. 2025 Jun;4(6 Pt 1):101821.

doi: 10.1016/j.jacadv.2025.101821. Epub 2025 May 22.

Derivation and Validation of ESC-0/1-h Algorithm for High-Sensitivity Troponin T and I in Cancer Patients

Paolo Bima¹, Pedro Lopez-Ayala², Luca Koechlin³, Fulvio Morello⁴, Jasper Boeddinghaus⁵, Mihaela Dimitrova², Carlos C Spagnuolo², Emel Kaplan², Thomas Nestelberger², Jonas Glaeser², Karin Wildi², Jeanne du Fay de Lavallaz², Beata Morawiec⁶, Oscar Miro⁷, Gemma Martínez-Nadal⁷, Francisco J Martin-Sanchez⁸, Michael Christ⁹, Ksenija Slankamenac¹⁰, Giulia Labarile⁴, Bertil Lindahl¹¹, Evangelos Giannitsis¹², Enrico Lupia⁴, Christian Mueller¹³; APACE and TRAPID-AMI Investigators

Collaborators, Affiliations

Collaborators

APACE and TRAPID-AMI Investigators:
Maria Rubini Gimenez², Bernhard Okamura², Tamar S Muench-Gerber², Alessandra Sanzone², Tobias Zimmermann², Desiree Wussler², Joan Walter², Patrick Badertscher², Christian Puelacher¹⁴, Dagmar Keller¹⁵, Tobias Breidthardt¹⁶, Eliska Potlukova², Damian Kawecki¹⁷, Nicolas Geigy¹⁸, Katharina Rentsch¹⁹, Piotr Munzk¹⁷, Gemma Martinez-Nadal²⁰, Esther Rodriguez Adrada²¹, Eva Ganovská²², Jiri Parenica²², Arnold von Eckardstein²³, Isabel Campodarve²⁴, James McCord²⁵, Richard Nowak²⁶, Richard Body²⁷, Christopher R deFilippi²⁸, Robert H Christenson²⁹, Mauro Panteghini³⁰, Mario Plebani³¹, Franck Verschuren³², John French³³, Silvia Weiser³⁴, Tomas Jernberg³⁵, Aitor Alquézar-Arbé³⁶, Jordi Ordonez-Llanos³⁷

Affiliations

¹ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy; Dipartimento di Scienze Mediche, Università degli Studi di Torino, Torino, Italy. Electronic address: paolo.bima@usb.ch.
² Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy.
³ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy; Department of Cardiac Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
⁴ Dipartimento di Scienze Mediche, Università degli Studi di Torino, Torino, Italy.
⁵ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy; BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
⁶ 2nd Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Katowice, Katowice, Poland.
⁷ Emergency Department, Hospital Clinic, Barcelona, Catalonia, Spain.
⁸ Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.
⁹ Department of Emergency Medicine, Luzerner Kantonsspital, Luzern, Switzerland.
¹⁰ Emergency Department, University Hospital Zurich, Zurich, Switzerland.
¹¹ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹² Department of Medicine III, University Hospital Heidelberger, Heidelberg, Germany.
¹³ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy. Electronic address: christian.mueller@usb.ch.
¹⁴ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy; Department of Cardiology, University Hospital Innsbruck, Innsbruck, Austria.
¹⁵ Emergency Department, University Hospital Zürich, Zürich, Switzerland.
¹⁶ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy; Department of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
¹⁷ GREAT Network, Rome, Italy; 2nd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Katowice, Katowice, Poland.
¹⁸ Emergency Department, Kantonsspital Liestal, Liestal, Switzerland.
¹⁹ Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
²⁰ GREAT Network, Rome, Italy; Emergency Department, Hospital Clinic, Barcelona, Catalonia, Spain.
²¹ GREAT Network, Rome, Italy; Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.
²² GREAT Network, Rome, Italy; Department of Cardiology, University Hospital Brno, Czech Republic and Medical Faculty, Masaryk University, Brno, Czech Republic.
²³ Department of Laboratory Medicine, University Hospital Zurich, Zurich, Switzerland.
²⁴ Hospital del Mar, Barcelona, Spain.
²⁵ Heart and Vascular Institute, Henry Ford Health System, Detroit, Michigan, USA.
²⁶ Department of Emergency Medicine, Henry Ford Health System, Detroit, Michigan, USA.
²⁷ Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
²⁸ Inova Heart and Vascular Institute, Falls Church, Virginia, USA.
²⁹ Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Maryland School of Medicine, Baltimore, Maryland, USA.
³⁰ University of Milan Medical School, Milan, Italy.
³¹ Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy.
³² Department of Acute Medicine, Cliniques Universitaires St-Luc and Universite Catholique de Louvain, Brussels, Belgium.
³³ Liverpool Hospital and University of New South Wales, Liverpool, New South Wales, Australia.
³⁴ Roche Diagnostics Germany, Penzberg, Germany.
³⁵ Department of Medicine, Karolinksa Institutet, Huddinge, Sweden.
³⁶ Emergency Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
³⁷ Department of Clinical Biochemistry, Universitat Autonoma, Barcelona, Spain.

