Comparison of the performances of cardiac troponins, including sensitive assays, and copeptin in the diagnostic of acute myocardial infarction and long-term prognosis between women and men.

BACKGROUND: Concerns have been raised about possible gender disparities in cardiac investigations and/or outcome. This study sought to examine and compare the diagnostic and prognostic performance of selected cardiac biomarkers in women versus men. METHODS: In a prospective, multicenter cohort of patients with acute chest pain cardiac troponin T (cTnT) (fourth-generation Roche assay), high-sensitivity cTnT (hs-cTnT), and copeptin were measured at presentation. RESULTS: Of 1,247 patients, 420 were women and 827 were men. Although the rate of acute myocardial infarction was similar in women (14.5%) and men (16.6%, P = .351), women more frequently had cardiac but noncoronary causes of chest pain (17.4% vs 10.8%, P = .001) and less frequently had unstable angina (8.8% vs 16.6%, P = .002) than men. Diagnostic accuracy as quantified by the area under the receiver operating characteristic curve (AUC) for acute myocardial infarction in women was 0.90 (95% CI 0.84-0.95) for cTnT, which was lower than the AUC for hs-cTnT alone (0.94, 95% CI [0.91-0.98]), the combination of cTnT with copeptin (0.96, 95% CI [0.94-0.98]) or the combination of hs-cTnT with copeptin (0.96, 95% CI [0.93-0.98]) (P = .008, P = .006, and P = .002, respectively). Prognostic accuracy as quantified by the AUCs for 1-year mortality was 0.69 (0.56-0.83), 0.86 (0.79-0.93), 0.87 (0.81-0.94), and 0.87 (0.80-0.94), respectively. No relevant gender differences in AUCs were observed. CONCLUSION: The diagnostic and prognostic performance of cTnT, hs-cTnT, and copeptin is as good in women as in men. High-sensitivity cTnT and the combination of cTnT and copeptin outperform cTnT alone, both in women and men.

Uric acid for diagnosis and risk stratification in suspected myocardial infarction.

BACKGROUND: Hypoxia precedes cardiomyocyte necrosis in acute myocardial infarction (AMI). We therefore hypothesized that uric acid - as a marker of oxidative stress and hypoxia - might be useful in the early diagnosis and risk stratification of patients with suspected AMI. MATERIALS AND METHODS: In this prospective observational study, uric acid was measured at presentation in 892 consecutive patients presenting to the emergency department with suspected AMI. The final diagnosis was adjudicated by two independent cardiologists. Patients were followed 24 months regarding mortality. Primary outcome was the diagnosis of AMI, secondary outcome was short- and long-term mortality. RESULTS: Uric acid at presentation was higher in patients with AMI than in patients without (372 µM vs. 336 µM; P < 0·001). The diagnostic accuracy of uric acid for AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0·60 (95%Cl 0·56-0·65). When added to cardiac troponin T (cTnT), uric acid significantly increased the AUC of cTnT from 0·89 (95%Cl 0·85-0·93) to 0·92 (95%Cl 0·89-0·95, P = 0·020 for comparison). Cumulative 24-month mortality rates were 2·2% in the first, 5·4% in the second and the third and 15·6% in the fourth quartile of uric acid (P < 0·001 for log-rank). Uric acid predicted 24-month mortality independently. Adding uric acid to TIMI and GRACE risk score improved their prognostic accuracy as shown by an integrated discrimination improvement of 0·04 (P = 0·007) respective 0·02 (P = 0·021). CONCLUSIONS: Uric acid, an inexpensive widely available biomarker, improves both the early diagnosis and risk stratification of patients with suspected AMI.

Additive value of blood neutrophil gelatinase-associated lipocalin to clinical judgement in acute kidney injury diagnosis and mortality prediction in patients hospitalized from the emergency department.

INTRODUCTION: Acute kidney injury (AKI) is a common complication among hospitalized patients. The aim of this study was to evaluate the utility of blood neutrophil gelatinase-associated lipocalin (NGAL) assessment as an aid in the early risk evaluation for AKI development in admitted patients. METHODS: This is a multicenter Italian prospective emergency department (ED) cohort study in which we enrolled 665 patients admitted to hospital from the ED. RESULTS: Blood NGAL and serum creatinine (sCr) were determined at ED presentation (T0), and at: 6 (T6), 12 (T12), 24 (T24) and 72 (T72) hours after hospitalization. A preliminary assessment of AKI by the treating ED physician occurred in 218 out of 665 patients (33%), while RIFLE AKI by expert nephrologists was confirmed in 49 out of 665 patients (7%). The ED physician's initial judgement lacked sensitivity and specificity, overpredicting the diagnosis of AKI in 27% of the cohort, while missing 20% of those with AKI as a final diagnosis. CONCLUSIONS: Our study demonstrated that assessment of a patient's initial blood NGAL when admitted to hospital from the ED improved the initial clinical diagnosis of AKI and predicted in-hospital mortality. Blood NGAL assessment coupled with the ED physician's clinical judgment may prove useful in deciding the appropriate strategies for patients at risk for the development of AKI.See related commentary by Legrand et al., http://ccforum.com/content/17/2/132.

