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B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial.
Myhre, PL, Vaduganathan, M, Claggett, B, Packer, M, Desai, AS, Rouleau, JL, Zile, MR, Swedberg, K, Lefkowitz, M, Shi, V, et al
Journal of the American College of Cardiology. 2019;(11):1264-1272
Abstract
BACKGROUND Natriuretic peptides are substrates of neprilysin; hence, B-type natriuretic peptide (BNP) concentrations rise with neprilysin inhibition. Thus, the clinical validity of measuring BNP in sacubitril/valsartan-treated patients has been questioned, and use of N-terminal pro-B-type natriuretic peptides (NT-proBNP) has been preferred and recommended. OBJECTIVES The purpose of this study was to determine the prognostic performance of BNP measurements before and during treatment with sacubitril/valsartan. METHODS BNP and NT-proBNP were measured before and after 4 to 6 weeks, 8 to 10 weeks, and 9 months of treatment with sacubitril/valsartan in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. We assessed the association of levels of these natriuretic peptides with the subsequent risk of cardiovascular death or hospitalization for HF. RESULTS Median BNP concentration (before treatment: 202 ng/l [Q1 to Q3: 126 to 335 ng/l]) increased to 235 ng/l (Q1 to Q3: 128 to 422 ng/l) after 8 to 10 weeks of treatment. BNP concentrations doubled in 141 (18%) patients and tripled in 49 (6%) patients during the first 8 to 10 weeks of sacubitril/valsartan. In contrast, such striking increases in NT-proBNP following the use of the neprilysin inhibitor were extremely rare. Treatment with sacubitril/valsartan caused a rightward shift in the distribution of BNP when compared with NT-proBNP, but both peptides retained their prognostic accuracy (C-statistics of 63% to 67% for BNP and C-statistics of 64% to 70% for NT-proBNP) with no difference between the 2 biomarkers. Increases in both BNP and NT-proBNP during 8 to 10 weeks of sacubitril/valsartan were associated with worse outcomes (p = 0.003 and p = 0.005, respectively). CONCLUSIONS Circulating levels of BNP may increase meaningfully early after initiation of sacubitril/valsartan. In comparison, NT-proBNP is not a substrate of neprilysin inhibition, and thus may lead to less clinical confusion when measured within 8 to 10 weeks of drug initiation. However, during treatment, either biomarker predicts the risk of major adverse outcomes in patients treated with angiotensin receptor-neprilysin inhibitors. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).
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SERUM cardiac-specific biomarkers and atrial fibrillation in myotonic dystrophy type I.
Russo, V, Rago, A, Atripaldi, L, Leonardi, S, Papa, AA, Politano, L, Golino, P, Potpara, TS, Nigro, G
Journal of cardiovascular electrophysiology. 2019;(12):2914-2919
Abstract
INTRODUCTION The aim of the present study was to evaluate the role of high-sensitivity cardiac troponin I, N terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase-MB mass concentration (CK-MB mass) and copeptin (CP) in predicting incident atrial fibrillation (AF) in myotonic dystrophy type 1 (DM1) patients. MATERIALS AND METHODS The study enrolled 60 consecutive DM1 patients (age 50.3 ± 7.3 years, 34 male) who underwent pacemaker (PM) implantation for cardiac rhythm abnormalities and 60 PM recipients whose age and sex matched served as control group. All DM1 patients underwent a 12-lead electrocardiogram, 2D color Doppler echocardiogram, biomarkers measurements and device interrogation at implantation, 1 month after and every 6 months thereafter for a minimum of 2-year follow-up. RESULTS The study population was divided into two groups according to the presence of AF (AF group vs non-AF group). The AF group was older (47.3 ± 8 vs 38.6 ± 7 years, P = .03) and showed higher serum levels of NT-proBNP (151 ± 38.4 vs 107.3 ± 24.2 pg/mL, P < .001) and CP (18.9 ± 4.5 vs 7 ± 2.3 P < .001) than non-AF Group. NT-proBNP (P < .001) and CP (P < .001) were found to be an independent predictor of AF. Based on the receiver-operating characteristics curve analysis, the cut-off value for NT-proBNP that best predicted AF event in DM1 patients was 123 pg/ml (sensitivity of 83.3% and specificity of 86.5%); the cut-off value for CP that best predicted AF event in DM1 patients was 9 pmol/L (sensitivity of 89% and specificity of 87%). CONCLUSION NT-proBNP and CP represent two independent predictors of AF onset in DM1 population with conduction disturbances underwent PM implantation.
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Elevated MR-proANP plasma concentrations are associated with sepsis and predict mortality in critically ill patients.
