Markus Noveanu

Early Diagnosis of Myocardial Infarction with Sensitive Cardiac Troponin Assays

BACKGROUNDnThe rapid and reliable diagnosis of acute myocardial infarction is a major unmet clinical need.nnnMETHODSnWe conducted a multicenter study to examine the diagnostic accuracy of new, sensitive cardiac troponin assays performed on blood samples obtained in the emergency department from 718 consecutive patients who presented with symptoms suggestive of acute myocardial infarction. Cardiac troponin levels were determined in a blinded fashion with the use of four sensitive assays (Abbott-Architect Troponin I, Roche High-Sensitive Troponin T, Roche Troponin I, and Siemens Troponin I Ultra) and a standard assay (Roche Troponin T). The final diagnosis was adjudicated by two independent cardiologists.nnnRESULTSnAcute myocardial infarction was the adjudicated final diagnosis in 123 patients (17%). The diagnostic accuracy of measurements obtained at presentation, as quantified by the area under the receiver-operating-characteristic curve (AUC), was significantly higher with the four sensitive cardiac troponin assays than with the standard assay (AUC for Abbott-Architect Troponin I, 0.96; 95% confidence interval [CI], 0.94 to 0.98; for Roche High-Sensitive Troponin T, 0.96; 95% CI, 0.94 to 0.98; for Roche Troponin I, 0.95; 95% CI, 0.92 to 0.97; and for Siemens Troponin I Ultra, 0.96; 95% CI, 0.94 to 0.98; vs. AUC for the standard assay, 0.90; 95% CI, 0.86 to 0.94). Among patients who presented within 3 hours after the onset of chest pain, the AUCs were 0.93 (95% CI, 0.88 to 0.99), 0.92 (95% CI, 0.87 to 0.97), 0.92 (95% CI, 0.86 to 0.99), and 0.94 (95% CI, 0.90 to 0.98) for the sensitive assays, respectively, and 0.76 (95% CI, 0.64 to 0.88) for the standard assay. We did not assess the effect of the sensitive troponin assays on clinical management.nnnCONCLUSIONSnThe diagnostic performance of sensitive cardiac troponin assays is excellent, and these assays can substantially improve the early diagnosis of acute myocardial infarction, particularly in patients with a recent onset of chest pain. (ClinicalTrials.gov number, NCT00470587.)

Use of Myeloperoxidase for Risk Stratification in Acute Heart Failure

BACKGROUNDnMyeloperoxidase (MPO) is a biomarker of inflammation and oxidative stress produced by neutrophils, monocytes, and endothelial cells. Concentrations of MPO predict mortality in patients with chronic heart failure. This study sought to investigate the diagnostic accuracy and prognostic value of MPO in patients with acute heart failure (AHF).nnnMETHODSnWe prospectively enrolled 667 patients presenting to the emergency department with dyspnea and observed them for 1 year. MPO and B-type natriuretic peptide (BNP) were measured at presentation. Two independent cardiologists adjudicated final discharge diagnoses.nnnRESULTSnMPO concentrations were similar in patients with AHF (n = 377, median 139 pmol/L) and patients with noncardiac causes of dyspnea (n = 290, median 150 pmol/L, P = 0.26). The diagnostic accuracy of MPO for AHF was limited [area under the ROC curve (AUC) 0.53] and inferior to that of BNP (AUC 0.95, P < 0.001). In patients with AHF, MPO concentrations above the lowest tertile (MPO >99 pmol/L) were associated with significantly increased 1-year mortality (hazard ratio 1.58, P = 0.02). The combination of MPO (< or = 99 vs >99 pmol/L) and BNP (median of < or = 847 vs >847 ng/L) improved the prediction of 1-year mortality (hazard ratio 2.80 for both variables increased vs both low, P < 0.001). After adjustment for cardiovascular risk factors in multivariable Cox proportional hazard analysis, increases in MPO contributed significantly toward the prediction of 1-year mortality (hazard ratio 1.51, P = 0.045).nnnCONCLUSIONSnMPO is an independent predictor of 1-year mortality in AHF, is additive to BNP, and could be helpful in identifying patients with a favorable prognosis despite increased BNP concentrations.

