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Low concentrations of natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). African American individuals (AA) have lower NP levels and are disproportionately burdened by T2D. The purpose of this study was to test the hypothesis that higher post‐challenge insulin in AA adults is associated with lower plasma N‐terminal pro‐atrial natriuretic peptide (NT‐proANP). A secondary purpose was to explore associations between NT‐proANP and adipose depots. Participants were 112 AA and European American (EA) adult men and women. Measures of insulin were obtained from an oral glucose tolerance test and hyperinsulinemic‐euglycemic glucose clamp. Total and regional adipose depots were measured from DXA and MRI. Multiple linear regression analysis was used to assess associations of NT‐proANP with measures of insulin and adipose depots. Lower NT‐proANP concentrations in AA participants was not independent of 30‐min insulin area under the curve (AUC). NT‐proANP was inversely associated with 30‐min insulin AUC in AA participants, and with fasting insulin and HOMA‐IR in EA participants. Thigh subcutaneous adipose tissue and perimuscular adipose tissue were positively associated with NT‐proANP in EA participants. Higher post‐challenge insulin may contribute to lower ANP concentrations in AA adults. [ABSTRACT FROM AUTHOR]

Over the last several years, the use of biomarkers in the diagnosis of patients with heart failure (HF) has skyrocketed. Natriuretic peptides are currently the most widely used biomarker in the diagnosis and prognosis of individuals with HF. Proenkephalin (PENK) activates delta-opioid receptors in cardiac tissue, resulting in a decreased myocardial contractility and heart rate. However, the goal of this meta-analysis is to evaluate the association between the PENK level at the time of admission and prognosis in patients with HF, such as all-cause mortality, rehospitalization, and decreasing renal function. High PENK levels have been associated with a worsened prognosis in patients with HF. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a progressive condition with periods of apparent stability and repeated worsening HF events. Over time, unless optimization of HF treatment, worsening HF events become more frequent and patients enter into a cycle of recurrent events with high morbidity and mortality. In patients with HF there is an activation of deleterious neurohormonal pathways, such as the renin angiotensin aldosterone system and the sympathetic system, and an inhibition of protective pathways, including natriuretic peptides and guanylate cyclase. Therefore, HF burden can be reduced only through a holistic approach that targets all neurohormonal systems. In this context, vericiguat may play a key role, as it is the only HF drug that activates the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate system. On the other hand, it has been described relevant disparities in the management of HF population. Consequently, it is necessary to homogenize the management of these patients, through an integrated patient-care pathway that should be adapted at the local level. In this context, the development of new technologies (ie, video call, specific platforms, remote control devices, etc.) may be very helpful. In this manuscript, a multidisciplinary group of experts analyzed the current evidence and shared their own experience to provide some recommendations about the therapeutic optimization of patients with recent worsening HF, with a particular focus on vericiguat, and also about how the integrated patient-care pathway should be performed. [ABSTRACT FROM AUTHOR]

The N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is a widely used heart failure (HF) biomarker. Commercial NT-proBNP immunoassays detect only a subfraction of endogenous NT-proBNP, as the antibodies target a region of NT-proBNP that could be glycosylated at Ser44. The diagnostic utility of immunoassays measuring total NT-proBNP remains unclear. NT-proBNP was measured in 183 HF and 200 non-HF patients diagnosed by two independent cardiologists blinded to NT-proBNP results. Plasma samples either non-treated or treated with a mixture of glycosidases were analyzed by the Elecsys proBNP II assay (Roche Diagnostics, based on antibodies targeting a glycosylated region of NT-proBNP) and the SuperFlex NT-proBNP assay (PerkinElmer, based on antibodies targeting regions of NT-proBNP that are free of O-glycans). The diagnostic accuracy of the two assays was analyzed by comparison of ROC curves. The ROC-AUC for the proBNP II assay was 0.943 (95% CI 0.922–0.964) for NT-proBNP measured in untreated samples and 0.935 (0.913–0.958) for NT-proBNP measured in glycosidase-treated samples. The SuperFlex NT-proBNP assay in untreated samples gave a ROC-AUC of 0.930 (95% CI 0.907–0.954). The median percentage of non-glycosylated NT-proBNP to total NT-proBNP was 1.5–1.6-fold lower in the non-HF group compared to that in the HF group. The clinical value of total NT-proBNP for HF diagnosis was similar to the subfraction of NT-proBNP that was non-glycosylated at Ser44. The lower percentage of non-glycosylated NT-proBNP to total NT-proBNP in non-HF patients suggests that total NT-proBNP might be more sensitive in individuals without current or prior symptoms of HF. [ABSTRACT FROM AUTHOR]

Screening for left ventricular systolic dysfunction (LVSD), defined as reduced left ventricular ejection fraction (LVEF), deserves renewed interest as the medical treatment for the prevention and progression of heart failure improves. We aimed to review the updated literature to outline the potential and caveats of using artificial intelligence–enabled electrocardiography (AIeECG) as an opportunistic screening tool for LVSD. We searched PubMed and Cochrane for variations of the terms "ECG," "Heart Failure," "systolic dysfunction," and "Artificial Intelligence" from January 2010 to April 2022 and selected studies that reported the diagnostic accuracy and confounders of using AIeECG to detect LVSD. Out of 40 articles, we identified 15 relevant studies; eleven retrospective cohorts, three prospective cohorts, and one case series. Although various LVEF thresholds were used, AIeECG detected LVSD with a median AUC of 0.90 (IQR from 0.85 to 0.95), a sensitivity of 83.3% (IQR from 73 to 86.9%) and a specificity of 87% (IQR from 84.5 to 90.9%). AIeECG algorithms succeeded across a wide range of sex, age, and comorbidity and seemed especially useful in non-cardiology settings and when combined with natriuretic peptide testing. Furthermore, a false-positive AIeECG indicated a future development of LVSD. No studies investigated the effect on treatment or patient outcomes. This systematic review corroborates the arrival of a new generic biomarker, AIeECG, to improve the detection of LVSD. AIeECG, in addition to natriuretic peptides and echocardiograms, will improve screening for LVSD, but prospective randomized implementation trials with added therapy are needed to show cost-effectiveness and clinical significance. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) is a final link in most diseases of cardiovascular system, and despite the successes in the treatment of CHF, mortality remains high, and the prognosis is disappointing. Currently, the symptoms and objective signs of HF have been described in detail. However, the specific laboratory tests are limited to a single group of markers - natriuretic peptides. The known limitations for natriuretic peptides and the complexity of CHF pathophysiology condition the topicality of searching for other indicators with the aim to search biological and clinical information. In this regard, the biomarkers involved with other pathophysiological mechanisms of CHF appear to be of interest. A significant role of a new biomarker, stimulating a growth factor ST2, also known as "mechanical" myocardial stress is considered in this article. The mentioned biomarker has shown a high prognostic potential in the patients with HF. The increase of its soluble form sST2 is associated with the depth of the damage, the severity of disease course and its outcome. The assessment of prognostic value of the biomarker determination, as the predictor of cardio-vascular diseases and their outcomes has been performed. The topicality of searching for new therapeutic drugs in the combination with "traditional" means of CHF treatment is given in this article. Based on sST2 concentration in the blood, not only CHF degree and effectiveness of performed therapy can be judged, but also more accurately stratify the risk of progressive complications and, thereby, prevent unfavorable clinical outcome. [ABSTRACT FROM AUTHOR]

