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Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) Study

Applicant Mueller Christian
Number 135434
Funding scheme Project funding (Div. I-III)
Research institution Abteilung für Allgemeine Innere Medizin Medizinische Universitätsklinik A Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Internal Medicine
Start/End 01.04.2011 - 31.03.2014
Approved amount 376'926.00
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All Disciplines (2)

Discipline
Internal Medicine
Clinical Cardiovascular Research

Keywords (5)

chest pain; acute dyspnea; diagnosis; myocardial infarction; troponin

Lay Summary (English)

Lead
Lay summary

Acute myocardial Infarction (AMI) is the leading cause of death and morbidity in Europe and the US. Its rapid and accurate diagnosis is an unmet clinical need. Delayed “rule in” increases morbidity and mortality. Delayed “rule out” prolongs the time spent in the emergency department (ED), increasing patients’ anxiety and causes enormous costs for the health care system D

Our international multicenter study aims to contribute to an improvement in the early diagnosis of AMI. We investigate three the three key variables that build the pillars of the clinical diagnosis: detailed patient history including chest pain characteristics, biomarkers including cardiac troponin (cTn) assays, and the 12-lead ECG.

In the first phase of the study some very exciting results emerged, particularly those related to the clinical use of new blood tests that increase the early diagnostic accuracy for AMI. Many questions remain regarding the best possible clinical use of these new tools. These questiosn will be addressed in the current phase of the study.

Secondly, we will in more detail explore the clinical utility of established as well as new signals in the 12-lead ECG

Thirdly, we will explore the clinical challenges in important subgroups, e.g. the elderly.

