The predictive value of NT-proBNP and hs-TnT for risk of death in cardiac surgical patients

Background: European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is used for risk stratification before cardiac surgery, but whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) may add prognostic information to EuroSCORE II is not known. Methods: Preoperative (n = 640) and postoperative (n = 629) blood samples were available from cardiac surgical patients with 961-day follow-up (FINNAKI Heart study; cohort #1). The accuracy of a parsimonious risk model with NT-proBNP measurements was also tested in 90 patients with respiratory failure after cardiac surgery (FINNALI study; cohort #2). Results: Sixty-one patients (9.5%) died during follow-up in cohort #1. Preoperative NT-proBNP and hs-TnT concentrations correlated (rho = 0.58; p <0.001) and were higher in non-survivors compared to survivors: median 2027 (Q1-3 478-5387) vs. 373 (134-1354) ng/L [NT-proBNP] and 39 (16-191) vs. 13 (8-32) ng/L [hs-TnT]; p <0.001 for both. Preoperative NT-proBNP concentrations were associated with time to death after adjustment for EuroSCORE II (HR [lnNT-proBNP] 1.33 [95% CI 1.08-1.64]), p = 0.008 and reclassified patients on top of EuroSCORE II (net reclassification index 0.39 [95% CI 0.14-0.64], p = 0.003). Pre-and postoperative NT-proBNP concentrations were closely correlated (rho = 0.80, p <0.001) and postoperative NT-proBNP concentrations were also associated with long-term mortality after adjustment for EuroSCORE II. A parsimonious risk model that included age, creatinine clearance, chronic pulmonary disease, and NT-proBNP measurements provided comparable prognostic accuracy as EuroSCORE II in cohort #1 and #2 for risk of long-term mortality. hs-TnT measurements did not add to NT-proBNP measurements Conclusion: NT-proBNP measurements could improve and simplify risk prediction in cardiac surgical patients.Peer reviewe

Physician accuracy for diagnosing heart failure in unselected patients hospitalised with dyspnoea

ABSTRACT Aim: To examine variables associated with heart failure (HF) and determine accuracy of Emergency Department (ED) physicians to diagnose HF in a Norwegian teaching hospital without point-of-care natriuretic peptide testing. Methods and results: We included 150 consecutive patients hospitalised for dyspnoea and collected the results of clinical examination and the probability of HF (0-100%) from the ED physicians. HF was adjudicated according to guidelines by two independent senior physicians. Of 150 patients, 68 patients (45%) were diagnosed with HF as the primary cause of the hospitalisation. HF patients were older (75.1 vs. 68.0 y, p<0.001) and more likely to be male (57% vs. 37%, p=0.01). There was no difference in New York Heart Association functional class or the duration of symptoms prior to hospitalization between HF patients and patients with non-HF dyspnoea. Several clinical variables previously reported to be predictive of HF were associated with HF by crude analysis in our patients, but only history of HF (HR 11.14 [OR 2.73-45.47], p<0.001), history of hypertension (HR 3.22 [OR 1.12-9.22], p=0.03), and atrial fibrillation (HR 3.22 [OR 1.21-10.58], p=0.02) were independently associated with HF in multivariate analysis. The area under the curve for ED physician diagnosis of HF was 0.85 (95% CI 0.79-0.91, p<0.001 vs. chance). Conclusion: The accuracy of the ED physicians for diagnosing HF was sub-optimal in this cohort of mainly elderly subjects hospitalised for dyspnoea. Physician should be aware of the increased likelihood of HF in dyspneic patients with atrial fibrillation, history of hypertension, or history of HF

Biomarkers for Risk Prediction in Cardiac Surgical Patients

Circulating cardiac biomarkers are used clinically to diagnose and risk stratify patients with different types of heart disease. Preoperative risk stratification models in patients subjected to cardiac surgery are well established, and the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II model is widely used, but currently these models do not include circulating cardiac biomarkers. Jon Brynildsen, MD, has investigated the use of circulating cardiac biomarkers to risk stratify patients before or after cardiac surgery. The established cardiac biomarkers troponin T and N-terminal pro-B-type natriuretic peptide and the novel cardiac biomarker secretoneurin were compared with the EuroSCORE II model. The results demonstrate substantial additional prognostic information by established and novel circulating cardiac biomarkers to the established risk models in patients undergoing or being evaluated for cardiac surgery. The results also show that it is possible to simplify risk models without losing prognostic information by combining biomarker measurements with some key clinical risk factors in cardiac surgical patients

Prognostic and diagnostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 study

