Cardiac biomarker responses following high-intensity interval and continuous exercise: the influence of ACE-I/D gene polymorphism and training status in men.

This study aimed to investigate the relationship between pre- and postexercise cardiac biomarker release according to athletic status (trained vs. untrained) and to establish whether the I/D polymorphism in the angiotensin-converting enzyme (ACE) gene had an influence on cardiac biomarkers release with specific regard on the influence of the training state. We determined cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in 29 trained and 27 untrained male soccer players before and after moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) running tests. Trained soccer players had higher pre (trained: 0.014 ± 0.007 ng/mL; untrained: 0.010 ± 0.005 ng/mL) and post HIIE (trained: 0.031 ± 0.008 ng/mL; untrained: 0.0179 ± 0.007) and MICE (trained: 0.030 ± 0.007 ng/mL; untrained: 0.018 ± 0.007) cTnI values than untrained subjects, but the change with exercise (ΔcTnI) was similar between groups. There was no significant difference in baseline and postexercise NT-proBNP between groups. NT-proBNP levels were elevated after both HIIE and MICE. Considering three ACE genotypes, the mean pre exercise cTnI values of the trained group (DD: 0.015 ± 0.008 ng/mL, ID: 0.015 ± 0.007 ng/mL, and II: 0.014 ± 0.008 ng/mL) and their untrained counterparts (DD: 0.010 ± 0.004 ng/mL, ID: 0.011 ± 0.004 ng/mL, and II: 0.010 ± 0.006 ng/mL) did not show any significant difference. To sum up, noticeable difference in baseline cTnI was observed, which was related to athletic status but not ACE genotypes. Neither athletic status nor ACE genotypes seemed to affect the changes in cardiac biomarkers in response to HIIE and MICE, indicating that the ACE gene does not play a significant role in the release of exercise-induced cardiac biomarkers indicative of cardiac damage in Iranian soccer players.NEW & NOTEWORTHY Our study investigated the impact of athletic status and angiotensin-converting enzyme (ACE) gene I/D polymorphism on cardiac biomarkers in soccer players. Trained players showed higher baseline cardiac troponin I (cTnI) levels, whereas postexercise ΔcTnI remained consistent across groups. N-terminal pro-brain natriuretic peptide increased after exercise in both groups, staying within normal limits. ACE genotypes did not significantly affect pre-exercise cTnI. Overall, athletic status influences baseline cTnI, but neither it nor ACE genotypes significantly impact exercise-induced cardiac biomarker responses in this population.

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.

Correlation of n-terminal pro-brain-type natriuretic peptide levels with the severity of single mitral regurgitation or accompanied by mild aorta valve dysfunction in patients with rheumatic heart disease in Sanglah general hospital.

BACKGROUND: The most frequent abnormality of the valves involved in rheumatic heart disease is mitral regurgitation. A promising supportive diagnostic tool for rheumatic heart disease is the N-terminal pro-brain natriuretic peptide, which can identify mitral valve damage. OBJECTIVE: To prove a positive correlation between N-terminal pro-brain natriuretic peptide levels and the severity of mitral regurgitation or accompanied by mild aortic valve dysfunction in children with rheumatic heart disease. MATERIAL AND METHOD: Children aged 1-18 years who had been identified as having rheumatic heart disease with a single mitral regurgitation or accompanied by mild aortic issues at Sanglah General Hospital, Denpasar, met the inclusion criteria for this cross-sectional study. Mitral regurgitation severity was determined using the parameters of vena contracta width, effective regurgitation orifice area, regurgitant jet area, and regurgitation volume. Bivariate analysis using the Spearman correlation test. RESULTS: From 36 research subjects, the mean age was 11.32 years. In this study, there was a moderate positive correlation between the levels of N-terminal pro-brain natriuretic peptide and the regurgitation jet area. N-terminal pro-brain natriuretic peptide levels also had a moderately positive correlation with the vena contracta width and a weakly positive correlation with the regurgitation volume. Effective regurgitation orifice area and N-terminal pro-brain natriuretic peptide levels did not significantly correlate. CONCLUSION: There was a moderately positive correlation between N-terminal pro-brain natriuretic peptide levels and the severity of mitral regurgitation on regurgitation jet area, a moderately positive correlation with the vena contracta width, and a weakly positive correlation with regurgitation volume in rheumatic heart disease patients.

