Clinical trial NCT00470587: Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) Study
Official title: Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myocardial Infarction
Angina, Unstable
Keywords: chest pain
myocardial infarction
unstable angina
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2007-05-08
Enrollment: 10000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients presenting to the emergency department with typical angina pectoris or other thoracic sensations at rest or minor exertion that are suspected to be caused by myocardial ischemia. Onset of symptoms within the last 12 hours prior to presentation.

Brief summary: The triage of patients with suspected acute coronary syndrome in the emergency room is a time-consuming diagnostic challenge. Therefore high sensitive early markers for myocardial damage are needed for more rapidly rule out of acute myocardial infarction (AMI) - especially for the first 3 to 4 hours after onset of chest pain in AMI ("troponin-blind" period).

Therefore we test the hypothesis that the use meticulous patient history and novel cardiac markers can provide a faster detection or exclusion of AMI in patients presenting with acute chest pain to the emergency department.

The prospective cohort study is designed to enrol patients presenting with acute chest pain at rest within the last 12 hours to the emergency department. Several blood samples for detection of the new markers will be drawn and compared with the gold standard for the diagnosis of AMI (high-sensitivity cardiac troponin T). All patients will be contacted by telephone at 3, 12, 24 and 60 months to determine functional status, major adverse cardiac events (death, myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention), and the results of cardiac examination (stress test, coronary angiography) if performed.

Detailed description: Background: The triage of patients with suspected acute coronary syndrome in the emergency room is a time-consuming diagnostic challenge. Triage and management of patients with low probability of coronary artery disease often cause excessive hospital costs. Therefore high sensitive early markers for myocardial damage are needed for more rapidly rule out of acute myocardial infarction (AMI).

Cardiac troponins (T and I) are currently the gold standard for definitive AMI diagnosis due to their high sensitivity and specificity for detection of myocardial cell injury. Unfortunately, troponin is undetectable by current assays in peripheral blood within 3 to 4 hours after onset of chest pain in AMI ("troponin-blind" period).

New cardiac markers such as the novel high-sensitive troponin I/T, ischemia modified albumin and placental growth factor have demonstrated certain advantages compared to troponin such as high negative predictive value for AMI, earlier verifiability in peripheral blood and possible value as independent risk marker. However, clinical evaluation in a large cohort of unselected patients presenting to an emergency department is still lacking.

Aim: To test the hypothesis that the use meticulous patient history and novel cardiac markers (including high-sensitive troponin I/T, myeloperoxidase, ischemia modified albumin, placental growth factor) can provide a faster detection or exclusion of AMI in patients presenting with acute chest pain to the emergency department.

Patients and Methods: The prospective cohort study is designed to enrol unselected patients presenting with acute chest pain at rest within the last 12 hours to the emergency department. Several blood samples for detection of the new markers will be drawn (baseline, 1, 2, 3 and 6 hours) and compared with the gold standard for the diagnosis of AMI (high-sensitivity cardiac troponin T). Timing and treatment of patients are left to the discretion of the attending physician and will be performed according to the standard house routine of the hospital. All patients will be contacted by telephone at 6, 12, 24 and 60 months to determine functional status, major adverse cardiac events (death, myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention), and the results of cardiac examination (stress test, coronary angiography) if performed.

Expected results: It is our hypothesis that the use meticulous patient history and novel cardiac markers can improve the detection of AMI by providing an early diagnosis for AMI with a high negative predictive value within the "troponin-blind" period.

Significance: The earlier detection of myocardial necrosis in peripheral blood could help to rule out AMI more rapidly. In addition it will allow a more rapid diagnosis and appropriate therapy of AMI. This can lead to a significant improvement in patient management and a reduction of in-hospital costs.

Eligibility criteria: Inclusion Criteria:

* Patients presenting to the emergency department
* Typical angina pectoris or other thoracic sensations that are suspected to be caused by myocardial ischemia
* Symptoms at rest or minor exertion
* Onset of symptoms within the last 12 hours prior to presentation
* Written informed consent

Exclusion Criteria:

* Age \< 18 years
* Cardiogenic shock
* Terminal kidney disease requiring regular dialysis