PMID: 40408798
PMCID: PMC12152628
DOI: 10.1016/j.jacadv.2025.101821

Derivation and Validation of ESC-0/1-h Algorithm for High-Sensitivity Troponin T and I in Cancer Patients

Paolo Bima et al. JACC Adv. 2025 Jun.

. 2025 Jun;4(6 Pt 1):101821.

doi: 10.1016/j.jacadv.2025.101821. Epub 2025 May 22.

Authors

Collaborators

APACE and TRAPID-AMI Investigators:
Maria Rubini Gimenez², Bernhard Okamura², Tamar S Muench-Gerber², Alessandra Sanzone², Tobias Zimmermann², Desiree Wussler², Joan Walter², Patrick Badertscher², Christian Puelacher¹⁴, Dagmar Keller¹⁵, Tobias Breidthardt¹⁶, Eliska Potlukova², Damian Kawecki¹⁷, Nicolas Geigy¹⁸, Katharina Rentsch¹⁹, Piotr Munzk¹⁷, Gemma Martinez-Nadal²⁰, Esther Rodriguez Adrada²¹, Eva Ganovská²², Jiri Parenica²², Arnold von Eckardstein²³, Isabel Campodarve²⁴, James McCord²⁵, Richard Nowak²⁶, Richard Body²⁷, Christopher R deFilippi²⁸, Robert H Christenson²⁹, Mauro Panteghini³⁰, Mario Plebani³¹, Franck Verschuren³², John French³³, Silvia Weiser³⁴, Tomas Jernberg³⁵, Aitor Alquézar-Arbé³⁶, Jordi Ordonez-Llanos³⁷

