Incremental Value of a Metabolic Risk Score for Heart Failure Mortality: A Population-Based Study.

BACKGROUND: Heart failure is heterogeneous syndrome with persistently high mortality. Nuclear magnetic resonance spectroscopy enables high-throughput metabolomics, suitable for precision phenotyping. We aimed to use targeted metabolomics to derive a metabolic risk score (MRS) that improved mortality risk stratification in heart failure. METHODS: Nuclear magnetic resonance was used to measure 21 metabolites (lipoprotein subspecies, branched-chain amino acids, alanine, GlycA (glycoprotein acetylation), ketone bodies, glucose, and citrate) in plasma collected from a heart failure community cohort. The MRS was derived using least absolute shrinkage and selection operator penalized Cox regression and temporal validation. The association between the MRS and mortality and whether risk stratification was improved over the Meta-Analysis Global Group in Chronic Heart Failure clinical risk score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels were assessed. RESULTS: The study included 1382 patients (median age, 78 years, 52% men, 43% reduced ejection fraction) with a 5-year survival rate of 48% (95% CI, 46%-51%). The MRS included 9 metabolites measured. In the validation data set, a 1 standard deviation increase in the MRS was associated with a large increased rate of death (hazard ratio, 2.2 [95% CI, 1.9-2.5]) that remained after adjustment for Meta-Analysis Global Group in Chronic Heart Failure score and NT-proBNP (hazard ratio, 1.6 [95% CI, 1.3-1.9]). These associations did not differ by ejection fraction. The integrated discrimination and net reclassification indices, and Uno's C statistic, indicated that the addition of the MRS improved discrimination over Meta-Analysis Global Group in Chronic Heart Failure and NT-proBNP. CONCLUSIONS: This MRS developed in a heart failure community cohort was associated with a large excess risk of death and improved risk stratification beyond an established risk score and clinical markers.

Prognostic Importance of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) Following High-Risk Myocardial Infarction in the PARADISE-MI Trial.

BACKGROUND: NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a potent predictor of death and heart failure (HF) across multiple populations. We evaluated the prognostic importance of NT-proBNP in patients with acute myocardial infarction (MI) complicated by left ventricular systolic dysfunction, pulmonary congestion, or both and ≥1 of 8 risk-augmenting factors enrolled in the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction). METHODS: Patients were randomized to sacubitril/valsartan 200 mg or ramipril 5 mg twice daily within 0.5 to 7 days of a MI. Patients with prior HF were excluded. NT-proBNP and hs-cTnT (high-sensitivity troponin T) were collected at randomization in a prespecified substudy of 1129 patients. The primary end point of PARADISE-MI was a composite of cardiovascular death or incident HF (hospitalization or outpatient symptomatic HF), analyzed as time-to-first event; additional end points included all-cause death and the composite of fatal or nonfatal MI or stroke. RESULTS: Median NT-proBNP was 1757 ng/L (25th-75th percentiles, 896-3462 ng/L) at randomization (4.0±1.8 days after the index MI). Patients in the highest quartile of NT-proBNP were older, more commonly women and had more hypertension, atrial fibrillation, renal dysfunction, and pulmonary congestion on presentation (all P<0.001). NT-proBNP was strongly associated with the primary end point (adjusted hazard ratio, 1.45 per doubling of NT-proBNP; [95% CI, 1.23-1.70]), adjusted for clinical variables and baseline hs-cTnT. NT-proBNP was also independently associated with all-cause death (adjusted hazard ratio, 1.74 [95% CI, 1.38-2.21]) and fatal or nonfatal MI or stroke (adjusted hazard ratio, 1.24 [95% CI, 1.05-1.45]). NT-proBNP did not significantly modify the neutral treatment effect of sacubitril/valsartan relative to ramipril (P interaction=0.46). CONCLUSIONS: Within the first week of a high-risk MI NT-proBNP is associated with incident HF, death and atherosclerotic events. This prognostic information is independent of hs-cTnT. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02924727.

Transient decrease in B-type natriuretic peptide level after liver transplantation does not ensure favorable post-transplant 30-day outcomes.

BACKGROUND: High B-type natriuretic peptide (BNP) levels within the first 3 postoperative days (postBNPPOD3) after liver transplantation (LT) are greatly predictive of the 30-day mortality. We evaluated clinical impact of transient decrease in postBNPPOD3 compared to pretransplant BNP (preBNP) level on mortality and major adverse cardiac event (MACE) within 30 days after LT. METHODS: We retrospectively evaluated 3,811 LT patients who measured delta BNP (deltaBNP), defined by serial postBNPPOD3 minus preBNP. Thirty-day all-cause mortality and MACE were estimated in patients with deltaBNP < 0 (n = 594, 15.6%) and > 0 (n = 3,217, 84.4%), respectively. Kaplan-Meier survival and multivariable Cox regression analysis were used. RESULTS: Within 30 days, 100 (2.6%) of all patients died. Unexpectedly, 30-day mortality rate (6.1% [95% CI: 4.2-8.4%] vs. 2.0% [95% CI: 1.5-2.5%], P < 0.001) and MACE (24.2% [95% CI: 20.4-28.5%] vs. 15.3% [95% CI: 14.0-16.7%], P < 0.001) were higher in patients with deltaBNP < 0 compared to those with deltaBNP > 0, respectively. Patients with deltaBNP < 0 had higher preBNP level (median [interquartile range], 251 [118, 586] vs. 43 [21, 92] pg/ml, P < 0.001) and model for end-stage liver disease score (26 [14, 37] vs. 14 [9, 23], P < 0.001) and more transfused intraoperatively. DeltaBNP < 0 remained significant after adjustments for potential confounders in multivariable analysis of 30-day mortality and MACE. CONCLUSIONS: DeltaBNP < 0 within the first 3 postoperative days is mainly attributed to pre-LT severe liver and cardiac disease status, therefore, transient decrease in BNP level after LT does not ensure favorable post-LT 30-day outcomes.