Primary outcomes:
measure: Diagnostic utility of various biomarkers, detailed patient's history and examination as well as ECG findings for the early diagnosis of acute myocardial infarction
timeFrame: at admission
Secondary outcomes:
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: Masaryk University Brno
city: Genova
country: Italy
facility: Emergency Department San Martino Hospital
city: Zabrze
country: Poland
facility: Medical University of Silesia
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Basel
country: Switzerland
facility: University Hospital of Basel
city: Bottmingen
country: Switzerland
facility: Kantonsspital Baselland, Standort Bruderholz
city: Liestal
country: Switzerland
facility: Kantonsspital Baselland, Standort Liestal
city: Luzern
country: Switzerland
facility: Klinik St. Anna
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: Schlieren
country: Switzerland
facility: Spital Limmattal
city: Zurich
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: University Hospital of Basel
name: Christian Mueller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koechlin L, Boeddinghaus J, Lopez-Ayala P, Nestelberger T, Wussler D, Mais F, Twerenbold R, Zimmermann T, Wildi K, Koppen AM, Miro O, Martin-Sanchez FJ, Kawecki D, Geigy N, Keller DI, Christ M, Buser A, Gimenez MR, Bernasconi L, Hammerer-Lercher A, Mueller C; APACE investigators. Diagnostic discrimination of a novel high-sensitivity cardiac troponin I assay and derivation/validation of an assay-specific 0/1h-algorithm. Am Heart J. 2023 Jan;255:58-70. doi: 10.1016/j.ahj.2022.10.007. Epub 2022 Oct 13.
citation: Koechlin L, Boeddinghaus J, Nestelberger T, Lopez-Ayala P, Shrestha S, Wussler D, Haeni N, Walter JE, Twerenbold R, Eckstein FS, Reuthebuch O, McCord J, Nowak RM, Christenson RH, deFilippi CR, Apple FS, Mueller C; APACE and High-US investigators. Lower diagnostic accuracy of hs-cTnI in patients with prior coronary artery bypass grafting. Int J Cardiol. 2022 May 1;354:1-6. doi: 10.1016/j.ijcard.2022.02.025. Epub 2022 Feb 18.
citation: Kaier TE, Twerenbold R, Lopez-Ayala P, Nestelberger T, Boeddinghaus J, Alaour B, Huber IM, Zhi Y, Koechlin L, Wussler D, Wildi K, Shrestha S, Strebel I, Miro O, Martin-Sanchez JF, Christ M, Kawecki D, Keller DI, Rubini Gimenez M, Marber M, Mueller C; APACE Investigators. A 0/1h-algorithm using cardiac myosin-binding protein C for early diagnosis of myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2022 Jun 7;11(4):325-335. doi: 10.1093/ehjacc/zuac007.
citation: Prepoudis A, Koechlin L, Nestelberger T, Boeddinghaus J, Lopez-Ayala P, Wussler D, Zimmermann T, Rubini Gimenez M, Strebel I, Puelacher C, Shrestha S, Keller DI, Christ M, Gualandro DM, Twerenbold R, Martinez-Nadal G, Lopez-Barbeito B, Miro O, Mueller C; APACE investigators. Incidence, clinical presentation, management, and outcome of acute pericarditis and myopericarditis. Eur Heart J Acute Cardiovasc Care. 2022 Feb 8;11(2):137-147. doi: 10.1093/ehjacc/zuab108.
citation: Koechlin L, Boeddinghaus J, Nestelberger T, Lopez-Ayala P, Wussler D, Shrestha S, Resa T, Wildi K, Bakula A, Frey S, Miro O, Martin-Sanchez FJ, Strebel I, Gualandro DM, Eckstein FS, Reuthebuch O, Keller DI, Twerenbold R, Gimenez MR, Mueller C; APACE investigators. Performance of the ESC 0/2h-algorithm using high-sensitivity cardiac troponin I in the early diagnosis of myocardial infarction. Am Heart J. 2021 Dec;242:132-137. doi: 10.1016/j.ahj.2021.08.008. Epub 2021 Sep 9.
citation: Boeddinghaus J, Lopez-Ayala P, Nestelberger T, Koechlin L, Munch T, Miro O, Gimenez MR, Mueller C; APACE Investigators. Prospective Validation of the ESC 0/1h-Algorithm Using High-Sensitivity Cardiac Troponin I. Am J Cardiol. 2021 Nov 1;158:152-153. doi: 10.1016/j.amjcard.2021.08.007. Epub 2021 Aug 30. No abstract available.
citation: Lopez-Ayala P, Nestelberger T, Boeddinghaus J, Koechlin L, Ratmann PD, Strebel I, Gehrke J, Meier S, Walter J, Rubini Gimenez M, Mutschler E, Miro O, Lopez-Barbeito B, Martin-Sanchez FJ, Rodriguez-Adrada E, Keller DI, Newby LK, Twerenbold R, Giannitsis E, Lindahl B, Mueller C; APACE and TRAPID-AMI Investigatorsdagger. Novel Criteria for the Observe-Zone of the ESC 0/1h-hs-cTnT Algorithm. Circulation. 2021 Sep 7;144(10):773-787. doi: 10.1161/CIRCULATIONAHA.120.052982. Epub 2021 Aug 11.
