HEARTBEAT-TROP. Polyethylene Glycol Precipitation to Unmask Macrotroponin (MACRO-TROP)

HEARTBEAT-TROP. Testing of Polyethylene Glycol Precipitation to Unmask Macrotroponin in Acute Coronary Syndrome and Marathon Runners.

Troponin elevation can, among others, be due to myocardial infarction, acute inflammation or structural heart disease. Formation of macrocomplexes against troponin is an underestimated cause for persistent troponin elevation. Polyethlylene glycol precipitation (PEG) can differentiate macrotroponin from real troponin elevation, but cut-off values for PEG have not been established. PEG is analyzed in patients with acute coronary syndrome undergoing invasive coronary angiography and compared to healthy marathon runners who have undergone cardiological pre-participation screening and have rested for 24 hours.

Study Overview

• Status: Recruiting
• Conditions: Diagnoses Disease
• Intervention / Treatment: Diagnostic test: Polyethylene glycol precipitation; Diagnostic test: Transthoracic echocardiography

Detailed Description

Troponin elevation can be caused by acute coronary syndrome, myocarditis or structural heart disease. In most cases, troponin levels drop back to normal after the acute phase of the disease. In some cases, troponin elevation may persist despite clinical recovery due to macrocomplex formation. In athletes, this may cause unnecessary exclusion from competitive sport. Polypethylene glycol precipitation (PEG) has emerged as a cost-effective and feasible laboratory method to reveal macrotroponin. However, cut-off values have not been established for macrotroponin. PEG will be assessed in patients presenting with acute coronary syndrome (ACS) and undergoing invasive coronary angiography and compared to healthy controls, marathon runners who have undergone cardiological pre-participation screening and have been cleared for competition. 24 hours of rest are required before troponin levels are assessed in these athletes. In the control group of marathon runners, PEG will also be analyzed within one hour after crossing the finishing line. In both groups, blood lipids (LDL-cholesterol, lipoprotein a), blood glucose and hemoglobin 1Ac will be assessed at baseline. Transthoracic echocardiography will be performed in both groups at baseline. Also, in the marathon group echocardiography will be performed within one hour after completion of the race. PEG and echocardiography will also be repeated in the group of ACS within 24 hours before hospital discharge. The primary outcome is PEG recovery in both groups at presentation (upon emergency presentation in ACS and baseline examination in athletes). Secondary outcomes are PEG recovery values in the second exam (before discharge in ACS and within one hour after marathon completion in athletes), left and right ventricular ejection fraction in both groups during both exams. Athletes are defined as marathon participants older than 18 years without overt cardiovascular disease.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Simon Wernhart, MD, PhD; Phone Number: +491751830099; Email: simon.wernhart@gmx.de
• Study Contact Backup: Name: Sebastian Zenk, MD; Phone Number: +49821227800; Email: sebastian.zenk@synlab.com

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany
      • Recruiting
      • Technical University Munich
      • Contact: Simon Wernhart, MD, PhD; Phone Number: +491751830099; Email: simon.wernhart@gmx.de
      • Contact: Sebastian Zenk, MD; Phone Number: +49821227800; Email: sebastian.zenk@synlab.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age above 18 years
• Group with acute coronary syndrome (ACS): Diagnosis of ACS (ST-segment elevation or non-ST-segment elevation myocardial infarction according to the European Society of Cardiology Guidelines 2023 with at least one measurement of high sensitive troponin I or T above the 99th percentile of reference).
• Marathon runners: Participation in a marathon following cardiological pre-participation screening and medical clearance for competition. No clinical signs of cardiovascular or structural heart disease

Exclusion Criteria:

