Relationship between initial B-type natriuretic peptide levels and detection of atrial fibrillation with an insertable cardiac monitor in cryptogenic stroke: CRYPTON-ICM registry.

High B-type natriuretic peptide (BNP) levels are associated with new atrial fibrillation (AF). This study investigated the distribution of AF detection rates according to BNP levels in patients with cryptogenic stroke (CS) using an insertable cardiac monitor (ICM). We enrolled consecutive patients with CS who underwent ICM implantation between October 2016 and September 2020 at eight stroke centers in Japan. Those with BNP levels were divided into three groups by tertiles. We evaluated the association of BNP levels with AF detection. Youden's index was calculated to identify the optimal cutoff for BNP. Of 417 patients, we analyzed 266 patients with BNP data. The tertile range of BNP level was 19.0 to 48.5 pg/mL. AF detection rate was 13.3%/year, 12.8%/year, and 53.7%/year in the low-BNP (≤19.0), mid-BNP (19.1-48.4), and high-BNP (≥48.5) groups, respectively (log-rank trend p < 0.01). Compared with low-BNP group, the adjusted hazard ratios for AF detection in mid-and high-BNP groups were 0.91 [95% confidence interval (CI) 0.46-1.78] and 2.17 (95% CI 1.14-4.13), respectively. Receiver operating characteristic curve analysis showed the optimal cutoff value was 43.4 pg/mL. The area under curve using BNP to predict AF detection was 0.69. The BNP level was associated with AF detection in patients with CS. This relationship changed around the BNP levels of 40-50 pg/mL.

N-terminal pro-brain natriuretic peptide is associated with pulmonary hypertension or diastolic dysfunction in patients with systemic sclerosis: An Australian prospective cross-sectional study.

Introduction: Pulmonary arterial hypertension and left ventricular diastolic dysfunction are associated with significant morbidity and mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide has been proposed as part of composite screening algorithms for pulmonary arterial hypertension. Our aim was to assess the prevalence of pulmonary hypertension and diastolic dysfunction, and evaluate their association with serum N-terminal pro-brain natriuretic peptide in systemic sclerosis patients. Methods: Patients with systemic sclerosis were prospectively enrolled to undergo N-terminal pro-brain natriuretic peptide testing and transthoracic echocardiography at a tertiary Australian centre from January to October 2022. We collected demographic and transthoracic echocardiography variables including pulmonary hypertension estimated by tricuspid regurgitant velocity and diastolic dysfunction assessed by the ASE/EACVI 2016 guidelines. Pearson's correlation coefficient was used to evaluate association between N-terminal pro-brain natriuretic peptide and echocardiographic parameters. Results: Sixty-one patients were enrolled (median age = 62 years (interquartile range = 55-69 years); 84% female). Two-thirds of patients had limited systemic sclerosis (40/61). Five patients (8%) had high likelihood of pulmonary hypertension by transthoracic echocardiography. Seven patients (11%) had diastolic dysfunction; however, seven patients (11%) had indeterminate diastology. Six patients underwent right heart catheterisation, with five patients diagnosed with pulmonary hypertension. N-terminal pro-brain natriuretic peptide in patients with pulmonary hypertension or diastolic dysfunction was significantly higher (median = 207 and 226 pg/mL, respectively) compared to patients without either condition (median = 69 pg/mL, p = 0.01). N-terminal pro-brain natriuretic peptide showed a statistically significant although limited correlation with estimated pulmonary pressures measured by tricuspid regurgitant velocity (r = 0.44, p = 0.002) and left ventricular filling pressures (r = 0.27, p = 0.04). Conclusion: Pulmonary hypertension and diastolic dysfunction are both observed in systemic sclerosis. N-terminal pro-brain natriuretic peptide is associated with both conditions; however, it cannot distinguish between the two disease processes. Right heart catheterisation may be required to make this distinction.

Atrial natriuretic peptide (ANP) modulates stress-induced autophagy in endothelial cells.