citation: Nestelberger T, Boeddinghaus J, Gimenez MR, Lopez-Ayala P, Ratmann PD, Badertscher P, Wildi K, Wussler D, Koechlin L, Arslani K, Zimmermann T, Freese M, Rinderknecht T, Miro O, Martin-Sanchez FJ, Kawecki D, Geigy N, Keller D, Twerenbold R, Muller C; APACE investigators. Direct comparison of high-sensitivity cardiac troponin T and I in the early differentiation of type 1 vs. type 2 myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2022 Jan 12;11(1):62-74. doi: 10.1093/ehjacc/zuab039.
citation: Boeddinghaus J, Nestelberger T, Lopez-Ayala P, Koechlin L, Buechi M, Miro O, Keller DI, Gimenez MR, Twerenbold R, Mueller C; APACE Investigators. Diagnostic Performance of the European Society of Cardiology 0/1-h Algorithms in Late Presenters. J Am Coll Cardiol. 2021 Mar 9;77(9):1264-1267. doi: 10.1016/j.jacc.2021.01.004. No abstract available.
citation: Koechlin L, Boeddinghaus J, Nestelberger T, Miro O, Fuenzalida C, Martinez-Nadal G, Lopez B, Wussler D, Walter J, Zimmermann T, Troester V, Lopez-Ayala P, Baumgartner B, Ratmann PD, Diebold M, Prepoudis A, Huber J, Christ M, Wildi K, Rubini Gimenez M, Strebel I, Gualandro DM, Martin-Sanchez FJ, Kawecki D, Keller DI, Reuthebuch O, Eckstein FS, Reichlin T, Twerenbold R, Mueller C; APACE investigators. Clinical presentation of patients with prior coronary artery bypass grafting and suspected acute myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2021 Oct 1;10(7):746-755. doi: 10.1093/ehjacc/zuaa020.
citation: Troester V, Strebel I, Nestelberger T, Boeddinghaus J, Rubini Gimenez M, Lopez-Ayala P, Koechlin L, Glarner N, Prepoudis A, Miro O, Martin-Sanchez FJ, Kawecki D, Keller DI, Twerenbold R, Mueller C; APACE Investigators *. Association of Previous Myocardial Infarction and Time to Presentation With Suspected Acute Myocardial Infarction. J Am Heart Assoc. 2021 Jan 5;10(1):e017829. doi: 10.1161/JAHA.120.017829. Epub 2020 Dec 26. No abstract available.
citation: Rubini Gimenez M, Wildi K, Wussler D, Koechlin L, Boeddinghaus J, Nestelberger T, Badertscher P, Sedlmayer R, Puelacher C, Zimmermann T, du Fay de Lavallaz J, Lopez-Ayala P, Leu K, Rentsch K, Miro O, Lopez B, Martin-Sanchez FJ, Bustamante J, Kawecki D, Parenica J, Lohrmann J, Kloos W, Buser A, Keller DI, Reichlin T, Twerenbold R, Mueller C. Early kinetics of cardiac troponin in suspected acute myocardial infarction. Rev Esp Cardiol (Engl Ed). 2021 Jun;74(6):502-509. doi: 10.1016/j.rec.2020.04.008. Epub 2020 May 22. English, Spanish.
citation: Boeddinghaus J, Nestelberger T, Koechlin L, Wussler D, Lopez-Ayala P, Walter JE, Troester V, Ratmann PD, Seidel F, Zimmermann T, Badertscher P, Wildi K, Rubini Gimenez M, Potlukova E, Strebel I, Freese M, Miro O, Martin-Sanchez FJ, Kawecki D, Keller DI, Gualandro DM, Christ M, Twerenbold R, Mueller C; APACE Investigators. Early Diagnosis of Myocardial Infarction With Point-of-Care High-Sensitivity Cardiac Troponin I. J Am Coll Cardiol. 2020 Mar 17;75(10):1111-1124. doi: 10.1016/j.jacc.2019.12.065.
citation: Haller PM, Boeddinghaus J, Neumann JT, Sorensen NA, Hartikainen TS, Gossling A, Nestelberger T, Twerenbold R, Lehmacher J, Keller T, Zeller T, Blankenberg S, Mueller C, Westermann D. Performance of the ESC 0/1-h and 0/3-h Algorithm for the Rapid Identification of Myocardial Infarction Without ST-Elevation in Patients With Diabetes. Diabetes Care. 2020 Feb;43(2):460-467. doi: 10.2337/dc19-1327. Epub 2019 Dec 16.
citation: Nestelberger T, Boeddinghaus J, Greenslade J, Parsonage WA, Than M, Wussler D, Lopez-Ayala P, Zimmermann T, Meier M, Troester V, Badertscher P, Koechlin L, Wildi K, Anwar M, Freese M, Keller DI, Reichlin T, Twerenbold R, Cullen L, Mueller C; APACE and ADAPT Investigators. Two-Hour Algorithm for Rapid Triage of Suspected Acute Myocardial Infarction Using a High-Sensitivity Cardiac Troponin I Assay. Clin Chem. 2019 Nov;65(11):1437-1447. doi: 10.1373/clinchem.2019.305193. Epub 2019 Sep 30.
citation: Boeddinghaus J, Twerenbold R, Nestelberger T, Koechlin L, Wussler D, Meier M, Troester V, Zimmermann T, Badertscher P, Wildi K, Rubini Gimenez M, Lopez-Ayala P, Potlukova E, Miro O, Martin-Sanchez FJ, Kawecki D, Geigy N, Keller DI, Reichlin T, Mueller C; APACE investigators. Clinical Use of a New High-Sensitivity Cardiac Troponin I Assay in Patients with Suspected Myocardial Infarction. Clin Chem. 2019 Nov;65(11):1426-1436. doi: 10.1373/clinchem.2019.304725. Epub 2019 Sep 30.
