstrated a superior blood pressure-lowering effect compared with renin-angiotensin system inhibitors in several clinical trials. However, there has been no available evidence on the comparison between sacubitril/valsartan and calcium channel blockers (CCBs), a well-established class of antihypertensive drugs. In this open-label, multicenter study, we aimed to demonstrate the efficacy and safety of sacubitril/valsartan versus amlodipine, one of the most widely used CCBs, after 8 weeks of treatment. A total of 359 Japanese patients with essential hypertension (office systolic blood pressure [SBP] ≥ 150 to < 180 mmHg), aged 18-79, were randomly assigned to receive either once-daily sacubitril/valsartan 200 mg or once-daily amlodipine 5 mg in a 1:1 allocation ratio. The primary endpoint was the noninferiority of sacubitril/valsartan compared with amlodipine in mean change in 24-h SBP from baseline to Week 8, followed by a significance test as a secondary endpoint analysis. The mean change in 24-h SBP in sacubitril/valsartan was noninferior to that in amlodipine (between-treatment difference -0.62 mmHg [95% confidential interval: -3.23 to 1.98; p = 0.003 for noninferiority; independent t-test with noninferiority margin 3.0 mmHg]), with no significant difference observed (p = 0.637). There was no significant difference in the incidence of adverse events (AEs). These results suggested that the blood pressure-lowering effect of sacubitril/valsartan is comparable to that of amlodipine, with no marked differences in tolerability between the two groups. Sacubitril/valsartan, a potent antihypertensive drug comparable to amlodipine, is expected to improve blood pressure control in clinical practice.

Hypertension, a prevalent cardiovascular condition globally, remains a significant public health concern due to its association with increased cardiovascular morbidity and mortality. Despite the availability of various antihypertensive therapies, achieving optimal blood pressure control in patients remains a challenge. Valsartan/sacubitril (ARNi), marketed as Entresto by Novartis, combines valsartan, an angiotensin receptor blocker, with sacubitril, an inhibitor of neprilysin. Neprilysin is responsible for breaking down natriuretic peptides and other vasoactive substances. Inhibiting neprilysin prevents the degradation of natriuretic peptides, enhancing their beneficial effects on blood pressure regulation. Natriuretic Peptides, including atrial natriuretic peptide (ANP) and brain natriuretic peptides (BNP), play pivotal roles in regulating blood pressure and cardiovascular homeostasis by promoting vasodilation, natriuresis, and antagonizing the renin-angiotensin-aldosterone system. Therefore, this combo drug lessens sensitivity to natriuretic peptides and tackles the processes in hypertension that activate the renin-angiotensin-aldosterone system. This review provides an overview of how natriuretic peptides (NPs) contribute to blood pressure regulation for the treatment of hypertension through inhibiting neprilysin. It highlights the ARNi's dual action that works synergistically by blocking the harmful effects of angiotensin II on blood vessels while simultaneously increasing the levels of beneficial natriuretic peptides. Schematic representation of the mechanism of action of ARNi. Abbreviation: -Renin angiotensin aldosterone system (RAAS), Natriuretic peptides (NP), Atrial Natriuretic peptide (ANP), Brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), Angiotensin II (Ang II), Angiotensin receptor neprilysin inhibitor (ARNI).

Gastrointestinal (GI) cancers are an important health problem globally. Natriuretic peptides are hormones that have a crucial role in human physiology. There are a variety of treatments for GI cancer, but conventional therapies have side effects and low efficacy. Studies have demonstrated that natriuretic peptides are therapeutic in different cancer types. Natriuretic peptides are best known for their involvement in regulating blood pressure and blood volume. The anti-tumor effect exerted by natriuretic peptides is via their inhibitory effects on DNA synthesis and by their effects on apoptosis. The anti-proliferative role of natriuretic peptides has been shown in human breast cancer, prostate, colon, pancreatic, lung, ovarian, and other tumors. The roles of natriuretic peptides in these cancers are diverse and not well understood. Therefore, we have reviewed the recent literature on natriuretic peptides in GI cancers as a common malignancy in adults to assess the pathways that NPs are involved in the progression of GI cancers and its effect on the prevention or treatment of GI cancers.

Vericiguat has demonstrated efficacy in improving the prognosis of patients with heart failure with reduced ejection fraction (HFrEF) following recent clinical deterioration. However, its real-world impact on reducing N-terminal B-type natriuretic peptide (NT-proBNP) levels and improving ventricular remodeling remains uncertain in stable HFrEF patients receiving guideline-directed medical therapy (GDMT) over the short term.

This multicenter, observational cohort study included 200 HFrEF patients. Patients were grouped based on their preference for vericiguat use. We evaluated the impact of vericiguat on HFrEF patients by analyzing the difference in the proportion of patients with NT-proBNP levels ≤1000 pg/ml between two groups after a 6-month follow-up, using logistic regression and covariance analysis. Changes in echocardiographic parameters, left ventricular reverse remodeling (LVRR) ratio, and safety outcomes were also evaluated.

During the 6-month follow-up, 105 patients (82.68 %) in the vericiguat group and 46 patients (63.01 %) in the control group reached the primary endpoint. Multivariate logistic regression confirmed vericiguat as a significant factor in reducing NT-proBNP levels (Model 2: odds ratio (OR) = 2.67, 95 % confidence interval (CI): 1.24-5.77, P = 0.013), but it showed no significant association with LVRR (Model 2: OR = 0.52, 95 % CI: 0.24-1.13, P = 0.097). The safety analysis indicated a higher incidence of mild to moderate gastrointestinal symptoms in the vericiguat group compared to the control group (23.62 % vs. 2.74 %, P < 0.001).

Vericiguat significantly reduced NT-proBNP levels in patients with chronic HErEF under GDMT but was ineffective for LVRR during the 6-month follow-up.