Genophenotypic correlates and long-term outcome prognosticators of left ventricular non-compaction in children.

BACKGROUND: To investigate the outcomes, clinical prognosticators, and genetic profiles of pediatric left ventricular non-compaction (LVNC). METHODS: All subjects were <18 years old, diagnosed with LVNC between January 2008 and December 2020. Whole-exome sequencing was undertaken. The primary endpoint was composite outcome, including death, heart transplant, and left ventricular assist device implantation. RESULTS: Thirty-three patients were enrolled, males predominating (57.6%). Median age at diagnosis was 0.33 (0.1-7.2) years. Family history was documented in four (12.1%). Five (15.2%) had sustained arrhythmias. Mean follow-up period was 9.5 years, and 5- and 10-year event-free survival were 84.8% and 66.9%, respectively. Seven died of heart failure, four received heart transplants, and one required left ventricular assist device placement. Log of baseline NT-proBNP (adjusted odds ratio [aOR] = 4.4, p = 0.012) and lack of improvement in NT-proBNP (aOR = 41.2, p = 0.033) impacted the primary outcome most significantly. Eighteen out of 25 genetic testing (72%) revealed chromosomal anomalies, or pathogenic or likely pathogenic variants. Three genetic variants (PLEKHM2 p.G419R, RYR2 p.V2571A, and SCN5A p.M1676I) were significantly associated with the primary outcome (p = 1.52 × 10-6). CONCLUSIONS: Pediatric LVNC is a rare disorder with variable genetic underpinnings. Baseline NT-proBNP values and lack of improvement in NT-proBNP levels were important predictors of poor long-term outcomes. Pathogenic genetic variants or chromosomal anomalies are not unusual.

Are the results from a multiplex proteomic assay and a conventional immunoassay for NT-proBNP and GDF-15 comparable?

BACKGROUND: We aimed to compare absolute plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) obtained by a conventional immunoassay with the corresponding relative concentrations from a proximity extension assay (PEA) and compare the prognostic impact of the protein levels obtained from these assays. METHODS: We evaluated 437 patients with peripheral arterial disease (PAD) and a population-based cohort of 643 individuals without PAD. Correlations were calculated using Spearman's rank correlation coefficients (rho). The discriminatory accuracy of the protein levels to predict future cardiovascular events was analyzed with Cox regression and presented as time-dependent areas under the receiver-operator-characteristic curves (tdAUCs). RESULTS: For NT-proBNP, the two assays correlated with rho 0.93 and 0.93 in the respective cohort. The PEA values leveled off at higher values in both cohorts. The corresponding correlations for GDF-15 were 0.91 and 0.89. At 5 years follow-up, the tdAUCs in the patient cohort were similar for NT-proBNP and GDF-15 regardless of assay used (0.65-0.66). The corresponding tdAUCs in the population-based cohort were between 0.72 and 0.77. CONCLUSION: Except for the highest levels of NT-proBNP, we suggest that PEA data for NT-proBNP and GDF-15 reliably reflects absolute plasma levels and contains similar prognostic information.

Study on the Efficacy of Sacubitril/Valsartan in Patients with Heart Failure with Preserved Ejection Fraction Undergoing Peritoneal Dialysis.