citation: Nestelberger T, Boeddinghaus J, Wussler D, Twerenbold R, Badertscher P, Wildi K, Miro O, Lopez B, Martin-Sanchez FJ, Muzyk P, Koechlin L, Baumgartner B, Meier M, Troester V, Rubini Gimenez M, Puelacher C, du Fay de Lavallaz J, Walter J, Kozhuharov N, Zimmermann T, Gualandro DM, Michou E, Potlukova E, Geigy N, Keller DI, Reichlin T, Mueller C; APACE Investigators. Predicting Major Adverse Events in Patients With Acute Myocardial Infarction. J Am Coll Cardiol. 2019 Aug 20;74(7):842-854. doi: 10.1016/j.jacc.2019.06.025.
citation: Neumann JT, Twerenbold R, Ojeda F, Sorensen NA, Chapman AR, Shah ASV, Anand A, Boeddinghaus J, Nestelberger T, Badertscher P, Mokhtari A, Pickering JW, Troughton RW, Greenslade J, Parsonage W, Mueller-Hennessen M, Gori T, Jernberg T, Morris N, Liebetrau C, Hamm C, Katus HA, Munzel T, Landmesser U, Salomaa V, Iacoviello L, Ferrario MM, Giampaoli S, Kee F, Thorand B, Peters A, Borchini R, Jorgensen T, Soderberg S, Sans S, Tunstall-Pedoe H, Kuulasmaa K, Renne T, Lackner KJ, Worster A, Body R, Ekelund U, Kavsak PA, Keller T, Lindahl B, Wild P, Giannitsis E, Than M, Cullen LA, Mills NL, Mueller C, Zeller T, Westermann D, Blankenberg S; COMPASS-MI Study Group. Application of High-Sensitivity Troponin in Suspected Myocardial Infarction. N Engl J Med. 2019 Jun 27;380(26):2529-2540. doi: 10.1056/NEJMoa1803377.
citation: Nestelberger T, Cullen L, Lindahl B, Reichlin T, Greenslade JH, Giannitsis E, Christ M, Morawiec B, Miro O, Martin-Sanchez FJ, Wussler DN, Koechlin L, Twerenbold R, Parsonage W, Boeddinghaus J, Rubini Gimenez M, Puelacher C, Wildi K, Buerge T, Badertscher P, DuFaydeLavallaz J, Strebel I, Croton L, Bendig G, Osswald S, Pickering JW, Than M, Mueller C; APACE, ADAPT and TRAPID-AMI Investigators. Diagnosis of acute myocardial infarction in the presence of left bundle branch block. Heart. 2019 Oct;105(20):1559-1567. doi: 10.1136/heartjnl-2018-314673. Epub 2019 May 29.
citation: Hillinger P, Strebel I, Abacherli R, Twerenbold R, Wildi K, Bernhard D, Nestelberger T, Boeddinghaus J, Badertscher P, Wussler D, Koechlin L, Zimmermann T, Puelacher C, Rubini Gimenez M, du Fay de Lavallaz J, Walter J, Geigy N, Keller DI, Reichlin T, Mueller C; APACE Investigators. Prospective validation of current quantitative electrocardiographic criteria for ST-elevation myocardial infarction. Int J Cardiol. 2019 Oct 1;292:1-12. doi: 10.1016/j.ijcard.2019.04.041. Epub 2019 Apr 11.
citation: Boeddinghaus J, Nestelberger T, Twerenbold R, Koechlin L, Meier M, Troester V, Wussler D, Badertscher P, Wildi K, Puelacher C, du Fay de Lavallaz J, Rubini Gimenez M, Zimmermann T, Hafner B, Potlukova E, Miro O, Martin-Sanchez FJ, Keller DI, Reichlin T, Mueller C; APACE investigators. High-Sensitivity Cardiac Troponin I Assay for Early Diagnosis of Acute Myocardial Infarction. Clin Chem. 2019 Jul;65(7):893-904. doi: 10.1373/clinchem.2018.300061. Epub 2019 Apr 15.
citation: Morawiec B, Boeddinghaus J, Wussler D, Badertscher P, Koechlin L, Metry F, Twerenbold R, Nestelberger T, Kawecki D, Mueller C; APACE Investigators. Modified HEART Score and High-Sensitivity Cardiac Troponin in Patients With Suspected Acute Myocardial Infarction. J Am Coll Cardiol. 2019 Feb 26;73(7):873-875. doi: 10.1016/j.jacc.2018.12.013. No abstract available.
citation: Wildi K, Nestelberger T, Wussler D, Boeddinghaus J, Badertscher P, Koechlin L, Duwe P, Rubini Gimenez M, Twerenbold R, Mueller C. Impact of Food and Drug Administration Regulatory Approach on the 0/2-Hour Algorithm for Rapid Triage of Suspected Myocardial Infarction. Circ Cardiovasc Qual Outcomes. 2019 Jan;12(1):e005188. doi: 10.1161/CIRCOUTCOMES.118.005188. No abstract available.
citation: Boeddinghaus J, Nestelberger T, Badertscher P, Twerenbold R, Fitze B, Wussler D, Strebel I, Rubini Gimenez M, Wildi K, Puelacher C, du Fay de Lavallaz J, Oehen L, Walter J, Miro O, Martin-Sanchez FJ, Morawiec B, Potlukova E, Keller DI, Reichlin T, Mueller C; APACE Investigators. Predicting Acute Myocardial Infarction with a Single Blood Draw. Clin Chem. 2019 Mar;65(3):437-450. doi: 10.1373/clinchem.2018.294124. Epub 2019 Jan 9.
citation: Wildi K, Boeddinghaus J, Nestelberger T, Twerenbold R, Badertscher P, Wussler D, Gimenez MR, Puelacher C, du Fay de Lavallaz J, Dietsche S, Walter J, Kozhuharov N, Morawiec B, Miro O, Javier Martin-Sanchez F, Subramaniam S, Geigy N, Keller DI, Reichlin T, Mueller C; APACE investigators. Comparison of fourteen rule-out strategies for acute myocardial infarction. Int J Cardiol. 2019 May 15;283:41-47. doi: 10.1016/j.ijcard.2018.11.140. Epub 2018 Dec 3.