In heart failure with preserved ejection fraction (HFpEF), natriuretic peptide (NP) levels are frequently lower. In several trials, the outcome differed between patients with low and high NP levels. This suggests that NP could be used to identify distinct stages of left ventricular (LV) remodeling and myocardial tissue composition. This study investigated cardiac remodeling/dysfunction and myocardial tissue characteristics assessed by echocardiography and cardiac magnetic resonance (CMR) in HFpEF patients in relation to NP levels. Clinical and echocardiographic data of 152 HFpEF patients were derived from outpatient visits. A total of 71 HFpEF patients underwent CMR-derived T1-mapping. Multivariable regression analyses were performed to examine the association of NT-proBNP categories ( median) and NT-proBNP as continuous variable with echocardiography and CMR-derived T1-mapping. Mean age was 71 ± 9, 93% of patients were women and median NT-proBNP was 195 pg/mL, with 35% of patients below the diagnostic cut-off value (<125 pg/mL). Patients with high NT-proBNP had comparable LV systolic function and LV relaxation but significantly worse LV stiffness and left atrial function compared with patients with low NT-proBNP. Higher NT-proBNP was significantly associated with higher LV stiffness and extracellular volume fraction (ECV) (β = 1.82, 95% CI: 0.19;3.44, p = 0.029). Higher NT-proBNP levels identify HFpEF patients with worse LV stiffness because of more severe myocardial extracellular matrix remodeling, representing an advanced stage of HFpEF. [ABSTRACT FROM AUTHOR]

Cardiovascular biomarkers play a major diagnostic role for cardiologists. Different biomarkers provide different insights into a variety of cardiovascular conditions and in doing so they improve diagnosis and management. Often, these biomarkers are deployed without carefully evaluating the use of sex-specific cut off values. It is now becoming apparent that the use of such cut off values can improve prognostication and discrimination in some clinical situations. This review paper will focus on the data indicating that there is benefit to the use of sex-specific thresholds. It should be clear that these thresholds will vary depending on the analyte being measured and the specific clinical indication for which the patients are being evaluated; and sex-specific cut off values may be important in some situations but not others. Nonetheless, it is now clear that when evaluating sex-specific cut off values, one often finds benefit. We will highlight these situations using specific cardiac biomarkers as examples. [ABSTRACT FROM AUTHOR]

Early detection and treatment of cancer have led to a noticeable reduction in both mortality and morbidity. However, chemotherapy and radiotherapy could exert cardiovascular (CV) side effects, impacting survival and quality of life, independent of the oncologic prognosis. In this regard, a high clinical index of suspicion is required by the multidisciplinary care team in order to trigger specific laboratory tests (namely natriuretic peptides and high-sensitivity cardiac troponin) and appropriate imaging techniques (transthoracic echocardiography along with cardiac magnetic resonance, cardiac computed tomography, and nuclear testing (if clinically indicated)), leading to timely diagnosis. In the near future, we do expect a more tailored approach to patient care within the respective community along with the widespread implementation of digital health tools. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac biomarkers, such as high-sensitivity cardiac troponin T (hs-cTnT), are frequently elevated in ischemic stroke patients but the mechanisms underlying this elevation are insufficiently understood. We determined the presence of cardiac damage, assessed using cardiac magnetic resonance imaging (CMR), in stroke patients with elevated hs-cTnT and brain natriuretic peptide (BNP). Methods: This is a post hoc analysis of the prospective, investigator-initiated, cross-sectional HEart and BRain interfaces in Acute Stroke (HEBRAS) study. All patients underwent the measurement of hs-cTnT and BNP as well as gadolinium-enhanced CMR in the acute phase of ischemic stroke. We performed unadjusted and adjusted logistic regression models to assess the association between hs-cTnT and BNP elevation and the presence of pathological CMR findings. Results: Two hundred and thirty-three stroke patients (median age 67 years, 33% female) were included, of whom 43 (21%) had elevated hs-cTnT and 109 (47%) had elevated BNP. Hundred of the 233 (43%) patients had pathological findings on CMR had focal fibrosis as detected by late-gadolinium enhancement (LGE) in 51 (23%), left-ventricular hypertrophy (LVH) in 38 (16%), reduced LVEF in 32 (14%), and left-atrial dilatation in 34 (15%). After adjustment for potential confounders, both hs-cTnT (adjOR 5.0 (95%CI 2.1–11.7), p < 0.001) and BNP (adjOR 4.1 (95%CI 2.3–7.3), p < 0.001) were significantly associated with pathological findings on CMR. Hs-cTnT was associated with LGE, LVEF, and LVH, whereas BNP was associated with left-atrial dilatation and LVEF, LVH. Conclusion: Elevated cardiac biomarkers in acute stroke including CMR are strongly associated with pathological findings on CMR. In acute stroke patients, the elevation of cardiac biomarkers may identify patients who require a more thorough cardiology work-up. [ABSTRACT FROM AUTHOR]

Key message: Novel function and mechanism of a PNP molecule VaEG45 from adzuki bean involved in plant immunity. Plant natriuretic peptides (PNPs) can affect a broad spectrum of physiological responses in plants acting as peptidic signaling molecules. However, PNPs may play additional roles in plant immunity. Our previous transcriptome data of adzuki bean (Vigna angularis) in response to Uromyces vignae infection revealed association of PNP-encoding gene VaEG45 with U. vignae resistance. To determine the function of VaEG45 in disease resistance, we cloned the 589 bp nucleotide sequence of VaEG45 containing 2 introns, encoding a putative 13.68 kDa protein that is 131 amino acids in length. We analyzed expression in different resistant cultivars of V. angularis and found significant induction of VaEG45 expression after U. vignae infection. Transient expression of VaEG45 improved tobacco resistance against Botrytis cinerea. We next analyzed the mechanism by which VaEG45 protects plants from fungal infection by determination of the biological activity of the prokaryotic expressed VaEG45. The results showed that the fusion protein VaEG45 can significantly inhibit urediospores germination of U. vignae, mycelial growth, and the infection of tobacco by B. cinerea. Further analysis revealed that VaEG45 exhibits β-1, 3-glucanase activity. These findings uncover the function of a novel PNP molecule VaEG45 and provide new evidence about the mechanism of PNPs in plant immunity. [ABSTRACT FROM AUTHOR]