Overall, our study will provide findings that will have an immediate clinical impact on the early diagnosis of AMI in Switzerland and worldwide.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Diagnostic accuracy of combined cardiac troponin and copeptin assessment for early rule-out of myocardial infarction: a systematic review and meta-analysis.
Raskovalova T (2014), Diagnostic accuracy of combined cardiac troponin and copeptin assessment for early rule-out of myocardial infarction: a systematic review and meta-analysis., in Eur Heart J Acute Cardiovasc Care. 2014 Mar 1;3(1):18-27., 18-27.
Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays
Haaf Philip (2014), Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays, in Eur Heart J. 2014 Feb;35(6):365-75., 365-375.
SEX-SPECIFIC CHEST PAIN CHARACTERISTICS IN THE EARLY DIAGNOSISOF ACUTE MYOCARDIAL INFARCTION
Rubini Gimenez MAria (2014), SEX-SPECIFIC CHEST PAIN CHARACTERISTICS IN THE EARLY DIAGNOSISOF ACUTE MYOCARDIAL INFARCTION, in JAMA Internal Medicine 2014 Feb 1;174(2):241-9., 241-249.
Utility of c-terminal pro-endothelin in the early diagnosis and risk-stratification of patients with suspected acute myocardial infarction
Haaf Philip (2014), Utility of c-terminal pro-endothelin in the early diagnosis and risk-stratification of patients with suspected acute myocardial infarction, in Can J Cardiol 2014; Feb;30(2):195-203., 195-203.
Comparison of the performances of cardiac troponins, including sensitive assays, and copeptin in the diagnosis of acute myocardial infarction and long-term prognosis between women and men.
Balmelli Catharina (2013), Comparison of the performances of cardiac troponins, including sensitive assays, and copeptin in the diagnosis of acute myocardial infarction and long-term prognosis between women and men., in Am Heart J. 2013 Jul;166(1):30-7, 30-37.
Consideration of high-sensitivity troponin values below the 99th percentile at presentation: does it improve diagnostic accuracy?
Meune Christophe (2013), Consideration of high-sensitivity troponin values below the 99th percentile at presentation: does it improve diagnostic accuracy?, in Int J Cardiol 2013; Oct 9;168(4):3752-7, 3752-3757.
Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction.
Reiter Miriam, Twerenbold Raphael, Reichlin Tobias, Mueller Mira, Hoeller Rebecca, Moehring Berit, Haaf Philip, Wildi Karin, Merk Salome, Bernhard Denise, Mueller Christa Zellweger, Freese Michael, Freidank Heike, Campodarve Botet Isabel, Mueller Christian (2013), Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction., in Heart (British Cardiac Society), 99(10), 708-14.
Prevalence, extent, and independent predictors of silent myocardial infarction.
Arenja Nisha, Mueller Christian, Ehl Niklas F, Brinkert Miriam, Roost Katharina, Reichlin Tobias, Sou Seoung Mann, Hochgruber Thomas, Osswald Stefan, Zellweger Michael J (2013), Prevalence, extent, and independent predictors of silent myocardial infarction., in The American journal of medicine, 126(6), 515-22.
Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin
Rubini Gimenez Maria (2013), Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin, in Int J Cardiol 2013; Oct 9;168(4):3896-901, 3896-3901.
Risk stratification in patients with unstable angina using absolute serial changes of 3 high-sensitive troponin assays.
Reichlin Tobias, Twerenbold Raphael, Maushart Claudia, Reiter Miriam, Moehring Berit, Schaub Nora, Balmelli Cathrin, Rubini Gimenez Maria, Hoeller Rebeca, Sakarikos Konstantin, Drexler Beatrice, Haaf Philip, Osswald Stefan, Mueller Christian (2013), Risk stratification in patients with unstable angina using absolute serial changes of 3 high-sensitive troponin assays., in American heart journal, 165(3), 371-371.
Serial changes in high-sensitivity cardiac troponin I in the early diagnosis of acute myocardial infarction
Wildi Karin (2013), Serial changes in high-sensitivity cardiac troponin I in the early diagnosis of acute myocardial infarction, in Int J Cardiol 2013;168(4):4103-10, 4103-4110.
Uric acid for diagnosis and risk stratification in suspected myocardial infarction.
Wildi Karin, Haaf Philip, Reichlin Tobias, Acemoglu Resat, Schneider Jeannine, Balmelli Cathrin, Drexler Beatrice, Twerenbold Raphael, Mosimann Tamina, Reiter Miriam, Mueller Mira, Ernst Susanne, Ballarino Paola, Zellweger Christa, Moehring Berit, Vilaplana Carles, Freidank Heike, Mueller Christian (2013), Uric acid for diagnosis and risk stratification in suspected myocardial infarction., in European journal of clinical investigation, 43(2), 174-82.
Validation of high-sensitivity troponin I in a 2-h diagnostic strategy to assess 30-day outcomes in emergency-department patients with possible acute coronary syndrome