citation: Boeddinghaus J, Nestelberger T, Twerenbold R, Neumann JT, Lindahl B, Giannitsis E, Sorensen NA, Badertscher P, Jann JE, Wussler D, Puelacher C, Rubini Gimenez M, Wildi K, Strebel I, Du Fay de Lavallaz J, Selman F, Sabti Z, Kozhuharov N, Potlukova E, Rentsch K, Miro O, Martin-Sanchez FJ, Morawiec B, Parenica J, Lohrmann J, Kloos W, Buser A, Geigy N, Keller DI, Osswald S, Reichlin T, Westermann D, Blankenberg S, Mueller C; APACE, BACC, and TRAPID-AMI Investigators. Impact of age on the performance of the ESC 0/1h-algorithms for early diagnosis of myocardial infarction. Eur Heart J. 2018 Nov 7;39(42):3780-3794. doi: 10.1093/eurheartj/ehy514.
citation: Boeddinghaus J, Twerenbold R, Nestelberger T, Badertscher P, Wildi K, Puelacher C, du Fay de Lavallaz J, Keser E, Rubini Gimenez M, Wussler D, Kozhuharov N, Rentsch K, Miro O, Martin-Sanchez FJ, Morawiec B, Stefanelli S, Geigy N, Keller DI, Reichlin T, Mueller C; APACE Investigators. Clinical Validation of a Novel High-Sensitivity Cardiac Troponin I Assay for Early Diagnosis of Acute Myocardial Infarction. Clin Chem. 2018 Sep;64(9):1347-1360. doi: 10.1373/clinchem.2018.286906. Epub 2018 Jun 25.
citation: Wildi K, Singeisen H, Twerenbold R, Badertscher P, Wussler D, Klinkenberg LJJ, Meex SJR, Nestelberger T, Boeddinghaus J, Miro O, Martin-Sanchez FJ, Morawiec B, Muzyk P, Parenica J, Keller DI, Geigy N, Potlukova E, Sabti Z, Kozhuharov N, Puelacher C, du Fay de Lavallaz J, Rubini Gimenez M, Shrestha S, Marzano G, Rentsch K, Osswald S, Reichlin T, Mueller C; APACE Investigators. Circadian rhythm of cardiac troponin I and its clinical impact on the diagnostic accuracy for acute myocardial infarction. Int J Cardiol. 2018 Nov 1;270:14-20. doi: 10.1016/j.ijcard.2018.05.136. Epub 2018 Jun 4.
citation: van der Linden N, Wildi K, Twerenbold R, Pickering JW, Than M, Cullen L, Greenslade J, Parsonage W, Nestelberger T, Boeddinghaus J, Badertscher P, Rubini Gimenez M, Klinkenberg LJJ, Bekers O, Schoni A, Keller DI, Sabti Z, Puelacher C, Cupa J, Schumacher L, Kozhuharov N, Grimm K, Shrestha S, Flores D, Freese M, Stelzig C, Strebel I, Miro O, Rentsch K, Morawiec B, Kawecki D, Kloos W, Lohrmann J, Richards AM, Troughton R, Pemberton C, Osswald S, van Dieijen-Visser MP, Mingels AM, Reichlin T, Meex SJR, Mueller C. Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction. Circulation. 2018 Sep 4;138(10):989-999. doi: 10.1161/CIRCULATIONAHA.117.032003.
citation: Rubini Gimenez M, Badertscher P, Twerenbold R, Boeddinghaus J, Nestelberger T, Wussler D, Miro O, Martin-Sanchez FJ, Reichlin T, Mueller C. Impact of the US Food and Drug Administration-Approved Sex-Specific Cutoff Values for High-Sensitivity Cardiac Troponin T to Diagnose Myocardial Infarction. Circulation. 2018 Apr 24;137(17):1867-1869. doi: 10.1161/CIRCULATIONAHA.117.031940. No abstract available.
citation: Badertscher P, Boeddinghaus J, Nestelberger T, Twerenbold R, Wildi K, Sabti Z, Puelacher C, Rubini Gimenez M, Pfaffli J, Flores D, du Fay de Lavallaz J, Miro O, Martin-Sanchez FJ, Morawiec B, Lohrmann J, Buser A, Keller DI, Geigy N, Reichlin T, Mueller C. Effect of Acute Coronary Syndrome Probability on Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin. Clin Chem. 2018 Mar;64(3):515-525. doi: 10.1373/clinchem.2017.279513. Epub 2018 Jan 17.
citation: Twerenbold R, Badertscher P, Boeddinghaus J, Nestelberger T, Wildi K, Puelacher C, Sabti Z, Rubini Gimenez M, Tschirky S, du Fay de Lavallaz J, Kozhuharov N, Sazgary L, Mueller D, Breidthardt T, Strebel I, Flores Widmer D, Shrestha S, Miro O, Martin-Sanchez FJ, Morawiec B, Parenica J, Geigy N, Keller DI, Rentsch K, von Eckardstein A, Osswald S, Reichlin T, Mueller C. 0/1-Hour Triage Algorithm for Myocardial Infarction in Patients With Renal Dysfunction. Circulation. 2018 Jan 30;137(5):436-451. doi: 10.1161/CIRCULATIONAHA.117.028901. Epub 2017 Nov 3.
citation: Kaier TE, Twerenbold R, Puelacher C, Marjot J, Imambaccus N, Boeddinghaus J, Nestelberger T, Badertscher P, Sabti Z, Gimenez MR, Wildi K, Hillinger P, Grimm K, Loeffel S, Shrestha S, Widmer DF, Cupa J, Kozhuharov N, Miro O, Martin-Sanchez FJ, Morawiec B, Rentsch K, Lohrmann J, Kloos W, Osswald S, Reichlin T, Weber E, Marber M, Mueller C. Direct Comparison of Cardiac Myosin-Binding Protein C With Cardiac Troponins for the Early Diagnosis of Acute Myocardial Infarction. Circulation. 2017 Oct 17;136(16):1495-1508. doi: 10.1161/CIRCULATIONAHA.117.028084. Epub 2017 Sep 26.
