AHA Scientific Sessions 2019 Presentation for HART CADhs

Derivation and External Validation of a High Sensitivity Troponin Based Proteomic Model to Predict the Presence of Obstructive Coronary Artery Disease: Value in the Troponin “Indeterminant Zone”


November 18, 2019


  • Current non-invasive modalities utilized to diagnose obstructive coronary artery disease (CAD) are limited by variable sensitivity and specificity, the need for ionizing radiation or contrast, and cost. 

  • In this study, we sought to derive and validate a biomarker clinical/proteomic panel inclusive of high sensitivity cardiac troponin for the diagnosis of obstructive CAD.

  • In a prospective cohort of 636 patients referred for a diagnostic coronary angiography enrolled in the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) Study (ClinicalTrials.Gov NCT00842868), predictors of ≥70% stenosis in at least 1 major coronary vessel were identified from six clinical variables and 109 biomarkers. 

  • The model was trained/developed on patient samples from CASABLANCA (n=636); the model was then internally validated (AUC=0.85) on a separate cohort from CASABLANCA (n=275) and then positively validated (AUC=0.86) on a different cohort of 241 patients presenting to the ED with suspicion for myocardial infarction (MI) who were enrolled in the Biomarkers in Acute Cardiac Care (BACC) prospective cohort study (ClinicalTrials.Gov NCT02355457) where ≥50% stenosis in >1 coronary vessel was considered significant. 

  • Notably, the score performance had high accuracy (AUC=0.88) among patients in the indeterminant zone (patients who were neither rule-in or rule-out for MI) of the BACC cohort at the optimal cut-off.

  • Biomarkers in this model all have plausible biologic links to atherosclerosis. Score components of age, sex, prior coronary PCI, kidney injury molecule-1, and hs-cTn positively correlated with obstructive CAD while there was an inverse relationship between adiponectin concentrations and obstructive CAD.

  • Clinically, this score could act as a gatekeeper prior to imaging or invasive testing. Thus, reducing cost and exposures to intravenous contrast and/or ionizing radiation.

  • In the acute setting, the score may also be useful for triaging the up to 30% of acute chest pain patients in the indeterminant zone who neither rule-in nor rule-out for acute MI.

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AHA Scientific Sessions 2019 Presentation for HART CADhs