• Patients with acute coronary syndrome: Known macrotroponin, terminal renal disease (glomerular filtration rate below 10ml per minute), diagnosis of cancer, pregnancy
• Marathon runners: Coronary artery disease, structural heart disease, diagnosis of cancer, pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Marathon runners; Marathon runners are expected to have no elevated troponin at baseline after 24 hours of rest	Diagnostic test: Polyethylene glycol precipitation; PEG will be assessed in patients with acute coronary syndrome upon presentation and before hospital discharge. Athletes will receive this intervention at baseline and within one hour after completion of the marathon; Diagnostic test: Transthoracic echocardiography; Patients with acute coronary syndrome will receive echocardiography upon presentation and before hospital discharge. Athletes will receive echocardiography at baseline and within one after marathon completion.
Other: Patients with acute coronary syndrome; Troponin will be elevated in acute coronary syndrome per definition	Diagnostic test: Polyethylene glycol precipitation; PEG will be assessed in patients with acute coronary syndrome upon presentation and before hospital discharge. Athletes will receive this intervention at baseline and within one hour after completion of the marathon; Diagnostic test: Transthoracic echocardiography; Patients with acute coronary syndrome will receive echocardiography upon presentation and before hospital discharge. Athletes will receive echocardiography at baseline and within one after marathon completion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery of troponin after polyethylene glycole precipitation in health and disease	Comparison of polyethylene glycol recovery in athletes at rest and patients during acute coronary syndrome	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery of troponin after polyethylene glycol precipitation after marathon running	Recovery of troponin after polyethlyene glycol will be assessed within one hour after completion of a marathon	Day 2
Recovery of troponin after polyethylene glycole precipitation in patients with acute coronary syndrome upon hospital discharge	Recovery of troponin after polyethylene glycole precipitation within 24 hours before hospital discharge following treatment of acute coronary syndrome	Day 2
Left and right ventricular ejection fraction in athletes at baseline	Left and right ventricular ejection fraction in athletes at baseline	Day 1
Left and right ventricular ejection fraction after marathon running	Left and right ventricular ejection fraction will be assessed with one hour after completion of a marathon	Day 2
Left and right ventricular ejection fraction during acute coronary syndrome	Left and right ventricular ejection fraction during acute presentation with acute coronary syndrome	Day 1
Left and right ventricular ejection fraction after acute coronary syndrome	Left and right ventricular ejection fraction after acute coronary syndrome, echocardiography will be performed within one day before hospital discharge	Day 2

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Simon Wernhart, MD, PhD, TUM - Technische Universität München

Publications and helpful links

General Publications

• Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, Claeys MJ, Dan GA, Dweck MR, Galbraith M, Gilard M, Hinterbuchner L, Jankowska EA, Juni P, Kimura T, Kunadian V, Leosdottir M, Lorusso R, Pedretti RFE, Rigopoulos AG, Rubini Gimenez M, Thiele H, Vranckx P, Wassmann S, Wenger NK, Ibanez B; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. No abstract available.
• Stekelenburg JO, Berge K, Janssen SLJE, Omland T, Myhre PL, Thompson PD, Aengevaeren VL, Eijsvogels TMH. Prevalence and Predictors of Cardiac Troponin Elevations Following Exercise: a Systematic Review, Meta-analysis, and Meta-regression. Eur J Prev Cardiol. 2026 Apr 15:zwag218. doi: 10.1093/eurjpc/zwag218. Online ahead of print.
• Salaun E, Drory S, Cote MA, Tremblay V, Bedard E, Steinberg C, Pare D, O'Connor K, Cieza T, Cote N, Poirier P, Douville P, Blais J, Desmeules P, Kalavrouziotis D, Mohammadi S, Voisine P, Bernier M, Pibarot P, Theriault S. Role of Antitroponin Antibodies and Macrotroponin in the Clinical Interpretation of Cardiac Troponin. J Am Heart Assoc. 2024 Jun 18;13(12):e035128. doi: 10.1161/JAHA.123.035128. Epub 2024 Jun 15.
• Hammarsten O, Warner JV, Lam L, Kavsak P, Lindahl B, Aakre KM, Collinson P, Jaffe AS, Saenger AK, Body R, Mills NL, Omland T, Ordonez-Llanos J, Apple FS. Antibody-mediated interferences affecting cardiac troponin assays: recommendations from the IFCC Committee on Clinical Applications of Cardiac Biomarkers. Clin Chem Lab Med. 2023 Mar 24;61(8):1411-1419. doi: 10.1515/cclm-2023-0028. Print 2023 Jul 26.
• Hammarsten O, Becker C, Engberg AE. Methods for analyzing positive cardiac troponin assay interference. Clin Biochem. 2023 Jun;116:24-30. doi: 10.1016/j.clinbiochem.2023.03.004. Epub 2023 Mar 6.
• Wernhart S, Halle M, Zenk S. Handling persistent cardiac troponin elevation in asymptomatic athletes: The role of macrocomplexes. Am Heart J Plus. 2026 May 25;67:100804. doi: 10.1016/j.ahjo.2026.100804. eCollection 2026 Jul.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 18, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 24, 2026

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: athletes; troponin; polyethylene glycol precipitation
• Additional Relevant MeSH Terms: Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Diagnostic Techniques, Cardiovascular; Heart Function Tests; Cardiac Imaging Techniques; Ultrasonography; Echocardiography
• Other Study ID Numbers: 2026-319-S-CT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be provided upon reasonable request and adherence to national data security policy
• IPD Sharing Time Frame: Information will be made available upon reasonable request starting from 01.01.2028 until 31.12.2028.
• IPD Sharing Access Criteria: Direct contact to the principal investigator will be needed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No