Cullen Louise (2013), Validation of high-sensitivity troponin I in a 2-h diagnostic strategy to assess 30-day outcomes in emergency-department patients with possible acute coronary syndrome, in J Am Coll Cardiol. 2013 Oct 1;62(14):1242-9, 1242-1249.
Auto-antibodies: diagnostic tools in acute myocardial infarction?
Mueller C (2012), Auto-antibodies: diagnostic tools in acute myocardial infarction?, in Journal of internal medicine, 271(5), 433-5.
Combined copeptin and troponin to rule out myocardial infarction in patients with chest pain and a history of coronary artery disease.
Ray Patrick, Charpentier Sandrine, Chenevier-Gobeaux Camille, Reichlin Tobias, Twerenbold Raphael, Claessens Yann-Erick, Jourdain Patrick, Riou Bruno, Mueller Christian (2012), Combined copeptin and troponin to rule out myocardial infarction in patients with chest pain and a history of coronary artery disease., in The American journal of emergency medicine, 30(3), 440-8.
Counterpoint: Detection of myocardial infarction--is it all troponin? Role of new markers.
Mueller Christian (2012), Counterpoint: Detection of myocardial infarction--is it all troponin? Role of new markers., in Clinical chemistry, 58(1), 162-4.
Determinants of high-sensitivity troponin T among patients with a noncardiac cause of chest pain.
Irfan Affan, Twerenbold Raphael, Reiter Miriam, Reichlin Tobias, Stelzig Claudia, Freese Michael, Haaf Philip, Hochholzer Willibald, Steuer Stephan, Bassetti Stefano, Zellweger Christa, Freidank Heike, Peter Federico, Campodarve Isabel, Meune Christophe, Mueller Christian (2012), Determinants of high-sensitivity troponin T among patients with a noncardiac cause of chest pain., in The American journal of medicine, 125(5), 491-491.
Determinants of high-sensitivity troponin T among patients with a noncardiac cause of chest pain.
Irfan Affan, Twerenbold Raphael, Reiter Miriam, Reichlin Tobias, Stelzig Claudia, Freese Michael, Haaf Philip, Hochholzer Willibald, Steuer Stephan, Bassetti Stefano, Zellweger Christa, Freidank Heike, Peter Federico, Campodarve Isabel, Meune Christophe, Mueller Christian (2012), Determinants of high-sensitivity troponin T among patients with a noncardiac cause of chest pain., in The American journal of medicine, 125(5), 491-491.
Diagnostic and prognostic impact of copeptin and high-sensitivity cardiac troponin T in patients with pre-existing coronary artery disease and suspected acute myocardial infarction.
Potocki Mihael, Reichlin Tobias, Thalmann Simone, Zellweger Christa, Twerenbold Raphael, Reiter Miriam, Steuer Stephan, Bassetti Stefano, Drexler Beatrice, Stelzig Claudia, Freese Michael, Winkler Katrin, Haaf Philip, Balmelli Cathrin, Hochholzer Willibald, Osswald Stefan, Mueller Christian (2012), Diagnostic and prognostic impact of copeptin and high-sensitivity cardiac troponin T in patients with pre-existing coronary artery disease and suspected acute myocardial infarction., in Heart (British Cardiac Society), 98(7), 558-65.
Early diagnosis of acute myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays.
Reiter Miriam, Twerenbold Raphael, Reichlin Tobias, Benz Benjamin, Haaf Philip, Meissner Julia, Hochholzer Willibald, Stelzig Claudia, Freese Michael, Heinisch Corinna, Balmelli Cathrin, Drexler Beatrice, Freidank Heike, Winkler Katrin, Campodarve Isabel, Gea Joaquim, Mueller Christian (2012), Early diagnosis of acute myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays., in European heart journal, 33(8), 988-97.
Growth differentiation factor-15 in the early diagnosis and risk stratification of patients with acute chest pain.
Schaub Nora, Reichlin Tobias, Twerenbold Raphael, Reiter Miriam, Steuer Stephan, Bassetti Stefano, Stelzig Claudia, Wolf Claudia, Winkler Katrin, Haaf Philip, Meissner Julia, Drexler Beatrice, Mueller Christian (2012), Growth differentiation factor-15 in the early diagnosis and risk stratification of patients with acute chest pain., in Clinical chemistry, 58(2), 441-9.
High Sensitivity Cardiac Troponin in the Distinction of Acute Myocardial Infarction from Acute Cardiac Non-Coronary Artery Disease.
Haaf Philip, Drexler Beatrice, Reichlin Tobias, Twerenbold Raphael, Reiter Miriam, Meissner Julia, Schaub Nora, Stelzig Claudia, Freese Michael, Heinzelmann Amely, Meune Christophe, Balmelli Cathrin, Freidank Heike, Winkler Katrin, Denhaerynck Kris, Hochholzer Willibald, Osswald Stefan, Mueller Christian (2012), High Sensitivity Cardiac Troponin in the Distinction of Acute Myocardial Infarction from Acute Cardiac Non-Coronary Artery Disease., in Circulation, 1-12.
High-sensitive troponin T measurements: what do we gain and what are the challenges?