Affiliations

¹ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy; Dipartimento di Scienze Mediche, Università degli Studi di Torino, Torino, Italy. Electronic address: paolo.bima@usb.ch.
² Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy.
³ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy; Department of Cardiac Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
⁴ Dipartimento di Scienze Mediche, Università degli Studi di Torino, Torino, Italy.
⁵ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy; BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
⁶ 2nd Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Katowice, Katowice, Poland.
⁷ Emergency Department, Hospital Clinic, Barcelona, Catalonia, Spain.
⁸ Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.
⁹ Department of Emergency Medicine, Luzerner Kantonsspital, Luzern, Switzerland.
¹⁰ Emergency Department, University Hospital Zurich, Zurich, Switzerland.
¹¹ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹² Department of Medicine III, University Hospital Heidelberger, Heidelberg, Germany.
¹³ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy. Electronic address: christian.mueller@usb.ch.
¹⁴ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy; Department of Cardiology, University Hospital Innsbruck, Innsbruck, Austria.
¹⁵ Emergency Department, University Hospital Zürich, Zürich, Switzerland.
¹⁶ Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; GREAT Network, Rome, Italy; Department of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
¹⁷ GREAT Network, Rome, Italy; 2nd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Katowice, Katowice, Poland.
¹⁸ Emergency Department, Kantonsspital Liestal, Liestal, Switzerland.
¹⁹ Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
²⁰ GREAT Network, Rome, Italy; Emergency Department, Hospital Clinic, Barcelona, Catalonia, Spain.
²¹ GREAT Network, Rome, Italy; Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.
²² GREAT Network, Rome, Italy; Department of Cardiology, University Hospital Brno, Czech Republic and Medical Faculty, Masaryk University, Brno, Czech Republic.
²³ Department of Laboratory Medicine, University Hospital Zurich, Zurich, Switzerland.
²⁴ Hospital del Mar, Barcelona, Spain.
²⁵ Heart and Vascular Institute, Henry Ford Health System, Detroit, Michigan, USA.
²⁶ Department of Emergency Medicine, Henry Ford Health System, Detroit, Michigan, USA.
²⁷ Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
²⁸ Inova Heart and Vascular Institute, Falls Church, Virginia, USA.
²⁹ Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Maryland School of Medicine, Baltimore, Maryland, USA.
³⁰ University of Milan Medical School, Milan, Italy.
³¹ Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy.
³² Department of Acute Medicine, Cliniques Universitaires St-Luc and Universite Catholique de Louvain, Brussels, Belgium.
³³ Liverpool Hospital and University of New South Wales, Liverpool, New South Wales, Australia.
³⁴ Roche Diagnostics Germany, Penzberg, Germany.
³⁵ Department of Medicine, Karolinksa Institutet, Huddinge, Sweden.
³⁶ Emergency Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
³⁷ Department of Clinical Biochemistry, Universitat Autonoma, Barcelona, Spain.

PMID: 40408798
PMCID: PMC12152628
DOI: 10.1016/j.jacadv.2025.101821

Abstract

Background: The diagnostic performance of high-sensitivity cardiac troponin T/I (hs-cTnT/I) and the efficacy of the European Society of Cardiology (ESC) 0/1-h hs-cTnT/I algorithms for the early diagnosis of non-ST-elevation myocardial infarction are lower in cancer patients.

Objectives: The authors aimed to derive new cutoffs for ESC 0/1-h hs-cTnT/I algorithms optimized for use in patients with active or past cancer.

Methods: Patients presenting with suspected non-ST-elevation myocardial infarction to the emergency department enrolled in an international multicenter study were analyzed. Final diagnoses were centrally adjudicated by 2 independent cardiologists according to the fourth universal definition of myocardial infarction. External validation was performed in 2 independent cohorts.

Results: Among 541 eligible cancer patients, cancer-optimized ESC 0/1-h hs-cTnT cutoffs, <8 ng/L at presentation (if chest pain onset >3 hours) or <14 ng/L if 0/1 h-delta is <3 ng/L for rule-out and ≥54 ng/L or 0/1-h delta ≥4 ng/L for rule-in, increased the efficacy vs the current cutoffs from 58.6% (95% CI: 54.4-62.7) to 68.0% (95% CI: 64.0-71.8; P < 0.001). Sensitivity and specificity remained high and comparable. Similarly, among 516 eligible patients, cancer-optimized ESC 0/1-h hs-cTnI-Architect cutoffs, <7 ng/L at presentation (if chest pain onset >3 hours) or <10 ng/L if 0/1-h delta is <3 ng/L for rule-out and ≥61 ng/L or 0/1-h delta ≥5 ng/L for rule-in, increased the efficacy vs the current cutoffs from 59.3% (95% CI: 55.0-63.5) to 78.9% (95% CI: 75.2-82.2; P < 0.001). Sensitivity and specificity again remained high and comparable. Findings were confirmed in internal and external validation cohorts (n = 130 and n = 195 patients, respectively).

Conclusions: Cancer-optimized ESC 0/1-h hs-cTnT/I algorithm cutoffs increased efficacy maintaining high safety.

Keywords: cancer; cardiac troponin; cutoffs; diagnosis; myocardial infarction; prognosis.