Effects of Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: A Secondary Analysis of the Randomized LOOP Study.

BACKGROUND: Research suggests NT-proBNP (N-terminal pro-B-type natriuretic peptide) to be a strong predictor of incident atrial fibrillation (AF) and stroke. However, its utility in AF screening remains unknown. The aim of this study was to investigate NT-proBNP as a potential marker for screening efficacy with respect to AF yield and stroke prevention. METHODS: In the LOOP Study (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals), 6004 AF-naïve individuals at least 70 years old and with additional stroke risk factors were randomized 1:3 to either screening with an implantable loop recorder (ILR) and initiation of anticoagulation upon detection of AF episodes lasting ≥6 minutes or usual care (control). This post hoc analysis included study participants with available NT-proBNP measurement at baseline. RESULTS: A total of 5819 participants (96.9% of the trial population) were included. The mean age was 74.7 years (SD, 4.1 years) and 47.5% were female. The median NT-proBNP level was 15 pmol/L (interquartile range, 9-28 pmol/L) corresponding to 125 pg/mL (interquartile range, 76-233 pg/mL). NT-proBNP above median was associated with an increased risk of AF diagnosis both in the ILR group (hazard ratio, 1.84 [95% CI, 1.51-2.25]) and the control group (hazard ratio, 2.79 [95% CI, 2.30-3.40]). Participants with NT-proBNP above the median were also at higher risk of clinical events compared with those having lower levels (hazard ratio, 1.21 [95% CI, 0.96-1.54] for stroke or systemic embolism [SE], 1.60 [95% CI, 1.32-1.95] for stroke/SE/cardiovascular death, and 1.91 [95% CI, 1.61-2.26] for all-cause death). Compared with usual care, ILR screening was associated with significant reductions in stroke/SE and stroke/SE/cardiovascular death among participants with NT-proBNP above median (hazard ratio, 0.60 [95% CI, 0.40-0.90] and 0.70 [95% CI, 0.53-0.94], respectively) but not among those with lower levels (Pinteraction=0.029 for stroke/SE and 0.045 for stroke/SE/cardiovascular death). No risk reduction in all-cause death was observed in either NT-proBNP subgroup for ILR versus control (Pinteraction=0.68). Analyzing NT-proBNP as a continuous variable yielded similar findings. CONCLUSIONS: In an older population with additional stroke risk factors, ILR screening for AF was associated with a significant reduction in stroke risk among individuals with higher NT-proBNP levels but not among those with lower levels. These findings should be considered hypothesis generating and warrant further study before clinical implementation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02036450.

Association between N-Terminal Prohormone Brain Natriuretic Peptide and Decreased Skeletal Muscle Mass in a Healthy Adult Population: A Cross-Sectional Study.

BACKGRUOUND: Although an inverse association between the N-terminal prohormone brain natriuretic peptide (NT-proBNP) and obesity exists, only few major studies have assessed the association between NT-proBNP levels and skeletal muscle mass in asymptomatic healthy adults. Therefore, this cross-sectional study was conducted. METHODS: We assessed participants who underwent health examinations at Kangbuk Samsung Hospital in South Korea from January 2012 to December 2019. Appendicular skeletal muscle mass was measured using a bioelectrical impedance analyzer, and the skeletal muscle mass index (SMI) was calculated. Participants were divided into the control, mildly low skeletal muscle mass (LMM) (-2 standard deviation [SD] < SMI ≤-1 [SD]), and severely LMM groups (SD ≤-2) based on their SMI. The association between elevated NT-proBNP level (≥125 pg/mL) and skeletal muscle mass was assessed using multivariable logistic regression analysis with adjustment for confounding factors. RESULTS: This study enrolled 15,013 participants (mean age, 37.52±9.52; men, 54.24%; control, n=12,827; mildly LMM, n=1,998; severely LMM, n=188). Prevalence of elevated NT-proBNP was higher in mildly and severely LMM groups than in the control group (control, 1.19%; mildly LMM, 1.4%; severely LMM, 4.26%; P=0.001). The adjusted odds ratio (OR) of elevated NT-proBNP was significantly higher in severely LMM (OR, 2.87; 95% confidence interval [CI], 1.3 to 6.37) than in control (OR, 1.00; reference) or mildly LMM groups (OR, 1.24; 95% CI, 0.81 to 1.89). CONCLUSION: Our results showed that NT-proBNP elevation were more prevalent in participants with LMM. In addition, our study showed an association between skeletal muscle mass and NT-proBNP level in a relatively young and healthy adult population.