Central venous pressure and impaired renal function in patients with acute heart failure

To determine the relationship between central venous pressure (CVP) and renal function in patients with acute heart failure (AHF) presenting to the emergency department.

Midregional pro-Adrenomedullin in addition to b-type natriuretic peptides in the risk stratification of patients with acute dyspnea: an observational study

IntroductionThe identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of the newly described midregional fragment of the pro-Adrenomedullin molecule (MR-proADM) alone and combined to B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in patients with acute dyspnea.MethodsWe conducted a prospective, observational cohort study in the emergency department of a University Hospital and enrolled 287 unselected, consecutive patients (48% women, median age 77 (range 68 to 83) years) with acute dyspnea.ResultsMR-proADM levels were elevated in non-survivors (n = 77) compared to survivors (median 1.9 (1.2 to 3.2) nmol/L vs. 1.1 (0.8 to 1.6) nmol/L; P < 0.001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.81 (95% CI 0.73 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for MR-proADM, NT-proBNP and BNP, respectively (MRproADM vs. NTproBNP P = 0.38; MRproADM vs. BNP P = 0.009). For one-year mortality the AUC were 0.75 (95% CI 0.69 to 0.81), 0.75 (95% CI 0.68 to 0.81), 0.69 (95% CI 0.62 to 0.76) for MR-proADM, NT-proBNP and BNP, respectively without any significant difference. Using multivariate linear regression analysis, MR-proADM strongly predicted one-year all-cause mortality independently of NT-proBNP and BNP levels (OR = 10.46 (1.36 to 80.50), P = 0.02 and OR = 24.86 (3.87 to 159.80) P = 0.001, respectively). Using quartile approaches, Kaplan-Meier curve analyses demonstrated a stepwise increase in one-year all-cause mortality with increasing plasma levels (P < 0.0001). Combined levels of MR-proADM and NT-proBNP did risk stratify acute dyspneic patients into a low (90% one-year survival rate), intermediate (72 to 82% one-year survival rate) or high risk group (52% one-year survival rate).ConclusionsMR-proADM alone or combined to NT-proBNP has a potential to assist clinicians in risk stratifying patients presenting with acute dyspnea regardless of the underlying disease.

Comparison of midregional pro-atrial natriuretic peptide with N-terminal pro-B-type natriuretic peptide in the diagnosis of heart failure

Objectives.u2002 The concentration of atrial natriuretic peptide (ANP) in the circulation is approximately 10‐ to 50‐ fold higher than B‐type natriuretic peptide (BNP). We sought to compare the accuracy of midregional pro‐atrial natriuretic peptide (MRproANP) measured with a novel sandwich immunoassay with N‐terminal pro‐B‐type natriuretic peptide (NTproBNP) in the diagnosis of heart failure.

Copeptin and risk stratification in patients with acute dyspnea.

IntroductionThe identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of Copeptin, the C-terminal part of the vasopressin prohormone alone and combined to N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea.MethodsWe conducted a prospective, observational cohort study in the emergency department of a university hospital and enrolled 287 patients with acute dyspnea.ResultsCopeptin levels were elevated in non-survivors (n = 29) compared to survivors at 30 days (108 pmol/l, interquartile range (IQR) 37 to 197 pmol/l) vs. 18 pmol/l, IQR 7 to 43 pmol/l; P < 0.0001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.83 (95% confidence interval (CI) 0.76 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for Copeptin, NT-proBNP and BNP, respectively (Copeptin vs. NTproBNP P = 0.21; Copeptin vs. BNP P = 0.002). When adjusted for common cardiovascular risk factors and NT-proBNP, Copeptin was the strongest independent predictor for short-term mortality in all patients (HR 3.88 (1.94 to 7.77); P < 0.001) and especially in patients with acute decompensated heart failure (ADHF) (HR 5.99 (2.55 to 14.07); P < 0.0001). With the inclusion of Copeptin to the adjusted model including NTproBNP, the net reclassification improvement (NRI) was 0.37 (P < 0.001). An additional 30% of those who experienced events were reclassified as high risk, and an additional 26% without events were reclassified as low risk.ConclusionsCopeptin is a new promising prognostic marker for short-term mortality independently and additive to natriuretic peptide levels in patients with acute dyspnea.