PubMed Disclaimer

Conflict of interest statement

Funding support and author disclosures APACE was supported by research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the University Hospital Basel, the University of Basel, Abbott, Beckman Coulter, Idorsia, LSI-Medience, Roche, Ortho Clinical Diagnostics, Quidel, Siemens, SpinChip, and Singulex. The Turin-cancer cohort study was supported by the Fondazione Ricerca Molinette (Torino, Italy; Bando d'Eccellenza 2023 to EL) and by the Università degli Studi di Torino (grants MORF_RILO_21_02 and 23_03 to FM). We disclose that Dr Bima has received a research grant from the Swiss Heart Foundation (FF23062), unrelated to the present work. Dr Lopez-Ayala has received research grants from the Swiss Heart Foundation (FF20079 and FF21103) and speaker honoraria from Quidel, paid to the institution, outside the submitted work. Dr Nestelberger has received research support from the Swiss National Science Foundation (P400PM_191037/1), the Prof Dr Max Cloëtta Foundation, the Margarete und Walter Lichtenstein-Stiftung (3MS1038), and the University of Basel, the University Hospital Basel, as well as speaker/consulting honoraria or research support from Edwards Lifesciences, Pronova Medical, Meril, Boston Scientific, Medtronic, Abbott, Beckman Coulter, Bayer, Ortho Clinical Diagnostics, and Orion Pharma, outside the submitted work. Dr Boeddinghaus is supported by an Edinburgh Doctoral College Scholarship and received research grants from the University of Basel, the University Hospital of Basel, the Division of Internal Medicine, the Swiss Academy of Medical Sciences, the Gottfried and Julia Bangerter-Rhyner Foundation, the Swiss National Science Foundation, and the “Freie Akademische Gesellschaft Basel”; honoraria from Siemens Healthineers, Roche Diagnostics, Ortho Clinical Diagnostics, Quidel Corporation, and Beckman Coulter; and travel support from Medtronic and Cordis, all outside the submitted work. Dr Koechlin has received a research grant from the University of Basel, the Swiss Academy of Medical Sciences, and the Gottfried and Julia Bangerter-Rhyner Foundation, as well as the “Freiwillige Akademische Gesellschaft Basel,” and speaker honoraria from Roche Diagnostics, Abbott, and Siemens, outside the submitted work. Dr Martin-Sanchez has received speaker, advisory, or consulting fees from Novartis, MSD, Bristol-Myers Squibb, Pfizer, The Medicine Company, Otsuka, Thermo Fisher, Cardiorentis, and Sanofi and research grants from the Spanish Ministry of Health and FEDER, Mapfre, Novartis, Bayer, MSD, Abbott, and Orion-Pharma, outside the submitted work. Dr Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the University Hospital Basel, the University of Basel, Abbott, Beckman Coulter, Brahms, Idorsia, LSI-Medience, Novartis, Ortho Clinical, Quidel, Roche, Siemens, Singulex, SpinChip, Upstream, and Sphingotec, as well as speaker honoraria/consulting honoraria from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, BMS, Osler, Novartis, Roche, Siemens, SpinChip, and Singulex, outside the submitted work, all paid to the institution. Dr Wildi reports funding from the University of Basel, the Swiss National Foundation (320030-231521), the Wesley Medical Research Foundation, and the University of Queensland, all outside submitted work. Dr Morello received grants from the University of Torino. Dr Lupia received grant support from Università degli Studi di Torino and Fondazione Ricerca Molinette. All other authors declare that they have no conflict of interest with this study. The investigated hs-cTn assay was donated by the manufacturer, who had no role in the design of the study, the analysis of the data, the preparation of the manuscript, or the decision to submit the manuscript for publication. The authors designed the study, gathered and analyzed the data, vouch for the data and analysis, wrote the paper, and decided to publish. Drs Bima, Lopez-Ayala, Wildi, Nestelberger, Boeddinghaus, and Mueller had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors have read and approved the manuscript. The sponsors had no role in designing or conducting the study and no role in gathering or analyzing the data or writing the manuscript. The manuscript and its contents have not been published previously and are not being considered for publications elsewhere in whole or in part in any language, including publicly accessible web sites or e-print servers.