citation: Nestelberger T, Boeddinghaus J, Badertscher P, Twerenbold R, Wildi K, Breitenbucher D, Sabti Z, Puelacher C, Rubini Gimenez M, Kozhuharov N, Strebel I, Sazgary L, Schneider D, Jann J, du Fay de Lavallaz J, Miro O, Martin-Sanchez FJ, Morawiec B, Kawecki D, Muzyk P, Keller DI, Geigy N, Osswald S, Reichlin T, Mueller C; APACE Investigators. Effect of Definition on Incidence and Prognosis of Type 2 Myocardial Infarction. J Am Coll Cardiol. 2017 Sep 26;70(13):1558-1568. doi: 10.1016/j.jacc.2017.07.774.
citation: Twerenbold R, Badertscher P, Boeddinghaus J, Nestelberger T, Wildi K, Rubini Gimenez M, Miro O, Martin-Sanchez FJ, Reichlin T, Mueller C. Effect of the FDA Regulatory Approach on the 0/1-h Algorithm for Rapid Diagnosis of MI. J Am Coll Cardiol. 2017 Sep 19;70(12):1532-1534. doi: 10.1016/j.jacc.2017.07.746. No abstract available.
citation: Wildi K, Cullen L, Twerenbold R, Greenslade JH, Parsonage W, Boeddinghaus J, Nestelberger T, Sabti Z, Rubini-Gimenez M, Puelacher C, Cupa J, Schumacher L, Badertscher P, Grimm K, Kozhuharov N, Stelzig C, Freese M, Rentsch K, Lohrmann J, Kloos W, Buser A, Reichlin T, Pickering JW, Than M, Mueller C. Direct Comparison of 2 Rule-Out Strategies for Acute Myocardial Infarction: 2-h Accelerated Diagnostic Protocol vs 2-h Algorithm. Clin Chem. 2017 Jul;63(7):1227-1236. doi: 10.1373/clinchem.2016.268359. Epub 2017 May 17.
citation: Boeddinghaus J, Nestelberger T, Twerenbold R, Wildi K, Badertscher P, Cupa J, Burge T, Machler P, Corbiere S, Grimm K, Gimenez MR, Puelacher C, Shrestha S, Flores Widmer D, Fuhrmann J, Hillinger P, Sabti Z, Honegger U, Schaerli N, Kozhuharov N, Rentsch K, Miro O, Lopez B, Martin-Sanchez FJ, Rodriguez-Adrada E, Morawiec B, Kawecki D, Ganovska E, Parenica J, Lohrmann J, Kloos W, Buser A, Geigy N, Keller DI, Osswald S, Reichlin T, Mueller C. Direct Comparison of 4 Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I. Circulation. 2017 Apr 25;135(17):1597-1611. doi: 10.1161/CIRCULATIONAHA.116.025661. Epub 2017 Mar 10.
citation: Klinkenberg LJ, Wildi K, van der Linden N, Kouw IW, Niens M, Twerenbold R, Rubini Gimenez M, Puelacher C, Daniel Neuhaus J, Hillinger P, Nestelberger T, Boeddinghaus J, Grimm K, Sabti Z, Bons JA, van Suijlen JD, Tan FE, Ten Kate J, Bekers O, van Loon LJ, van Dieijen-Visser MP, Mueller C, Meex SJ. Diurnal Rhythm of Cardiac Troponin: Consequences for the Diagnosis of Acute Myocardial Infarction. Clin Chem. 2016 Dec;62(12):1602-1611. doi: 10.1373/clinchem.2016.257485. Epub 2016 Oct 5.
citation: Hillinger P, Twerenbold R, Wildi K, Rubini Gimenez M, Jaeger C, Boeddinghaus J, Nestelberger T, Grimm K, Reichlin T, Stallone F, Puelacher C, Sabti Z, Kozhuharov N, Honegger U, Ballarino P, Miro O, Denhaerynck K, Ekrem T, Kohler C, Bingisser R, Osswald S, Mueller C. Gender-specific uncertainties in the diagnosis of acute coronary syndrome. Clin Res Cardiol. 2017 Jan;106(1):28-37. doi: 10.1007/s00392-016-1020-y. Epub 2016 Jul 12.
citation: Twerenbold R, Jaeger C, Rubini Gimenez M, Wildi K, Reichlin T, Nestelberger T, Boeddinghaus J, Grimm K, Puelacher C, Moehring B, Pretre G, Schaerli N, Campodarve I, Rentsch K, Steuer S, Osswald S, Mueller C. Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. Eur Heart J. 2016 Nov 21;37(44):3324-3332. doi: 10.1093/eurheartj/ehw232. Epub 2016 Jun 29.
citation: Parsonage WA, Mueller C, Greenslade JH, Wildi K, Pickering J, Than M, Aldous S, Boeddinghaus J, Hammett CJ, Hawkins T, Nestelberger T, Reichlin T, Reidt S, Rubin Gimenez M, Tate JR, Twerenbold R, Ungerer JP, Cullen L. Validation of NICE diagnostic guidance for rule out of myocardial infarction using high-sensitivity troponin tests. Heart. 2016 Aug 15;102(16):1279-86. doi: 10.1136/heartjnl-2016-309270. Epub 2016 Jun 10.
citation: Abacherli R, Isaksen J, Schmid R, Leber R, Schmid HJ, Generali G. Digital DC-Reconstruction of AC-Coupled Electrophysiological Signals with a Single Inverting Filter. PLoS One. 2016 Mar 3;11(3):e0150207. doi: 10.1371/journal.pone.0150207. eCollection 2016.
citation: Hillinger P, Twerenbold R, Jaeger C, Wildi K, Reichlin T, Rubini Gimenez M, Engels U, Miro O, Boeddinghaus J, Puelacher C, Nestelberger T, Rothlisberger M, Ernst S, Rentsch K, Mueller C. Optimizing Early Rule-Out Strategies for Acute Myocardial Infarction: Utility of 1-Hour Copeptin. Clin Chem. 2015 Dec;61(12):1466-74. doi: 10.1373/clinchem.2015.242743. Epub 2015 Aug 31.