Atrial natriuretic peptide (ANP), a cardiac hormone involved in the regulation of water/sodium balance and blood pressure, is also secreted by endothelial cells, where it exerts protective effects in response to stress. Autophagy is an intracellular self-renewal process involved in the degradation of dysfunctional cytoplasmic elements. ANP was recently reported to act as an extracellular regulator of cardiac autophagy. However, its role in the regulation of endothelial autophagy has never been investigated. Here, we tested the effects of ANP in the regulation of autophagy in human umbilical vein endothelial cells (HUVECs). We found that ANP rapidly increases autophagy and autophagic flux at physiological concentrations through its predominant pathway, mediated by natriuretic peptide receptor type A (NPR-A) and protein kinase G (PKG). We further observed that ANP is rapidly secreted by HUVEC under stress conditions, where it mediates stress-induced autophagy through autocrine and paracrine mechanisms. Finally, we found that the protective effects of ANP in response to high-salt loading or tumor necrosis factor (TNF)-α are blunted by concomitant inhibition of autophagy. Overall, our results suggest that ANP acts as an endogenous autophagy activator in endothelial cells. The autophagy mechanism mediates the protective endothelial effects exerted by ANP.

Impact of first-line antihypertensive drug class and intensity on NT-proBNP improvement and cardiovascular outcomes among hypertensive patients with pre-heart failure: findings from SPRINT trial.

Five first-line classes of antihypertensive drugs are recommended for hypertension treatment. However, it is unclear which class should be chosen for hypertensive patients with pre-heart failure (pre-HF). The study aimed to investigate the association between antihypertensive drug classes and intensity with probability of NT-proBNP (N-terminal pro-B-type natriuretic peptide) improvement and risk of cardiovascular events among pre-HF hypertensive patients. Utilizing the data from SPRINT, we included pre-HF hypertensive patients, identified by NT-proBNP ≥125 pg/mL at baseline. NT-proBNP improvement is defined as a reduction of ≥50% to a level below 125 pg/mL. A total of 3293 patients (mean age: 71.9 years; female: 43.8%) were included. NT-proBNP improvement was observed in 415 patients (12.6%) over 1-year follow up. Thiazide-type diuretics users were associated with a higher likelihood of NT-proBNP improvement (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.05-1.70), a lower risk of HF (hazard ratio [HR], 0.54; 95% CI, 0.37-0.78) and primary composite outcome (HR, 0.72; 95% CI, 0.57-0.89). ACEI/ARB users were only associated with a lower risk of primary composite outcome (HR, 0.80; 95% CI, 0.63-0.99). In contrast, beta-blockers users were associated with a lower likelihood of NT-proBNP improvement (OR, 0.43; 95% CI, 0.34-0.55), while a higher risk of HF (HR, 1.79; 95% CI, 1.21-2.64) and primary composite outcome (HR, 1.48; 95% CI, 1.18-1.87). These associations varied across subgroups of different drug intensities. This post hoc analysis supports the use of thiazide-type diuretics and ACEI/ARB for prevention of cardiovascular events. The use of beta-blockers is associated with an increased risk of HF and primary outcomes, which requires further validation. Association between antihypertensive drug classes and intensity with NT-proBNP improvement and long-term clinical outcome.

Deletion of AT1a receptors selectively in the proximal tubules alters the hypotensive and natriuretic response to ANP via NPRA/cGMP/NO Signaling.

In the kidney, vasoactive peptide hormones angiotensin II (Ang II), via AT1a receptors, and atrial natriuretic peptide (ANP), via NPRA receptors, reportedly play counteracting roles to regulate proximal tubule Na+ reabsorption and maintain blood pressure homeostasis. However, how AT1a and NPRA receptors interact in the proximal tubules and whether deletion of AT1 (AT1a) receptors selectively in the proximal tubules alters the hypotensive and natriuretic effects of ANP) have not been studied previously. The present study used a novel mouse model with proximal tubule-specific knockout of AT1a receptors to test the hypothesis that deletion of AT1a receptors selectively in the proximal tubules augments the hypotensive and natriuretic responses to ANP. Basal blood pressure was about 16 ± 3 mmHg lower, fractional proximal tubule Na+ reabsorption was significantly lower, whereas 24 h urinary Na+ excretion was significantly higher in PT-Agtr1a-/- than in wild-type mice (P<0.01). Infusion of ANP for 2 weeks (0.5 mg/kg/day, i.p.) further significantly decreased blood pressure and increased the natriuretic response in PT-Agtr1a-/- mice by inhibiting proximal tubule Na+ reabsorption (P<0.01). These augmented hypotensive and natriuretic responses to ANP in PT-Agtr1a-/- mice were associated with increased plasma and kidney cGMP levels (P<0.01), kidney cortical NPRA and NPRC mRNA expression (P<0.01), total and phosphorylated endothelial nitric oxide synthase (eNOS) (P<0.01), and urinary nitric oxide (NO) excretion (P<0.01). Taken together, the results of the present study support important physiological roles of Ang II/AT1a and ANP/NPRA signaling pathways in the proximal tubules to regulate proximal tubule reabsorption and maintain blood pressure homeostasis.