Adverse Outcomes Associated With Interleukin-6 in Patients Recently Hospitalized for Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Inflammation may play a role in the pathophysiology of heart failure with preserved ejection fraction. We examined whether circulating levels of interleukin-6 identify patients at greater risk of adverse outcomes following hospitalization with heart failure with preserved ejection fraction. METHODS: We assessed relationships between interleukin-6 (IL-6) tertiles (T1-3) and all-cause death, cardiovascular death, and subsequent heart failure hospitalization (sHFH) in 286 patients recently hospitalized with heart failure with preserved ejection fraction. Associations between IL (interleukin)-6 and outcomes were examined in a Cox-regression model adjusted for risk factors including BNP (B-type natriuretic peptide). Biomarkers including hsCRP (high-sensitivity C-reactive protein) were assessed. RESULTS: The range of IL-6 (pg/mL) in each tertile was T1 (0.71-4.16), T2 (4.20-7.84), and T3 (7.9-236.32). Compared with T1, patients in the highest IL-6 tertile were more commonly male (56% versus 35%) and had higher creatinine (117±45 versus 101±36 µmol/L), hsCRP (11.6 [4.9-26.6]mg/L versus 2.3[1.1-4.2] mg/L). In univariable analysis, rates of all-cause death, cardiovascular death, and sHFH were higher in T3 versus T1. All-cause and cardiovascular death rates remained higher in T3 versus T1 after adjustment (P<0.001). One log unit increase in IL-6 was associated with higher risk of all-cause death (hazard ratio, 1.46 [1.17-1.81]), cardiovascular death (hazard ratio, 1.40 [1.10-1.77]), and sHFH (hazard ratio, 1.24 [1.01-1.51]) after adjustment. One log unit increase in hsCRP was associated with a higher risk of cardiovascular death and all-cause death before and after adjustment for other factors but was not associated with risk of sHFH before or after adjustment. CONCLUSIONS: In patients recently hospitalized with heart failure with preserved ejection fraction, IL-6 is an independent predictor of all-cause mortality, cardiovascular death, and sHFH after adjustment for risk factors including BNP. These findings are of particular relevance in the context of current anti-IL-6 drug development.

Analysis of risk factors for acute moderate to high risk pulmonary thromboembolism in adults / 中国医师杂志

Objective:To investigate the risk factors according to the clinical data of the adult patients with acute moderate to high risk pulmonary thromboembolism (PTE).Methods:The clinical data of 100 adult patients with acute moderate-risk PTE in Hunan Provincial People′s Hospital from June 2019 to March 2022 were analyzed retrospectively. According to the risk stratification, they were divided into moderate to low risk group (34 cases) and moderate to high risk group (66 cases). The laboratory data and clinical data of all adult patients were collected, and the independent risk factors of acute moderate to high risk PTE in adults were analyzed by binary logistic regression; Receiver operating characteristic (ROC) curve was used to analyze the predictive ability of independent risk factors for acute moderate to high risk PTE.Results:There were 34 patients with moderate to low risk PTE, 20 males and 14 females, aged 16-86 (60.2±15.5)years, 66 patients with moderate to high risk PTE, 36 males and 30 females, aged 34-82(63.6±9.6)years. There was no significant difference in age, gender and risk factors between the two groups (all P>0.05). The tumor history of concomitant diseases in moderate to high risk group was significantly higher than that in moderate to low risk group, and the symptoms of dyspnea and shortness of breath in moderate to high risk group were significantly higher than those in moderate to low risk group (all P>0.05). The levels of troponin I, shock index (SI) and N-terminal B-type brain natriuretic peptide precursor (NT-proBNP) in moderate to high risk group were significantly higher than those in moderate to low risk group, while the levels of PaO 2 and oxygenation index in moderate to high risk group were significantly lower than those in moderate to low risk group, with statistical significant difference (all P<0.05). Echocardiographic results showed that there were significant differences in right ventricular inner diameter (RV), left ventricular inner diameter (LV), RV/LV, tricuspid regurgitation velocity and pulmonary systolic pressure between moderate to high risk PTE patients and moderate to low risk PTE patients (all P>0.05). CTPA results showed that RV, RV/LV, main pulmonary artery diameter and thrombus load in moderate to high risk PTE patients were significantly higher than those in moderate to low risk PTE patients (all P<0.05). Multivariate binary logistic regression analysis showed that SI, NT-proBNP and RV were independent predictors of moderate to high risk PTE (all P<0.05). The combined detection of SI, NT-proBNP and RV had a good predictive value for moderate to high risk PTE. The area under ROC curve (AUC) was 0.984, the sensitivity and specificity were 90.32% and 97.73%, respectively. The negative predictive value was 87.8%, and the positive predictive value was 98.2%. Conclusions:SI, NT-proBNP, RV of echocardiography and RV of CTPA are the predictors of acute moderate to high risk PTE in adults, which provided a strong supplement for the risk stratification of acute moderate risk PTE in adults.

Efficacy of sacubitril and valsartan combined with bisoprolol in the treatment of chronic heart failure and its effect on N-terminal pro-brain natriuretic peptide level / 中国基层医药

Objective:To investigate the clinical efficacy of sacubitril and valsartan combined with bisoprolol in the treatment of chronic heart failure and its effect on N-terminal pro-brain natriuretic peptide (NT-pro BNP) level.Methods:The clinical data of 89 patients with chronic heart failure who received treatment in Jinan 2 nd People's Hospital from January 2020 to April 2022 were retrospectively analyzed. These patients were divided into Group A ( n = 48) and Group B ( n = 41) according to different treatment methods. Group A was treated with sacubitril and valsartan combined with bisoprolol. Group B was treated with sacubitril and valsartan combined with metoprolol. All patients were treated for 3 months. Clinical efficacy as well as heart function and NT-pro BNP level pre- and post-treatment were compared between the two groups. The incidence of adverse reactions was calculated in each group. Results:Total response rate in group A was significantly higher than that in group B [95.83% (46/48) vs. 82.93% (34/41), χ2 = 4.05, P < 0.05]. After treatment, the left ventricular ejection fraction in both groups increased significantly and the left ventricular ejection fraction in group A was significantly higher than that in group B ( t = 2.19, P < 0.05). After treatment, NT-pro BNP level in group A was (416.51 ± 30.56) ng/L, which was significantly lower than (450.20 ± 35.79) ng/L in group B ( t = 4.79, P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:The efficacy of sacubitril and valsartan combined with bisoprolol in the treatment of chronic heart failure is superior to that of sacubitril and valsartan combined with metoprolol. The former can greatly decrease NT-pro BNP level. Corresponding drugs can be selected for the treatment of chronic heart failure according to the actual needs of patients.