Neprilysin is a cell surface metallo-endopeptidase, commonly identified as neutral endopeptidase (NEP), that plays a crucial role in the cleavage of peptides, for example, natriuretic peptides, angiotensin II, enkephalins, endothelin, bradykinin, substance P, glucagon-like peptide and amyloid beta. In the case of heart failure, a significant upsurge in NEP activity and expression enhances the degradation of natriuretic peptides. Therefore, NEP inhibitors have gained attention in the field of cardiology. NEP has been studied for over 40 years; however, it has recently gained attention with the US FDA approval of a fixed dose combination of sacubitril (NEP inhibitor) and valsartan (AT-1 inhibitor) for chronic heart failure treatment. The present review elucidates the role of neprilysin in cardiorenal disease, its pathophysiology, and how NEP inhibition benefits. It also summarizes the research advances in NEP inhibitors (NEPi) and their structure-activity relationships. Moreover, the review provides insight into NEPi effectiveness - alone or combined with other cardiorenal protective agents. It is expected to help medicinal chemists synthesize and develop novel NEPi.

The intricate physiological and pathological diversity of the Renin-Angiotensin-Aldosterone System (RAAS) underpins its role in maintaining bodily equilibrium. This paper delves into the classical axis (Renin-ACE-Ang II-AT1R axis), the protective arm (ACE2-Ang (1-7)-MasR axis), the prorenin-PRR-MAP kinases ERK1/2 axis, and the Ang IV-AT4R-IRAP cascade of RAAS, examining their functions in both physiological and pathological states. The dysregulation or hyperactivation of RAAS is intricately linked to numerous diseases, including cardiovascular disease (CVD), renal damage, metabolic disease, eye disease, Gastrointestinal disease, nervous system and reproductive system diseases. This paper explores the pathological mechanisms of RAAS in detail, highlighting its significant role in disease progression. Currently, in addition to traditional drugs like ACEI, ARB, and MRA, several novel therapeutics have emerged, such as angiotensin receptor-enkephalinase inhibitors, nonsteroidal mineralocorticoid receptor antagonists, aldosterone synthase inhibitors, aminopeptidase A inhibitors, and angiotensinogen inhibitors. These have shown potential efficacy and application prospects in various clinical trials for related diseases. Through an in-depth analysis of RAAS, this paper aims to provide crucial insights into its complex physiological and pathological mechanisms and offer valuable guidance for developing new therapeutic approaches. This comprehensive discussion is expected to advance the RAAS research field and provide innovative ideas and directions for future clinical treatment strategies.

Heart failure (HF) and renal dysfunction often coexist and interact in many complex and bidirectional pathways, leading to detrimental effects on patient outcomes. The treatment of HF patients with renal dysfunction presents a significant clinical challenge. Interestingly, sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), may have beneficial effects on cardiac and renal outcomes in patients with HF with reduced ejection fraction, particularly by slowing the rate of decrease in the estimated glomerular filtration rate compared to a single angiotensin-converting enzyme inhibitor. Recently, more reports have emphasized the renal protection of sacubitril/valsartan in patients with HF. In HF patients with renal dysfunction, however, there is no strong evidence supporting the use of sacubitril/valsartan to reduce the absolute risk of hyperkalemia and worsening renal function; therefore, the administration of ARNI requires a careful balance between the benefits and risks. Furthermore, the lack of evidence-based management highlights the importance of an individualized approach based on published experience and multidisciplinary collaborations, as well as underlines the need for in-depth studies investigating the underlying mechanisms in cardiorenal interactions with a focus on treatments.

The Sugen 5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension (PAH) demonstrates most of the distinguishing features of PAH in humans, including increased wall thickness and obstruction of the small pulmonary arteries along with plexiform lesion formation. Recently, significant advancement has been made describing the epidemiology, genomics, biochemistry, physiology, and pharmacology in Su/Hx challenge in rats. For example, there are differences in the overall reactivity to Su/Hx challenge in different rat strains and only female rats respond to estrogen treatments. These conditions are also encountered in human subjects with PAH. Also, there is a good translation in both the biochemical and metabolic pathways in the pulmonary vasculature and right heart between Su/Hx rats and humans, particularly during the transition from the adaptive to the nonadaptive phase of right heart failure. Noninvasive techniques such as echocardiography and magnetic resonance imaging have recently been used to evaluate the progression of the pulmonary vascular and cardiac hemodynamics, which are important parameters to monitor the efficacy of drug treatment over time. From a pharmacological perspective, most of the compounds approved clinically for the treatment of PAH are efficacious in Su/Hx rats. Several compounds that show efficacy in Su/Hx rats have advanced into phase II/phase III studies in humans with positive results. Results from these drug trials, if successful, will provide additional treatment options for patients with PAH and will also further validate the excellent translation that currently exists between Su/Hx rats and the human PAH condition.

Background Acute ST-elevation myocardial infarction (STEMI) is the most common cause of mortality across the world. The electrocardiogram (ECG) Tpeak-Tend/QT interval appears to be a measure of the left ventricle's transmural dispersion of repolarization (TDR). Prolongation of this time could indicate adverse cardiac events like heart failure, arrhythmias, etc. Heart failure is a clinical syndrome that includes signs and symptoms such as peripheral edema and high jugular vein pressure. N-terminal pro B-type natriuretic peptide (NT-proBNP) is an effective predictor of left ventricular function and also helps in predicting the disease prognosis. Elevated levels of NT-proBNP are seen in many cases of left ventricular dysfunction. This study aims to evaluate the predictive utility of the Tpeak-Tend/QT interval ratio in predicting major adverse cardiac events (MACEs), such as heart failure, by examining the Tend/QT interval ratio values with NT-proBNP in STEMI. Methodology This cross-sectional study was conducted at a tertiary hospital between April 2024 and June 2024. It included STEMI patients, excluding those with non-STEMI (NSTEMI), valvular heart diseases, bundle branch block, or pacemakers. The patients with a Tpeak-Tend/QT ratio < 0.3 were included in group A, and the Tpeak-Tend/QT ratio > 0.3 in group B. They were monitored for MACE-like heart failure during hospitalization and were compared with a study of the Tpeak-Tend/QT interval ratio in predicting heart failure in STEMI and its correlation with NT-proBNP levels. Results In this study, out of 45 patients, male predominance was observed, with 35 (78%) being men and 10 (22%) being women. In group A, the most common age group was 60-70 years, with 16 (51%) patients; in Group B, it was 50-60 years, with six (42.8%) patients. Out of 31 patients in group A, 25 were male, and six were female. In group B, out of 14 patients, 10 were male, and four were female. In this study, out of the 45 patients included, 12 (85%) among 14 patients who had MACEs like heart failure had a Tpeak-Tend/QT interval ratio of more than 0.3, and their measured NT-proBNP levels were also more than 900 pg/mL, thus showing a statistically significant association between Tpeak-Tend/QT interval ratio and NT-proBNP. Conclusion The present study showed an increased Tpeak-Tend/QT interval ratio and NT-proBNP in patients who developed heart failure in STEMI. As ECG is a readily available and affordable tool, the Tpeak-Tend/QT interval ratio can be used along with conventional markers like NT-proBNP to predict MACE in patients with STEMI.