Background: Demographic changes have led to an increase in the proportion of older patients undergoing heart surgery. The number of endocarditis cases is also steadily increasing. Given the sharp increase in patients who have received valve prostheses or electrophysiological implants, who are on chronic dialysis or taking immunosuppressants, the interdependence of these two developments is quite obvious. We have studied the situation of older patients suffering from endocarditis compared to younger ones. Are they more susceptible, and are there differences in outcomes? Patients and Methods: A total of 162 patients was studied from our database, enrolled from 2020 to 2022. Fifty-four of them were older than 75 years of age (mean age 79.9 ± 3.8 years). The remaining 108 patients had a mean age of 61.6 ± 10.1 years. EuroSCORE II (ES II) was higher in the older patients (19.3 ± 19.7) than in the younger ones (13.2 ± 16.84). The BMI was almost identical. The preoperative NYHA proportions did not differ. A statistical analysis was performed using R. Results: Older patients had a lower left ventricular ejection fraction (LVEF), a higher proportion of coronary heart disease (CHD), a higher amount of N-terminal probrain natriuretic peptides (NT-proBNPs), worse coagulation function, worse renal function than younger patients, and were more often valve prosthesis carriers compared to the younger patients. The diagnostic interval was 66.85 ± 49.53 days in the younger cohort, whereas it was only 50.98 ± 30.55 in the elderly (p = 0.081). Significantly fewer septic emboli were observed in the older patients than in the younger patients, but postoperative delirium and critical illness polyneuropathy and critical illness myopathy (CIP/CIM) were observed significantly more frequently compared to younger patients. In-hospital mortality was higher in older patients than in younger patients, but did not reach statistical significance (29.91% vs. 40.38%; p = 0.256). The postoperative clinical status was worse in older patients than in the younger ones (NYHA-stage, p = 0.022). Conclusions: Age did have an impact on the outcome, probably due to causing a higher number of cumulative preoperative risk factors. However, an interesting phenomenon was that older patients had fewer septic emboli than younger patients. It can only be speculated whether this was due to a shorter diagnostic interval or lower mobility, i.e., physical exertion. Older patients suffered more frequently than younger ones from typical age-related postoperative complications, such as delirium and CIP/CIM. In-hospital mortality was high, but not significantly higher compared to the younger patients. Considering the acceptable mortality risks, and in light of the lack of alternatives, older patients should not be denied surgery. However, individual consideration is necessary. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of type 2 diabetes mellitus on plasma N-terminal prohormone B-type natriuretic peptide levels in patients with heart failure and correlate it with glycosylated haemoglobin levels. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Chemical Pathology in collaboration with the Department of Cardiology, Combined Military Hospital, Multan Pakistan, from Feb to Sep 2021. Methodology: We assayed plasma NT-pro BNP levels in 194 individuals with established heart failure, (98 non-diabetics, and 96 patients with diabetes). Plasma NT-pro BNP levels were compared between groups in addition, the correlation of glycosylated haemoglobin with plasma NT-pro BNP levels was explored. Results: The mean plasma NT-pro BNP values were higher in patients with diabetes (15826.08 ± 8143.434pg/mL) than in non-diabetics (12534.06±6323.92pg/mL) with a p-value 0.02. When NT-pro BNP was compared there was no significant found difference between the non-diabetic group and the Controlled Diabetes-Group (p-value 0 .882), but it was significantly higher in the Uncontrolled Diabetes-Group (p-value<0.001). A moderate positive association was found between NT-pro BNP and glycosylated haemoglobin (r=0.541, p-value<0.001). Conclusion: Although obesity has an inverse relation with plasma natriuretic peptides level and most patients with diabetes are overweight, the plasma NT-pro BNP is still a very informative tool and holds its significance as a diagnostic and prognosis marker in diabetic patients with heart failure. [ABSTRACT FROM AUTHOR]

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Background: We examined the effect of switching from angiotensin receptor-neprilysin inhibitor (ARNI) to angiotensin-receptor blocker (ARB) on plasma levels of natriuretic peptides and myocardial remodeling. Methods: This is a prospective study that included 11 patients with heart failure (HF) treated with ARNI. The patients were divided into two groups: 5 patients who continued treatment with sacubitril/valsartan 194/206 mg/day (ARNI-continue group) and 6 patients who were switched to valsartan 160 mg/day (ARB-switch group). The primary endpoint was percent change (%Change) in plasma A-, B-, and N-terminal pro-B-type natriuretic peptide (ANP, BNP, and NT-proBNP) levels from the baseline to week 24. The secondary endpoint was the change in echocardiographic parameters related to myocardial remodeling from the baseline to week 24. Results: ANP levels in the ARB-switch group significantly decreased (from 1155.7 ± 592.6 pg/mL to 231.6 ± 233.8 pg/mL, p = 0.035), whereas those in the ARNI-continue group were not significant (p = 0.180). The %Change of decrease in ANP levels was significantly greater in the ARB-switch group than the ARNI-continue group (− 76.9% vs. −9.1%, p = 0.009). BNP levels were not significantly different between the baseline and week 24 in both groups. NT-proBNP levels in the ARB-switch group increased from 1185.3 ± 835.6 pg/mL to 1515.2 ± 1213.5 pg/mL, although the changes were not statistically significant (p = 0.345). The %Change of increase in NT-proBNP levels was significantly greater in the ARB-switch group than the ARNI-continue group (57.9% vs. 17.3%, p = 0.016). In the ARB-switch group, there was a significant increase in left ventricular (LV) end-systolic volume (from 41.3 ± 24.1 mL/m2 to 71.4 ± 8.8 mL/m2, p = 0.043) and LV peak-systolic wall stress (from 187.0 ± 42.7 × 103 dynes/cm2 to 279.7 ± 34.1 × 103 dynes/cm2, p = 0.012) from the baseline to week 24 and a trend toward a decrease in LV ejection fraction (p = 0.080). In the ARNI-continue group, no differences in echocardiographic parameters were observed from the baseline to week 24. Conclusion: Switching from ARNI to ARB may worsen HF due to returning to myocardial remodeling induced by a sustained decline in ANP levels. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) undergoing coronary catheterization are at increased risk of cardiovascular events (CVE). Measuring biomarkers before the procedure may guide clinicians in identifying patients at higher risk of future cardiovascular events. In this sub-study the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA), 927 patients underwent coronary catheterization and were followed up for two years. Using machine learning algorithm and targeted proteomics from samples of patients with CKD, 4 biomarkers (kidney injury molecule-1, N-terminal pro B-type natriuretic peptide, osteopontin, and tissue inhibitor of metalloproteinase-1) were integrated into a prognostic algorithm to predict CVE. Results from the panel are expressed in a graded fashion (CVE higher risk and lower risk) using a data-driven cutoff optimized for balanced sensitivity and specificity. During the 2-year follow-up, 74 CVE were ascertained. 51 (rate: 51/378 = 13.5%) events occurred in stage 1–2 CKD and 23 (rate: 23/68 = 33.8%) events occurred in stage 3–5 CKD. The C-statistic for predicting 2-years cardiovascular events in all 446 patients was 0.77 (0.72, 0.82). The model was well-calibrated (Hosmer-Lemeshow test p -value >0.40). Considering patients at CVE lower-risk within each CKD staging group as a reference, the hazard ratio (95% confidence interval) of cardiovascular events was 2.82 (1.53, 5.22) for CKD stage 1–2/CVE higher-risk, and 8.32 (1.12, 61.76) for CKD stage 3–5/CVE higher-risk. Measuring biomarker panel prior to coronary catheterization may be useful to individualize CVE risk assessment among patients with CKD. HART-CVE panel can help clinicians recognize individuals at high risk of cardiovascular events prior to angiographic procedures among patients at different stages of chronic kidney disease. *Incidence rates are presented as cases per 100 person years. Abbreviations: IR: incidence rate, CKD: chronic kidney disease, CVE: cardiovascular event, HR: hazard ratio, CI: confidence interval, KIM-1: kidney injury molecule-1, NTproBNP: N terminal pro B-type natriuretic peptides, TIMP-1: Tissue inhibitor matrix metalloproteinase-1. [Display omitted] • Patients with chronic kidney disease are at increased risk of cardiovascular events following coronary catheterization. Preceding coronary catheterization is an ideal time to measure biomarkers and estimate risk for future cardiovascular events. • Using a machine learning algorithm and targeted proteomics, we demonstrated that measuring four biomarkers (kidney injury molecule-1, N-terminal pro B-type natriuretic peptide, osteopontin, and tissue inhibitor of metalloproteinase-1) can individualize cardiovascular events risk assessment among patients with chronic kidney disease • Future clinical trials may assess the efficacy of implementing the HART CVE model in lowering cardiovascular events compared to the standard of care [ABSTRACT FROM AUTHOR]