INTRODUCTION: Cardiovascular disease is the most common cause of death and morbidity in patients with end-stage renal disease. Sacubitril/valsartan (SAC/VAL) can reduce the risk of cardiovascular mortality among patients with heart failure (HF). The present study set out to evaluate the efficacy of SAC/VAL in the treatment of patients with HF with preserved ejection fraction (HFpEF) undergoing peritoneal dialysis (PD) (HFpEF&PD). METHODS: A total of 160 patients with HFpEF&PD were enrolled and randomly divided into the control group (N = 80) and SAC/VAL group (N = 80). The cardiac function efficacy, HF scoring efficacy, echocardiographic parameters, serological indicators, and 6-minute walking test were compared before and after treatment. RESULTS: After 6 months of treatment, the total number of patients who responded to treatment in the SAC/VAL group was higher than that of the control group in terms of cardiac function and HF scoring efficacy. After treatment, levels of early diastolic/late diastolic filling velocity and left ventricular ejection fraction were increased in both groups, while the levels of left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, inter-ventricular septal diameter, and left ventricular posterior wall diameter were decreased; the NT-proBNP levels were diminished in both groups, while hemoglobin levels and the 6-minute walk distance were increased; the systolic blood pressure, diastolic blood pressure, and 24-h ultrafiltration volume were lowered in all patients. The changes in these indexes in the SAC/VAL group were more obvious than those in the controls. CONCLUSION: SAC/VAL can significantly improve cardiac function in patients with HFpEF&PD.

Urinary N-Terminal Pro-Brain Natriuretic Peptide Predicts Acute Kidney Injury and Severe Disease in COVID-19.

INTRODUCTION: The ongoing COVID-19 pandemic is placing an extraordinary burden on our health care system with its limited resources. Accurate triage of patients is necessary to ensure medical care for those most severely affected. In this regard, biomarkers could contribute to risk evaluation. The aim of this prospective observational clinical study was to assess the relationship between urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) and acute kidney injury (AKI) as well as severe disease in patients with COVID-19. METHODS: 125 patients treated with an acute respiratory infection in the emergency department of the University Hospital Regensburg were analyzed. These patients were divided into a COVID-19 cohort (n = 91) and a cohort with infections not caused by severe acute respiratory syndrome-coronavirus-2 (n = 34). NT-proBNP was determined from serum and fresh urine samples collected in the emergency department. Clinical endpoints were the development of AKI and a composite one consisting of AKI, intensive care unit admission, and in-hospital death. RESULTS: 11 (12.1%) COVID-19 patients developed AKI during hospitalization, whereas 15 (16.5%) reached the composite endpoint. Urinary NT-proBNP was significantly elevated in COVID-19 patients who suffered AKI or reached the composite endpoint (each p < 0.005). In a multivariate regression analysis adjusted for age, chronic kidney disease, chronic heart failure, and arterial hypertension, urinary NT-proBNP was identified as independent predictor of AKI (p = 0.017, OR = 3.91 [CI: 1.28-11.97] per standard deviation [SD]), as well as of the composite endpoint (p = 0.026, OR 2.66 [CI: 1.13-6.28] per SD). CONCLUSION: Urinary NT-proBNP might help identify patients at risk for AKI and severe disease progression in COVID-19.

Diseases associated with prematurity in correlation with N-terminal pro-brain natriuretic peptide levels during the early postnatal life.

The aim of this observational study was to investigate the influence of different typical preterm diseases on NT-proBNP serum levels in the early postnatal period of life of a preterm infant. NT-proBNP levels of 118 preterm infants born ≤ 31 weeks GA were determined at the first week of life, after 4 ± 1 weeks of life, and at a corrected gestational age of 36 + 2 weeks. Relevant complications with a possible influence on NT-proBNP values in the first week of life such as early neonatal infection, hemodynamically significant PDA (hsPDA), early pulmonary hypertension (early PH), and intraventricular hemorrhage (IVH) were evaluated; at 4 ± 1 weeks of life, bronchopulmonary dysplasia (BPD), BPD-related pulmonary hypertension (BPD-associated PH), late infection, IVH, and intestinal complications were evaluated. At a corrected gestational age of 36 ± 2 weeks, we examined the effect of retinopathy of prematurity (ROP), BPD, BPD-associated PH, and late infection on NT-proBNP levels. In the first days of life, only the isolated occurrence of hsPDA resulted in significantly increased NT-proBNP levels. In multiple linear regression analysis, early infection remained independently associated with NT-proBNP levels. At 4 ± 1 weeks of age, the isolated presence of BPD and BPD-related PH resulted in increased levels, and the effect remained significant in the multiple regression analysis. At a corrected gestational age of 36 ± 2 weeks, infants with relevant complications at this final evaluation time tended to have lower NT-proBNP values than our exploratory reference values.    Conlusion: NT-proBNP in the first week of life seems to be mainly influenced by an hsPDA and infection or inflammation. BPD and BPD-related PH are the most important factors influencing NT-proBNP serum levels in the first month of life. When preterm infants reach a corrected GA of 36 ± 2 weeks, chronological age rather than complications of prematurity must be considered when interpreting NT-proBNP levels. What is Known: • Several complications associated with prematurity, such as hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been shown to influence NT-proBNP levels in preterm infants in their early postnatal life. What is New: • Hemodynamically relevant PDA is a major factor in the increase of NT-proBNP levels in the first week of life. • Bronchopulmonary dysplasia and pulmonary hypertension associated with bronchopulmonary dysplasia are important factors in the increase in NT-proBNP levels in preterm infants at approximately 1 month of age.