Natriuretic Peptides, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: N-terminal pro-B-type natriuretic peptides (NT-proBNPs) are guideline-recommended biomarkers for risk stratification in patients with heart failure. However, NT-proBNP levels are often elevated in chronic kidney disease, introducing uncertainty about their prognostic relevance in persons across a broad range of estimated glomerular filtration rate (eGFR). OBJECTIVES: The aim of this study was to assess the association of NT-proBNP with cardiovascular and mortality outcomes in patients with heart failure and mildly reduced or preserved ejection fraction, stratified by baseline kidney function. METHODS: A pooled analysis was conducted of participants with NT-proBNP and eGFR measured at baseline in the I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction), TOPCAT (Americas region) (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function), PARAGON (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction), and DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) trials. The relationship between NT-proBNP and eGFR was assessed using piecewise linear regression. Using multivariable Cox and Poisson regression models, the association of NT-proBNP with outcomes across a range of eGFR was evaluated. The primary outcome was hospitalization for heart failure or cardiovascular death. RESULTS: Among 14,831 participants (mean age: 72.1 years; 50.3% female; mean eGFR: 63.3 mL/min/1.73 m2, and median NT-proBNP: 840 pg/mL) followed up for a median 33.5 months, there were 3,092 primary outcomes. NT-proBNP levels increased by 9%, 8%, and 23% per 10 mL/min/1.73 m2 lower eGFR in patients with baseline eGFR ≥60, 45-<60, and <45 mL/min/1.73 m2, respectively (P for nonlinearity < 0.001). Each doubling in NT-proBNP was associated with a 37% relative increase in the primary outcome (HR: 1.37; 95% CI: 1.34-1.41), consistent across different eGFR categories (P for interaction = 0.42). For the same incidence of the primary outcome, NT-proBNP levels were approximately 2.5- to 3.5-fold lower in patients with eGFR <45 mL/min/1.73 m2, compared with patients with eGFR ≥60 mL/min/1.73 m2. Similar patterns were observed across all outcomes studied, including cardiovascular and noncardiovascular death. CONCLUSIONS: The same NT-proBNP concentration predicts a substantially higher absolute risk of adverse outcomes for people with heart failure and reduced kidney function, compared with those with preserved kidney function. These data call into question proposals for higher NT-proBNP references ranges in people with CKD, and suggest that reduced kidney function per se should not be a reason to disregard higher NT-proBNP levels.

Cardiomyocyte-derived C-type natriuretic peptide diminishes myocardial ischaemic injury by promoting revascularisation and limiting fibrotic burden.