Yagmur, E, Sckaer, JH, Koek, GH, Weiskirchen, R, Trautwein, C, Koch, A, Tacke, F
Journal of translational medicine. 2019;(1):415
Abstract
BACKGROUND AND AIMS Mid-regional pro atrial natriuretic peptide (MR-proANP) is an established biomarker for heart failure, based on its key role in regulating homeostasis of water balance and blood pressure. The aim of the study was to determine the value of MR-proANP as a clinical biomarker in critical illness and/or sepsis. Upon admission to the medical intensive care unit (ICU), we investigated MR-proANP plasma concentrations in 217 critically ill patients (144 with sepsis, 73 without sepsis). Results were compared with 65 healthy controls. RESULTS MR-proANP plasma levels were significantly elevated in critically ill patients, when compared to healthy controls. Notably, MR-proANP levels were significantly higher in ICU patients with sepsis. MR-proANP levels were not associated with metabolic comorbidities like diabetes or obesity. In critically ill patients, MR-proANP plasma concentrations correlated with inflammatory cytokines, markers of organ dysfunction and several adipocytokines, such as resistin, retinol-binding protein 4 (RBP4) and adiponectin. Importantly, high MR-proANP plasma levels were associated with mortality, as MR-proANP levels above 227.0 pmol/l indicated a particularly increased mortality risk in ICU patients. The association between MR-proANP and mortality was independent of single organ failure and inflammation markers. CONCLUSION Our study emphasizes the role of circulating MR-proANP as a biomarker in critically ill patients, in which high MR-proANP indicates organ dysfunction, sepsis and mortality risk. The association between high MR-proANP and inflammatory as well as adipose tissue-derived endocrine mediators warrants further pathophysiological investigations.
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Short-term treatment of irbesartan and hydrochlorothiazide decreases plasma N-terminal pro-brain natriuretic peptide levels in subjects with acute exacerbations of COPD.
Jiang, GY, Li, Q, Lv, YX
International journal of chronic obstructive pulmonary disease. 2019;:73-80
Abstract
BACKGROUND Plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are elevated in subjects with COPD, and high plasma NT-proBNP levels are correlated with a poor prognosis. Thus, it is crucial to decrease the plasma NT-proBNP levels at the early stage of disease. We aimed to assess the effects of short-term treatment of irbesartan and hydrochlorothiazide on plasma NT-proBNP levels and health-related quality of life (HRQOL) in subjects with acute exacerbations of COPD (AECOPD). SUBJECTS AND METHODS Eighty subjects with AECOPD and high plasma NT-proBNP levels, without any clinical evidence of cor pulmonale, were enrolled. The subjects were randomly allocated into two groups of 40 subjects. In addition to standard treatment for AECOPD, the subjects in group I were treated with irbesartan alone, and those in group II were treated with irbesartan and hydrochlorothiazide for a week. Forty subjects with stable COPD were enrolled as a control group. Plasma NT-proBNP concentrations were measured on admission and on the first, fourth, and seventh days. The subjects' health-related quality of life was evaluated applying the 36-item short-form questionnaire on the first day before treatment and on the seventh day after treatment. RESULTS Treatment of irbesartan and hydrochlorothiazide significantly decreased plasma NT-proBNP levels in subjects with AECOPD, and this reduction was more significant in group II than that in group I. There were no significant differences in 36-item short-form domain scores between subjects with stable COPD and those with AECOPD who were treated with irbesartan and hydrochlorothiazide. CONCLUSION Treatment of irbesartan and hydrochlorothiazide rapidly decreased plasma NT-proBNP levels in subjects with AECOPD, and the treatment did not impair their physical status.
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Effects of sacubitril/valsartan on B-type natriuretic peptide circulating levels and loop diuretic dose in a case series of stabilized heart failure patients with left ventricular ejection fraction ≤35.
Pugliese, NR, Fabiani, I, Zywicki, V, Mazzola, M, D'Agostino, A, Galeotti, GG, Dini, FL
Current medical research and opinion. 2019;(sup3):13-18
Abstract
Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor, was shown to improve outcome in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). There are reasons for believing that the concept that the lower the B-type natriuretic peptide (BNP) circulating level the better the prognosis may no longer be correct in patients treated with sacubitril/valsartan, since sacubitril may interfere with BNP clearance. We reported a case series of ten patients with stable chronic HF and LVEF ≤35% (mean age: 64 ± 8 years; 30% female), referred to our outpatient HF clinic, treated with sacubitril/valsartan, in whom the global amelioration of NYHA class and LVEF was coupled with a clinically significant decrease in BNP levels and a reduction of loop diuretic dose. Average sacubitril/valsartan daily dose was 220 mg. The median duration of treatment was 15 months (range: 6-21 months). Seventy percent of patients exhibited an improvement in exercise tolerance, as indicated by the change in NYHA class. There was also an improvement in LVEF from 28 ± 5% to 39 ± 7%. Clinically significant reductions in BNP levels were evident, with a median change from 181 pg/ml to 70 pg/ml. Furosemide daily dose decreased from a median of 43.3 mg to 12.5 mg. This case series suggests that BNP may still be valuable for the assessment of ambulatory HF patients, after the optimization of sacubitril/valsartan therapy.