Higher Levels of Admission N-Terminal Pro-brain Natriuretic Peptide are Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) greatly influences the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to determine whether higher levels of admission N-terminal pro-brain natriuretic peptide (NT-pro BNP) were related to neurogenic cardiac injury and predicted DCI occurrence in patients with aSAH. METHODS: We retrospectively reviewed consecutive patients with aSAH between January 2018 and April 2021 in our department. Patients with admission NT-pro BNP were included for analysis. The associations between admission NT-pro BNP levels and admission cardiac troponin T levels and electrocardiogram characteristics, as well as the incidence of DCI, were investigated. RESULTS: A total of 415 patients with aSAH were included, among whom DCI occurred in 53 (12.8%). The admission NT-pro BNP levels were positively correlated with the cardiac troponin T levels and were significantly higher in patients with abnormal electrocardiogram characteristics. The admission log NT-pro BNP levels were higher in patients with DCI than in those without DCI. Multivariable analysis revealed that admission log NT-pro BNP levels and modified Fisher scale were independent predictors of the incidence of DCI. Compared with the modified Fisher scale alone (area under the curve = 0.739), combining the modified Fisher scale with admission NT-pro BNP (area under the curve = 0.794) significantly improved the prediction accuracy for DCI (p < 0.001). CONCLUSIONS: Higher admission levels of NT-pro BNP correlated with neurogenic cardiac injury and predicted the occurrence of DCI in patients with aSAH. A combination of the modified Fisher scale and admission NT-pro BNP significantly improved the prediction accuracy for DCI.

Comparison of serum N-terminal pro-brain natriuretic peptide levels, conventional echocardiography, exercise parameters, and dyssynchrony measurements in Fontan patients.

INTRODUCTION: Little data are available concerning the methods used in the long-term follow-up of Fontan patients. We analyzed the association between serum N-terminal pro-brain natriuretic peptide levels, conventional echocardiography findings, exercise parameters, and dyssynchrony measurements in patients who underwent Fontan surgery. METHODS: This study included 28 patients who underwent Fontan surgery (mean age 12.8 ± 4.36 years) and 27 healthy controls (mean age 12.5 ± 3.76 years). Echocardiography examinations and exercise tests were performed in both groups. The systemic ventricle was examined via echocardiography, dyssynchrony measurement was performed, the systemic ventricular myocardial performance index was calculated, and serum N-terminal pro-brain natriuretic peptide levels were measured for all subjects. RESULTS: Lower cardiac output, stroke volume, maximal work, chronotropic index, maximal oxygen uptake, and higher N-terminal pro-brain natriuretic peptide levels were observed in the Fontan group than in the control group (p < 0.05). A negative correlation was found between physical exercise parameters and N-terminal pro-brain natriuretic peptide levels and dyssynchrony measurements. CONCLUSION: Measurements of exercise capacity, serum N-terminal pro-brain natriuretic peptide levels, and dyssynchrony measurement were more valuable than conventional methods for assessing patients' clinical and functional status. Dyssynchrony measurements provided better information about ventricular status than did conventional echocardiography studies. While patients' systolic function determined by conventional echocardiography was normal, dyssynchrony measurements showed the opposite result. The negative relationship between serum N-terminal pro-brain natriuretic peptide levels, dyssynchrony measurements, and exercise capacity suggests that these parameters should be investigated further in Fontan patients.