BACKGROUND: C-type natriuretic peptide (CNP) is a significant player in the maintenance of cardiac and vascular homeostasis regulating local blood flow, platelet and leukocyte activation, heart structure and function, angiogenesis and metabolic balance. Since such processes are perturbed in myocardial infarction (MI), we explored the role of cardiomyocyte-derived CNP, and pharmacological administration of the peptide, in offsetting the pathological consequences of MI. METHODS: Wild type (WT) and cardiomyocyte-restricted CNP null (cmCNP-/-) mice were subjected to left anterior descending coronary artery (LADCA) ligation and acute effects on infarct size and longer-term outcomes of cardiac repair explored. Heart structure and function were assessed by combined echocardiographic and molecular analyses. Pharmacological administration of CNP (0.2mg/kg/day; s.c.) was utilized to assess therapeutic potential. RESULTS: Compared to WT littermates, cmCNP-/- mice had a modestly increased infarct size following LADCA ligation but without significant deterioration of cardiac structural and functional indices. However, cmCNP-/- animals exhibited overtly worse heart morphology and contractility 6 weeks following MI, with particularly deleterious reductions in left ventricular ejection fraction, dilatation, fibrosis and revascularization. This phenotype was largely recapitulated in animals with global deletion of natriuretic peptide receptor (NPR)-C (NPR-C-/-). Pharmacological administration of CNP rescued the deleterious pathology in WT and cmCNP-/-, but not NPR-C-/-, animals. CONCLUSIONS AND IMPLICATIONS: Cardiomyocytes synthesize and release CNP as an intrinsic protective mechanism in response to MI that reduces cardiac structural and functional deficits; these salutary actions are primarily NPR-C-dependent. Pharmacological targeting of CNP may represent a new therapeutic option for MI.

Plasma N-terminal pro-brain natriuretic peptide concentrations may help to identify patients with very low-risk acute pulmonary embolism: A preliminary study.

BACKGROUND: Patients with an acute pulmonary embolism (APE) are a heterogeneous group, and some of them may benefit from early discharge and an ambulatory care referral. We aimed to evaluate the use of N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma level assessment in patients with low-risk APE based on clinical findings (0 points on the simplified Pulmonary Embolism Severity Index (sPESI)). MATERIAL AND METHODS: Preliminary analysis of an ongoing prospective study including 1,151 normotensive patients with at least a segmental APE. In the final analysis, 348 patients with a 0-point sPESI were included. Blood samples were collected within the first 24 h of admission. The clinical endpoint (CE) included APE-related mortality and/or rescue thrombolysis in patients with clinical deterioration. RESULTS: Clinical endpoints occurred in 3 patients who had higher plasma NT-proBNP levels than study participants with a favorable clinical course (164 [64-650] pg/mL compared to 2,930 [2,285.5-13,965] pg/mL; p = 0.01). Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) for NT-proBNP for the prediction of the CEs was 0.918 (95% confidence interval [95% CI]: 0.831-1.00; p = 0.013). We defined the cutoff value of NT-proBNP at ≥1,641 pg/mL. CONCLUSIONS: Among subjects with 0 points on the sPESI, those with concentrations of NT-proBNP exceeding 1,641 pg/mL might require closer attention; remaining patients could be considered candidates for outpatient treatment. However, these findings warrant further investigation in a large, prospective group of patients.

Action on elevated natriuretic peptide in primary care: a retrospective cohort study.

BACKGROUND: Natriuretic peptides (NPs) are released by increased ventricular wall stress, most often caused by heart failure (HF). NP level measurement helps select patients clinically suspected of HF who need echocardiography. Yet, the diagnostic actions following NP testing in daily primary care are poorly studied. AIM: To assess the diagnostic actions taken by general practitioners (GPs) in patients with an elevated NP level. DESIGN & SETTING: Retrospective observational study in general practices in the Netherlands. METHOD: In patients with an elevated NP level between July 2017 and July 2022 diagnostic actions were gathered during three months following NP testing. We compared patients with an elevated NP level referred for echocardiography to those not referred by univariable analyses. RESULTS: Among 902 patients, 394 (43.7%) had an elevated NP level. Median age was 75.0 (IQR 18.0) years, 68.8% were female. In total, 166 (42.1%) were referred for echocardiography and 114 (28.9%) underwent additional ECG recording. 30/166 (18.1%) referred patients were labelled HF by the cardiologist within three months after NP testing compared to 29/228 (12.7%) not referred. Referred patients were compared to those not referred younger (69.7 vs. 74.1 years, P<.001), less already known to a cardiologist (46.3% vs. 62.3%, P=.002), and had less marginally increased BNP levels (35-50 pg/mL) (19.9% vs. 37.5%, P<.001). CONCLUSIONS: Three out of five patients with an elevated NP level are not referred for echocardiography by GPs. Restraint to refer patients were older age, a marginally elevated BNP value, and already being under control of a cardiologist.