Cardiovascular disease (CVD) represents the primary cause of mortality in patients afflicted with end-stage renal disease and undergoing peritoneal dialysis (PD) treatment. Galectin-3 (Gal-3), a molecule known to exhibit a correlation with CVD mortality garners considerable interest. The objective of this study was to explore the potential association between serum Gal-3 levels and other CVD risk factors among PD patients.

In this cross-sectional study, a total of 114 PD patients with a minimum of 3 months of PD treatment were enrolled. Serum Gal-3 levels were quantified using an enzyme-linked immunosorbent assay. The data of patients with Gal-3 levels higher and lower than 26.744 pg/ml were compared using Mann-Whitney U tests or t tests. Pearson's correlation or Spearman's correlation analysis and multivariate regression were used to assess the associations between the known risk factors for CVD and Gal-3.

In comparison to the inter-group baseline data, the low Gal-3 group exhibited a higher glomerular filtration rate (GFR). Gal-3 levels correlate positively with PD duration, B-type natriuretic peptide (BNP), growth differentiation factor 15 (GDF-15), interventricular septal thickness in diastolic (IVST), and left ventricular mass index (LVMI). Conversely, Gal-3 exhibited a negative correlation with albumin levels. Multivariate linear regression analysis demonstrated a positive correlation between Gal-3 levels and BNP, GDF-15, PD duration, IVST and LVMI. Gal-3 levels were negatively correlated with albumin levels.

Gal-3 was strongly associated with BNP, GDF-15, IVST and LVMI in patients undergoing PD treatment. Prospective studies should be carried out to determine whether Gal-3 can be a promising biomarker in predicting increased risk of adverse cardiovascular events in PD patients.

The left atrial appendage (LAA) is often thought of as a vestigial organ serving as a nidus for clot formation in those with atrial fibrillation (A-fib). The LAA, however, has unique anatomy which allows it to serve special functions in the human body. Closing the LAA has been shown to decrease the risk of thromboembolic events in patients who cannot tolerate anticoagulation. Several methods of closure exist including percutaneous endocardial closure, epicardial closure, and surgical clipping. In addition to decreasing stroke risk, there appears to be physiologic changes that occur after LAA closure. This comprehensive review aims to describe the functions of the LAA, compare the different methods of closure, and propose a new method for identifying which patients may benefit from LAA closure versus anticoagulation based on each patients' individual comorbidities rather than their contraindications.

We present an innovative, reliable, and antibody-free analytical method to determine multiple intact natriuretic peptides in human plasma. These biomolecules are routinely used to confirm the diagnosis and monitor the evolution of heart failure, so that their determination is essential to improve diagnosis and monitor the efficacy of treatment. However, common immunoassay kits suffer from main limitations due to high cross-reactivity with structurally similar species. In our method, we pre-treated the sample by combining salting-out with ammonium sulfate with microextraction by packed sorbent technique. Analyses were then carried out by ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry. The use of 3-nitrobenzyl alcohol as a supercharger reagent enhanced the ESI ionization and improved the signal-to-noise ratio. The analytical protocol showed good linearity over one order of magnitude, recovery in the range of 94-105 %, and good intra- and inter-day reproducibility (RSD<20 %), and the presence of a matrix effect. Limits of detection were in the range of pg/mL for all peptides (0.2-20 pg/mL). Stability study in plasma samples demonstrated that proper protease inhibitors need to be included in blood collection tubes to avoid peptide degradation. Preliminary analyses on plasma samples from heart failure patients allow the quantification of ANP 1-28 as the most abundant species and the detection of ANP 5-28, BNP 1-32, and BNP 5-32. The method could be used to investigate how cross-reactivity issues among structurally similar species impact determinations by ELISA kits.

Background: The fibrous root of ginseng (GFR) is the dried thin branch root or whisker root of Ginseng (Panax ginseng C. A. Mey). It is known for its properties such as tonifying qi, producing body fluid, and quenching thirst. Clinically, it is used to treat conditions such as cough, hemoptysis, thirst, stomach deficiency, and vomiting. While GFR and Ginseng share similar metabolites, they differ in their metabolites ratios and efficacy. Furthermore, the specific role of GFR in protecting the body remains unclear. Methods: We employed ultra-high performance liquid chromatography-triple quadrupole mass spectrometry to examine alterations in brain neurotransmitters and elucidate the impact of GFR on the central nervous system. Additionally, we analyzed the serum and brain metabolic profiles of rats using ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry to discern the effect and underlying mechanism of GFR in delaying aging in naturally aged rats. Results: The findings of the serum biochemical indicators indicate that the intervention of GFR can enhance cardiovascular, oxidative stress, and energy metabolism related indicators in naturally aging rats. Research on brain neurotransmitters suggests that GFR can augment physiological functions such as learning and memory, while also inhibiting central nervous system excitation to a certain degree by maintaining the equilibrium of central neurotransmitters in aged individuals. Twenty-four abnormal metabolites in serum and seventeen abnormal metabolites in brain could be used as potential biomarkers and were involved in multiple metabolic pathways. Among them, in the brain metabolic pathways, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, histidine metabolism, and tyrosine metabolism were closely related to central neurotransmitters. Butanoate metabolism improves energy supply for life activities in the aging body. Cysteine and methionine metabolism contributes to the production of glutathione and taurine and played an antioxidant role. In serum, the regulation of glycerophospholipid metabolism pathway and proline metabolism demonstrated the antioxidant capacity of GFR decoction. Conclution: In summary, GFR plays a role in delaying aging by regulating central neurotransmitters, cardiovascular function, oxidative stress, energy metabolism, and other aspects of the aging body, which lays a foundation for the application of GFR.