Risk factors for postoperative recurrence of nonvalvular paroxysmal and persistent atrial fibrillation / 中国基层医药

Objective:To analyze the risk factors of postoperative recurrence of nonvalvular paroxysmal and persistent atrial fibrillation.Methods:A total of 100 patients who received treatment in Haining People's Hospital from October 2019 to October 2021 were included in this study. All patients were followed up for 1 year. Thirty patients with postoperative recurrence of atrial fibrillation were included in the observation group, and seventy patients without postoperative recurrence of atrial fibrillation were included in the control group. Univariate and multivariate logistic regression analyses were performed to analyze the risk factors of postoperative recurrence of atrial fibrillation after radiofrequency ablation.Results:Logistic regression analysis results revealed that age, body mass index, diabetes mellitus, hypertension, rheumatic heart disease, anteroposterior diameter of the left atrium, glycosylated hemoglobin, brain natriuretic peptide are the risk factors of recurrent atrial fibrillation after radiofrequency ablation (all P < 0.05) ( OR = 1.31, 1.33, 1.32, 1.34, 1.26, 1.24, 1.36, 1.33; 95% CI = 1.028-1.442, 1.031-1.427, 1.042-1.434, 1.124-1.452, 1.013-1.385, 1.005-1.326, 1.039-1.482, 1.064-1.478). Conclusion:The recurrence of nonvalvular paroxysmal and persistent atrial fibrillation after radiofrequency ablation is related to many factors. The risk factors should be taken into account in clinical practice, and targeted treatment should be given as early as possible to reduce the recurrence rate of atrial fibrillation and improve prognosis.

Effects of phentolamine on cardiac function, myocardial injury index, and hemodynamics in septic patients with myocardial injury / 中国基层医药

Objective:To investigate the efficacy of phenolamine in the treatment of sepsis-induced myocardial dysfunction and its effect on cardiac function, myocardial injury index, and hemodynamics in patients.Methods:The clinical data of 79 patients with sepsis-induced myocardial dysfunction who received treatment in Huangshi Central Hospital, Edong Healthcare Group from February 2017 to February 2020 were retrospectively analyzed. These patients were divided into a control group (without phenolamine treatment, n = 41) and an observation group (with phenolamine treatment, n = 38) according to whether they received phenolamine treatment or not. Clinical efficacy, cardiac function, myocardial injury index, and hemodynamic index pre- and post-treatment were compared between the two groups. Results:There was no significant difference in 28-day mortality rate between the two groups ( P > 0.05). Intensive care unit length of stay and mechanical ventilation duration in the observation group were (9.33 ± 3.52) days and 83.00 (28.50, 138.00) hours, which were significantly shorter than (12.17 ± 4.15) days and 111.00 (47.50, 169.00) hours in the control group ( t = 3.26, Z = -2.27, both P < 0.05). The response rate in the observation group was significantly higher than that in the control group [81.58% (31/38) vs. 60.98% (25/41), χ2 = 4.05, P < 0.05]. After 7 days of treatment, the left ventricular ejection fraction in each group was significantly increased, and the left ventricular end-diastolic diameter and left ventricular end-systolic diameter in each group were significantly decreased compared with before treatment (all P < 0.05). After 7 days of treatment, the left ventricular ejection fraction in the observation group was significantly higher than that in the control group ( t = 3.29, P < 0.05), and left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly lower than those in the control group ( t = 5.94, 11.21, both P < 0.05). N-terminal pro-brain natriuretic peptide and cardiac troponin I levels in each group were significantly decreased with time (both P < 0.05). At 24 and 72 hours and 7 days after treatment, N-terminal pro-brain natriuretic peptide and cardiac troponin I levels in the observation group were significantly lower than those in the control group (both P < 0.05). After 7 days of treatment, heart rate in each group decreased significantly compared with that before treatment (both P < 0.05), mean arterial pressure, cardiac index, and stroke output index in each group increased significantly compared with those before treatment (all P < 0.05). After 7 days of treatment, heart rate in the observation group was significantly lower than that in the control group ( t = 4.90, P < 0.05), and mean arterial pressure, cardiac index, and stroke output index in the observation group were significantly higher than those in the control group ( t = 4.37, 3.23, 6.01, all P < 0.05). Conclusion:Phentolamine can improve hemodynamics, reduce myocardial injury and improve cardiac function in patients with sepsis-induced myocardial dysfunction.