Herbal medicine Oryeongsan (Wulingsan): Cardio-renal effects via modulation of renin-angiotensin system and atrial natriuretic peptide system.

Background: Oryeongsan (Wulingsan, Goreisan) has long been used for the treatment of impaired body fluid metabolism. However, the action mechanisms have not been clearly defined. Recently, effects of Oryeongsan on the body fluid and Na+ metabolism and the action mechanisms have been shown more clearly. The present review focuses on the recent findings on the effects of Oryeongsan in the cardio-renal system in relation with body fluid metabolism and action mechanisms leading to a decrease in blood pressure in animal models of hypertension. Methods: The new and recent findings were searched by using searching systems including PubMed-NCBI and Google-Scholar. Results: Oryeongsan induced an increase in glomerular filtration rate, and natriuresis and diuresis with a decreased osmolality and resulted in a contraction of the body fluid and Na+ balance. These findings were associated with a suppression of abundance of Na+-H +-exchanger isoform 3 expression and V2 receptor/aquaporin2 water channel signaling pathway in the kidney. Further, treatment with Oryeongsan accentuated atrial natriuretic peptide secretion in the atria from spontaneously hypertensive rats in which the secretion was suppressed. In addition, Oryeongsan ameliorated impaired vasodilation in spontaneously hypertensive rats. Conclusion: The effects of Oryeongsan in the kidney, atria, and vessel were accompanied by a suppression of AT1 receptor and concurrent accentuation of abundance of AT2/Mas receptors expression and modulation of the natriuretic peptide system in these organs from hypertensive rats. The review shows multiple sites of action of Oryeongsan and mechanisms involved in the regulation of volume and pressure homeostasis in the body.

Changes in urinary output due to concomitant administration of sacubitril/valsartan and atrial natriuretic peptide in patients with heart failure: a multicenter retrospective cohort study.

BACKGROUND: Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that inhibits the degradation of endogenous natriuretic peptides. Therefore, ARNIs may increase the efficacy of human atrial natriuretic peptide (hANP), a drug for acute heart failure, by mediating its pharmacological mechanism. This study was aimed at evaluating the effects of ARNIs on the pharmacological effects of hANP by using surrogate marker, such as urinary output, in patients with heart failure. METHODS: In this multicenter retrospective cohort study, adult patients with heart failure who were taking angiotensin II receptor blockers (ARB) or ARNIs combined with hANP were enrolled. Information on basic characteristics, clinical laboratory data, medical history, and severity of cardiac insufficiency were collected from electronic medical records. The primary outcome was the change in adjusted fluid balance, calculated by IN-volume (mL/day) - OUT-volume (mL/day) / daily hANP dosage (µg). RESULTS: Ninety-two and 62 patients in the ARB + hANP and ARNI + hANP groups, respectively, were eligible for analysis. The adjusted fluid balance in the ARNI + hANP group was significantly lower than that in the ARB + hANP group (p = 0.001). After propensity score matching, 27 patients from each group were included. Similarly, there was a significant reduction in adjusted fluid balance in the ARNI + hANP group after propensity score matching (p = 0.026). CONCLUSIONS: These findings suggest that ARNIs may enhance the efficacy of hANP and the combination of the two may be effective in the treatment of heart failure.

International prevalence of transthyretin amyloid cardiomyopathy in high-risk patients with heart failure and preserved or mildly reduced ejection fraction.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF). METHODS: This epidemiology study assessed the international prevalence of ATTR-CM among patients aged ≥60 years with a history of HF, left ventricular ejection fraction (LVEF) >40%, an end-diastolic interventricular septum thickness (IVST) ≥12 mm, but without diagnosed amyloidosis, history of LVEF ≤40%, cardiomyopathy of known cause, severe valvular, or coronary heart disease. ATTR-CM was determined using cardiac scintigraphy alongside exclusionary testing for light chain amyloidosis. The study was terminated early due to slow recruitment, without safety concerns. RESULTS: Overall, 56/315 (18%; 95% CI: 13.7-22.5) patients with evaluable scintigraphy had ATTR-CM, with a numerically higher prevalence in: Europe (24%) vs. other regions (9% Asia; 5% North America); at specialist vs non-specialist centres (26% vs. 11%); in males vs. females (24% vs. 10%); and in older vs. younger patients (e.g. >40% among those ≥85 years). Other risk markers (p<.05) included a history of carpal tunnel syndrome, higher N-terminal pro B-type natriuretic peptide concentration, and higher end-diastolic IVST. CONCLUSIONS: ATTR-CM was diagnosed in 18% (95% CI: 13.7-22.5) of evaluable patients with HF, LVEF >40%, and risk markers for ATTR-CM, but no previous diagnosis of amyloidosis. Recruitment bias may have contributed to regional variability. NCT04424914.