Background Copeptin is a novel biomarker that predicts mortality in lower respiratory tract infections and heart failure (HF), but the diagnostic value of copeptin in acute dyspnea and the prognostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not clear. Method We determined copeptin and NT-proBNP concentrations at hospital admission in 314 patients with acute dyspnea who were categorized by diagnosis. Survival was registered after a median follow-up of 816 days, and the prognostic and diagnostic properties of copeptin and NT-proBNP were analyzed in acute HF (n = 143) and AECOPD (n = 84) separately. Results The median concentration of copeptin at admission was lower in AECOPD compared to acute HF (8.8 [5.2–19.7] vs. 22.2 [10.2–47.9]) pmol/L, p < 0.001), but NT-proBNP discriminated acute HF from non-HF related dyspnea more accurately than copeptin (ROC-AUC 0.85 [0.81–0.89] vs. 0.71 [0.66–0.77], p < 0.0001). Adjusted for basic risk factors, increased copeptin concentrations predicted mortality in AECOPD (HR per log (ln) unit 1.72 [95% CI 1.21–2.45], p = 0.003) and acute HF (1.61 [1.25–2.09], p < 0.001), whereas NT-proBNP concentrations predicted mortality only in acute HF (1.62 [1.27–2.06], p < 0.001). On top of a basic model copeptin reclassified a significant proportion of patients into a more accurate risk strata in AECOPD (NRI 0.60 [0.19–1.02], p = 0.004) and acute HF (0.39 [0.06–0.71], p = 0.020). Conclusion Copeptin is a strong prognostic marker in both AECOPD and acute HF, while NT-proBNP concentrations predict mortality only in patients with acute HF. NT-proBNP levels are superior to copeptin levels to diagnose acute HF in patients with acute dyspnea

Diagnostic and Prognostic Properties of Osteoprotegerin in Patients with Acute Dyspnoea: Observations from the Akershus Cardiac Examination (ACE) 2 Study

Background: Circulating osteoprotegerin (OPG) levels are increased in patients with chronic heart failure (HF). The diagnostic and prognostic merit of OPG measurement in patients admitted with acute dyspnoea is unknown. Objectives: To evaluate the diagnostic and prognostic value of measuring OPG in patients admitted to hospital with acute dyspnoea. Methods: OPG was analysed by ELISA in 308 patients admitted due to acute dyspnoea. Investigators blinded to OPG results adjudicated the diagnosis for the index hospitalization. Clinical outcomes were obtained from hospital records. Results: In total, 139 patients (45%) were hospitalized with acute HF. OPG levels on hospital admission were higher in patients with acute HF vs. no acute HF, 7.8 (5.5–10.4) vs. 5.4 (3.8–7.2) pmol/L, p<0.001. The area under the receiver operator characteristic curve (ROC AUC) of OPG to discriminate between HF vs. non-HF was 0.695 [95% CI 0.636–0.754]. OPG did not provide incremental information to the ED physician’s prediction or N-terminal pro-B-type natriuretic peptide regarding the diagnosis of acute HF. OPG levels (log transformed) were associated with mortality in crude analysis (HR (95% CI) 1.87 (1.34 to 2.61), p<0.001), butthis association was attenuated and no longer significant after including established cardiac biomarkers into the model. Conclusion: In patients admitted to hospital with acute dyspnoea, OPG levels are higher in patients with acute HF than in those with dyspnoea from other causes. However, OPG does not provide incremental information beyond ED physician assessment for the diagnosis of acute HF or beyond clinical risk variables and established cardiac biomarkers concerning prognosis

Cardiac troponin I measured with a very high sensitivity assay predicts subclinical carotid atherosclerosis: The Akershus Cardiac Examination 1950 Study

Aims Concentrations of cardiac troponin I (cTnI) are associated with incident ischemic stroke and predict the presence and severity of coronary atherosclerosis. Accordingly, we hypothesized that concentrations of cTnI measured with a very high sensitivity (hs-) assay would be associated with subclinical stages of carotid atherosclerosis in the general population. Methods We measured hs-cTnI on the Singulex Clarity System in 1745 women and 1666 men participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants were free from known coronary heart disease and underwent extensive cardiovascular phenotyping at baseline, including carotid ultrasound. We quantified carotid atherosclerosis by the carotid plaque score, carotid intima-media thickness (cIMT) and the presence of hypoechoic plaques. Results Concentrations of hs-cTnI were measurable in 99.8% of study participants and were significantly associated with increased carotid plaque score (odds ratio for quartile 4 of hs-cTnI 1.59, 95% CI 1.22 to 2.07, p for trend < 0.001) and cIMT (odds ratio for quartile 4 of hs-cTnI 1.57, 95% CI 1.02 to 2.42, p for trend = 0.036), but not with the presence of hypoechoic plaques. hs-cTnI concentrations significantly improved reclassification and discrimination models in predicting carotid plaques when added to cardiovascular risk factors, no improvements were evident in predicting cIMT or hypoechoic plaques. Conclusion Concentrations of cTnI measured with a very high sensitivity assay are predictive of carotid atherosclerotic burden, a phenomenon likely attributable to common risk factors of subclinical myocardial injury, coronary and carotid atherosclerosis

Circulating secretoneurin concentrations in patients with moderate to severe aortic stenosis