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Clinical factors related to morbidity and mortality in high-risk heart failure patients: the GUIDE-IT predictive model and risk score.
O'Connor, C, Fiuzat, M, Mulder, H, Coles, A, Ahmad, T, Ezekowitz, JA, Adams, KF, Piña, IL, Anstrom, KJ, Cooper, LS, et al
European journal of heart failure. 2019;(6):770-778
Abstract
BACKGROUND Most heart failure (HF) risk scores have been derived from cohorts of stable HF patients and may not incorporate up to date treatment regimens or deep phenotype characterization that change baseline risk over the short- and long-term follow-up period. We undertook the current analysis of participants in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial to address these limitations. METHODS AND RESULTS The GUIDE-IT study randomized 894 high-risk patients with HF and reduced ejection fraction (≤ 40%) to biomarker-guided treatment strategy vs. usual care. We performed risk modelling using Cox proportional hazards models and analysed the relationship between 35 baseline clinical factors and the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, the secondary endpoint of all-cause mortality, and the exploratory endpoint of 90-day HF hospitalization or death. Prognostic relationships for continuous variables were examined and key predictors were identified using a backward variable selection process. Predictive models and risk scores were developed. Over a median follow-up of 15 months, the cumulative number of HF hospitalizations and CV deaths was 328 out of 894 patients (Kaplan-Meier event rate 34.5% at 12 months). Frequency of all-cause deaths was 143 out of 894 patients (Kaplan-Meier event rate 12.2% at 12 months). Outcomes for the primary and secondary endpoints between strategy arms of the study were similar. The most important predictor that was present in all three models was the baseline natriuretic peptide level. Hispanic ethnicity, low sodium and high heart rate were present in two of the three models. Other important predictors included the presence or absence of a device, New York Heart Association class, HF duration, black race, co-morbidities (sleep apnoea, elevated creatinine, ischaemic heart disease), low blood pressure, and a high congestion score. CONCLUSION Risk models using readily available clinical information are able to accurately predict short- and long-term CV events and may be useful in optimizing care and enriching patients for clinical trials. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov ID number NCT01685840.
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Analytical barriers in clinical B-type natriuretic peptide measurement and the promising analytical methods based on mass spectrometry technology.
Xiao, P, Li, H, Li, X, Song, D
Clinical chemistry and laboratory medicine. 2019;(7):954-966
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Abstract
B-type natriuretic peptide (BNP) is a circulating biomarker that is mainly applied in heart failure (HF) diagnosis and to monitor disease progression. Because some identical amino acid sequences occur in the precursor and metabolites of BNP, undesirable cross-reactions are common in immunoassays. This review first summarizes current analytical methods, such as immunoassay- and mass spectrometry (MS)-based approaches, including the accuracy of measurement and the inconsistency of the results. Second, the review presents some promising approaches to resolve the current barriers in clinical BNP measurement, such as how to decrease cross-reactions and increase the measurement consistency. Specific approaches include research on novel BNP assays with higher-specificity chemical antibodies, the development of International System of Units (SI)-traceable reference materials, and the development of structure characterization methods based on state-of-the-art ambient and ion mobility MS technologies. The factors that could affect MS analysis are also discussed, such as biological sample cleanup and peptide ionization efficiency. The purpose of this review is to explore and identify the main problems in BNP clinical measurement and to present three types of approaches to resolve these problems, namely, materials, methods and instruments. Although novel approaches are proposed here, in practice, it is worth noting that the BNP-related peptides including unprocessed proBNP were all measured in clinical BNP assays. Therefore, approaches that aimed to measure a specific BNP or proBNP might be an effective way for the standardization of a particular BNP form measurement, instead of the standardization of "total" immunoreactive BNP assays in clinical at present.
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Short-term effects of Finnish sauna bathing on blood-based markers of cardiovascular function in non-naive sauna users.