Plasma renin activity as a marker for predicting the antihypertensive effect of switching to sacubitril/valsartan in treated hypertensive patients: Usefulness in daily clinical practice.

The authors investigated the antihypertensive effect of sacubitril/valsartan (Sac/Val) when switching from other drugs and assessed whether brain natriuretic peptide (BNP) or plasma renin activity (PRA) before drug switching was a predictor of blood pressure lowering after switching to Sac/Val. In 92 patients with treated hypertension, clinic blood pressure, plasma BNP, and PRA were examined before and after switching to Sac/Val. Clinic systolic and diastolic blood pressures significantly decreased after drug switching to Sac/Val (p < .0001, respectively). The level before drug switching of BNP had no correlation with the change in systolic blood pressure (Δ-SBP) before and after switching to Sac/Val, but that of PRA was significantly correlated with Δ-SBP (r = .3807, p = .0002). A multiple regression analysis revealed that PRA before drug switching was an independent determinant of Δ-SBP. Our findings suggest that low PRA may become a useful marker to predict the antihypertensive effect of switching to Sac/Val in treated hypertensive patients.

Assessment of the role of N-terminal pro-B-type natriuretic peptide as a predictive biomarker of mortality in acute aluminum phosphide poisoning.

BACKGROUND: In Egypt, aluminum phosphide (ALP) is a known lethal poison due to its cardiotoxicity. This study aimed to evaluate the predictive ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for mortality in ALP-poisoned patients. METHODS: This prospective study was conducted on patients with ALP poisoning admitted to the Poison Control Center Ain Shams University Hospitals between July and December 2022. Upon admission, all patients were followed up and had their levels of NT-proBNP, troponin I (cTnI), and creatine kinase myocardial band (CK-MB) analyzed. RESULTS: Thirty patients were enrolled in the study and were divided into survivors and non-survivors. The initial NT-proBNP levels were significantly higher among non-survivors in contrast to the initial cTnI and CK-MB levels. The study identified that the best cutoff point of NT-proBNP for predicting mortality was ≥72 pg/ml, with AUC (0.869). CONCLUSION: It can be concluded that NT-proBNP can serve as an early predictor of mortality in ALP poisoning.

Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction.

Metabolic comorbidities, such as obesity and diabetes, are associated with subclinical alterations in both cardiac structure/function and natriuretic peptides prior to the onset of heart failure (HF). Despite this, the exact metabolic pathways of cardiac dysfunction which precede HF are not well-defined. Among older individuals without HF in the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of 47 circulating metabolites measured by 1H-NMR with echocardiographic measures of cardiac structure and function. We then evaluated associations of significant metabolites with circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a separate cohort, we evaluated differences between top metabolites in patients with HF with preserved ejection fraction (HFpEF) and comorbidity-matched controls. Genetic variants associated with top metabolites (mQTLs) were then related to echocardiographic measures and NT-proBNP. Among 3440 individuals with metabolic and echocardiographic data in MESA (62 ± 10 years, 52% female, 38% White), 10 metabolites broadly reflective of glucose and amino acid metabolism were associated with at least 1 measure of cardiac structure or function. Of these 10 metabolites, 4 (myo-inositol, glucose, dimethylsulfone, carnitine) were associated with higher NT-proBNP and 2 (d-mannose, acetone) were associated with lower NT-proBNP. In a separate cohort, patients with HFpEF had higher circulating myo-inositol levels compared with comorbidity-matched controls. Genetic analyses revealed that 1 of 6 known myo-inositol mQTLs conferred risk of higher NT-proBNP. In conclusion, metabolomic profiling identifies several novel metabolites associated with cardiac dysfunction in a cohort at high risk for HF, revealing pathways potentially relevant to future HF risk.