Interleukin family member ST2 and mortality in acute dyspnoea

Abstract.u2002 Socrates T, deFilippi C, Reichlin T, Twerenbold R, Breidhardt T, Noveanu M, Potocki M, Reiter M, Arenja N, Heinisch C, Meissner J, Jaeger C, Christenson R, Mueller C. (Department of Internal Medicine, University Hospital Basel, Basel, Switzerland; University of Maryland, School of Medicine, Baltimore, MD, USA). Interleukin family member ST2 and mortality in acute dyspnoea. J Intern Med 2010; 268: 493–500.

Impact of a high-dose nitrate strategy on cardiac stress in acute heart failure : a pilot study

Abstract.u2002 Breidthardt T, Noveanu M, Potocki M, Reichlin T, Egli P, Hartwiger S, Socrates T, Gayat E, Christ M, Mebazaa A, Mueller C (University Hospital, Basel, Switzerland, University Paris, Paris, France, and Klinikum Nürnberg, Nürnberg, Germany). Impact of a high‐dose nitrate strategy on cardiac stress in acute heart failure: a pilot study. J Intern Med 2010; 267: 322–330.

Value of arterial blood gas analysis in patients with acute dyspnea: an observational study

IntroductionThe diagnostic and prognostic value of arterial blood gas analysis (ABGA) parameters in unselected patients presenting with acute dyspnea to the Emergency Department (ED) is largely unknown.MethodsWe performed a post-hoc analysis of two different prospective studies to investigate the diagnostic and prognostic value of ABGA parameters in patients presenting to the ED with acute dyspnea.ResultsWe enrolled 530 patients (median age 74 years). ABGA parameters were neither useful to distinguish between patients with pulmonary disorders and other causes of dyspnea nor to identify specific disorders responsible for dyspnea. Only in patients with hyperventilation from anxiety disorder, the diagnostic accuracy of pH and hypoxemia rendered valuable with an area under the receiver operating characteristics curve (AUC) of 0.86. Patients in the lowest pH tertile more often required admission to intensive care unit (28% vs 12% in the first tertile, P < 0.001) and had higher in-hospital (14% vs 5%, P = 0.003) and 30-day mortality (17% vs 7%, P = 0.002). Cumulative mortality rate was higher in the first (37%), than in the second (28%), and the third tertile (23%, P = 0.005) during 12 months follow-up. pH at presentation was an independent predictor of 12-month mortality in multivariable Cox proportional hazard analysis both for patients with pulmonary (P = 0.043) and non-pulmonary disorders (P = 0.038).ConclusionsABGA parameters provide limited diagnostic value in patients with acute dyspnea, but pH is an independent predictor of 12 months mortality.

Accuracy of chest radiographs in the emergency diagnosis of heart failure

The purpose of this study was to determine the diagnostic accuracy of chest radiographic findings of heart failure (HF) in current patients presenting with dyspnea in the emergency department. In a secondary analysis of the BASEL study, initial chest radiographs of 277 patients with acute dyspnea were evaluated by two radiologists blinded to the adjudicated diagnosis (56% had the final diagnosis of HF). Predefined radiographic criteria of HF were used. Statistical analysis included receiver-operating characteristic (ROC) analysis and calculation of a logistic regression model including B-type natriuretic peptide (BNP) levels. The reader’s overall impression showed the highest area under the ROC curve for the diagnosis of HF in both supine and erect patient positions (0.855 and 0.857). Among individual radiographic findings, peribronchial cuffing in the supine position (0.829) showed the highest accuracies. The lowest accuracy was found for the vascular pedicle width in the supine position (0.461). Logistic regression analysis showed no significant differences between the reader’s overall impression, the radiographic model, and BNP testing. In our study, the combination of radiographic features provided valuable information and was of comparable accuracy as BNP-testing for the diagnosis of HF.