Ruling out acute coronary syndrome in primary care: a diagnostic trial (POB-HELP)

Simone van den Bulk; Annelieke HJ Petrus; Robert Willemsen; Mattijs E Numans; Mark J. Boogers; Maaike PJ. Hermans; Joan G. Meeder; Braim Rahel; Marcel Janssen; Geertjan Dinant; Christa M. Cobbaert; Tobias N Bonten

doi:10.3399/BJGP.2026.0167

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When is a negative troponin reassuring enough?
Simone van den Bulk

Published on: 25 September 2026
When is a negative troponin reassuring enough?
Kinan Mokbel

Published on: 16 September 2026

Published on: (25 September 2026)
Page navigation anchor for When is a negative troponin reassuring enough?
When is a negative troponin reassuring enough?
Simone van den Bulk, General practitioner in training, LUMC
We thank Professor Mokbel for his comments on our article and appreciate the opportunity to clarify these issues.

First, our primary aim was to evaluate the clinical decision rule (CDR) as a clinical pathway. The CDR combines clinical assessment with point-of-care high-sensitivity (hs-)troponin and allows for cardiologist consultation and GP override when considered necessary. We additionally report the performance of the CDR without these safeguards to assess its intrinsic safety, and that of a single hs-troponin measurement to describe the biomarker alone. Thus, our study evaluated the CDR as used in clinical practice, while the additional analyses help to disentangle the contribution of its individual components. The efficiency of such a pathway will, however, depend on local care organisation.

Second, the case of severe LAD disease illustrates that troponin should not replace clinical assessment. This is why hs-troponin was integrated into a CDR rather than used in isolation. Moreover, not referring a patient to the emergency department does not mean the diagnostic process ends; short-term outpatient assessment may be appropriate.

Finally, we included patients from one hour after symptom onset based on the ESC 2020 guideline,¹ which stated that hs-troponin levels usually rise within one hour after symptom onset. We agree that the 68 patients presenting within 1–3 hours are too few to draw conclusions, particularly given the low...
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We thank Professor Mokbel for his comments on our article and appreciate the opportunity to clarify these issues.

First, our primary aim was to evaluate the clinical decision rule (CDR) as a clinical pathway. The CDR combines clinical assessment with point-of-care high-sensitivity (hs-)troponin and allows for cardiologist consultation and GP override when considered necessary. We additionally report the performance of the CDR without these safeguards to assess its intrinsic safety, and that of a single hs-troponin measurement to describe the biomarker alone. Thus, our study evaluated the CDR as used in clinical practice, while the additional analyses help to disentangle the contribution of its individual components. The efficiency of such a pathway will, however, depend on local care organisation.

Second, the case of severe LAD disease illustrates that troponin should not replace clinical assessment. This is why hs-troponin was integrated into a CDR rather than used in isolation. Moreover, not referring a patient to the emergency department does not mean the diagnostic process ends; short-term outpatient assessment may be appropriate.

Finally, we included patients from one hour after symptom onset based on the ESC 2020 guideline,¹ which stated that hs-troponin levels usually rise within one hour after symptom onset. We agree that the 68 patients presenting within 1–3 hours are too few to draw conclusions, particularly given the low incidence of ACS. Further evidence is needed to establish the safety of single-sample rule-out in very early presenters. Meanwhile, we recommend single-sample rule-out after three hours of symptoms.

Reference

1. Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021;42(14):1289-1367. doi:10.1093/eurheartj/ehaa575.
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Competing Interests: None declared.
Published on: (16 September 2026)
Page navigation anchor for When is a negative troponin reassuring enough?
When is a negative troponin reassuring enough?
Kinan Mokbel, Honorary Professor at Brunel University London, Senior Lecturer (Advanced Clinical Practice, Clinical Pharmacy, Pharmacology), University of Exeter
Van den Bulk et al. show what hs-cTnI may add to primary care. Their GP-integrated rule achieved an NPV of 99.7% for ACS and missed no MI. Yet what has actually been validated: a biomarker or a care pathway?

The stand-alone rule would theoretically have referred 80% of patients, versus 54.6% with GP-integrated care; cardiologists were consulted in 32.3%. So, efficiency therefore came not from troponin alone but from combining a biomarker with clinical judgement and specialist support. This matters because troponin detects myocardial injury, not coronary disease. We recently reported a patient with exertional and rest chest pain, normal ECG and negative troponin, whose CT coronary angiography showed severe LAD disease, later confirmed invasively, requiring CABG.¹ This does not challenge troponin’s value. It illustrates a cognitive hazard: can “no biochemical evidence of injury” too easily become “safe to send home”?

Timing sharpens the question. POB-HELP included patients from one hour after symptom onset and observed no ACS misses among 68 presenting within 1–3 hours. Yet the 2025 ACC/AHA ACS guideline advises that when a clinical decision pathway uses a single hs-cTn value, sampling should occur at least three hours after symptom onset.² Sixty-eight early presenters are encouraging but cannot settle that tension.

Perhaps the study’s most useful message is not that a finger-prick troponin can rule...
Show More

Van den Bulk et al. show what hs-cTnI may add to primary care. Their GP-integrated rule achieved an NPV of 99.7% for ACS and missed no MI. Yet what has actually been validated: a biomarker or a care pathway?

The stand-alone rule would theoretically have referred 80% of patients, versus 54.6% with GP-integrated care; cardiologists were consulted in 32.3%. So, efficiency therefore came not from troponin alone but from combining a biomarker with clinical judgement and specialist support. This matters because troponin detects myocardial injury, not coronary disease. We recently reported a patient with exertional and rest chest pain, normal ECG and negative troponin, whose CT coronary angiography showed severe LAD disease, later confirmed invasively, requiring CABG.¹ This does not challenge troponin’s value. It illustrates a cognitive hazard: can “no biochemical evidence of injury” too easily become “safe to send home”?

Timing sharpens the question. POB-HELP included patients from one hour after symptom onset and observed no ACS misses among 68 presenting within 1–3 hours. Yet the 2025 ACC/AHA ACS guideline advises that when a clinical decision pathway uses a single hs-cTn value, sampling should occur at least three hours after symptom onset.² Sixty-eight early presenters are encouraging but cannot settle that tension.

Perhaps the study’s most useful message is not that a finger-prick troponin can rule out ACS in primary care, but that it may do so within a carefully designed system. Before point-of-care troponin is normalised in general practice, should we be validating the assay or the pathway around it?

References

1. Gill S, Emblin K, Daniels R, Mokbel K. Chest Pain at Rest With Unremarkable ECG and Cardiac Enzymes: Case Study Emphasising the Importance of Clinical Suspicion in the Diagnosis of Coronary Artery Disease. In Vivo. 2025;39(1):524-531. doi:10.21873/invivo.13856.

2. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2025;85(22):2135-2237. doi:10.1016/j.jacc.2024.11.009.
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Competing Interests: None declared.