Serum N-Terminal Pro-B-Type Natriuretic Peptide Is Associated With Insulin Resistance in Chinese: Danyang Study.

The association of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) with insulin resistance (IR), as measured by homeostasis model assessment of insulin resistance (HOMA-IR), in the general population is unclear. Our study aimed to characterize its relationship in a large community-based population. Subjects were recruited from the Danyang city between 2017 and 2019. Serum NT-proBNP was measured using an enhanced chemiluminescence immunoassay. IR was defined by a HOMA-IR in the highest sex-specific quartile. Categorical and continuous analyses were performed with sex-specific NT-proBNP tertiles and naturally logarithmically transformed NT-proBNP (lnNTproBNP), respectively. The 2945 participants (mean age 52.8 years) included 1728 (58.7%) women, 1167 (39.6%) hypertensive patients, 269 (9.1%) diabetic patients, and 736 (25.0%) patients with IR. In simple and multivariate-adjusted regression analyses, serum lnNTproBNP were both negatively associated with HOMA-IR (ß = -0.19 to -0.25; p < 0.0001). Similar results were also obtained in multiple subgroup analyses. In multiple logistic regression analyses, elevated serum NT-proBNP was associated with lower risks of IR (odds ratios: 0.68 and 0.39; 95% confidence intervals: 0.61-0.74 and 0.30-0.50 for lnNTproBNP and top vs. bottom tertiles, respectively; p < 0.0001). In conclusion, increased serum NT-proBNP level was strongly associated with a lower risk of IR in Chinese.

Clinical characteristics and outcomes of neonatal SARS-CoV-2 infection after the release of the epidemic situation of COVID-19.

BACKGROUND: With the release of the coronavirus disease 2019 (COVID-19) pandemic in late 2022 in China, the number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) roared, including neonatal cases. However, there were few studies on neonatal COVID-19, especially multi-center case reports. This study aimed to explore clinical characteristics and short-term outcomes of neonatal COVID-19 in China. METHODS: We reviewed 187 cases of neonatal COVID-19 between December 11, 2022, and January 12, 2023. The diagnosis was assessed by symptoms, laboratory tests, X-ray manifestations, and diagnosis code. Clinical characteristics and outcomes were evaluated. RESULTS: In 187 neonatal cases with COVID-19, 84 (44.9%) had severe SARS-CoV-2 infection. Most patients had confirmed exposure to SARS-CoV-2. Fever and respiratory symptoms were common (75.4% and 71.7%, respectively). Severe patients were more likely to have high alanine transaminase (ALT) (> 40U/L) (11.9% vs. 3.9%) and high N-terminal pro-brain natriuretic peptide (NT-proBNP) (> 2000pg/mL) (38.0% vs. 19.6%), compared with nonsevere ones (P < 0.05). None of the patients received COVID-19-specific medical interventions. A few severe patients received corticosteroids (1.1%), and immunoglobulin (0.5%), respectively. All patients were discharged home after the medical care with a median length of stay (LOS) of four days and none of them met the criteria of multisystem inflammatory syndrome in neonates (MIS-N). CONCLUSIONS: After the release of the epidemic situation of COVID-19 in late 2022 in China, more neonatal cases with severe COVID-19 had high ALT and NT-proBNP level. Few specific medical interventions were given, and the outcome was satisfying.