Twerenbold Raphael, Jaffe Allan, Reichlin Tobias, Reiter Miriam, Mueller Christian (2012), High-sensitive troponin T measurements: what do we gain and what are the challenges?, in European heart journal, 33(5), 579-86.
How safe is the outpatient management of patients with acute chest pain and mildly increased cardiac troponin concentrations?
Meune Christophe, Reichlin Tobias, Irfan Affan, Schaub Nora, Twerenbold Raphael, Meissner Julia, Reiter Miriam, Lüthi Adrian, Haaf Philip, Balmelli Cathrin, Drexler Beatrice, Winkler Katrin, Hochholzer Willibald, Osswald Stefan, Mueller Christian (2012), How safe is the outpatient management of patients with acute chest pain and mildly increased cardiac troponin concentrations?, in Clinical chemistry, 58(5), 916-24.
Introduction of high-sensitivity troponin assays: impact on myocardial infarction incidence and prognosis.
Reichlin Tobias, Twerenbold Raphael, Reiter Miriam, Steuer Stephan, Bassetti Stefano, Balmelli Cathrin, Winkler Katrin, Kurz Sabine, Stelzig Claudia, Freese Michael, Drexler Beatrice, Haaf Philip, Zellweger Christa, Osswald Stefan, Mueller Christian (2012), Introduction of high-sensitivity troponin assays: impact on myocardial infarction incidence and prognosis., in The American journal of medicine, 125(12), 1205-1205.
Markers of plaque instability in the early diagnosis and risk stratification of acute myocardial infarction.
Schaub Nora, Reichlin Tobias, Meune Christophe, Twerenbold Raphael, Haaf Philip, Hochholzer Willibald, Niederhauser Nadine, Bosshard Piet, Stelzig Claudia, Freese Michael, Reiter Miriam, Gea Joachim, Buser Andreas, Mebazaa Alexandre, Osswald Stefan, Mueller Christian (2012), Markers of plaque instability in the early diagnosis and risk stratification of acute myocardial infarction., in Clinical chemistry, 58(1), 246-56.
Midregional pro-A-type natriuretic peptide for diagnosis and prognosis in patients with suspected acute myocardial infarction.
Meune Christophe, Twerenbold Raphael, Drexler Beatrice, Balmelli Cathrin, Wolf Claudia, Haaf Philip, Reichlin Tobias, Irfan Affan, Reiter Miriam, Zellweger Christa, Meissner Julia, Stelzig Claudia, Freese Michael, Capodarve Isabel, Mueller Christian (2012), Midregional pro-A-type natriuretic peptide for diagnosis and prognosis in patients with suspected acute myocardial infarction., in The American journal of cardiology, 109(8), 1117-23.
One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T.
Reichlin Tobias, Schindler Christian, Drexler Beatrice, Twerenbold Raphael, Reiter Miriam, Zellweger Christa, Moehring Berit, Ziller Ronny, Hoeller Rebeca, Rubini Gimenez Maria, Haaf Philip, Potocki Mihael, Wildi Karin, Balmelli Cathrin, Freese Michael, Stelzig Claudia, Freidank Heike, Osswald Stefan, Mueller Christian (2012), One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T., in Archives of internal medicine, 172(16), 1211-8.
Serial changes in highly sensitive cardiac troponin improve the early diagnosis of acute myocardial infarction.
Reichlin Tobias, Mueller Christian (2012), Serial changes in highly sensitive cardiac troponin improve the early diagnosis of acute myocardial infarction., in Evidence-based medicine, 17(6), 10-10.
Serial changes in highly sensitive cardiac troponin improve the early diagnosis of acute myocardial infarction.
Reichlin Tobias, Mueller Christian (2012), Serial changes in highly sensitive cardiac troponin improve the early diagnosis of acute myocardial infarction., in Evidence-based medicine, 1-4.
Utility of 14 novel biomarkers in patients with acute chest pain and undetectable levels of conventional cardiac troponin.
Meune Christophe, Balmelli Cathrin, Twerenbold Raphael, Reiter Miriam, Reichlin Tobias, Ziller Ronny, Drexler Beatrice, Stelzig Claudia, Freese Michael, Wolf Claudia, Haaf Philip, Osswald Stefan, Mueller Christian (2012), Utility of 14 novel biomarkers in patients with acute chest pain and undetectable levels of conventional cardiac troponin., in International journal of cardiology, 1-10.
Why all the struggle about CK-MB and PCI?
Jaffe Allan S, Apple Fred S, Lindahl Bertil, Mueller Christian, Katus Hugo A (2012), Why all the struggle about CK-MB and PCI?, in European heart journal, 33(9), 1046-8.
"Universal definition" methodology and conclusions are a concern.
Irfan Affan, Zellweger Michael J, Mueller Christian (2011), "Universal definition" methodology and conclusions are a concern., in Journal of the American College of Cardiology, 58(3), 313-314.
B-type Natriuretic Peptide and Chest Pain: Do Not Forget Left Ventricle Function Reply
Haaf P, Reichlin T, Mueller C (2011), B-type Natriuretic Peptide and Chest Pain: Do Not Forget Left Ventricle Function Reply, in AMERICAN JOURNAL OF MEDICINE, 124(12), 13-14.