Upper Reference Limits for High-Sensitivity Cardiac Troponin T and N-Terminal Fragment of the Prohormone Brain Natriuretic Peptide in Patients With CKD.

RATIONALE & OBJECTIVE: The utility of conventional upper reference limits (URL) for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We studied participants of the Chronic Renal Insufficiency Cohort (CRIC) with CKD and no self-reported history of cardiovascular disease. EXPOSURE: Estimated glomerular filtration rate (eGFR). OUTCOME: NT-proBNP and hsTnT at baseline. ANALYTICAL APPROACH: We described the proportion of participants above the conventional URL for NT-proBNP (125pg/mL) and hsTnT (14ng/L) overall and by eGFR. We then estimated 99th percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99th percentile, we modeled the association of eGFR with NT-proBNP and hsTnT. RESULTS: Among 2,312 CKD participants, 40% and 43% had levels of NT-proBNP and hsTnT above the conventional URL, respectively. In those with eGFR <30mL/min/1.73m2, 71% and 68% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, respectively. Among all CKD participants, the 99th percentile for NT-proBNP was 3,592 (95% CI, 2,470-4,849) pg/mL and for hsTnT it was 126 (95% CI, 100-144) ng/L. Each 15mL/min/1.73m2 decrement in eGFR was associated with a ~40% higher threshold for the 99th percentile of NT-proBNP (1.43 [95% CI, 1.21-1.69]) and hsTnT (1.45 [95% CI, 1.31-1.60]). LIMITATIONS: Study included ambulatory patients, and we could not test the accuracy of the URL of NT-proBNP and hsTnT in the acute care setting. CONCLUSIONS: In this ambulatory CKD population with no self-reported history of cardiovascular disease, a range of 40%-88% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, depending on eGFR strata. Developing eGFR-specific thresholds for these commonly used cardiac biomarkers in the setting of CKD may improve their utility for evaluation of suspected heart failure and myocardial infarction.

Circulating Biomarkers Predict Symptomatic but Not Asymptomatic Carotid Artery Stenosis.

BACKGROUND: Subjects exposed to risk factors such as age, gender, hypertension, diabetes mellitus, and smoking are prone to atherosclerotic events. AIMS: The main aim of this longitudinal cohort study was to determine whether the role of novel plasma biomarkers for atherosclerotic carotid artery disease is different in subjects developing symptomatic carotid artery stenosis (CAS), as opposed to those with incident asymptomatic CAS. METHODS: The following biomarkers were measured in 5,550 middle-aged subjects in a population-based cohort study: C-reactive protein (CRP), lipoprotein-associated phospholipase A2 mass and activity, proneurotensin, midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT pro-BNP), copeptin, and cystatin C. After exclusion of those with prevalent CAS, subjects were thereafter followed in national patient registers for 23.4 (interquartile range 19.5-24.3) years regarding incident symptomatic and asymptomatic CAS. RESULTS: Among 110 patients with confirmed incident CAS, 56 were symptomatic and 54 were asymptomatic. When including conventional risk markers in a Cox regression analysis, NT pro-BNP (hazard ratio [HR] 1.59; 95% confidence interval [CI]: 1.20-2.11), MR-proADM (HR 1.40; CI: 1.13-1.73), cystatin C (HR 1.21; CI: 1.02-1.43), and CRP (HR 1.53; CI: 1.13-1.73) were independently associated with incident symptomatic CAS, whereas no plasma biomarker was associated with incident asymptomatic CAS. CONCLUSION: Plasma biomarkers NT pro-BNP, MR-proADM, cystatin C, and CRP were independently associated with incident symptomatic CAS, whereas no such association could be demonstrated with incident asymptomatic CAS. As these biomarkers indicate future development of clinically relevant atherosclerotic CAS, their potential utility in relation to intensified preventive measures and selection of potential candidates for carotid surgery should be further evaluated.