Background: The sulfide-hydrogen sulfide brine balneotherapy (HSBB), including a combination of dissolved hydrogen sulfide (H2S) gas, inorganic sulfur ions (S2-), and hydrosulfide ions (HS-), is one of the most important and most effective forms of spa treatment in patients with osteoarticular disorders (OADs). Some cardiovascular diseases (CVDs) are often considered to be contraindications to HSBB since the presence of thiol groups may lead to an increased quantity of reactive oxygen species (ROS), which damage the vascular endothelium, and endothelial dysfunction is considered to be the main cause of atherosclerosis. However, there are a number of literature reports suggesting this theory to be false. H2S is a member of the endogenous gaseous transmitter family and, since it is a relatively recent addition, it has the least well-known biological properties. H2S-NO interactions play an important role in oxidative stress in CVDs. The general objective of this study was to assess the cardiovascular safety of HSBB and analyze the effect of HSBB on selected cardiovascular risk markers. Methods: A total of 100 patients at the age of 76.3 (±7.5) years from the Włókniarz Sanatorium in Busko-Zdrój were initially included in the study. The following parameters were assessed: age, sex, height, body weight, body surface area (BSA), body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), heart rate, the diagnosis of OAD that was the indication for balneotherapy, creatinine (CREAT), glomerular filtration rate (GFR), lipid panel, C-reactive protein (CRP), uric acid (UA), and fibrinogen (FIBR) and cardiovascular markers: (cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP). Results: A significant decrease in DBP and a trend towards SBP reduction were observed over the course of the study. A significant decrease was observed in CRP levels decreasing from 2.7 (±3.6) mg/L to 2.06 (±1.91) mg/L, whereas FIBR rose significantly from 2.95 (±0.59) g/L to 3.23 (±1.23) g/L. LDL-C levels decreased slightly, statistically significant, from 129.36 (±40.67) mg/dL to 123.74 (±36.14) mg/dL. HSBB did not affect the levels of evaluated cardiovascular biomarkers, namely NT-proBNP (137.41 (±176.52) pg/mL vs. 142.89 (±182.82) pg/mL; p = 0.477) and cTnT (9.64 (±4.13) vs. 9.65 (±3.91) ng/L; p = 0.948). A multiple regression analysis of pre-balneotherapy and post-balneotherapy values showed cTnT levels to be independently correlated only with CREAT levels and GFR values. None of the assessed parameters independently correlated with the NT-proBNP level. Conclusions: HSBB resulted in a statistically significant improvement in a subclinical pro-inflammatory state. HSBB has a beneficial effect in modifying key cardiovascular risk factors by reducing LDL-C levels and DBP values. HSBB has a neutral effect on cardiovascular ischemia/injury. Despite slightly elevated baseline levels of the biochemical marker of HF (NT-proBNP), HSBB causes no further increase in this marker. The use of HSBB in patients with OAD has either a neutral effect or a potentially beneficial effect on the cardiovascular system, which may constitute grounds for further studies to verify the current cardiovascular contraindications for this form of therapy.

The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo-responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B-type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank-sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo-responsiveness to NPs.

To investigate the correlation between retinal vessel density (VD) parameters with serum B-type natriuretic peptide (BNP) in patients with coronary heart disease (CHD) using novel optical coherence tomography angiography (OCTA) denoising images based on artificial intelligence (AI).

OCTA images of the optic nerve and macular area were obtained using a Canon-HS100 OCT device in 176 patients with CHD. Baseline information and blood test results were recorded.

Retinal VD parameters of the macular and optic nerves on OCTA were significantly decreased in patients with CHD after denoising. Retinal VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary (RPC) was strongly correlated with serum BNP levels in patients with CHD. Significant differences were noted in retinal thickness and retinal VD (SCP, DCP and RPC) between the increased BNP and normal BNP groups in patients with CHD.

Deep learning denoising can remove background noise and smooth rough vessel surfaces. SCP,DCP and RPC may be potential clinical markers of cardiac function in patients with CHD. Denoising shows great potential for improving the sensitivity of OCTA images as a biomarker for CHD progression.

Contrast-induced nephropathy (CIN) is a form of acute kidney injury (AKI) occurring in patients undergoing cardiac catheterization, such as coronary angiography (CAG) or percutaneous coronary intervention (PCI). Although the conventional criterion for CIN detection involves a rise in creatinine levels within 72 h after contrast media injection, several limitations exist in this definition. Up to now, various meta-analyses have been undertaken to assess the accuracy of different biomarkers of CIN prediction. However, the existing body of research lacks a cohesive overview. To address this gap, a comprehensive umbrella review was necessary to consolidate and summarize the outcomes of prior meta-analyses. This umbrella study aimed to offer a current, evidence-based understanding of the prognostic value of biomarkers in predicting CIN.

A systematic search of international databases, including PubMed, Scopus, and Web of Science, from inception to December 12, 2023, was conducted to identify meta-analyses assessing biomarkers for CIN prediction. Our own meta-analysis was performed by extracting data from the included studies. Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were assessed using Meta-Disc and CMA softwares.

