Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction

Aims Angiogenic factors play an important role in the development of atherosclerosis and show pronounced changes during acute myocardial infarction (AMI). We analysed the impact of placental growth factor (PlGF) and its endogen opponent, soluble fms-like tyrosine kinase-1 (sFlt-1), on clinical outcome and the early diagnosis of AMI. Methods and results This multicentre study enrolled patients presenting with symptoms suggestive of AMI. The final diagnosis was adjudicated by two independent physicians. Levels of sFlt-1 and PlGF were compared with results of a standard troponin T and a novel high-sensitive troponin (hsTnT) assay. Of the 763 patients enrolled, 132 were diagnosed with AMI. Multivariable Cox regression analysis demonstrated sFlt-1 >84 ng/L [hazard ratios (HR) 2.6, 95% confidence intervals (CI) 1.2-5.4, P=0.01] and PlGF >20 ng/L (HR 3.6, 95% CI 1.3-10.4, P=0.02) as predictors for mortality during 1-year follow-up, independent from information provided by troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). However, only sFlt-1 persisted as independent predictor for mortality when analysed together with hsTnT and NT-proBNP, and after adjusting for significant clinical parameters. For the diagnosis of AMI, the combination of troponin T and sFlt-1 improved the performance of troponin T alone and led to a negative predictive value of 98.3% already at time of presentation. However, sFlt-1 and PlGF added only limited diagnostic information when used together with hsTnT. Conclusion Only sFlt-1 but not PlGF provides overall independent prognostic information in patients presenting with symptoms suggestive of AMI. After the introduction of hsTnT in clinical routine, sFlt-1 and PlGF can only add limited diagnostic information for the detection or exclusion of AMI. Clinical Trial Registration Information: ClinicalTrials.gov, NCT0047058

Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction

Angiogenic factors play an important role in the development of atherosclerosis and show pronounced changes during acute myocardial infarction (AMI). We analysed the impact of placental growth factor (PlGF) and its endogen opponent, soluble fms-like tyrosine kinase-1 (sFlt-1), on clinical outcome and the early diagnosis of AMI.; This multicentre study enrolled patients presenting with symptoms suggestive of AMI. The final diagnosis was adjudicated by two independent physicians. Levels of sFlt-1 and PlGF were compared with results of a standard troponin T and a novel high-sensitive troponin (hsTnT) assay. Of the 763 patients enrolled, 132 were diagnosed with AMI. Multivariable Cox regression analysis demonstrated sFlt-1 <84 ng/L [hazard ratios (HR) 2.6, 95% confidence intervals (CI) 1.2-5.4, P=0.01] and PlGF <20 ng/L (HR 3.6, 95% CI 1.3-10.4, P=0.02) as predictors for mortality during 1-year follow-up, independent from information provided by troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). However, only sFlt-1 persisted as independent predictor for mortality when analysed together with hsTnT and NT-proBNP, and after adjusting for significant clinical parameters. For the diagnosis of AMI, the combination of troponin T and sFlt-1 improved the performance of troponin T alone and led to a negative predictive value of 98.3% already at time of presentation. However, sFlt-1 and PlGF added only limited diagnostic information when used together with hsTnT.; Only sFlt-1 but not PlGF provides overall independent prognostic information in patients presenting with symptoms suggestive of AMI. After the introduction of hsTnT in clinical routine, sFlt-1 and PlGF can only add limited diagnostic information for the detection or exclusion of AMI. Clinical Trial Registration Information: ClinicalTrials.gov, NCT00470587

Multimarker strategy for risk prediction in patients presenting with acute dyspnea to the emergency department

BACKGROUND: Multimarker approaches improve risk prediction in patients presenting with acute coronary syndrome. We hypothesized that simultaneous assessment of B-type natriuretic peptide (BNP), cardiac troponin I (cTNI) and C-reactive protein (CRP) enables clinicians to better predict risk among patients with acute dyspnea presenting to the emergency department. METHODS AND RESULTS: In this post-hoc analysis of the B-Type natriuretic peptide for Acute Shortness of Breath Evaluation (BASEL) study, above biomarkers were available in 305 patients. Death occurred in 123 (40%) patients within 24 months of follow-up. Using prospectively defined cut-off points (BNP0.001 for trend). Elevated biomarkers significantly predicted increased risk of death at 24 months of follow-up in univariate Cox models (BNP: RR 4.78, 95%CI: 2.51-9.14; p>0.001; cTNI: RR: 2.29, 95%CI: 1.61-3.26, p>0.001; CRP: RR 1.98, 95%CI: 1.28-3.08; p=0.002). Multivariable Cox regression analysis revealed that elevated levels of BNP (p>0.001) and TNI levels (p>0.002) indicated increased risk of death during long-term follow-up, while only a statistical trend was seen for elevated CRP (p=0.09). Comparably, risk of death or rehospitalization significantly increased with the number of elevated biomarkers. CONCLUSIONS: Our findings suggest that a simple multimarker approach with simultaneous assessment of BNP, and cTNI demonstrates potential to assist clinicians in predicting risk of death and/or rehospitalization in patients presenting with acute dyspnea in the emergency department