Clinical diagnostic value of NT-proBNP in peridialysis chronic kidney disease patients / 中华肾脏病杂志

Objective:To explore the clinical value of N terminal pro B type natriuretic peptide (NT-proBNP) in diagnosing or predicting heart failure in peridialysis chronic kidney disease (CKD) population.Methods:It was a single-center retrospective study. Patients with peridialysis CKD who visited the Department of Nephrology, First Affiliated Hospital of Zhengzhou University from January 2021 to June 2021 were collected and divided into 4 groups according to the presence or absence of heart failure and the level of left ventricular ejection fraction (LVEF), namely the non-heart failure group, heart failure with reduced ejection fraction (HFrEF) group (LVEF<40%), heart failure with mid-range ejection fraction (HFmrEF) group (40％≤LVEF<50％), and heart failure with preserved ejection fraction (HFpEF) group (LVEF≥50％). The NT-proBNP, echocardiography and other indicators of the 4 groups were compared. The value of plasma NT-proBNP in diagnosing heart failure, HFpEF, HFmrEF and HFrEF was analyzed by drawing receiver operating characteristic curve (ROC curve). Logistic regression analysis was used to analyze the related factors of heart failure in peridialysis CKD patients.Results:A total of 508 patients were included, including 11 cases in the HFrEF group, 29 cases in the HFmrEF group, 152 cases in the HFpEF group, and 316 cases without heart failure. The differences in age, 24-h urine volume, hemodialysis proportion, non-dialysis proportion, serum creatinine, estimated glomerular filtration rate, hemoglobin, serum albumin, C-reactive protein, NT-proBNP, cardiac troponin I, left ventricular internal diameter, LVEF, pulmonary artery systolic pressure, left ventricular end-diastolic volume, E/A value, septal thickness, and left ventricular posterior wall thickness among the four groups were statistically significant ( P < 0.05, respectively). A two-pair comparison (all P values corrected by Bonferroni method) revealed that the 24-h urine volume was higher in the non-heart failure group than in the other three groups (corrected P<0.05, respectively), while the proportion of hemodialysis patients and the levels of NT-proBNP and C-reactive protein were lower in the non-heart failure group than in the other three groups (corrected P<0.001, respectively); the levels of hemoglobin and serum albumin were lower in the HFpEF group than in the non-heart failure group (corrected P<0.001, respectively); troponin I was lower in the non-heart failure group than in the HFpEF group (corrected P<0.001), HFmrEF group (corrected P=0.001) and HFrEF group (corrected P<0.001), and troponin I was lower in the HFpEF group than in the HFrEF group (corrected P=0.008); LVEF was higher in the non-heart failure group than in the other three groups (corrected P<0.001, respectively), and LVEF in the HFpEF group was higher than in the HFmrEF and HFrEF groups (corrected P<0.001, respectively). For patients with peridialysis CKD, the cut-off values of plasma NT-proBNP for diagnosing or predicting heart failure, HFpEF, HFmrEF and HFrEF were 4 943.33 ng/L, 4 976.83 ng/L, 14 964.5 ng/L and 17 847.55 ng/L, respectively. Multivariate logistic regression analysis showed that NT-proBNP (every 500 ng/L increase, OR=1.390, 95% CI 1.287-1.501, P<0.001), LVEF ( OR=0.747, 95% CI 0.656-0.851, P<0.001) and 24-h urine volume (every 100 ml increase, OR=0.842, 95% CI 0.763-0.929, P=0.001) were independently correlated with heart failure. Conclusions:The cut-off value of plasma NT-proBNP for diagnosing or predicting heart failure in peridialysis CKD patients is much higher than that in patients with normal renal function. NT-proBNP, LVEF and 24-h urine volume are independently associated with heart failure in peridialysis CKD patients.

Association of serum biomarkers with frailty in elderly hospitalized patients / 中华老年医学杂志

Objective:To evaluate the association of different biomarkers with frailty in elderly hospitalized patients.Methods:In this cross-sectional study, a total of 319 elderly patients aged 65 years or older hospitalized in Beijing Hospital between September 2018 and February 2019 were enrolled.Patients had a mean age of(75.0±6.6)years and 151(47.3%)were women.Based on the Fried phenotype, patients were divided into a non-frail group(244 cases, 76.5%)and a frail group(75 cases, 23.5%). The clinical characteristics and biomarker levels of the two groups were compared.The association of different biomarkers with frailty was evaluated by using the receiver operating characteristic(ROC)curve.The Youden index was used for the optimal cutoff values and the area under the curve(AUC)were calculated.AUCs of different biomarkers were compared to assess their correlations with frailty.Results:Hemoglobin, lipid levels(triglycerides, total cholesterol and low-density lipoprotein cholesterol), and prealbumin were significantly lower in the frail group than in the non-frail group( P<0.05), while N-terminal pro-B type natriuretic peptide(NT-proBNP)and high-sensitivity C reactive protein(hsCRP)levels were significantly higher than in the non-frail group( P<0.05). Thyrotropin(TSH)and free triiodothyronine(FT3)levels were significantly lower( P<0.05)and trans-triiodothyronine(rT3)was significantly higher( P<0.05)in the frail group.The combination of six biomarkers[hemoglobin, prealbumin, hsCRP, 25-dihydroxy vitamin D3[25(OH)D3], rT3 and NT-pro BNP]had the most powerful correlation with frailty(AUC=0.705, 95% CI: 0.652-0.755), but the correlation was not significantly different from that of the combination of 3 markers(hemoglobin, rT3 and hsCRP)(ROC=0.010, 95% CI: -0.0106-0.0306, P>0.05). Either of the two combinations was significantly better than the combination of 2 markers(hemoglobin and rT3)(ROC=0.143, 95% CI: 0.0406-0.245; ROC=0.153, 95% CI: 0.0498-0.256; all P<0.01). Conclusions:Hemoglobin, lipids, prealbumin, TSH and FT3 levels decrease while NT-proBNP and hsCRP levels increase in elderly hospitalized frail patients.The 6-biomarker combination[hemoglobin, prealbumin, hsCRP, 25(OH)D3, rT3 and NT-pro BNP]and 3-biomarker combination(hemoglobin, rT3 and hsCRP)have better correlation with frailty than the 2-biomarker combination(hemoglobin and rT3).