Twelve studies were ultimately included in the umbrella review. The results revealed that neutrophil gelatinase-associated lipocalin (NGAL) exhibited the highest area under the curve (AUC), followed by cystatin-C, urinary kidney injury molecule-1 (uKIM-1), and brain natriuretic peptide (BNP) with AUCs of 0.91, 0.89, 0.85, and 0.80, respectively. NGAL also demonstrated the highest positive likelihood ratio [effect size (ES): 6.02, 95% CI 3.86-9.40], followed by cystatin-C, uKIM-1, and BNP [ES: 4.35 (95% CI 2.85-6.65), 3.58 (95% CI 2.75-4.66), and 2.85 (95% CI 2.13-3.82), respectively]. uKIM-1 and cystatin-C had the lowest negative likelihood ratio, followed by NGAL and BNP [ES: 0.25 (95% CI 0.17-0.37), ES: 0.25 (95% CI 0.13-0.50), ES: 0.26 (95% CI 0.17-0.41), and ES: 0.39 (0.28-0.53) respectively]. NGAL emerged as the biomarker with the highest diagnostic odds ratio for CIN, followed by cystatin-C, uKIM-1, BNP, gamma-glutamyl transferase, hypoalbuminemia, contrast media volume to creatinine clearance ratio, preprocedural hyperglycemia, red cell distribution width (RDW), hyperuricemia, neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), high-sensitivity CRP, and low hematocrit (P < 0.05).

NGAL demonstrated superior diagnostic performance, exhibiting the highest AUC, positive likelihood ratio, and diagnostic odds ratio among biomarkers for CIN, followed by cystatin-C, and uKIM-1. These findings underscore the potential clinical utility of NGAL, cystatin-C and uKIM-1 in predicting and assessing CIN.

Heart failure (HF) represents a significant global health challenge, characterized by a variety of symptoms resulting from cardiac dysfunction. This dysfunction often leads to systemic and pulmonary congestion. The pathophysiology of HF is complex, involving stimulation of the sympathetic nervous system, which is insufficiently balanced by the release of natriuretic peptide. This imbalance leads to progressive hypertrophy and dilatation of the heart's chambers, impairing its pumping efficiency and increasing the risk of arrhythmias and conduction disorders. The prevalence of HF is exceptionally high in industrialized nations and is expected to increase owing to an aging population and advancements in diagnostic methods. This study emphasizes the critical role of early diagnosis in reducing morbidity and mortality associated with HF, focusing specifically on the evolving importance of biomarkers in managing this condition. Biomarkers have played a key role in transforming the diagnosis and treatment of HF. Traditional biomarkers such as b-type natriuretic peptide and N-terminal pro-b-type natriuretic peptide have been widely adopted for their cost-effectiveness and ease of access. However, the rise of novel biomarkers such as growth differentiation factor 15 and adrenomedullin has shown promising results, offering superior sensitivity and specificity. These new biomarkers enhance diagnostic accuracy, risk stratification, and prognostic evaluation in HF patients. Despite these advancements, challenges remain, such as limited availability, high costs, and the need for further validation in diverse patient populations. Through a comprehensive literature review across databases such as PubMed, Google Scholar, and the Cochrane Library, this study compiles and analyzes data from 18 relevant studies, offering a detailed understanding of the current state of HF biomarkers. The study examines both traditional and emerging biomarkers such as galectin-3 and soluble suppression of tumorigenicity 2 in HF, exploring their clinical roles and impact on patient outcomes.

Heart failure (HF) is a complex clinical syndrome associated with high rates of morbidity and mortality. Over the years, it has been crucial to find accurate biomarkers capable of doing a precise monitor of HF and provide an early diagnosis. Of these, it has been established an important role of natriuretic peptides in HF assessment. Moreover, the development of biosensors has been garnering interest as new diagnostic medical tools. In this review we first provide a general overview of HF, its pathogenesis, and diagnostic features. We then discuss the role of natriuretic peptides in heart failure by characterizing them and point out their potential as biomarkers. Finally, we adress the evolution of biosensors development and the available natriuretic peptides biosensors for disease monitoring.

Heart failure is an increasing public health issue with substantial morbidity and mortality rates. This study aimed to evaluate the efficacy, safety, and long-term outcomes of angiotensin receptor neprilysin inhibitor (ARNi) in the treatment of heart failure with reduced ejection fraction (HFrEF) 5 years after treatment initiation. This retrospective study analyzed a cohort of 75 patients diagnosed with HFrEF over a period of 5 years after the initiation of ARNi therapy. The initial clinical condition, laboratory and echocardiographic measurements including left ventricular ejection fraction (LVEF), New York Heart Association functional classes (NYHA-FC) and the prognostic nutritional index were compared to the corresponding values obtained after a 5-year period of ARNi therapy. In addition, the number of annual hospitalizations, mortality rates and any history of adverse effects during the follow-up period were recorded. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level, LVEF, and NYHA-FC values demonstrated significant improvement at the end of the 5-year follow-up period (all parameters, P < .001). Although the observed increase in the prognostic nutritional index was not statistically significant (P = .077), it is worth noting. A significant reduction in daily diuretic doses and hospitalizations due to heart failure was observed following the use of ARNi (all comparisons, P < .001). The prevalence of hypotension was around 16% (being symptomatic in 4%), making it the most frequently observed adverse event. The 5-year cardiovascular mortality rate was 17.3%. The use of ARNi in HFrEF patients was associated with a notable improvement in NYHA-FC, LVEF, and NT-proBNP levels in the long-term, while also leading to a better nutritional status and reduced need for diuretics and annual hospitalization. Additionally, ARNi usage has been associated with improved nutritional status, decreased reliance on diuretics, and reduced frequency of annual hospitalizations. These effects were associated with a lack of significant increase in adverse effects. These results may contribute to a better understanding of ARNi's long-term effects on patient outcomes.

Heart failure is defined as a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. The natriuretic peptide is known to exert its biological action on the kidney, heart, blood vessels, renin-angiotensin system, autonomous nervous system, and central nervous system. The natriuretic peptide-natriuretic receptor system plays an important role in the regulation of blood pressure and body fluid volume through its pleiotropic effects.