Background Secretoneurin (SN) concentrations provide important prognostic information in patients with myocardial dysfunction. Whether preoperative SN concentrations improve risk assessment in patients with moderate to severe aortic stenosis (AS) is unknown. Methods We included 57 patients with moderate to severe AS referred for presurgical evaluation. All patients were examined with comprehensive echocardiography, electrocardiogram (ECG), and biochemical measurements and compared to 10 age- and sex-matched healthy subjects. Results Median (quartile 1–3) SN concentrations were 141 (121–163) pmol/L in AS patients and 132 (106–148) pmol/L in control subjects (p = .17). Lower estimated creatinine clearance and use of diuretics, but not standard ECG or echocardiographic indices and cardiac biomarkers, were associated with increasing SN concentrations. Fifteen patients (26%) died during 3.5 years median follow-up. SN concentrations were higher in non-survivors than survivors: 156 (133–209) vs. 140 (116–155) pmol/L, p = .007. Higher SN concentrations were associated with increased risk of mortality also after adjustment for established risk indices, biomarkers, and status regarding valvular surgery: hazard ratio per lnSN 15.13 (95% CI 1.05–219.00); p = .046. Receiver operating characteristics area under the curve for SN to predict mortality was 0.74 (95% CI 0.60–0.88) compared to 0.73 (0.59–0.87) for high-sensitivity cardiac troponin T and 0.67 (0.51–0.82) for N-terminal pro-B-type natriuretic peptide. The previously identified cut-off of SN >204 pmol/L in cardiac surgical patients predicted mortality also in this cohort. Conclusions SN concentrations improve risk assessment in patients with moderate to severe AS by providing additional prognostic information to established risk indices such as echocardiography, ECG, and established cardiac biomarkers

Fibroblast growth factor 23 in patients with acute dyspnea: Data from the Akershus Cardiac Examination (ACE) 2 Study

Background Circulating fibroblast growth factor 23 (FGF23) concentrations have been linked to left ventricular remodeling and unfavorable cardiovascular outcomes, but whether FGF23 is associated with heart failure (HF) diagnosis and outcome in unselected patients with dyspnea is unknown. Accordingly, we assessed the diagnostic and prognostic properties of FGF23 in patients presenting to the emergency department with acute dyspnea. Methods and results FGF23 was measured in 314 patients admitted with acute dyspnea and the diagnostic and prognostic merit was compared to that of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The diagnosis of acute HF was adjudicated by two independent physicians. Circulating FGF23 concentrations on hospital admission were higher in patients with acute HF vs. patients with non-HF related dyspnea: median 3.60 (IQR 1.24–8.77) vs. 1.00 (0.43–2.20) pmol/L; P < 0.001. The receiver-operating statistics area under the curve for acute HF diagnosis was 0.750 (0.699–0.797) for FGF23 and 0.853 (0.809–0.890) for NT-proBNP. Adjusting for clinical risk indices and cardiac biomarkers in multivariate Cox regression analysis, admission FGF23 concentrations were associated with mortality in the total study population (hazard ratio [HR] per 1 SD in lnFGF23 1.74 [1.40–2.16]). FGF23 also reclassified patients into their correct risk strata on top of clinical variables significantly associated with outcomes in the total cohort (net reclassification index 0.386 [0.161–0.612]). In patients with acute HF, both admission FGF23 and NT-proBNP concentrations were associated with mortality. Conclusion Circulating FGF23 concentrations provide incremental prognostic information to established risk indices in patients with acute dyspnea, but do not improve diagnostic accuracy over NT-proBNP measurements. Lyngbakken, Magnus Nakrem, et al. "Fibroblast growth factor 23 in patients with acute dyspnea: Data from the Akershus Cardiac Examination (ACE) 2 Study." Clinical biochemistry (2017). © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license

B-Type Natriuretic Peptide Is Associated with Indices of Left Ventricular Dysfunction in Healtahy Subjects from the General Population: The Akershus Cardiac Examination 1950 Study

Abstract Background Concentrations of B-type natriuretic peptide (BNP) reflect myocardial distension and stress, and are associated with poor prognosis in patients with cardiovascular disease. Accordingly, we hypothesized that concentrations of BNP would be associated with indices of adverse left ventricular (LV) remodeling and early stages of LV systolic and diastolic dysfunction in healthy participants from the general population. Methods We measured BNP in 1757 women and 1677 men free from known coronary heart disease participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants underwent extensive cardiovascular phenotyping at baseline, including detailed echocardiography with assessment of indexed LV mass (LVMI), diastolic [tissue Doppler e’, E/e’ ratio, indexed left atrial volume (LAVI), maximal tricuspid regurgitation velocity (TRVmax), and E/A ratio], and systolic [global longitudinal strain (GLS) and LV ejection fraction (LVEF)] function. Results Study participants with the highest BNP concentrations had higher GLS, LVMI, e’, E/e’ ratio, LAVI, TRVmax, and E/A ratio. In adjusted analyses, both GLS and LVEF exhibited significant nonlinear associations with BNP, with reduced LV systolic function observed in both the low and high concentration range of BNP. Conclusions In healthy participants recruited from the general population, concentrations of BNP exhibit nonlinear associations with LV systolic function, and both low and high concentrations are associated with reduced LV systolic function. This supports the notion that natriuretic peptides are beneficial and elicit cardioprotective effects, and may have important implications for the interpretation of BNP measurements in the general population