citation: Twerenbold R, Wildi K, Jaeger C, Gimenez MR, Reiter M, Reichlin T, Walukiewicz A, Gugala M, Krivoshei L, Marti N, Moreno Weidmann Z, Hillinger P, Puelacher C, Rentsch K, Honegger U, Schumacher C, Zurbriggen F, Freese M, Stelzig C, Campodarve I, Bassetti S, Osswald S, Mueller C. Optimal Cutoff Levels of More Sensitive Cardiac Troponin Assays for the Early Diagnosis of Myocardial Infarction in Patients With Renal Dysfunction. Circulation. 2015 Jun 9;131(23):2041-50. doi: 10.1161/CIRCULATIONAHA.114.014245. Epub 2015 May 6.
citation: Wildi K, Gimenez MR, Twerenbold R, Reichlin T, Jaeger C, Heinzelmann A, Arnold C, Nelles B, Druey S, Haaf P, Hillinger P, Schaerli N, Kreutzinger P, Tanglay Y, Herrmann T, Moreno Weidmann Z, Krivoshei L, Freese M, Stelzig C, Puelacher C, Rentsch K, Osswald S, Mueller C. Misdiagnosis of Myocardial Infarction Related to Limitations of the Current Regulatory Approach to Define Clinical Decision Values for Cardiac Troponin. Circulation. 2015 Jun 9;131(23):2032-40. doi: 10.1161/CIRCULATIONAHA.114.014129. Epub 2015 May 6.
citation: Reichlin T, Twerenbold R, Wildi K, Gimenez MR, Bergsma N, Haaf P, Druey S, Puelacher C, Moehring B, Freese M, Stelzig C, Krivoshei L, Hillinger P, Jager C, Herrmann T, Kreutzinger P, Radosavac M, Weidmann ZM, Pershyna K, Honegger U, Wagener M, Vuillomenet T, Campodarve I, Bingisser R, Miro O, Rentsch K, Bassetti S, Osswald S, Mueller C. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay. CMAJ. 2015 May 19;187(8):E243-E252. doi: 10.1503/cmaj.141349. Epub 2015 Apr 13.
citation: Rubini Gimenez M, Twerenbold R, Jaeger C, Schindler C, Puelacher C, Wildi K, Reichlin T, Haaf P, Merk S, Honegger U, Wagener M, Druey S, Schumacher C, Krivoshei L, Hillinger P, Herrmann T, Campodarve I, Rentsch K, Bassetti S, Osswald S, Mueller C. One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I. Am J Med. 2015 Aug;128(8):861-870.e4. doi: 10.1016/j.amjmed.2015.01.046. Epub 2015 Mar 31.
citation: Wildi K, Cuculi F, Twerenbold R, Marxer T, Rubini Gimenez M, Reichlin T, Haaf P, Monsch R, Marsch S, Hunziker P, Bingisser R, Osswald S, Erne P, Mueller C. Incidence and timing of serious arrhythmias after early revascularization in non ST-elevation myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2015 Aug;4(4):359-64. doi: 10.1177/2048872614557230. Epub 2014 Oct 27.
citation: Rubini Gimenez M, Reiter M, Twerenbold R, Reichlin T, Wildi K, Haaf P, Wicki K, Zellweger C, Hoeller R, Moehring B, Sou SM, Mueller M, Denhaerynck K, Meller B, Stallone F, Henseler S, Bassetti S, Geigy N, Osswald S, Mueller C. Sex-specific chest pain characteristics in the early diagnosis of acute myocardial infarction. JAMA Intern Med. 2014 Feb 1;174(2):241-9. doi: 10.1001/jamainternmed.2013.12199.
citation: Rubini Gimenez M, Hoeller R, Reichlin T, Zellweger C, Twerenbold R, Reiter M, Moehring B, Wildi K, Mosimann T, Mueller M, Meller B, Hochgruber T, Ziller R, Sou SM, Murray K, Sakarikos K, Ernst S, Gea J, Campodarve I, Vilaplana C, Haaf P, Steuer S, Minners J, Osswald S, Mueller C. Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin. Int J Cardiol. 2013 Oct 9;168(4):3896-901. doi: 10.1016/j.ijcard.2013.06.049. Epub 2013 Jul 20.
citation: Balmelli C, Meune C, Twerenbold R, Reichlin T, Rieder S, Drexler B, Rubini MG, Mosimann T, Reiter M, Haaf P, Mueller M, Ernst S, Ballarino P, Alafify AA, Zellweger C, Wildi K, Moehring B, Vilaplana C, Bernhard D, Merk S, Ebmeyer S, Freidank H, Osswald S, Mueller C. 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. Am Heart J. 2013 Jul;166(1):30-7. doi: 10.1016/j.ahj.2013.03.014. Epub 2013 Apr 30.
citation: Hoeller R, Rubini Gimenez M, Reichlin T, Twerenbold R, Zellweger C, Moehring B, Wildi K, Freese M, Stelzig C, Hartmann B, Stoll M, Mosimann T, Reiter M, Haaf P, Mueller M, Meller B, Hochgruber T, Balmelli C, Sou SM, Murray K, Freidank H, Steuer S, Minners J, Osswald S, Mueller C. Normal presenting levels of high-sensitivity troponin and myocardial infarction. Heart. 2013 Nov;99(21):1567-72. doi: 10.1136/heartjnl-2013-303643. Epub 2013 Apr 19.
citation: Cullen L, Mueller C, Parsonage WA, Wildi K, Greenslade JH, Twerenbold R, Aldous S, Meller B, Tate JR, Reichlin T, Hammett CJ, Zellweger C, Ungerer JPJ, Rubini Gimenez M, Troughton R, Murray K, Brown AFT, Mueller M, George P, Mosimann T, Flaws DF, Reiter M, Lamanna A, Haaf P, Pemberton CJ, Richards AM, Chu K, Reid CM, Peacock WF, Jaffe AS, Florkowski C, Deely JM, Than M. Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome. J Am Coll Cardiol. 2013 Oct 1;62(14):1242-1249. doi: 10.1016/j.jacc.2013.02.078. Epub 2013 Apr 10.