The relief of congestion is crucial to improve heart failure (HF) patient's quality of life and prognosis. N-terminal-pro-brain natriuretic peptide (NT-proBNP) is a well-known marker of congestion, although with limited specificity. Peak atrial longitudinal strain (PALS) by speckle tracking echocardiography (STE) is an index of intracardiac pressure and HF prognosis. We aimed to determine the association between NT-proBNP and PALS and its prognostic implications in patients with HF. Patients hospitalized for de-novo or recurrent HF and outpatients with chronic HF were included in this retrospective study. Patients with missing data, previous cardiac surgery, non-feasible STE were excluded. Clinical, laboratory and echocardiographic data were collected. STE was performed on echocardiographic records. Primary endpoint was a combination of all-cause death and HF hospitalization. Overall, 388 patients were included (172 acute HF, 216 chronic HF, mean age = 65 ± 12 years, 37% female). Mean LV ejection fraction = 31 ± 9%. Global PALS showed a significant inverse correlation with NT-proBNP in acute and chronic HF (all p < 0.001). During a median follow-up of 4 years, 180 patients reached the combined endpoint. NT-proBNP (AUC = 0.87) and global PALS (AUC = 0.82) were good predictors of the combined endpoint. Global PALS was the only independent predictor of the combined endpoint. Optimal risk stratification for the composite endpoint was provided combining PALS ≤15% and NTproBNP ≥874.5 ng/l. Global PALS is associated with NT-proBNP in acute and chronic HF and may be used as additional index of congestion to optimize therapeutic management. The combination of global PALS and NT-proBNP could enhance the prognostic stratification of HF. [Display omitted] • The relief of congestion is one of the main therapeutic targets in heart failure (HF). • Left atrial (LA) strain is correlated with NT-proBNP in acute and chronic HF. • Speckle tracking echocardiography adds prognostic information to NT-proBNP in HF. • The combination of LA strain and NT-proBNP provides optimal risk stratification in HF. [ABSTRACT FROM AUTHOR]

Aims Interest in targeted screening programmes for atrial fibrillation (AF) has increased, yet the role of genetics in identifying patients at highest risk of developing AF is unclear. Methods and results A total of 36,662 subjects without prior AF were analyzed from four TIMI trials. Subjects were divided into quintiles using a validated polygenic risk score (PRS) for AF. Clinical risk for AF was calculated using the CHARGE-AF model. Kaplan–Meier event rates, adjusted hazard ratios (HRs), C -indices, and net reclassification improvement were used to determine if the addition of the PRS improved prediction compared with clinical risk and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Over 2.3 years, 1018 new AF cases developed. AF PRS predicted a significant risk gradient for AF with a 40% increased risk per 1-SD increase in PRS [HR: 1.40 (1.32–1.49); P < 0.001]. Those with high AF PRS (top 20%) were more than two-fold more likely to develop AF [HR 2.45 (1.99–3.03), P < 0.001] compared with low PRS (bottom 20%). Furthermore, PRS provided an additional gradient of risk stratification on top of the CHARGE-AF clinical risk score, ranging from a 3-year incidence of 1.3% in patients with low clinical and genetic risk to 8.7% in patients with high clinical and genetic risk. The subgroup of patients with high clinical risk, high PRS, and elevated NT-proBNP had an AF risk of 16.7% over 3 years. The C -index with the CHARGE-AF clinical risk score alone was 0.65, which improved to 0.67 (P < 0.001) with the addition of NT-proBNP, and increased further to 0.70 (P < 0.001) with the addition of the PRS. Conclusion In patients with cardiovascular conditions, AF PRS is a strong independent predictor of incident AF that provides complementary predictive value when added to a validated clinical risk score and NT-proBNP. [ABSTRACT FROM AUTHOR]

Background: Pediatric Heart Failure Index (PHFI) and Modified Ross Score are a validated rating measures for evaluating pediatric heart failure that are useful because they can promote the assessment of treatment and analysis of outcomes. The present work aimed to evaluate the specificity and sensitivity of Modified Ross and Paediatric Heart Failure Index for quantifying severity of heart failure using pro-B-type Natriuretic peptide. Methods: A comparative study was conducted on 48 patients (26 males and 22 females) with congestive heart failure whose ages ranged from 4 months till 2 years, all cases have the Congestive Heart Failure (CHF) inclusion criteria. They were submitted to complete history taking, physical examination, X- ray chest and heart, ECG, echocardiography, classification of CHF severity according to PHFI Score, Modified Ross Score and laboratory investigations. The laboratory investigations were a routine such as: CBC and a special investigation as NT-pro-BNP serum level using NT-pro-BNP ELISA kit Results: our study showed a statistically significant positive correlation between M-ROSS scale and pro-BNP levels. There was a high statistically significant positive correlation between PHFI diagnostic scale and pro-BNP level and HR among studied patients. There is a positive correlation between PHFI score and modified Ross score According to modified Ross score. BOTH scores showed high ability to detect severe cases, as PHFI accuracy reaching up to 94.5% and, while accuracy of M-Ross was 90.5%. Conclusion: The study revealed that PHFI was more significant correlation with NT-proBNP than M-ROSS, so PHFI seems more accurate and sensitive to severe cases than M-ROSS. [ABSTRACT FROM AUTHOR]