Galectin-3 Predicts Long-Term Risk of Cerebral Disability and Mortality in Out-of-Hospital Cardiac Arrest Survivors.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is associated with high mortality and cerebral disability in survivors. Current models of risk prediction and survival are mainly based on resuscitation duration. We examined the prognostic value of circulating biomarkers in predicting mortality and severe cerebral disability for OHCA survivors, alongside traditional clinical risk indicators. METHODS: Biomarkers including BNP, troponin I, and galectin-3 were measured at hospital admission in resuscitated OHCA patients. Prognostic significance for mortality and cerebral disability involving circulating biomarkers, resuscitation duration, demographics, and laboratory and clinical characteristics was examined via univariate and multivariate Cox proportional hazards regression models. The incremental prognostic value of the index covariates was examined through model diagnostics, focusing on the Akaike information criterion (AIC) and Harrell's concordance statistic (c-statistic). RESULTS: In a combinatorial analysis of 144 OHCA survivors (median follow-up 5.7 years (IQR 2.9-6.6)), BNP, galectin-3, arterial pH, and resuscitation time were significant predictors of all-cause death and severe cerebral disability, whereas troponin I levels were not. Multivariate regression, adjusting for BNP, arterial pH, and resuscitation time, identified galectin-3 as an independent predictor of long-term mortality. Multiple linear regression models also confirmed galectin-3 as the strongest predictor of cerebral disability. The incorporation of galectin-3 into models for predicting mortality and cerebral disability enhanced fit and discrimination, demonstrating the incremental value of galectin-3 beyond traditional risk predictors. CONCLUSIONS: Galectin-3 is a significant, independent long-term risk predictor of cerebral disability and mortality in OHCA survivors. Incorporating galectin-3 into current risk stratification models may enhance early prognostication and guide targeted clinical interventions.

Insights into the Neutrophil-to-Lymphocyte Ratio and the Platelet-to-Lymphocyte Ratio as Predictors for the Length of Stay and Readmission in Chronic Heart Failure Patients.

Background/Objectives: Chronic heart failure (CHF) is characterized by complex pathophysiology, leading to increased hospitalizations and mortality. Inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) provide valuable diagnostic insights. METHODS: This study evaluates the prognostic relationship between NLR, PLR, and, in a specific subcohort, N-terminal pro B-type natriuretic peptide (NT-proBNP), alongside length of stay (LOS) and 90-day readmission rates in CHF patients, irrespective of heart failure phenotype. A retrospective analysis of 427 CHF admissions (males = 57.84%) was conducted. RESULTS: The mean age of the entire population was 68.48 ± 11.53 years. The average LOS was 8.33 ± 5.26 days, with a readmission rate of 73 visits (17.09%) for 56 patients. The NLR (3.79 ± 3.32) showed a low but positive correlation with the LOS (r = 0.222, p < 0.001). Conversely, the PLR (144.84 ± 83.08) did not demonstrate a significant association with the LOS. The NLR presented a low negative correlation for days until the next admission (r = -0.023, p = 0.048). In a prespecified subanalysis of 323 admissions, the NT-proBNP exhibited a low positive Pearson correlation with the NLR (r = 0.241, p < 0.001) and PLR (r = 0.151, p = 0.006). CONCLUSIONS: The impact of the NLR across heart failure phenotypes may suggest the role of systemic inflammation in understanding and managing CHF.

Assessment of B-Natriuretic Peptide Levels After Stage 1 Palliation in Hypoplastic Left Heart Syndrome Patients.

We describe the perioperative BNP trends in patients with HLHS from S1P until interstage discharge to home, death, or S2P. This prospective cohort study includes all newborns with hypoplastic left heart syndrome (HLHS) who underwent Norwood procedures (S1P) at Texas Children's Hospital from April 2018 through April 2019. Our study included 19 newborns with HLHS. There was no interstage mortality; 47% were discharged home prior to the S2P procedure. Nine patients (50%) had higher BNP levels immediately after arrival to the cardiac intensive care unit (ICU) after S1P compared to preoperative levels. BNP levels were higher in those with a shorter duration of mechanical intubation (P = 0.02) and those with moderately depressed right ventricular systolic function in the immediate postoperative period (P = 0.02). RVPAs patients had higher BNP levels (median 3357 pg/mL) than mBTTs (median 2862 pg/mL), that was not statistically significant (P = 0.4). Despite higher BNP levels in RVPAs in the early postoperative period, these subjects had shorter mechanical ventilation, ICU, and hospital length of stay duration. BNP trends for HLHS patients vary in the postoperative period after S1P. RVPAs had higher BNP levels than mBTTs in the early postoperative period after S1P; however, this was not associated with worse outcomes.