N-terminal pro-brain natriuretic peptide predicts hospitalization for ischemic stroke in Japanese hemodialysis patients.

BACKGROUND: The association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and stroke in Japanese hemodialysis (HD) outpatients is unclear. Therefore, in this study, we investigate whether high NT-proBNP levels are associated with future stroke events in this population. METHODS: This was a multicenter prospective observational study with post hoc analysis. Baseline NT-proBNP levels were measured at the first HD session of the week and classified into tertiles (first tertile: < 2255 pg/mL; second tertile: ≥ 2255 and < 5657 pg/mL; third tertile: ≥ 5657 pg/mL). Overall hospitalization-free survival rates were compared using the Kaplan-Meier method. The association between NT-proBNP level and hospitalization for stroke was assessed using the multivariate Cox proportional hazards models. RESULTS: During a 5-year follow-up of 1,229 patients, 103 (8.4%) were hospitalized and 23 (1.9%) died from stroke. The hospitalization-free survival rate for ischemic stroke was lowest in the third tertile (P < 0.01). The crude hazard ratio (HR) of hospitalization was higher in the third tertile compared with the first tertile for both ischemic stroke (HR: 3.92; 95% confidence interval [CI] 2.08-7.37; P < 0.01) and hemorrhagic stroke (HR: 3.75; 95% CI 1.35-10.43; P = 0.01). On multivariate Cox hazard analysis, the adjusted HRs for ischemic stroke were higher in the third tertile. The hospitalization-free survival rates for hemorrhagic stroke and the adjusted HRs did not differ significantly. CONCLUSIONS: Elevated NT-proBNP level was associated with hospitalization for ischemic stroke, suggesting that NT-proBNP level is a valid biomarker for predicting hospitalization for ischemic stroke in HD outpatients.

Predictive potential of age-group cut-off values of N-terminal pro-brain natriuretic peptide in Kawasaki disease.

BACKGROUND: The relationship between serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and the clinical features of patients with Kawasaki disease (KD) has been the subject of research. Recent studies have revealed that serum NT-proBNP levels vary with age. We therefore aimed to determine the utility of age-stratified cut-off values for NT-proBNP in predicting coronary artery lesions (CALs) in patients with KD. METHODS: We retrospectively assessed the electronic medical records of patients who were hospitalized for KD or incomplete KD between January 1, 2015, and August 31, 2019. The patients were divided into high and normal NT-proBNP groups using age-stratified cut-off based on serum NT-proBNP levels measured immediately before KD treatment initiation. RESULTS: The study comprised 242 cases, including 71 and 171 cases in high and normal NT-proBNP groups, respectively. Thirty-seven of them (15.3%) were resistant to treatment; 15 (6.2%) had CALs, with a higher incidence in the high NT-proBNP group than in the normal NT-proBNP group. On multivariate logistic regression analysis, high serum NT-proBNP levels were significantly correlated to CALs (OR, 9.76; 95% CI, 2.64-36.2). On logistic regression analysis to compare the predictive accuracy of the age-stratified and fixed cut-off for CALs, the age-stratified cut-off values showed a larger area under the receiver operating characteristic curve than fixed cut-off value. CONCLUSIONS: Based on age-stratified cut-off values for serum NT-proBNP, high NT-proBNP levels at the time of diagnosis were significantly associated with CALs in patients with KD. Higher predictive accuracy for CALs of the age-stratified cut-off values was also suggested.

Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial.

BACKGROUNDS/AIM: Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). METHODS: The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. RESULTS: In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by - 2.23% (95% CI - 5.72 to 1.25) at week 4, - 8.07% (- 12.76 to - 3.37) at week 12, and - 5.60% (- 9.87 to - 1.32) at week 24; eEV by - 70.3 mL (95% CI - 136.8 to - 3.8) at week 4, - 135.9 mL (- 209.6 to - 62.3) at week 12, and - 144.4 mL (- 226.3 to - 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. CONCLUSIONS: Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502.