New definition of myocardial infarction : impact on long-term mortality

BACKGROUND: The use of cardiac troponin allows the identification of additional patients developing myocardial necrosis during an acute coronary syndrome. Novel guidelines of European and American cardiac societies recommend labeling these events as myocardial infarction. Our study evaluated the long-term mortality in the group of patients with non-ST segment elevation myocardial infarction not meeting the older World Health Organization (WHO) criteria (creatine phosphokinase) but additionally identified by the novel definition of myocardial infarction. METHODS: This cohort study included 1024 consecutive patients with non-ST segment elevation acute coronary syndrome classified into "unstable angina," myocardial infarction according to the WHO definition ("WHO criteria"), and myocardial infarction additionally identified by the novel definition ("additional criteria"). All patients were treated with an early invasive strategy. The primary end point was all-cause mortality during follow-up of up to 36 months. RESULTS: During long-term follow-up (median 16 months, interquartile range 6-29 months), 67 deaths occurred. Kaplan-Meier analysis showed cumulative 3-year mortality rates of 5.6% in patients with "unstable angina," 9.1% in patients identified by "WHO criteria," and 17.5% in patients identified by "additional criteria" (P >.001). Cox regression analysis confirmed the "additional criteria" as a significant predictor of mortality (hazard ratio 3.1; 95% confidence interval, 1.9-5.0; P >.001). CONCLUSIONS: The new definition of myocardial infarction based on cardiac troponin testing identifies a high-risk group of additional patients with acute coronary syndrome that is, therefore, appropriately classified as myocardial infarction. In fact, long-term mortality in "additional criteria" patients is higher than in "WHO criteria" patients

Incremental value of high-sensitivity cardiac troponin T for risk prediction in patients with suspected acute myocardial infarction

High-sensitivity cardiac troponin assays have better analytical precision and sensitivity than earlier-generation assays when measuring cardiac troponin at low concentrations. We evaluated whether use of a high-sensitivity assay could further improve risk stratification compared with a standard cardiac troponin assay

The use of B-type natriuretic peptide in the management of patients with atrial fibrillation and dyspnea

The utility of B-type natriuretic peptide (BNP) testing in patients with atrial fibrillation (AF) is poorly defined. We analyzed patients (n=452) included in the BNP for Acute Shortness of Breath Evaluation (BASEL) study. Patients were randomly assigned to a diagnostic strategy with or without the use of BNP. Ninety-nine patients presented with AF (n=48 BNP group; n=51 control group). Although comparable with respect to gender and cardiopulmonary comorbidity, patients with AF were older and more often had heart failure as the cause of dyspnea. In addition, patients with AF had higher in-hospital mortality (13% versus 6%, P=0.012). The use of BNP significantly reduced time to discharge (BNP group median 8 days [1-16] versus 12 days [IQR 4-21] control group; P=0.046) in patients with AF. Initial total treatment costs (median) were $4239 [769-7422] in the BNP group and$5940 [4024-10848] in the control group (P=0.041). These benefits were maintained after 90 days: patients in the BNP group had spent fewer days in hospital (10 days [2-21] versus 15 days [IQR 9-27]; P=0.022) and induced lower total treatment costs ($4790 [1260-9387] versus$7179 [4311-13173]; P=0.016). In conclusion, the use of BNP seems to improve the management of patients with AF presenting with dyspnea

Incremental value of copeptin for rapid rule out of acute myocardial infarction

The purpose of this study was to examine the incremental value of copeptin for rapid rule out of acute myocardial infarction (AMI).; The rapid and reliable exclusion of AMI is a major unmet clinical need. Copeptin, the C-terminal part of the vasopressin prohormone, as a marker of acute endogenous stress may be useful in this setting.; In 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, we measured levels of copeptin at presentation, using a novel sandwich immunoluminometric assay in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists using all available data.; The adjudicated final diagnosis was AMI in 81 patients (17%). Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses (median 20.8 pmol/l vs. 6.0 pmol/l, p > 0.001). The combination of troponin T and copeptin at initial presentation resulted in an area under the receiver-operating characteristic curve of 0.97 (95% confidence interval: 0.95 to 0.98), which was significantly higher than the 0.86 (95% confidence interval: 0.80 to 0.92) for troponin T alone (p > 0.001). A copeptin level >14 pmol/l in combination with a troponin T > or =0.01 microg/l correctly ruled out AMI with a sensitivity of 98.8% and a negative predictive value of 99.7%.; The additional use of copeptin seems to allow a rapid and reliable rule out of AMI already at presentation and may thereby obviate the need for prolonged monitoring and serial blood sampling in the majority of patients. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587)