B-type Natriuretic Peptide in the Early Diagnosis and Risk Stratification of Acute Chest Pain
Haaf P, Reichlin T, Corson N, Twerenbold R, Reiter M, Steuer S, Bassetti S, Winkler K, Stelzig C, Heinisch C, Drexler B, Freidank H, Mueller C (2011), B-type Natriuretic Peptide in the Early Diagnosis and Risk Stratification of Acute Chest Pain, in AMERICAN JOURNAL OF MEDICINE, 124(5), 444-452.
B-type natriuretic peptide in the early diagnosis and risk stratification of acute chest pain.
Haaf Philip, Reichlin Tobias, Corson Nils, Twerenbold Raphael, Reiter Miriam, Steuer Stephan, Bassetti Stefano, Winkler Katrin, Stelzig Claudia, Heinisch Corinna, Drexler Beatrice, Freidank Heike, Mueller Christian (2011), B-type natriuretic peptide in the early diagnosis and risk stratification of acute chest pain., in The American journal of medicine, 124(5), 444-52.
Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays
Reiter M, Twerenbold R, Reichlin T, Haaf P, Peter F, Meissner J, Hochholzer W, Stelzig C, Freese M, Heinisch C, Breidthardt T, Freidank H, Winkler K, Campodarve I, Gea J, Mueller C (2011), Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays, in EUROPEAN HEART JOURNAL, 32(11), 1379-1389.
Endogenous stress response in Tako-Tsubo cardiomyopathy and acute myocardial infarction.
Meissner Julia, Nef Holger, Darga Joelyn, Kovacs Maria, Weber Michael, Hamm Christian, Möllmann Helge, Twerenbold Raphael, Reiter Miriam, Heinisch Corinna, Stelzig Claudia, Reichlin Tobias, Mueller Christian (2011), Endogenous stress response in Tako-Tsubo cardiomyopathy and acute myocardial infarction., in European journal of clinical investigation, 41(9), 964-70.
High-sensitive Troponin, B-type natriuretic peptide and coronary angiogram findings in patients with non ST-segment elevation acute coronary syndrome.
Meune Christophe, Balmelli Cathrin, Marxer Tanja, Meissner Julia, Twerenbold Raphael, Reiter Miriam, Reichlin Tobias, Haaf Philip, Drexler Beatrice, Irfan Affan, Stelzig Claudia, Freese Michael, Winkler Katrin, Mueller Christian (2011), High-sensitive Troponin, B-type natriuretic peptide and coronary angiogram findings in patients with non ST-segment elevation acute coronary syndrome., in International journal of cardiology, 153(3), 335-7.
Incremental Value of High-Sensitivity Cardiac Troponin T for Risk Prediction in Patients with Suspected Acute Myocardial Infarction
Hochholzer W, Reichlin T, Twerenbold R, Stelzig C, Hochholzer K, Meissner J, Haaf P, Schaub N, Steuer S, Bassetti S, Reiter M, Roost K, Freidank H, Winkler K, Mueller C (2011), Incremental Value of High-Sensitivity Cardiac Troponin T for Risk Prediction in Patients with Suspected Acute Myocardial Infarction, in CLINICAL CHEMISTRY, 57(9), 1318-1326.
Patients with acute coronary syndrome and normal high-sensitivity troponin.
Meune Christophe, Balmelli Cathrin, Twerenbold Raphael, Reichlin Tobias, Reiter Miriam, Haaf Philip, Steuer Stephan, Bassetti Stefano, Sakarikos Konstantin, Campodarve Isabel, Zellweger Christa, Irfan Affan, Drexler Beatrice, Mueller Christian (2011), Patients with acute coronary syndrome and normal high-sensitivity troponin., in The American journal of medicine, 124(12), 1151-7.
Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain
Devaux Yvan, Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain, in J Intern Med 2013 Dec 17.
Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations
Irfan Affan, Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations, in Am J Med 2013; Jul 18. Epub ahead of print..
Mid-regional pro-adrenomedullin in the early evaluation of acute chest pain patients.
Haaf Philip, Twerenbold Raphael, Reichlin Tobias, Faoro Jonathan, Reiter Miriam, Meune Christophe, Steuer Stephan, Bassetti Stefano, Ziller Ronny, Balmelli Cathrin, Campodarve Isabel, Zellweger Christa, Kilchenmann Ashley, Irfan Affan, Papassotiriou Jana, Drexler Beatrice, Mueller Christian, Mid-regional pro-adrenomedullin in the early evaluation of acute chest pain patients., in International journal of cardiology, 0(0), 0-0.
Normal presenting levels of high-sensitivity troponin and myocardial infarction.
Hoeller Rebeca, Rubini Giménez María, Reichlin Tobias, Twerenbold Raphael, Zellweger Christa, Moehring Berit, Wildi Karin, Freese Michael, Stelzig Claudia, Hartmann Beate, Stoll Melanie, Mosimann Tamina, Reiter Miriam, Haaf Philip, Mueller Mira, Meller Bernadette, Hochgruber Thomas, Balmelli Cathrin, Sou Seoung Mann, Murray Karsten, Freidank Heike, Steuer Stephan, Minners Jan, Osswald Stefan, Mueller Christian, Normal presenting levels of high-sensitivity troponin and myocardial infarction., in Heart (British Cardiac Society).