Prognostic value of NT-proBNP in patients with chronic coronary syndrome and normal left ventricular systolic function according to glucose status: a prospective cohort study.

BACKGROUND: The prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with coronary artery disease (CAD) with different glucose status has not been established. This study sought to evaluate the significance of NT-proBNP in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) and normal left-ventricular systolic function (LVSF) according to different glucose status, especially in those with abnormal glucose metabolism. METHODS: A total of 8062 patients with CCS and normal LVSF were consecutively enrolled in this prospective study. Baseline plasma NT-proBNP levels were measured. The follow-up data of all patients were collected. Kaplan-Meier and Cox regression analyses were used to assess the risk of MACEs according to NT-proBNP tertiles stratified by glucose status. RESULTS: Over an average follow-up of 59.13 ± 18.23 months, 569 patients (7.1 %) suffered from MACEs, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Kaplan-Meier analysis showed that high NT-proBNP levels had a significant association with MACEs in subjects with prediabetes mellitus (pre-DM) or DM, but not in patients with normoglycemia. Multivariate Cox regression analysis revealed that NT-proBNP remained an independent predictor of MACEs in patients with pre-DM [hazard ratio (HR): 2.56, 95% confidence interval (CI): 1.34-4.91] or DM (HR: 2.34, 95% CI: 1.32-4.16). Moreover, adding NT-proBNP to the original Cox model including traditional risk factors significantly increased the C-statistic by 0.035 in pre-DM and DM, respectively. CONCLUSIONS: The present study indicated that NT-proBNP could well predict worse outcomes in dysglycemic patients with CCS and normal LVSF, suggesting that NT-proBNP may help with risk stratification in this population.

Mid-regional pro-atrial natriuretic peptide independently predicts short-term mortality in COVID-19.

BACKGROUND: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a strong prognostic marker in several inflammatory, respiratory and cardiovascular conditions, but has not been studied in COVID-19 yet. METHODS: This prospective, observational study of patients with COVID-19 infection was conducted from 6 June to 26 November 2020 in different wards of a tertiary hospital. MR-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive cardiac troponin I levels on admission were collected and tested for their association with disease severity and 28-day mortality. RESULTS: A total of 213 eligible patients with COVID-19 were included in the final analyses of whom 13.2% (n = 28) died within 28 days. Median levels of MR-proANP at admission were significantly higher in nonsurvivors (307 pmol/L IQR, [161 - 532] vs 75 pmol/L [IQR, 43 - 153], P < .001) compared to survivors and increased with disease severity and level of hypoxaemia. The area under the ROC curve for MR-proANP predicting 28-day mortality was 0.832 (95% CI 0.753 - 0.912, P < .001). An optimal cut-off point of 160 pmol/L yielded a sensitivity of 82.1% and a specificity of 76.2%. MR-proANP was a significant predictor of 28-day mortality independent of clinical confounders, comorbidities and established prognostic markers of COVID-19 (HR 2.77, 95% CI 1.21 - 6.37; P = .016), while NT-proBNP failed to independently predict 28-day mortality and had a numerically lower AUC compared to MR-proANP. CONCLUSION: Higher levels of MR-proANP at admission are associated with disease severity of COVID-19 and act as a powerful and independent prognostic marker of 28-day mortality.

Reference values for N-terminal Pro-brain natriuretic peptide in premature infants during their first weeks of life.