The natriuretic peptides (NPs) hormone family, which consists mainly of atrial, brain, and C-type NPs (ANP, BNP, and CNP), play diverse roles in mammalian species, ranging from renal, cardiac, endocrine, neural, and vascular hemodynamics to metabolic regulations, immune responsiveness, and energy distributions. Over the last four decades, new data has transpired regarding the biochemical and molecular compositions, signaling mechanisms, and physiological and pathophysiological functions of NPs and their receptors. NPs are incremented mainly in eliciting natriuretic, diuretic, endocrine, vasodilatory, and neurological activities, along with antiproliferative, antimitogenic, antiinflammatory, and antifibrotic responses. The main locus responsible in the biological and physiological regulatory actions of NPs (ANP and BNP) is the plasma membrane guanylyl cyclase/natriuretic peptide receptor-A (GCA/ NPRA), a member of the growing multi-limbed GC family of receptors. Advances in this field have provided tremendous insights into the critical role of Npr1 (encoding GC-A/NPRA) in the reduction of fluid volume and blood pressure homeostasis, protection against renal and cardiac remodeling, and moderation and mediation of neurological disorders. The generation and use of genetically engineered animals, including gene-targeted (gene-knockout and gene-duplication) and transgenic mutant mouse models has revealed and clarified the varied roles and pleiotropic functions of GC-A/NPRA in vivo in intact animals. This review provides a chronological development of the biochemical, molecular, physiological, and pathophysiological functions of GC-A/NPRA, including signaling pathways, genomics, and gene regulation in both normal and disease states. [ABSTRACT FROM AUTHOR]

Globally, heart failure with preserved ejection fraction (HFpEF) is quickly becoming the dominant form of heart failure (HF) in ageing populations. However, there are still multiple gaps and challenges in making a firm diagnosis of HFpEF in many low-to-middle income Asian countries. In response to this unmet need, the Malaysian HFpEF Working Group (MY-HPWG) gathered and reviewed evidence surrounding the use of different diagnostic modalities indicated for patients with HFpEF to identify diagnostic tools that could be conveniently accessed across different healthcare settings. As a result, five recommendation statements were proposed and an accompanying algorithm was developed, with the aim of improving the diagnostic rate of HFpEF. The MY-HPWG recommends using more easily accessible and non-invasive tools, such as natriuretic peptide (NP) biomarkers and basic echocardiogram (ECHO), to ensure timely HFpEF diagnosis in the primary and secondary care settings, and prompt referral to a tertiary care centre for more comprehensive assessments in uncertain cases. [ABSTRACT FROM AUTHOR]

Aim: Recent data suggest that guideline‐directed medical therapy of patients with heart failure (HF) with reduced ejection fraction (HFrEF) might improve clinical outcomes in patients with HF up to a left ventricular ejection fraction (LVEF) of 55–65%, whereas patients with higher LVEF do not seem to benefit. Recent data have shown that LVEF may have a U‐shaped relation with outcome, with poorer outcome also in patients with supranormal values. This suggests that patients with supranormal LVEF may be a distinctive group of patients. Methods and results: RELAX‐AHF‐2 was a multicentre, placebo‐controlled trial on the effects of serelaxin on 180‐day cardiovascular (CV) mortality and worsening HF at day 5 in patients with acute HF. Echocardiograms were performed at hospital admission in 6128 patients: 155 (2.5%) patients were classified as HF with supranormal ejection fraction (HFsnEF; LVEF >65%), 1440 (23.5%) as HF with preserved ejection fraction (HFpEF; LVEF 50–65%), 1353 (22.1%) as HF with mildly reduced ejection fraction (HFmrEF; LVEF 41–49%) and 3180 (51.9%) as HFrEF (LVEF <40%). Patients with HFsnEF compared to HFpEF were more often women, had higher prevalence of non‐ischaemic HF, had lower levels of natriuretic peptides, were less likely to be treated with beta‐blockers and had higher blood urea nitrogen plasma levels. All‐cause mortality was not statistically different between groups, although patients with HFsnEF had the highest numerical rate. A declining trend was seen in the proportion of 180‐day deaths due to CV causes from HFrEF (290/359, 80.8%) to HFsnEF (14/24, 58.3%). The reverse was observed with death from non‐CV causes. No treatment effect of serelaxin was observed in any of the subgroups. Conclusions: In this study, only 2.5% of patients were classified as HFsnEF. HFsnEF was primarily characterized by female sex, lower natriuretic peptides and a higher risk of non‐CV death. [ABSTRACT FROM AUTHOR]

OBJECTIVE It is known that cancer patients are more prone to infections than the general population. We aimed to describe the risk factors affecting the survival of cancer patients infected with COVID-19 and clinical findings compared with a large COVID-19 patient population without cancer diagnosis. METHODS The clinical data of 61 cancer and 558 non-patients with COVID-19 infection who applied to the emergency room were compared retrospectively. Risk factors affecting overall survival in cancer patients were analyzed. RESULTS Gender and mean age were comparable in both groups. In the entire cohort, cancer diagnosis was found to be an independent poor prognostic factor (hazard ratio [HR] = 3.09, p<0.001) among other comorbidities. In univariate analysis; lung cancer, activated partial thromboplastin time >32 seconds, INR >1.1, N-terminal-pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, C-reactive protein >100 mg/L, and procalcitonin >0.23 ng/mL were determined as prognostic risk factors. Lung cancer (HR=5.277, p=0.012) and NT-proBNP >400 pg/ml (HR=0.139, p=0.021) were determined as independent prognostic risk factors in multivariate analysis. CONCLUSION Cancer patients with COVID-19 infection have poor survival outcomes. Lung cancer diagnosis and elevated NT-proBNP levels were identified as the most crucial prognostic risk factors in cancer patients infected with COVID-19. [ABSTRACT FROM AUTHOR]