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ESC Meeting Talk given at a conference Early diagnosis of AMI 31.08.2013 Amsterdam, Netherlands Zellweger Christa; Mueller Christian; Lee Gino;
ESC Meeting Talk given at a conference Early diagnosis of AMI 01.09.2012 München, Germany Höller Rebeca; Reichlin Tobias; Mueller Christian; Zellweger Christa;
ESC Heart Failure Association Talk given at a conference Use of biomarkers in AHF 19.05.2012 Belgrad, Serbien Mueller Christian;
ESC Meeting Talk given at a conference Early diagnosis of AMI 27.08.2011 Paris, France Mueller Christian; Reichlin Tobias;
ESC- Heart Failure Meeting Talk given at a conference Early diagnosis of AHF 21.05.2011 Götheburg, Sweden Mueller Christian;
SGIM 2011 Talk given at a conference Early diagnosis of AMI 11.05.2011 Lausanne, Switzerland Mueller Christian;


Self-organised

Title Date Place
International Great Meeting 2013 27.06.2013 Prag, Czech Republic
ESC-ACCA Meeting 20.10.2012 Istanbul, Turkey
GREAT International Meeting 2012 05.07.2012 Barcelona, Spain
International GREAT Meeting 07.07.2011 Paris, France

Associated projects

Number Title Start Funding scheme
138403 BASEL IX - Basel Syncope Evaluation Study 01.01.2012 Project funding (Div. I-III)
159495 Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) Study: Validation 01.04.2015 Project funding (Div. I-III)
119139 Integration von B-typ natriuretischem Peptid in die klinische Medizin 01.04.2008 SNSF Professorships
127005 Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study 01.01.2010 Project funding (Div. I-III)

Abstract

Summary of the research plan:Acute myocardial infarction (AMI) is a major cause of death and disability.Approximately 15 million patients per year in the United States and Europe present to the emergency department with chest pain or other symptoms suggestive of AMI. Rapid identification of AMI is critical for the initiation of effective evidence-based medical treatment and management. Electrocardiography (ECG) and cardiac troponin (cTn) form the current diagnostic cornerstones and complement clinical assessment. The ECG by itself is often insufficient to diagnose AMI since repolarization abnormalities may be observed in multiple other conditions. While the diagnostic performance of chest pain characteristics and the 12-lead ECG have received little scientific attention throughout the last decades, recent data from our group and others indicate that novel sensitive cTn assays as well as copeptin, a novel quantitative marker of endogenous stress, seem to overcome the sensitivity deficit of conventional cTn assays and therefore represent major improvements in the early diagnosis of AMI. Several important questions remain regarding the best possible clinical use of thesenovel tests, as well as the use of chest pain characteristics and the ECG.The objectives of the current application are to a) extend the sample size ofthe ongoing APACE study to 2400 patients and extend the follow-up period to 720 days b) evaluate the diagnostic performance of sensitive cTn assays in important subgroups such as women, the elderly, patients with preexisting coronary artery disease and patients with chronic kidney disease c) determine and validate an algorithm on how to best integrate the initial absolute cTn value at presentation and changes within the first hours with details of the clinical presentation and the 12-lead ECG in the rapid rule-in and rule-out of AMI d) evaluate the diagnostic performanceof a dual-marker approach combining sensitive cTn with copeptin e) determine potential implications of sensitive cTn and copeptin on resource use and calculate cost-effectiveness f) determine the prognostic performance of sensitive cTn assays and copeptin in the prediction of death and recurrent AMI during long-term follow up g) investigate the diagnostic performance of 33 predefined chest pain characteristicsh) investigate the diagnostic and prognostic performance of repolarizationabnormalities manifested as changes in the ST-T segment on the 12-lead ECG i) investigate the diagnostic and prognostic performance of electrocardiographic changes in the depolarization phase, detected and quantified by a novel software analyzing the high-frequency QRS components of the ECG.This study will provide insights that will contribute to improvements in the early diagnosis of AMI and will therefore have important clinical and economic implications on patient management in Switzerland and worldwide.
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