The clinical and animal studies suggest that natriuretic peptide-natriuretic receptors are important targets for the treatment of heart failure and other cardiovascular diseases. Even though attempts targeting natriuretic peptide receptors are underway for heart failure treatment, they seem insufficient despite the receptor systems' potential. This review summarizes natriuretic peptide-natriuretic receptor system's physiological actions and potential target for the treatment of heart failure. Natriuretic peptides play multiple roles in different parts of the body, almost all of the activities related to this receptor system appear to have the potential to be harnessed to treat heart failure or symptoms associated with heart failure.

Heart failure (HF) is a leading cause of morbidity and mortality and a major public health problem. Both overhydration and dehydration are non-physiological states of the body that can adversely affect human health. Congestion and residual congestion are common in patients hospitalized for HF and are associated with poor prognosis and high rates of rehospitalization. However, the clinical problem of dehydration is also prevalent in healthcare and community settings and is associated with increased morbidity and mortality. This article provides a comprehensive review of the issue of congestion and dehydration in HF, including HF guidelines, possible causes of dehydration in HF, confirmed and potential new diagnostic methods. In particular, a full database search on the relationship between dehydration and HF was performed and all available evidence in the literature was reviewed. The novel hypothesis of chronic subclinical hypohydration as a modifiable risk factor for HF is also discussed. It is concluded that maintaining euvolemia is the cornerstone of HF management. Physicians have to find a balance between decongestion therapy and the risk of dehydration.

Heart failure with reduced ejection fraction (HFrEF) is a clinical syndrome whose management has significantly evolved based on the pathophysiology and disease process. It is widely prevalent, has a relatively high mortality rate, and is comparatively more common in men than women. In HFrEF, the series of maladaptive processes that occur lead to an inability of the muscle of the left ventricle to pump blood efficiently and effectively, causing cardiac dysfunction. The neurohormonal and hemodynamic adaptations play a significant role in the advancement of the disease and are critical to guiding the treatment and management of HFrEF. The first-line therapy, which includes loop diuretics, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, hydralazine/isosorbide-dinitrate, and mineralocorticoid receptor antagonists (MRAs), has been proven to provide symptomatic relief and decrease mortality and complications. The newly recommended drugs for guideline-based therapy, angiotensin receptor/neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors, soluble guanylate cyclase, and myosin activators and modulators have also been shown to improve cardiac function, reverse cardiac remodeling, and reduce mortality rates. Recent studies have demonstrated that exercise-based therapy has resulted in an improved quality of life, exercise capacity, cardiac function, and decreased hospital readmission rates, but it has not had a considerable reduction in mortality rates. Combining multiple therapies alongside holistic advances such as exercise therapy may provide synergistic benefits, ultimately leading to improved outcomes for patients with HFrEF. Although first-line treatment, novel pharmacologic management, and exercise-based therapy have been shown to improve prognosis, the existing literature suggests a need for further studies evaluating the long-term effects of MRA and ARNI.

This review discusses the evolving topic of atrial cardiomyopathy concerning valvular heart disease. The pathogenesis of atrial cardiomyopathy involves multiple factors, such as valvular disease leading to atrial structural and functional remodeling due to pressure and volume overload. Atrial enlargement and dysfunction can trigger atrial tachyarrhythmia. The complex interaction between valvular disease and atrial cardiomyopathy creates a vicious cycle of aggravating atrial enlargement, dysfunction, and valvular disease severity. Furthermore, atrial remodeling and arrhythmia can predispose to atrial thrombus formation and stroke. The underlying pathomechanism of atrial myopathy involves molecular, cellular, and subcellular alterations resulting in chronic inflammation, atrial fibrosis, and electrophysiological changes. Atrial dysfunction has emerged as an essential determinant of outcomes in valvular disease and heart failure. Despite its predictive value, the detection of atrial fibrosis and dysfunction is challenging and is not included in the clinical routine. Transthoracic echocardiography and cardiac magnetic resonance imaging are the main diagnostic tools for atrial cardiomyopathy. Recently published data have revealed that both left atrial volumes and functional parameters are independent predictors of cardiovascular events in valvular disease. The integration of atrial function assessment in clinical practice might help in early cardiovascular risk estimation, promoting early therapeutic intervention in valvular disease.

Heart failure is a complex, debilitating condition and despite advances in treatment, it remains a significant cause of morbidity and mortality worldwide. Therefore, the need for alternative treatment strategies is essential. In this review, we explore the therapeutic strategies of augmenting natriuretic peptide receptors (NPR-A and NPR-B) and cyclic guanosine monophosphate (cGMP) in heart failure.

We aim to provide an overview of the evidence of preclinical and clinical studies on novel heart failure treatment strategies. Papers collected in this review have been filtered and screened following PubMed searches. This includes epigenetics, modulating enzyme activity in natriuretic peptide (NP) synthesis, gene therapy, modulation of downstream signaling by augmenting soluble guanylate cyclase (sGC) and phosphodiesterase (PDE) inhibition, nitrates, c-GMP-dependent protein kinase, synthetic and designer NP and RNA therapy.

The novel treatment strategies mentioned above have shown great potential, however, large randomized controlled trials are still lacking. The biggest challenge is translating the results seen in preclinical trials into clinical trials. We recommend a multi-disciplinary team approach with cardiologists, geneticist, pharmacologists, bioengineers, researchers, regulators, and patients to improve heart failure outcomes. Future management can involve telemedicine, remote monitoring, and artificial intelligence to optimize patient care.