In-hospital percentage BNP reduction is highly predictive for adverse events in patients admitted for acute heart failure: the Italian RED Study.

INTRODUCTION: Our aim was to evaluate the role of B-type natriuretic peptide (BNP) percentage variations at 24 hours and at discharge compared to its value at admission in order to demonstrate its predictive value for outcomes in patients with acute decompensated heart failure (ADHF). METHODS: This was a multicenter Italian (8 centers) observational study (Italian Research Emergency Department: RED). 287 patients with ADHF were studied through physical exams, lab tests, chest X Ray, electrocardiograms (ECGs) and BNP measurements, performed at admission, at 24 hours, and at discharge. Follow up was performed 180 days after hospital discharge. Logistic regression analysis was used to estimate odds ratios (OR) for the various subgroups created. For all comparisons, a P value < 0.05 was considered statistically significant. RESULTS: BNP median (interquartile range (IQR)) value at admission was 822 (412 - 1390) pg\mL; at 24 hours was 593 (270 - 1953) and at discharge was 325 (160 - 725). A BNP reduction of >46% at discharge had an area under curve (AUC) of 0.70 (P < 0.001) for predicting future adverse events. There were 78 events through follow up and in 58 of these patients the BNP level at discharge was >300 pg/mL. A BNP reduction of 25.9% after 24 hours had an AUC at ROC curve of 0.64 for predicting adverse events (P < 0.001). The odds ratio of the patients whose BNP level at discharge was <300 pg/mL and whose percentage decrease at discharge was <46% compared to the group whose BNP level at discharge was <300 pg/mL and whose percentage decrease at discharge was >46% was 4.775 (95% confidence interval (CI) 1.76 - 12.83, P < 0.002). The odds ratio of the patients whose BNP level at discharge was >300 pg/mL and whose percentage decrease at discharge was <46% compared to the group whose BNP level at discharge was <300 pg/mL and whose percentage decrease at discharge was >46% was 9.614 (CI 4.51 - 20.47, P < 0.001). CONCLUSIONS: A reduction of BNP >46% at hospital discharge compared to the admission levels coupled with a BNP absolute value < 300 pg/mL seems to be a very powerful negative prognostic value for future cardiovascular outcomes in patients hospitalized with ADHF.

An Italian registry of chest pain patients in the emergency department: clinical predictors of acute coronary syndrome.

BACKGROUND: The aim of this study was to describe the population of patients arriving in several Italian Emergency Departments (EDs) complaining of chest pain suggestive of acute coronary syndrome (ACS) in order to evaluate the incidence of ACS in this cohort and the association between ACS and different clinical parameters and risk factors. METHODS: This is an observational prospective study, conducted from the 1st January to the 31st December 2014 in 11 EDs in Italy. Patients presenting to ED with chest pain, suggestive of ACS, were consecutively enrolled. RESULTS: Patients with a diagnosis of ACS (N.=1800) resulted to be statistically significant older than those without ACS (NO ACS; N.=4630) (median age: 70 vs. 59, P<0.001), and with a higher prevalence of males (66.1% in ACS vs. 57.5% in NO ACS, P<0.001). ECG evaluation, obtained at ED admission, showed new onset alterations in 6.2% of NO ACS and 67.4% of ACS patients. Multiple logistic regression analysis showed that the following parameters were predictive for ACS: age, gender, to be on therapy for cardio-vascular disease (CVD), current smoke, hypertension, hypercholesterolemia, heart rate, ECG alterations, increased BMI, reduced SaO2. CONCLUSIONS: Results from this observational study strengthen the importance of the role of the EDs in ruling in and out chest pain patients for the diagnosis of ACS. The analysis put in light important clinical and risk factors that, if promptly recognized, can help Emergency Physicians to identify patients who are more likely to be suffering from ACS.

Gender-specific uncertainties in the diagnosis of acute coronary syndrome.