Aim: To investigate the impact of epicardial adipose tissue (EAT) thickness on cardiopulmonary performance in patients with type 2 diabetes (T2D) and normal heart function. Materials and methods: We analysed EAT thickness in subjects with T2D and normal biventricular systo‐diastolic functions undergoing a maximal cardiopulmonary exercise test combined with stress echocardiography, speckle tracking and pulmonary function assessment, as well as serum N‐terminal pro B‐type natriuretic peptide (NT‐proBNP). Results: In the 72 subjects enrolled, those with EAT thickness above the median (> 5 mm) showed higher body fat mass, smaller indexed left ventricular dimensions and marginally reduced diastolic function variables at rest. Higher EAT thickness was associated with lower peak oxygen uptake (VO2peak 17.1 ± 3.6 vs. 21.0 ± 5.7 ml/min/kg, P =.001), reduced systolic reserve (ΔS′ 4.6 ± 1.6 vs. 5.8 ± 2.5 m/s, P =.02) and higher natriuretic peptides (NT‐proBNP 64 [29‐165] vs. 31 [26‐139] pg/ml, P =.04), as well as chronotropic insufficiency and impaired heart rate recovery. Ventilatory variables and peripheral oxygen extraction were not different between groups. EAT was independently associated with VO2peak and linearly and negatively correlated with peak heart rate, heart rate recovery, workload, VO2 at the anaerobic threshold and at peak, and cardiac power output, and was directly correlated with natriuretic peptides. Conclusion: Higher EAT thickness in T2D is associated with worse cardiopulmonary performance and multiple traits of subclinical cardiac systolic dysfunction. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to examine the prognostic value of the 6 min walk test (6MWT) in a large cohort of outpatients with heart failure. Methods and results A total of 5519 outpatients with heart failure from the National Norwegian Heart Failure Registry (NNHFR), which is part of the Norwegian Cardiovascular Disease Registry, were included in this analysis. The NNHFR recommended the use of the 6MWT for prognostic assessment of all patients included in the registry. Patients were categorized according to the 6MWT: Category 1 walked the longest and Category 3 the shortest. During a median (25th-75th percentiles) follow-up of 24 (14-36), 12.9% of the patients died. Patients in Category 3 had the overall worst outcome than had patients in Categories 1 and 2. 6MWT used as a continuous variable was a highly significant independent predictor for mortality in a multivariate Cox regression model adjusted for 16 other variables with a hazard ratio of 0.979 [(95% confidence interval 0.972-0.986), P < 0.001]. The four most important predictors for mortality were active cancer in the last 5 years, age, 6MWT, and natriuretic peptides (all P < 0.001). Conclusions 6MWT is a strong independent predictor of mortality in outpatients with HF. The findings support the use of the 6MWT in the prognostic assessment of patients with HF irrespective of HF aetiology. [ABSTRACT FROM AUTHOR]

The development of clinical congestion resulting from volume overload, either by renal fluid retention or redistribution of blood volume from venous reservoirs, is a recurrent scenario in patients with chronic heart failure (HF). As a result, the treatment of congestion, most commonly by initiating aggressive diuretic therapy, is a front-line issue in the management of patients with HF. However, the association of clinical congestion and volume overload with physical signs and symptoms, as well as other surrogates of volume assessment, has limitations in accuracy and, therefore, reliability to direct appropriate interventions. The ability to quantitate intravascular volume and identify the variability in volume profiles among patients with HF can uniquely inform individualized volume management and aid in risk stratification. This tool is provided by contemporary nuclear medicine-based BVA-100 methodology, which uses the well-established indicator-dilution principle and is a requested topic for discussion in this review. [ABSTRACT FROM AUTHOR]

Introduction: Heart failure (HF) is a debilitating condition with an adverse outcome, especially during the advanced stage having higher morbidity and mortality rates. Various parameters have been used as prognostic markers in advanced HF. This study highlights about the comparative analysis of different prognostic markers in predicting mortality in advanced HF. Methods: This prospective observational study was conducted in patients of advanced HF admitted to the department of medicine intensive care unit in a rural tertiary care hospital from 2018 to 2020. Advanced HF was diagnosed using the updated HF Association-European Society of Cardiology criteria. The serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), six-minute walk test (6MWT), left ventricular ejection fraction (LVEF), estimated glomerular filtration rate, and glycosylated hemoglobin type A1c levels were measured on admission. Receiver operating characteristic (ROC) curve was also studied for the above-mentioned variables, and the area under ROC curve (AUROC) was also determined. Results: Seventy-five patients with an average age of 60.55 ± 14.04 years were evaluated. Out of 75, 48 (64%) were male and 27 (36%) were female. There was inhospital mortality in 20 (26.67%) patients. The mean NT-proBNP levels among the mortality group was 9826.95 ± 3485.10 pg/mL, while in nonmortality group, it was 6135.40 ± 2342.77 pg/mL (P = 0.001). The cutoff range in this study for on-admission serum NT-proBNP levels was 8990 pg/mL, with AUROC of 0.81, the sensitivity of 70.0%, and specificity of 90.9%. In multiple regression analysis keeping mortality as the dependent variable, it was seen that variables NT-proBNP, 6MWT (<300 m), and LVEF were significantly associated with mortality. Conclusion: Serum NT-proBNP and 6MWT (<300 m) were important predictors of mortality in advanced HF. [ABSTRACT FROM AUTHOR]

A substantial proportion of patients with heart failure (HF) receive suboptimal guideline-recommended therapy. We aimed to identify the factors leading to suboptimal drug prescription in HF and according to HF phenotypes. This retrospective, single-centre observational cohort study included 702 patients admitted for worsening HF (HF with a reduced ejection fraction [HFrEF], n = 198; HF with a mildly reduced EF [HFmrEF], n = 122; and HF with a preserved EF [HFpEF], n = 382). A score based on the prescription and dose percentage of ACEi/ARBs, β-blockers, and MRAs at discharge was calculated (a total score ranging from zero to six). Approximately 70% of patients received ACEi/ARBs/ARNi, 80% of patients received β-blockers, and 20% received MRAs. The mean HF drug dose was approximately 50% of the recommended dose, irrespective of the HF phenotype. Ischaemic heart disease was associated with a higher prescription score (ranging from 0.4 to 1) compared to no history of ischaemic heart disease, irrespective of the left ventricular EF (LVEF) level. A lower prescription score was associated with older age and male sex in HFrEF and diabetes in HFmrEF. The overall ability of the models to predict the optimal drug dose, including key HF variables (including natriuretic peptides at admission), was poor (R2 < 0.25). A higher prescription score was associated with a lower risk of re-hospitalization and death (HR: 0.75 (0.57–0.97), p = 0.03), irrespective of phenotype (p-interaction = 0.41). Despite very different HF management guidelines according to LVEF, the prescription pattern of HF drugs is poorly related to LVEF and clinical characteristics, thus suggesting that physician-driven factors may be involved in the setting of therapeutic inertia. It may also be related to drug intolerance or clinical stability that is not predicted by the patients' profiles. [ABSTRACT FROM AUTHOR]

Snake venoms are heterogeneous mixtures of proteins and peptides used for prey subjugation. With modern proteomics there has been a rapid expansion in our knowledge of snake venom composition, resulting in the venom proteomes of 30% of vipers and 17% of elapids being characterised. From the reasonably complete proteomic coverage of front-fanged snake venom composition (179 species—68 species of elapids and 111 species of vipers), the venoms of vipers and elapids contained 42 different protein families, although 18 were only reported in < 5% of snake species. Based on the mean abundance and occurrence of the 42 protein families, they can be classified into 4 dominant, 6 secondary, 14 minor, and 18 rare protein families. The dominant, secondary and minor categories account for 96% on average of a snake's venom composition. The four dominant protein families are: phospholipase A2 (PLA2), snake venom metalloprotease (SVMP), three-finger toxins (3FTx), and snake venom serine protease (SVSP). The six secondary protein families are: L-amino acid oxidase (LAAO), cysteine-rich secretory protein (CRiSP), C-type lectins (CTL), disintegrins (DIS), kunitz peptides (KUN), and natriuretic peptides (NP). Venom variation occurs at all taxonomic levels, including within populations. The reasons for venom variation are complex, as variation is not always associated with geographical variation in diet. The four dominant protein families appear to be the most important toxin families in human envenomation, being responsible for coagulopathy, neurotoxicity, myotoxicity and cytotoxicity. Proteomic techniques can be used to investigate the toxicological profile of a snake venom and hence identify key protein families for antivenom immunorecognition. [ABSTRACT FROM AUTHOR]