The natriuretic peptide system (NPS) and renin-angiotensin-aldosterone system (RAAS) function oppositely at multiple levels. While it has long been suspected that angiotensin II (ANGII) may directly suppress NPS activity, no clear evidence to date supports this notion. This study was designed to systematically investigate ANGII-NPS interaction in humans, in vivo, and in vitro. Circulating atrial, b-type, and c-type natriuretic peptides (ANP, BNP, CNP), cyclic guanosine monophosphate (cGMP), and ANGII were simultaneously investigated in 128 human subjects. Prompted hypothesis was validated in vivo to determine the influence of ANGII on ANP actions. The underlying mechanisms were further explored via in vitro approaches. In humans, ANGII demonstrated an inverse relationship with ANP, BNP, and cGMP. In regression models predicting cGMP, adding ANGII levels and the interaction term between ANGII and natriuretic peptides increased the predictive accuracy of the base models constructed with either ANP or BNP, but not CNP. Importantly, stratified correlation analysis further revealed a positive association between cGMP and ANP or BNP only in subjects with low, but not high, ANGII levels. In rats, co-infusion of ANGII even at a physiological dose attenuated cGMP generation mediated by ANP infusion. In vitro, we found the suppressive effect of ANGII on ANP-stimulated cGMP requires the presence of ANGII type-1 (AT1) receptor and mechanistically involves protein kinase C (PKC), as this suppression can be substantially rescued by either valsartan (AT1 blocker) or Go6983 (PKC inhibitor). Using surface plasmon resonance (SPR), we showed ANGII has low binding affinity to the guanylyl cyclase A (GC-A) receptor compared to ANP or BNP. Our study reveals ANGII is a natural suppressor for the cGMP-generating action of GC-A via AT1/PKC dependent manner and highlights the importance of dual-targeting RAAS and NPS in maximizing beneficial properties of natriuretic peptides in cardiovascular protection.

Dietary salt (NaCl) is essential to an organism's survival. However, today's diets are dominated by excessive salt intake, which significantly impacts individual and population health. High salt intake is closely linked to cardiovascular disease (CVD), especially hypertension, through a number of well-studied mechanisms. Emerging evidence indicates that salt overconsumption may also be associated with metabolic disorders. In this review, we first summarize recent updates on the mechanisms of salt-induced CVD, the effects of salt reduction and the use of salt substitution as a therapy. Next, we focus on how high salt intake can impact metabolism and energy balance, describing the mechanisms through which this occurs, including leptin resistance, the overproduction of fructose and ghrelin, insulin resistance and altered hormonal factors. A further influence on metabolism worth noting is the reported role of salt in inducing thermogenesis and increasing body temperature, leading to an increase in energy expenditure. While this result could be viewed as a positive metabolic effect because it promotes a negative energy balance to combat obesity, caution must be taken with this frame of thinking given the deleterious consequences of chronic high salt intake on cardiovascular health. Nevertheless, this review highlights the importance of salt as a noncaloric nutrient in regulating whole-body energy homeostasis. Through this review, we hope to provide a scientific framework for future studies to systematically address the metabolic impacts of dietary salt and salt replacement treatments. In addition, we hope to form a foundation for future clinical trials to explore how these salt-induced metabolic changes impact obesity development and progression, and to elucidate the regulatory mechanisms that drive these changes, with the aim of developing novel therapeutics for obesity and CVD.

The aim of this narrative review is to summarize contemporary evidence on the use of circulating cardiac biomarkers of heart failure (HF) and to identify a promising biomarker model for clinical use in personalized point-of-care HF management. We discuss the reported biomarkers of HF classified into clusters, including myocardial stretch and biomechanical stress; cardiac myocyte injury; systemic, adipocyte tissue, and microvascular inflammation; cardiac fibrosis and matrix remodeling; neurohumoral activation and oxidative stress; impaired endothelial function and integrity; and renal and skeletal muscle dysfunction. We focus on the benefits and drawbacks of biomarker-guided assistance in daily clinical management of patients with HF. In addition, we provide clear information on the role of alternative biomarkers and future directions with the aim of improving the predictive ability and reproducibility of multiple biomarker models and advancing genomic, transcriptomic, proteomic, and metabolomic evaluations.

Despite considerable advances in the field, heart failure (HF) still poses a significant disease burden among affected individuals since it continues to cause high morbidity and mortality rates. Inflammation is considered to play a key role in disease progression, but the exact underlying pathophysiological mechanisms involved have not yet been fully elucidated. The gut, as a potential source of inflammation, could feasibly explain the state of low-grade inflammation seen in patients with chronic HF. Several derangements in the composition of the microbiota population, coupled with an imbalance between favorable and harmful metabolites and followed by gut barrier disruption and eventually bacterial translocation, could contribute to cardiac dysfunction and aggravate HF. On the other hand, HF-associated congestion and hypoperfusion alters intestinal function, thereby creating a vicious cycle. Based on this evidence, novel pharmaceutical agents have been developed and their potential therapeutic use has been tested in both animal and human subjects. The ultimate goal in these efforts is to reverse the aforementioned intestinal derangements and block the inflammation cascade. This review summarizes the gut-related causative pathways implicated in HF pathophysiology, as well as the associated therapeutic interventions described in the literature.

Cardiovascular ailments are a major cause of mortality where over 1.3 billion people suffer from hypertension leading to heart-disease related deaths. Snake venoms possess a broad repertoire of natriuretic peptides with therapeutic potential for treating hypertension, congestive heart failure, and related cardiovascular disease. We now describe several taipan (Oxyuranus microlepidotus) natriuretic peptides TNPa-e which stimulated cGMP production through the natriuretic peptide receptor A (NPR-A) with higher potencies for the rat NPR-A (rNPR-A) over human NPR-A (hNPR-A). TNPc and TNPd were the most potent, demonstrating 100- and 560-fold selectivity for rNPR-A over hNPR-A. In vivo studies found that TNPc decreased diastolic and systolic blood pressure (BP) and increased heart rate (HR) in conscious normotensive rabbits, to a level that was similar to that of human atrial natriuretic peptide (hANP). TNPc also enhanced the bradycardia due to cardiac afferent stimulation (Bezold-Jarisch reflex). This indicated that TNPc possesses the ability to lower blood pressure and facilitate cardiac vagal afferent reflexes but unlike hANP does not produce tachycardia. The 3-dimensional structure of TNPc was well defined within the pharmacophoric disulfide ring, displaying two turn-like regions (RMSD = 1.15 Å). Further, its much greater biological stability together with its selectivity and potency will enhance its usefulness as a biological tool.