BACKGROUND: It is unknown whether higher rates of delayed diagnosis and misdiagnosis of acute coronary syndrome (ACS) in women might have contributed to the poorer outcome of women. METHODS: In a prospective diagnostic multicenter study, we recruited patients presenting to the emergency department (ED) with any kind of chest discomfort/chest pain with onset or peak within the last 12 h. We quantified early diagnostic uncertainty for the presence of ACS among treating physicians at the ED after 90 min, possibly responsible for delayed diagnosis, using a visual analogue scale. Late diagnostic uncertainty, possibly responsible for misdiagnosis, was defined as disagreement among two independent cardiologists' adjudication of the final diagnosis after complete work-up. RESULTS: Among 2795 patients (897 women and 1898 men), ACS was the adjudicated final diagnosis in 24 % of women and 35 % of men. Early diagnostic accuracy of clinical judgment of the ED physician for ACS as quantified by the area under the receiver-operating characteristics curve was 0.89 (95 % CI 0.87-0.92) in women and 0.86 (95 % CI 0.85-0.88) in men (p = 0.046). Late diagnostic uncertainty regarding the diagnosis of ACS was 5 % in women and 7 % in men (p = 0.069). CONCLUSION: Diagnostic uncertainty for the presence of ACS in women is not more common as compared to men and does, therefore, not explain the poorer outcome observed in women with ACS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00470587.

Cardiomyocyte injury induced by hemodynamic cardiac stress: Differential release of cardiac biomarkers.

OBJECTIVE: We explored whether hemodynamic cardiac stress leads to a differential release of cardiomyocyte injury biomarkers, used in the diagnosis of acute myocardial infarction (AMI). METHODS: In an observational international multicenter study, we enrolled 831 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists. Hemodynamic cardiac stress was quantified by levels of B-type natriuretic peptide (BNP). Spearman's rho correlation was used to analyze the correlations between BNP and high-sensitivity cardiac troponin T (hs-cTnT), Siemens cTnI-Ultra (cTnI-ultra), CK-MB and Myoglobin. Patients were categorized according to the extent of hemodynamic cardiac stress as quantified by BNP tertiles. RESULTS: Among all patients, the positive pair-wise correlation with BNP was strongest with hs-cTnT and cTnI-ultra (r=0.58 and 0.50, respectively), moderate for Myoglobin (r=0.43), and weakest with CK-MB (r=0.25; p<0.001 for each). Similar pattern of correlations was also observed among AMI patients. Among patients diagnosed with non-cardiac cause of chest pain (n=385, 46%) and cardiac but non-coronary (n=109, 13%), BNP had significant positive correlations with hs-cTnT, cTnI-ultra and Myoglobin (p<0.05), but not with CK-MB (p=NS). A similar pattern of stronger correlation between BNP and hs-cTnT, cTnI-ultra and Myoglobin as compared to that with CK-MB was also observed within the higher BNP tertile range. There was no correlation between BNP and other biomarkers within the 1st BNP tertile group. CONCLUSION: Hemodynamic cardiac stress, as quantified by BNP, as a likely cause of cardiomyocyte injury, is more closely reflected by concentrations of hs-cTnT, cTnI-ultra and Myoglobin than CK-MB.

Accelerated diagnostic protocol using high-sensitivity cardiac troponin T in acute chest pain patients.

BACKGROUND: We aimed to evaluate the efficacy and safety of using high-sensitivity cardiac troponin T (hs-cTnT) within an accelerated diagnostic protocol (ADP) in patients presenting with symptoms suggestive of acute myocardial infarction (AMI) for rapid rule-out of AMI. METHODS: In two independent large multicenter studies, levels of hs-cTnT at presentation and at 2 h were combined with the Thrombolysis In Myocardial Infarction (TIMI) risk score and ECG findings. The ADP defined patients with normal levels of hs-cTnT at presentation and 2 h, a TIMI score ≤1, and normal ECG findings as candidates for rapid rule-out of AMI and rapid discharge. Major adverse cardiac events (MACEs) occurring within 30-days were centrally adjudicated by two independent cardiologists. RESULTS: In the derivation cohort, among 1085 consecutive patients 198 patients (18.2%) had a MACE. The ADP classified 374 patients (34.5%) as low-risk. None of these patients had a MACE at 30 days, resulting in a negative predictive value (NPV) of 100% (95% CI, 99.0-100%) and a sensitivity of 100% (95% CI, 98.2%-100%). In the validation cohort, among 1590 consecutive patients 231 patients (14.5%) had a MACE. The ADP classified 641 patients (40.3%) as low-risk. 6 of these patients had a MACE at 30 days, resulting in a NPV of 99.1% (95% CI, 98.0-99.6%) and a sensitivity of 97.4% (95% CI, 94.5-98.8%). CONCLUSIONS: The ADP including hs-cTnT allows early identification 35 to 40% of patients to be at extremely low risk of MACE and therefore ideal candidates for outpatient management.