Multiparametric Strategy to Predict Early Disease Decompensation in Asymptomatic Severe Aortic Regurgitation.

BACKGROUND: Use of the current echocardiography-based indications for aortic regurgitation (AR) surgery might result in late valve replacement at the stage of irreversible myocardial damage. Therefore, we aimed to identify simple models combining multiple echocardiography or magnetic resonance imaging (MRI)-derived indices and natriuretic peptides (BNP [brain natriuretic peptide] or NT-proBNP [N-terminnal pro-B type natriuretic peptide]) to predict early disease decompensation in asymptomatic severe AR. METHODS: This prospective and multicenter study included asymptomatic patients with severe AR, preserved left ventricular ejection fraction (>50%), and sinus rhythm. The echocardiography and MRI images were analyzed centrally in the CoreLab. The study end point was the onset of indication for aortic valve surgery as per current guidelines. RESULTS: The derivative cohort consisted of 127 asymptomatic patients (age 45±14 years, 84% males) with 41 (32%) end points during a median follow-up of 1375 (interquartile range, 1041-1783) days. In multivariable Cox regression analysis, age, BNP, 3-dimensional vena contracta area, MRI left ventricular end-diastolic volume index, regurgitant volume, and a fraction were identified as independent predictors of end point (all P<0.05). However, a combined model including one parameter of AR assessment (MRI regurgitant volume or regurgitant fraction or 3-dimensional vena contracta area), 1 parameter of left ventricular remodeling (MRI left ventricular end-diastolic volume index or echocardiography 2-dimensional global longitudinal strain or E wave), and BNP showed significantly higher predictive accuracy (area under the curve, 0.74-0.81) than any parameter alone (area under the curve, 0.61-0.72). These findings were confirmed in the validation cohort (n=100 patients, 38 end points). CONCLUSIONS: In asymptomatic severe AR, multimodality and multiparametric model combining 2 imaging indices with natriuretic peptides, showed high accuracy to identify early disease decompensation. Further prospective studies are warranted to explore the clinical benefit of implementing these models to guide patient management. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02910349.

Enuresis and upper airway obstruction: BNP and ADH hormones behavior before and after airway surgery

ABSTRACT Introduction: Upper airway obstruction (UAO) is a common condition in all pediatric population, with a 27% prevalence. Primary monosymptomatic nocturnal enuresis (PMNE) is a condition related to UAO in 8% to 47% of these children. The specific pathophysiological mechanism of this bond is not well understood. Some authors suggest a connection between brain natrituretic peptide (BNP) and anti-diuretic hormone (ADH) during sleep. The aim of this study was to evaluate hormone profile (ADH and BNP) and improvement in dry nights in a sample of children before and after surgical treatment of the UAO. Methods: This is a longitudinal prospective interventionist study in children, 5 to 14 years of age, with UAO and PMNE recruited in a specialty outpatient clinic. Children presenting UAO and PMNE were evaluated with a 30-day dry night diary and blood samples were collected to evaluate ADH and BNP before and after upper airway surgery. Data were analyzed prior to surgery and 90-120 days after surgery. Results: Twenty-one children with a mean age of 9.7 years were included. Mean BNP before surgery was 116.5 ± 126.5 pg/mL and 156.2 ± 112.3 pg/mL after surgery (p<0.01). Mean ADH was 5.8 ± 3.2 pg/mL and 14.6 ± 35.4 before and after surgery, respectively (p=0.26). The percentage of dry nights went from 32.3 ± 24.7 before surgery to 75.4 ± 33.4 after surgery (p<0.01). Conclusion: Surgery for airway obstruction contributed to an increase in BNP without increasing ADH. A total of 85.8% of the children presented partial or complete improvement of their enuresis.

Predictive value of serum initial brain natriuretic peptide and troponin on functional prognosis in noncardiogenic patients with anterior and posterior circulation cerebral infarction / Valor preditivo dos níveis séricos iniciais do peptídeo natriurético cerebral e da troponina no prognóstico funcional em pacientes não cardiogênicos com acidente vascular cerebral isquêmico de circulação anterior e posterior

Abstract Background Brain natriuretic peptide (BNP) and troponin have a close relationship with cardiogenic cerebral embolism (CCE), but their relationship with noncardiogenic patients with anterior circulation ischemia (ACI) and posterior circulation ischemia (PCI) is not clear. Objective To explore the predictive value of serum initial BNP and troponin on the functional prognosis of patients with noncardiogenic ACI and PCI. Methods Consecutive patients with first-episode cerebral infarction within 12 hours of symptom onset were enrolled in the present 1-year prospective cohort study. Serum levels of BNP and troponin were collected within 12 hours of onset. Infarction location was classified as ACI and PCI by magnetic resonance imaging (MRI). According to the modified Rankin Scale (mRS) score at 90 days after onset, ACI and PCI cases were respectively divided into a good prognosis group (mRS score between 0 and 2) and a poor prognosis group (mRS score between 3 and 6). The general state of health and results of laboratory examinations and other auxiliary examinations of all patients were recorded. Single-factor analysis and multivariate logistic regression analysis were used to assess the relationship between serum levels of BNP, troponin, and functional outcome. Results The multivariate logistic regression found that higher levels of initial BNP (odds ratio [OR] = 1.024; 95% confidence interval [CI]: 1.006-1.041; p = 0.007) and C-reactive protein (CRP) (OR = 1.184; 95%CI: 1.024-1.369; p = 0.022) were independent predictors of poor functional prognosis of noncardiogenic PCI at 90 days after onset after adjusting for age, gender, ethnicity, history of hypertension and of diabetes. Conclusions The levels of initial BNP and CRP were related to poor functional outcomes in noncardiogenic PCI patients at 3 months, independent of troponin.