Heart has a recognized endocrine function as it produces several biologically active substances with hormonal properties. Among these hormones, the natriuretic peptide (NP) system has been extensively characterized and represents a prominent expression of the endocrine function of the heart. Over the years, knowledge about the mechanisms governing their synthesis, secretion, processing, and receptors interaction of NPs has been intensively investigated. Their main physiological endocrine and paracrine effects on cardiovascular and renal systems are mostly mediated through guanylate cyclase-A coupled receptors. The potential role of NPs in the pathophysiology of heart failure and particularly their counterbalancing action opposing the overactivation of renin-angiotensin-aldosterone and sympathetic nervous systems has been described. In addition, NPs are used today as key biomarkers in cardiovascular diseases with both diagnostic and prognostic significance. On these premises, multiple therapeutic strategies based on the biological properties of NPs have been attempted to develop new cardiovascular therapies. Apart from the introduction of the class of angiotensin receptor/neprilysin inhibitors in the current management of heart failure, novel promising molecules, including M-atrial natriuretic peptide (a novel atrial NP-based compound), have been tested for the treatment of human hypertension. The development of new drugs is currently underway, and we are probably only at the dawn of novel NPs-based therapeutic strategies. The present article also provides an updated overview of the regulation of NPs synthesis and secretion by microRNAs and epigenetics as well as interactions of cardiac hormones with other endocrine systems.

We aimed to analyze the correlation of urinary with serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations and its association with severity in acute bronchiolitis.

A pilot observational study was conducted between October 1, 2021 and March 31, 2022 including acute bronchiolitis cases who attended our institution. Serum and urinary NT-proBNP concentrations were determined using the Alere i NT-proBNP assay in time-matched urine and blood samples. The Mann-Whitney U test, Spearman's correlations, and simple linear regression were utilized to analyze the association of urine NT-proBNP levels with serum NT-proBNP and with variables indicative of severe bronchiolitis.

Seventeen infants (median age 68 [IQR: 36-91] days) with 36 time-matched samples were included. The urine NT-proBNP was positively and strongly correlated with the serum NT-proBNP concentrations (Spearman's ρ = 0.81 & R2  coefficient = 0.751; p < 0.001), and increased with higher C-reactive protein, (p = 0.004), procalcitonin (p = 0.001), and pCO2 (p = 0.029) levels. The initial urinary NT-proBNP concentrations were higher in those infants that required ventilatory support compared with those without this outcome (1.85 [IQR: 1.16-2.44] vs. 0.63 [IQR: 0.45-0.84] pg/mg); p < 0.001); and resulted positively and strongly correlated with the duration of the ventilatory support (Spearman's ρ = 0.76; p < 0.001) and the length of stay hospitalization (Spearman's ρ = 0.84; p < 0.001).

The urinary NT-proBNP concentrations could be a reliable surrogate for serum NT-proBNP levels and resulted elevated in cases of acute bronchiolitis with complicated evolution, suggesting a potential as a noninvasive tool to assess severity in this setting.

Heart failure (HF) is considered as a chronic long-term and lethal disease and will continue to be a major public health problem. Studying (circulating) biomarkers is a promising field of research and could be the first step toward HF tailored prognostic strategies as well as understanding the response to HF drugs in CHF patients.

In literature, there has been considerable research on elevated biomarker levels that are related to a poor prognosis for HF. Since biomarker levels change over time, it is important to study serial (repeated) biomarker measurements which may help us better understand the dynamic course of HF illness. However, the majority of research focuses predominantly on baseline values of biomarkers. Additionally, remote monitoring devices, like sensors, can be used to link hemodynamic information to freshen biomarker data in order to further ameliorate the management of HF.

Novel biomarkers and additional scientific insights with hemodynamic feedback strongly aid in the prognostication and risk prediction of chronic HF.

Natriuretic peptide system (NPS) and renin angiotensin aldosterone system (RAAS) function oppositely at multiple levels. While it has long been suspected that angiotensin II (ANGII) may directly suppress NPS activity, no clear evidence to date support this notion.

This study was designed to systematically investigate ANGII-NPS interaction in humans, in vivo, and in vitro for translational insights.

Circulating atrial, b-type, and c-type natriuretic peptides (ANP, BNP, CNP), cyclic guanosine monophosphate (cGMP), and ANGII were simultaneously investigated in 128 human subjects. Prompted hypothesis was validated in rat model to determine influence of ANGII on ANP actions. Multiple engineered HEK293 cells and surface plasmon resonance (SPR) technology were leveraged for mechanistic exploration.

In humans, ANGII showed inverse relationship with ANP, BNP, and cGMP. In regression models predicting cGMP, adding ANGII levels and interaction term between ANGII and natriuretic peptide increased predicting accuracy of base models constructed with either ANP or BNP, but not CNP. Importantly, stratified correlation analysis further revealed positive association between cGMP with ANP or BNP only in subjects with low, but not high, ANGII levels. In rats, co-infusion of ANGII even at physiological dose attenuated blood pressure reduction and cGMP generation triggered by ANP infusion. In vitro, we showed that the suppression effect of ANGII on ANP-stimulated cGMP requires the presence of ANGII type-1 (AT1) receptor and mechanistically involves protein kinase C (PKC), which can be substantially rescued by either valsartan (AT1 blocker) or Go6983 (PKC inhibitor). Using SPR, we showed ANGII has low affinity for particulate guanylyl cyclase A (GC-A) receptor binding compared to ANP or BNP.

Our study reveals ANGII as a natural suppressor for cGMP-generating action of GC-A via AT1/PKC dependent manner and highlights importance of dual-targeting RAAS and NPS in maximizing beneficial properties of natriuretic peptides in cardiovascular disease.