Figures

**Figure 1**
Diagnostic Performance of hs-cTnT Algorithm The diagnostic performance of the current (A) and cancer-optimized (B) ESC 0/1-h hs-cTnT algorithm in the APACE cohort is shown. APACE = Advantageous Predictors of Acute Coronary Syndromes Evaluation; CPO = chest pain onset; ESC = European Society of Cardiology; hs-cTnT = high-sensitivity cardiac troponin T; NPV = negative predictive value; NSTEMI = non-ST-segment elevation myocardial infarction; PPV = positive predictive value.

**Figure 2**
Diagnostic Performance of hs-cTnI Algorithm Diagnostic performance of the current (A) and cancer-optimized (B) ESC 0/1-h hs-cTnI algorithm in the APACE cohort is shown. APACE = Advantageous Predictors of Acute Coronary Syndromes Evaluation; ESC = European Society of Cardiology; hs-cTnI = high-sensitivity cardiac troponin I; NPV = negative predictive value; NSTEMI = non-ST-segment elevation myocardial infarction; PPV = positive predictive value.

**Figure 3**
Reclassification of Patients in the ESC Triage Groups These alluvial plots visualize the reclassification of patients according to the cancer-optimized ESC 0/1-h algorithms for hs-cTnT and hs-cTnI in the APACE cohort. APACE = Advantageous Predictors of Acute Coronary Syndromes Evaluation; ESC = European Society of Cardiology; hs-cTnI = high-sensitivity cardiac troponin I; hs-cTnT = high-sensitivity cardiac troponin T; MI = myocardial infarction.

**Figure 4**
Change in Key Performance Measures Change (cancer-optimized vs current ESC algorithm) in performance measures in all cohorts for hs-cTnT (A) and hs-cTnI (B) is shown. APACE = Advantageous Predictors of Acute Coronary Syndromes Evaluation; ESC = European Society of Cardiology; hs-cTnI = high-sensitivity cardiac troponin I; hs-cTnT = high-sensitivity cardiac troponin T; NPV = negative predictive value; PPV = positive predictive value; TRAPID-AMI = Troponin T assay for RAPID rule-out of acute MI.

**Figure 5**
5-Year All-Cause Mortality for hs-cTnT Five-year cumulative incidence curves for all-cause mortality stratified by the triage groups of the current (A) and cancer-optimized (B) ESC 0/1-h hs-cTnT algorithm are shown. ESC = European Society of Cardiology; hs-cTnT = high-sensitivity cardiac troponin T.

**Figure 6**
5-Year All-Cause Mortality for hs-cTnI Five-year cumulative incidence curves for all-cause mortality stratified by the triage groups of the current (A) and cancer-optimized (B) ESC 0/1-h hs-cTnI algorithm are shown. ESC = European Society of Cardiology; hs-cTnI = high-sensitivity cardiac troponin I.

**Central Illustration**
Derivation and Validation of Cancer-Optimized ESC 0/1-h hs-cTnT/I Algorithms Cancer patients with 0-h and 1-h hs-cTnT (Roche) and hs-cTnI (Abbott) available were used to derive, internally validate using a bootstrapping method, and externally validate cancer-optimized cutoffs to be used with the ESC 0/1-h algorithm. The cancer-optimized algorithms allowed for a significant reduction in the proportion of patients triaged to the observe zone without reducing sensitivity. APACE = Advantageous Predictors of Acute Coronary Syndromes Evaluation; ESC = European Society of Cardiology; hs-cTnI = high-sensitivity cardiac troponin I; hs-cTnT = high-sensitivity cardiac troponin T; TRAPID-AMI = Troponin T assay for RAPID rule-out of acute MI.

See this image and copyright information in PMC

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Derivation and Validation of ESC-0/1-h Algorithm for High-Sensitivity Troponin T and I in Cancer Patients

Collaborators

Affiliations

Derivation and Validation of ESC-0/1-h Algorithm for High-Sensitivity Troponin T and I in Cancer Patients

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

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