Kunutsor, SK, Häkkinen, A, Zaccardi, F, Laukkanen, T, Lee, E, Willeit, P, Khan, H, Laukkanen, JA
Heart and vessels. 2018;(12):1515-1524
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Abstract
Emerging evidence suggests that sauna bathing is associated with reduced risk of cardiovascular and all-cause mortality events. However, the biochemical pathways by which sauna bathing might confer its effects on cardiovascular function are not certain. We aimed to study the acute effects of Finnish sauna bathing on various blood-based cardiovascular biomarkers. The study included 102 non-naive sauna users (54% male) with mean age of 51.9 years, who had at least one cardiovascular risk factor. Participants underwent a 30-min single sauna session (mean temperature, 73 °C). Biochemical profiling was conducted before, immediately after sauna and 30-min post-sauna. Overall median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (n = 20 participants) was 46.0 ng/L before sauna exposure, which increased to 50.5 ng/l immediately after sauna (median change, + 12.00%; p < 0.001) and remained persistent at 30-min post-sauna (median change from pre-sauna to post-30-min sauna, + 13.93%; p < 0.001). The changes were more evident in males compared with females. There were no significant changes in overall levels of high sensitivity C-reactive protein, creatine kinase, high sensitivity troponin I, and creatine kinase-MBm. However, levels of creatine kinase increased in males (median change immediately after sauna, + 2.99%; p = 0.024). Levels of NT-proBNP increased after sauna exposure. The increase in levels of creatine kinase was more evident in males. Long-term interventional studies are warranted to evaluate if these biomarkers are involved in pathways underlying the associations of sauna bathing with cardiovascular outcomes.
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N-Terminal Pro-Brain Natriuretic Peptide Concentrations After Hypertensive Intracerebral Hemorrhage: Relationship With Hematoma Size, Hyponatremia, and Intracranial Pressure.
Li, F, Chen, QX, Xiang, SG, Yuan, SZ, Xu, XZ
Journal of intensive care medicine. 2018;(12):663-670
Abstract
INTRODUCTION The role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with hypertensive intracerebral hemorrhage (HICH) is poorly understood. This study aimed to investigate the secretion pattern of NT-proBNP in patients with HICH and to assess its relationship with hematoma size, hyponatremia, and intracranial pressure (ICP). METHODS This prospective study enrolled 147 isolated patients with HICH. Blood samples were obtained from each patient, and values of serum NT-proBNP, hematoma size, blood sodium, and ICP were collected for each patient. RESULTS The peak-to-mean concentration of NT-proBNP was 666.8 ± 355.1 pg/mL observed on day 4. The NT-proBNP levels in patients with hematoma volume >30 mL were significantly higher than those in patients with hematoma volume <30 mL ( P < .05). In patients with severe HICH, the mean concentration of NT-proBNP was statistically higher than that in patients with mild-moderate HICH ( P < .05), and the mean level of NT-proBNP in hyponatremia group was significantly higher than that in normonatremic group ( P < .05). In addition, the linear regression analysis indicated that serum NT-proBNP concentrations were positively correlated with ICP ( r = .703, P < .05) but negatively with blood sodium levels only in patients with severe HICH ( r = -.704, P < .05). The serum NT-proBNP levels on day 4 after admission were positively correlated with hematoma size ( r = .702, P < .05). CONCLUSION The NT-proBNP concentrations were elevated progressively and markedly at least in the first 4 days after HICH and reached a peak level on the fourth day. The NT-proBNP levels on day 4 were positively correlated with hematoma size. There was a notable positive correlation between plasma NT-proBNP levels and ICP in patients with severe HICH. Furthermore, only in patients with severe HICH, the plasma NT-proBNP levels presented a significant correlation with hyponatremia, which did not occur in patients with mild-moderate HICH.
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Evaluation of cardiac biomarkers in children with acute severe bronchial Asthma-A prospective study from tertiary care center in northern India.
Jain, M, Jain, D, Das, BK, Prasad, R, Sihag, BK
Indian heart journal. 2018;(Suppl 3):S204-S207
Abstract
OBJECTIVES During the attacks of acute severe bronchial asthma there are marked cardiopulmonary changes leading to hypoxia. The study aims to find the incidence of myocardial dysfunction in patients of acute severe bronchial asthma based on cardiac enzyme levels at admission and see whether the myocardial damage is transient or persistent even after stabilization of the patient based on enzyme levels at discharge. MATERIALS AND METHODS This prospective, case control study was done at Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University between October 2016 to May 2018. Sixty pediatric patients of acute severe bronchial asthma were taken as cases and 15 age and sex matched children served as controls. Blood samples were collected in Ethylene diamine tetra acetic acid vials before the start of treatment, for measurement of cardiac biomarkers Troponin I (TnI), Brain natriuretic peptide (BNP) and Creatine Kinase-muscle/brain (CK-MB) and repeat samples were taken before discharge. RESULTS Fifty percent of the cases had abnormal TnI levels, 15% had abnormal CK-MB levels and 8.3% had abnormal BNP levels at admission. At discharge, only 1 (1.7%) case had abnormal levels of CK-MB, whereas the levels of TnI and BNP normalized in all. The level of cardiac biomarkers were significantly raised at admission when compared to discharge values (p value < 0.001). CONCLUSIONS The raised cardiac biomarkers suggest myocardial stress during acute exacerbation of bronchial asthma. Though, the present study showed that the changes are of transient nature, larger follow up studies are required to document any permanent damage to myocardium.