citation: Reichlin T, Twerenbold R, Maushart C, Reiter M, Moehring B, Schaub N, Balmelli C, Rubini Gimenez M, Hoeller R, Sakarikos K, Drexler B, Haaf P, Osswald S, Mueller C. Risk stratification in patients with unstable angina using absolute serial changes of 3 high-sensitive troponin assays. Am Heart J. 2013 Mar;165(3):371-8.e3. doi: 10.1016/j.ahj.2012.11.010. Epub 2013 Jan 24.
citation: Haaf P, Twerenbold R, Reichlin T, Faoro J, Reiter M, Meune C, Steuer S, Bassetti S, Ziller R, Balmelli C, Campodarve I, Zellweger C, Kilchenmann A, Irfan A, Papassotiriou J, Drexler B, Mueller C. Mid-regional pro-adrenomedullin in the early evaluation of acute chest pain patients. Int J Cardiol. 2013 Sep 30;168(2):1048-55. doi: 10.1016/j.ijcard.2012.10.025. Epub 2012 Nov 27.
citation: Reichlin T, Twerenbold R, Reiter M, Steuer S, Bassetti S, Balmelli C, Winkler K, Kurz S, Stelzig C, Freese M, Drexler B, Haaf P, Zellweger C, Osswald S, Mueller C. Introduction of high-sensitivity troponin assays: impact on myocardial infarction incidence and prognosis. Am J Med. 2012 Dec;125(12):1205-1213.e1. doi: 10.1016/j.amjmed.2012.07.015.
citation: Haaf P, Drexler B, Reichlin T, Twerenbold R, Reiter M, Meissner J, Schaub N, Stelzig C, Freese M, Heinzelmann A, Meune C, Balmelli C, Freidank H, Winkler K, Denhaerynck K, Hochholzer W, Osswald S, Mueller C. High-sensitivity cardiac troponin in the distinction of acute myocardial infarction from acute cardiac noncoronary artery disease. Circulation. 2012 Jul 3;126(1):31-40. doi: 10.1161/CIRCULATIONAHA.112.100867. Epub 2012 May 23.
citation: Potocki M, Reichlin T, Thalmann S, Zellweger C, Twerenbold R, Reiter M, Steuer S, Bassetti S, Drexler B, Stelzig C, Freese M, Winkler K, Haaf P, Balmelli C, Hochholzer W, Osswald S, Mueller C. 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. Heart. 2012 Apr;98(7):558-65. doi: 10.1136/heartjnl-2011-301269. Epub 2012 Feb 15.
citation: Schaub N, Reichlin T, Meune C, Twerenbold R, Haaf P, Hochholzer W, Niederhauser N, Bosshard P, Stelzig C, Freese M, Reiter M, Gea J, Buser A, Mebazaa A, Osswald S, Mueller C. Markers of plaque instability in the early diagnosis and risk stratification of acute myocardial infarction. Clin Chem. 2012 Jan;58(1):246-56. doi: 10.1373/clinchem.2011.172940. Epub 2011 Nov 4.
citation: Reiter M, Twerenbold R, Reichlin T, Benz B, Haaf P, Meissner J, Hochholzer W, Stelzig C, Freese M, Heinisch C, Balmelli C, Drexler B, Freidank H, Winkler K, Campodarve I, Gea J, Mueller C. Early diagnosis of acute myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays. Eur Heart J. 2012 Apr;33(8):988-97. doi: 10.1093/eurheartj/ehr376. Epub 2011 Oct 31.
citation: 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. Incremental value of high-sensitivity cardiac troponin T for risk prediction in patients with suspected acute myocardial infarction. Clin Chem. 2011 Sep;57(9):1318-26. doi: 10.1373/clinchem.2011.162073. Epub 2011 Jul 19.
citation: Reichlin T, Irfan A, Twerenbold R, Reiter M, Hochholzer W, Burkhalter H, Bassetti S, Steuer S, Winkler K, Peter F, Meissner J, Haaf P, Potocki M, Drexler B, Osswald S, Mueller C. Utility of absolute and relative changes in cardiac troponin concentrations in the early diagnosis of acute myocardial infarction. Circulation. 2011 Jul 12;124(2):136-45. doi: 10.1161/CIRCULATIONAHA.111.023937. Epub 2011 Jun 27.
citation: 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. Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays. Eur Heart J. 2011 Jun;32(11):1379-89. doi: 10.1093/eurheartj/ehr033. Epub 2011 Feb 28.
citation: Hochholzer W, Reichlin T, Stelzig C, Hochholzer K, Meissner J, Breidthardt T, Reiter M, Duehsler B, Freidank H, Winkler K, Twerenbold R, Mueller C. 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. Eur Heart J. 2011 Feb;32(3):326-35. doi: 10.1093/eurheartj/ehq429. Epub 2010 Dec 7.
citation: Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, Biedert S, Schaub N, Buerge C, Potocki M, Noveanu M, Breidthardt T, Twerenbold R, Winkler K, Bingisser R, Mueller C. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med. 2009 Aug 27;361(9):858-67. doi: 10.1056/NEJMoa0900428.
citation: Reichlin T, Hochholzer W, Stelzig C, Laule K, Freidank H, Morgenthaler NG, Bergmann A, Potocki M, Noveanu M, Breidthardt T, Christ A, Boldanova T, Merki R, Schaub N, Bingisser R, Christ M, Mueller C. Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol. 2009 Jun 30;54(1):60-8. doi: 10.1016/j.jacc.2009.01.076.