Resumo Antecedentes O peptídeo natriurético cerebral (BNP, na sigla em inglês) e a troponina estão intimamente relacionados com a embolia cerebral cardiogênica (CCE, na sigla em inglês), mas a relação com pacientes não cardioembólicos com isquemia de circulação anterior (ICA) e isquemia de circulação posterior (ICP) não é clara. Objetivo Investigar o valor preditivo dos níveis séricos iniciais do BNP e da troponina no prognóstico de pacientes com AVC isquêmico não cardiogênico. Métodos Os níveis séricos de BNP e de troponina foram recolhidos de pacientes com primeiro episódio de acidente vascular cerebral (AVC) isquêmico dentro de 12 horas após o início dos sintomas, com localização classificada como ICA e ICP de acordo com exame de ressonância magnética (RM). De acordo com a pontuação modificada da escala de Rankin (mRS), aos 90 dias após o início dos sintomas, ICA e ICP foram divididas respectivamente em um grupo de bom prognóstico (mRS entre 0 e2) e em um grupo de mau prognóstico (mRS entre 3 e 6). Foram registrados exames laboratoriais e outros exames complementares de todos os pacientes. Foram utilizadas análise fatorial única e análise de regressão logística multivariada para investigar a relação entre os níveis séricos de BNP e de troponina e o resultado funcional. Resultados A regressão logística multivariada evidenciou que os níveis mais altos de BNP inicial (odds ratio [OR] = 1,024, intervalo de confiança [IC] de 95%: 1,006-1,041; p = 0,007) e proteína C reativa (CRP, na sigla em inglês) (OR = 1,184; 95%CI: 1,024-1,369; p = 0,022) foram preditores independentes de mau prognóstico funcional da ICP não cardiogênica aos 90 dias após o início dos sintomas. Conclusões Os níveis iniciais de BNP e CRP se associaram a maus resultados funcionais em pacientes com ICP não cardiogênica aos três meses, independentemente da troponina.

Enuresis and upper airway obstruction: BNP and ADH hormones behavior before and after airway surgery.

INTRODUCTION: Upper airway obstruction (UAO) is a common condition in all pediatric population, with a 27% prevalence. Primary monosymptomatic nocturnal enuresis (PMNE) is a condition related to UAO in 8% to 47% of these children. The specific pathophysiological mechanism of this bond is not well understood. Some authors suggest a connection between brain natrituretic peptide (BNP) and anti-diuretic hormone (ADH) during sleep. The aim of this study was to evaluate hormone profile (ADH and BNP) and improvement in dry nights in a sample of children before and after surgical treatment of the UAO. METHODS: This is a longitudinal prospective interventionist study in children, 5 to 14 years of age, with UAO and PMNE recruited in a specialty outpatient clinic. Children presenting UAO and PMNE were evaluated with a 30-day dry night diary and blood samples were collected to evaluate ADH and BNP before and after upper airway surgery. Data were analyzed prior to surgery and 90-120 days after surgery. RESULTS: Twenty-one children with a mean age of 9.7 years were included. Mean BNP before surgery was 116.5 ± 126.5 pg/mL and 156.2 ± 112.3 pg/mL after surgery (p<0.01). Mean ADH was 5.8 ± 3.2 pg/mL and 14.6 ± 35.4 before and after surgery, respectively (p=0.26). The percentage of dry nights went from 32.3 ± 24.7 before surgery to 75.4 ± 33.4 after surgery (p˂0.01). CONCLUSION: Surgery for airway obstruction contributed to an increase in BNP without increasing ADH. A total of 85.8% of the children presented partial or complete improvement of their enuresis.

Mitral Regurgitation and Serum N-Terminal Pro-Brain Natriuretic Peptide Levels in Children: A Modification of Adult Criteria.

Mitral regurgitation can result from congenital heart disease, rheumatic valve disease, or other congenital malformations of the mitral valve. Faulty valves require surgical repair or replacement. However, echocardiographic and biochemical parameters that inform surgical decision-making for adults may not be appropriate for children. To investigate whether adult parameters can be used in children, we correlated echocardiographic parameters with serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in children with chronic mitral regurgitation. Our sample comprised 45 patients and 38 healthy children. M-mode measurements, left atrial and left ventricular volumes, and Doppler and tissue Doppler echocardiograms were collected. We graded mitral regurgitation according to European Association of Echocardiography recommendations and indexed effective regurgitant area, vena contracta, and regurgitant volume to body surface area. Patients were grouped by regurgitation severity (mild vs moderate or severe) and left ventricular end-systolic dimension (normal vs enlarged). The NT-proBNP level was higher in patients than in controls (P=0.003), higher in patients with moderate or severe regurgitation (P=0.02), and higher in patients with an enlarged left ventricle (P=0.003). Serum NT-proBNP levels correlated with effective regurgitant area (r=0.47; P=0.002), vena contracta width (r=0.46; P=0.003), regurgitant volume (r=0.32; P=0.04), left ventricular end-systolic diameter (r=0.58; P <0.001), and left atrial diameter (r=0.62; P <0.001). An NT-proBNP value of 66 pg/mL differentiated the mild regurgitation group from the moderate or severe regurgitation group. Our results correlating NT-proBNP and echocardiographic parameters indexed to body surface area indicate that these adult criteria can be used in children to grade mitral regurgitation and inform surgical decision-making.

