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An algorithm for rule-in and rule-out of acute myocardial infarction using a novel troponin I assay
  1. Bertil Lindahl1,
  2. Tomas Jernberg2,3,
  3. Patrick Badertscher4,
  4. Jasper Boeddinghaus4,
  5. Kai M Eggers1,
  6. Mats Frick5,
  7. Maria Rubini Gimenez4,6,7,
  8. Rickard Linder8,
  9. Lina Ljung5,
  10. Arne Martinsson9,
  11. Dina Melki10,11,
  12. Thomas Nestelberger4,
  13. Katharina Rentsch12,
  14. Tobias Reichlin4,
  15. Zaid Sabti4,
  16. Marie Schubera4,
  17. Per Svensson13,14,
  18. Raphael Twerenbold4,
  19. Karin Wildi4,
  20. Christian Mueller4
  1. 1Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala, University, Uppsala, Sweden
  2. 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  3. 3Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
  4. 4Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland
  5. 5Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
  6. 6Pneumology Department, Parc de Salut Mar-IMIM-UPF, Parc de Salut Mar, Spain
  7. 7Emergency Department, Parc de Salut Mar, Spain
  8. 8Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden
  9. 9Capio St Görans Hospital, Stockholm, Sweden
  10. 10Department of Medicine, Karolinska Institutet, Huddinge, Sweden
  11. 11Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
  12. 12Department of Laboratory Medicine, University Hospital Basel, Basel, Switzerland
  13. 13Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  14. 14Department of Emergency Medicine, Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to Dr Bertil Lindahl, Uppsala Clinical Research Center, University Hospital, Uppsala SE-751 85, Sweden; bertil.lindahl{at}


Objective To derive and validate a hybrid algorithm for rule-out and rule-in of acute myocardial infarction based on measurements at presentation and after 2 hours with a novel cardiac troponin I (cTnI) assay.

Methods The algorithm was derived and validated in two cohorts (605 and 592 patients) from multicentre studies enrolling chest pain patients presenting to the emergency department (ED) with onset of last episode within 12 hours. The index diagnosis and cardiovascular events up to 30 days were adjudicated by independent reviewers.

Results In the validation cohort, 32.6% of the patients were ruled out on ED presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22% could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI 97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%) and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained undetermined after 2 hours. No patient in the rule-out group died during the 30-day follow-up in the two cohorts.

Conclusions This novel two-step algorithm based on cTnI measurements enabled just over a third of the patients with acute chest pain to be ruled in or ruled out already at presentation and an additional third after 2 hours. This strategy maximises the speed of rule-out and rule-in while maintaining a high NPV and PPV, respectively.

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