The aim of our study was to observe the temporal distribution of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in premature infants of ≤ 31 weeks of gestational age (GA) during the first weeks of life. NT-proBNP values of 118 preterm infants born ≤ 31 weeks GA were determined during the first week of life, after 4 ± 1 weeks of life, and at a corrected GA of 36 ± 2 weeks. Infants were divided into two groups: those without relevant complications and those with complications related to prematurity. NT-proBNP values of infants without complications define our exploratory reference values. The Median NT-proBNP level of these infants was 1896 ng/l (n = 27, interquartile range (IQR): 1277-5200) during the first week of life, 463 ng/l (n = 26, IQR: 364-704) at 4 ± 1 weeks of life, and 824 ng/l (n = 33, IQR: 714-1233) at a corrected GA of 36 ± 2 weeks. Infants born < 28 + 0 weeks GA had significantly higher NT-proBNP values (n = 9, median: 5200, IQR: 1750-8972) than infants born ≥ 28 + 0-31 weeks GA (n = 18, median: 1528, IQR: 838-3052; p = 0.017). Growth restriction or PDA status could not account for the difference in NT-proBNP values between GA groups.Conclusions: The results of our observational and cross-sectional study describe exploratory reference values for NT-proBNP levels in preterm infants of ≤ 31 weeks GA according to postnatal age. NT-proBNP levels during the first week of life are high and widely distributed in preterm infants and decrease subsequently to reach a distinctly lower and stable plateau at around 1 month of life. Our results suggest an influence of GA on NT-proBNP values in the first week of life. What is Known: • Several complications related to prematurity, e.g., hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been associated with a temporary rise in NT-proBNP values in preterm infants during their first weeks of life. What is New: • This observational study provides reference values for NT-proBNP levels of very and extremely preterm infants during their first weeks of life. • In premature infants without complications, NT-proBNP values during their first week of life depend on gestational age at birth.

N-terminal pro brain natriuretic peptide predicts both all-cause and cardiovascular disease mortality in Japanese hemodialysis patients.

BACKGROUND: The association between N-terminal pro brain natriuretic peptide (NT-proBNP) level and long-term mortality in Japanese hemodialysis patients has not been fully assessed. METHODS: This prospective, multicenter study included 1428 hemodialysis outpatients. Baseline NT-proBNP levels were measured at the first hemodialysis session of the week and participants were followed for 5 years. The areas under the curve were calculated from receiver operating characteristic curves. Groups determined by quartiles of baseline NT-proBNP level were assessed by the Kaplan-Meier method and log-rank test. The association between NT-proBNP level and mortality was assessed using multivariate Cox proportional hazards models. RESULTS: During the 5-year follow-up, we observed 370 deaths and 256 censored cases. The areas under the curve of pre-hemodialysis NT-proBNP for all-cause mortality and cardiovascular disease mortality after 1 year were 0.75 and 0.78, respectively, and significantly greater than the areas under the curve at the 3- and 5-year follow-up. Cut-off values for all-cause mortality and cardiovascular disease mortality after 1 year were 4550 and 5467 ng/L, respectively (sensitivity: 82% and 81%; specificity: 59% and 64%). Kaplan-Meier survival analysis showed that the group with pre-hemodialysis NT-proBNP ≥ 8805 ng/L had increased all-cause mortality (P < 0.001) and cardiovascular disease mortality (P < 0.001). Finally, multivariate Cox analysis showed that NT-proBNP level was associated with all-cause mortality (P < 0.001) and cardiovascular disease mortality (P = 0.004) independently from other clinical parameters. CONCLUSION: NT-proBNP is a useful marker to predict both all-cause and cardiovascular disease mortality in hemodialysis patients.

Diastolic Dysfunction Contributes to Impaired Cardiorespiratory Fitness in Patients with Lung Cancer and Reduced Lung Function Following Chest Radiation.

Cardiorespiratory fitness (CRF) is a robust and independent predictor of cardiovascular health and overall mortality. Patients with lung cancer often have chronic lung disease, contributing to impaired CRF. Radiation to the heart during lung cancer treatment may further reduce CRF. The determinants of CRF in this population are not well understood. We prospectively evaluated 12 patients with lung cancer without known cardiovascular disease with reduced lung function receiving curative intent thoracic radiotherapy to determine whether cardiac diastolic function, as assessed by Doppler echocardiography and N-terminal pro-brain natriuretic peptide (NTproBNP) levels, correlate with CRF measured by peak oxygen consumption (VO2). Doppler-derived measures of diastolic function and serum NTproBNP levels inversely correlated with peak VO2. In a multivariate regression model, NTproBNP was the strongest independent variable associated with peak VO2. These results suggest that diastolic dysfunction further contributes to reduced CRF in patients with lung cancer who have received radiotherapy.