Cardiovascular complications of COVID-19.

Cardiac injury associated with coronavirus disease 2019 (COVID-19) is associated with high fatality rates. We reviewed the literature on COVID-19-related cardiovascular complications to elucidate the putative causes, diagnosis, and management of cardiovascular complications of COVID-19. Putative causes of these cardiovascular complications include cytokine storm, myocarditis, coronary plaque rupture, hypercoagulability, stress cardiomyopathy or combinations thereof. Cardiac troponin, D-dimer, and N-terminal pro B-type natriuretic peptide levels all provide prognostic information on COVID-19-related cardiovascular complications: elevated levels correlate with poorer prognosis. Coronary thrombosis due to COVID-19 may be associated with a higher thrombus burden than that from other causes. Hypercoagulability can be extremely challenging to treat, and in the absence of contra-indications, thromboprophylaxis is generally indicated in intensive care unit patients. With the exception of percutaneous coronary intervention for acute myocardial infarction, there are no specific treatments for COVID-19-related cardiovascular complications and management is primarily supportive. Whether antiviral therapies, coupled with monoclonal antibodies administered early in the course of COVID-19 illness will prevent severe cardiovascular complications remains to be seen.

Natriuretic Peptide Oligomers Cause Proarrhythmic Metabolic and Electrophysiological Effects in Atrial Myocytes.

BACKGROUND: With aging, the human atrium invariably develops amyloid composed of ANP (atrial natriuretic peptide) and BNP (B-type natriuretic peptide). Preamyloid oligomers are the primary cytotoxic species in amyloidosis, and they accumulate in the atrium during human hypertension and a murine hypertensive model of atrial fibrillation susceptibility. We tested the hypothesis that preamyloid oligomers derived from natriuretic peptides cause cytotoxic and electrophysiological effects in atrial cells that promote arrhythmia susceptibility and that oligomer formation is enhanced for a mutant form of ANP linked to familial atrial fibrillation. METHODS: Oligomerization was assessed by Western blot analysis. Bioenergic profiling was performed using the Seahorse platform. Mitochondrial dynamics were investigated with immunostaining and gene expression quantitated using quantitative reverse transcription polymerase chain reaction. Action potentials and ionic currents were recorded using patch-clamp methods and intracellular calcium measured using Fura-2. RESULTS: Oligomer formation was markedly accelerated for mutant ANP (mutANP) compared with WT (wild type) ANP. Oligomers derived from ANP, BNP, and mutANP suppressed mitochondrial function in atrial HL-1 cardiomyocytes, associated with increased superoxide generation and reduced biogenesis, while monomers had no effects. In hypertensive mice, atrial cardiomyocytes displayed reduced action potential duration and maximal dV/dT of phase 0, with an elevated resting membrane potential, compared with normotensive mice. Similar changes were observed when atrial cells were exposed to oligomers. mutANP monomers produced similar electrophysiological effects as mutANP oligomers, likely due to accelerated oligomer formation, while ANP and BNP monomers did not. Oligomers decreased Na+ current, inward rectifier K+ current, and L-type Ca++ current, while increasing sustained and transient outward K+ currents, to account for these effects. CONCLUSIONS: These findings provide compelling evidence that natriuretic peptide oligomers are novel mediators of atrial arrhythmia susceptibility. Moreover, the accelerated oligomerization by mutANP supports a role for these mediators in the pathophysiology of this mutation in atrial fibrillation.

[Prognostic value of the absolute decrease of the N-terminal portion of B-type natriuretic propeptide in decompensated heart failure: secondary analysis of the CLUSTER-HF study]. / Valor pronóstico del descenso absoluto de la porción N-terminal del propéptido natriurético tipo B en insuficiencia cardiaca descompensada: análisis secundario del estudio CLUSTER-HF.

Objective: The purpose of this study is to determine the prognostic value of the absolute decrease in the N-terminal portion of pro-B-type natriuretic peptide (NT-proBNP) to prevent fewer clinical events, in the population of CLUSTER-HF (efficacy of ultrasound lung to guide therapy and prevent readmissions in heart failure). Materials and methods: This study was conducted in a subgroup of ninety-four patients with available NT-proBNP information at hospital discharge and prior to randomization in the CLUSTER-HF study. The primary objective of the study was to determine the prognostic value of absolute NT-proBNP decline below which fewer events of all-cause death, emergency room visits, and rehospitalization for heart failure at 180 days. Results: The absolute decrease in NT-proBNP below 3,350 pg/mL has a moderate discriminative capacity with AUC= 0.602, with a prognostic value in the combined event at 180 days (log-rank test, p=0.01). Also, according to the multivariable analysis, it is an independent marker of clinical events at 180 days OR 0.319 (0.102-0.995, p=0.04) above other clinical variables. Conclusions: An absolute decrease to 3,350 pg/mL of NT-proBNP or less at discharge from the hospitalization due to heart failure, was associated with fewer clinical events at 180 days.