The term "inflammageing" was introduced in 2000, with the aim of describing the chronic inflammatory state typical of elderly individuals, which is characterized by a combination of elevated levels of inflammatory biomarkers, a high burden of comorbidities, an elevated risk of disability, frailty, and premature death. Inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and rapid progression to heart failure. The great experimental and clinical evidence accumulated in recent years has clearly demonstrated that early detection and counteraction of inflammageing is a promising strategy not only to prevent cardiovascular disease, but also to slow down the progressive decline of health that occurs with ageing. It is conceivable that beneficial effects of counteracting inflammageing should be most effective if implemented in the early stages, when the compensatory capacity of the organism is not completely exhausted. Early interventions and treatments require early diagnosis using reliable and cost-effective biomarkers. Indeed, recent clinical studies have demonstrated that cardiac-specific biomarkers (i.e., cardiac natriuretic peptides and cardiac troponins) are able to identify, even in the general population, the individuals at highest risk of progression to heart failure. However, further clinical studies are needed to better understand the usefulness and cost/benefit ratio of cardiac-specific biomarkers as potential targets in preventive and therapeutic strategies for early detection and counteraction of inflammageing mechanisms and in this way slowing the progressive decline of health that occurs with ageing. [ABSTRACT FROM AUTHOR]

Kidney surgery often includes organ ischaemia with a risk of acute kidney injury. The present study tested if treatment with the combined angiotensin II–angiotensin II receptor type 1 and neprilysin blocker Entresto (LCZ696, sacubitril/valsartan) protects filtration barrier and kidney function after ischaemia and partial nephrectomy (PN) in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m diethylene-triamine-pentaacetate clearance was validated (n  = 6). Next, four groups of pigs were followed for 15 days (n  = 24) after PN (one-third right kidney, 60 min ischaemia) + Entresto (49/51 mg/day; n  = 8), PN + vehicle (n  = 8), sham + Entresto (49/51 mg/day; n  = 4) and sham + vehicle (n  = 4). GFR, diuresis and urinary albumin were measured at baseline and from each kidney after 15 days. The sum of single-kidney GFR (right 25 ± 6 mL/min, left 31 ± 7 mL/min) accounted for the total GFR (56 ± 14 mL/min). Entresto had no effect on baseline blood pressure, p-creatinine, mid-regional pro-atrial natriuretic peptide (MR-proANP), heart rate and diuresis. After 15 days, Entresto increased GFR in the uninjured kidney (+23 ± 6 mL/min, P  < .05) and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto; it increased to similar levels 2 h after surgery with and without Entresto. Fractional sodium excretion increased with Entresto. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto protects the filtration barrier and increases the functional adaptive response of the uninjured kidney. [ABSTRACT FROM AUTHOR]

Introduction: Concomitant risk factors challenge the mechanistic understanding of cardiac aging. We determined the degree to which the left atrial function could be distinguished by advanced cardiac magnetic resonance (CMR) imaging in older adults and assessed associations between the left atrial function and the plasma biomarkers related to biological aging and cardiovascular disease [serum monocyte chemoattractant protein-1 (MCP1), matrix metallopeptidase 9 (MMP-9), B-type natriuretic peptides (BNPs), galectin-3 (Gal-3), high-sensitivity cardiac troponin I (hsTn1), high-sensitivity C-reactive protein (hs-CRP), and soluble urokinase plasminogen activator receptor (sUPAR)]. Methods: Among a cross-sectional population-based cohort of older adults, longitudinal LA strain including reservoir strain (εs), conduit strain (εe), and booster strain (εa) as well as peak strain rates (SRs, SRe, SRa) were determined using CMR and studied in association with blood biomarkers. Results: We studied 243 community adults (42.8% female, mean age 70.3 ± 9.5 years). In bivariate analysis, εe and SRe were reduced in gradation with increasing risk factors (all p values <0.0001). Corresponding levels of sUPAR (ng/mL) were quantitatively higher in older adults with <2 risk factors (2.5 ± 1.6 vs. 1.7 ± 1.3, p = 0.0005), in those with ≥2 risk factors (3.3 ± 2.4 vs. 1.7 ± 1.3, p < 0.0001), compared to young adults; including between older adults with ≥2 risk factors and older adults with <2 risk factors (3.3 ± 2.4 vs. 2.5 ± 1.6, p = 0.017). Based on multivariate analysis, sUPAR was significantly associated with both εe (OR 1.52, p = 0.006) and SRe decline (OR 1.5, p = 0.019). The associations between Gal-3 and εe reduction (OR 1.2, p = 0.022) and between BNP and SRe decline were generally weaker (OR 1.03, p = 0.027). The addition of sUPAR to a model consisting of age, risk factors, Gal-3, and BNPs increased the area under the curve of εe from 0.72 to 0.77 (p = 0.015). Conclusion: By advanced CMR imaging, a panel of circulating biomarkers comprising galectin, MMP-9 and sUPAR were associated with left atrial dysfunction in older adults. Higher levels of Gal-3 and MMP-9 may be suggestive of fibrotic mechanisms in left atrial aging while impairments in left atrial strain seen in association with circulating sUPAR may be related to immune activation in the left atrium in response to left atrial remodeling and fibrotic processes. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVD) are the main cause of morbidity and mortality worldwide, especially affecting the population over 60 years of age, they can manifest depending on their origin in coronary disease (acute myocardial infarction, angina pectoris, sudden cardiac arrest, heart failure and sudden death) and cerebrovascular disease (strokes and transient ischemic events). Several risk factors associated with the development of CVD have been described, the classic factors (modifiable and non-modifiable), and others that have been added to the list as a result of new evidence, such as inflammation, thrombosis, stress, alterations in the levels of natriuretic peptides, heavy metals/environmental pollutants, renal insufficiency, and some infectious agents. The objective of this article is to present the state of the art associated with classic cardiovascular risk factors (CRFs) and the evidence that supports emerging CRFs. [ABSTRACT FROM AUTHOR]

Background: Heart disease and stroke are major and often unheralded causes of serious morbidity and premature death in middle age. Early detection of those most at risk is an urgent unmet need for instituting preventative measures. In an earlier community study (Canterbury Health, Ageing and Life Course [CHALICE]) of healthy people aged 50 years, contrary to previous reports, low levels of the heart hormone B-type natriuretic peptide (BNP) were associated with reduced measures of heart function and higher markers of vascular risk. A specific gene variant (rs198358) was found to be an independent contributor to higher BNP levels. A closely related vascular hormone (C-type natriuretic peptide [CNP]) showed opposite associations-higher levels were correlated with higher vascular risk and reduced cardiac function. To determine whether these novel findings predict serious heart or vascular disease in later life, this proposal re-examines the same CHALICE participants 15 years later. Objective: The primary objective is to determine the predictive value of (1) low plasma concentrations of the circulating cardiac hormones (atrial natriuretic peptide [ANP] and BNP) and (2) high levels of the vascular hormone CNP at age 50 years in detecting impaired cardiac and vascular function 15 years later. Secondary objectives are to determine specific associations of individual analytes (ANP, BNP, CNP, cyclic guanosine monophosphate [cGMP]) with echo-derived changes in cardiac performance at ages 50 years and 65 years. Methods: All of the 348 participants (205/348, 58.9% female; 53/348, 15.2% Māori or Pacifica ethnicity) participating in the original CHALICE study-free of history of heart or renal disease at age 50 years and who consented to further study-will be contacted, recruited, and restudied as previously described. Data will include intervening health history, physical examination, heart function (speckle-tracking echocardiography), vascular status (carotid intimal thickness), and genetic status (genome-wide genotyping). Laboratory measures will include fasting blood sampling and routine biochemistry, ANP, BNP, CNP, their downstream effector (cGMP), and their bio-inactive products. Humoral metabolic-cardiovascular risk factors will be measured after an overnight fast. Primary outcomes will be analyzed using multiple linear regression. Results: The study will commence in 2022 and be completed in 2024. Conclusions: Proving our hypothesis-that low BNP and high CNP at any age in healthy people predict premature aging of heart and blood vessels, respectively-opens the way to early detection and improved outcomes for those most at risk. Confirmation of our hypotheses would improve current methods of screening and, in appropriate cases, enable interventions aimed at increasing natriuretic hormones and reducing risk of serious cardiovascular complications using drugs already available. Such advances in detection, and from interventional corrections, have the potential to not only improve health in the community but also reduce the high costs inevitably associated with heart failure. [ABSTRACT FROM AUTHOR]

Natriuretic peptide signaling has been implicated in a broad range of physiological processes, regulating blood volume and pressure, ventricular hypertrophy, fat metabolism, and long bone growth. Here, we describe a completely novel role for natriuretic peptide signaling in the control of neural crest (NC) and cranial placode (CP) progenitors formation. Among the components of this signaling pathway, we show that natriuretic peptide receptor 3 (Npr3) plays a pivotal role by differentially regulating two developmental programs through its dual function as clearance and signaling receptor. Using a combination of MO-based knockdowns, pharmacological inhibitors and rescue assays we demonstrate that Npr3 cooperate with guanylate cyclase natriuretic peptide receptor 1 (Npr1) and natriuretic peptides (Nppa/Nppc) to regulate NC and CP formation, pointing at a broad requirement of this signaling pathway in early embryogenesis. We propose that Npr3 acts as a clearance receptor to regulate local concentrations of natriuretic peptides for optimal cGMP production through Npr1 activation, and as a signaling receptor to control cAMP levels through inhibition of adenylyl cyclase. The intracellular modulation of these second messengers therefore participates in the segregation of NC and CP cell populations.

Natriuretic peptides may be associated with the complex interaction between malnutrition and fluid overload. This study assessed the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP), body fluid composition, and quality of life (QOL) domains. A multicenter, cross-sectional study was conducted between 2019 and 2022. The QOL survey of 322 patients undergoing maintenance hemodialysis (227 men and 95 women; mean age, 65 ± 12 years) was conducted using the Kidney Disease QOL-Short Form v. 1.3. The patients in the higher NT-proBNP quartile group were older and had a longer dialysis vintage; lower body mass index, serum albumin, blood urea nitrogen, creatinine, sodium, uric acid, total cholesterol, triglycerides, and hemoglobin levels; lower geriatric nutritional risk index (GNRI), skeretal mascle mass index, and phase angle (PhA); and higher pre- and post-dialysis systolic blood pressure (BP), cardiothoracic index, and C-reactive protein (CRP) (p < 0.05). Multivariate analysis revealed that post-dialysis systolic BP, CRP, and GNRI or PhA were independently associated with NT-proBNP. The higher NT-proBNP group experienced muscle attenuation and/or inflammation and an enlarged left atrium. Consequently, the elevated NT-proBNP by such an imbalance in body fluid composition is associated with lower health-related QOL.

An always-rising prevalence of heart failure (HF), formerly classified as an emerging epidemic in 1997 and still representing a serious problem of public health, imposes on us to examine more in-depth the pathophysiological mechanisms it is based on. Over the last few years, several biomarkers have been chosen and used in the management of patients affected by HF. The research about biomarkers has broadened our knowledge by identifying some underlying pathophysiological mechanisms occurring in patients with both acute and chronic HF. This review aims to provide an overview of the role of biomarkers previously identified as responsible for the pathophysiological mechanisms subtending the disease and other emerging ones to conduct the treatment and identify possible prognostic implications that may allow the optimization of the therapy and/or influence a closer follow-up. Taking the high prevalence of HF-associated comorbidities into account, an integrated approach using various biomarkers has shown promising results in predicting mortality, a preferable risk stratification, and the decrease of rehospitalizations, reducing health care costs as well.

Soluble (s)ST2 has been proposed as a useful biomarker for heart failure (HF) patient management. Myocardial damage or mechanical stress stimulate sST2 release. ST2 competes with a membrane bound receptor (ST2 ligand, or ST2L) for interleukin-33 (IL-33) binding, inhibiting the effects induced by the ST2L/IL-33 interaction so that excessive sST2 may contribute to myocardial fibrosis and ventricular remodeling. Compared to natriuretic peptides (NPs), sST2 concentration is not substantially affected by age, sex, body mass index, kidney function, atrial fibrillation, anemia, or HF etiology, and has low intra-individual variation. Its prognostic role as an independent marker is well reported in the literature. However, there is a gap on its use in combination with NPs, currently the only biomarkers recommended by European and American guidelines for HF management. Reflecting the activation of two distinct biological systems, a benefit from the use of sST2 and NP in combination is advocated. The aim of this review is to report the current scientific knowledge on sST2 in the acute and chronic HF settings with a particular attention to its additive role to natriuretic peptides (NPs).

Purpose The pathophysiology of nocturia and nocturnal polyuria (NP), conditions that become more prevalent with aging, may in part be explained by changes in hormones involved in water homeostasis. The purpose of this study was to analyze the impact of aging on urinary natriuretic peptides in nocturia and NP. Methods Patients aged ≥18 years completed 24-hour bladder diaries for assessment of nocturia and NP. They were divided into subgroups of ≥65 years old and