False positive results of treadmill exercise ECG - we should minimize the unnecessary referrals to invasive coronary angiography

Purpose: False positive (FP) results are common in treadmill exercise ECG testing (TMT) performed for obstructive coronary artery disease (OCAD) screening. It is important to discriminate whether an ischemic response in TMT is a FP result, to avoid unnecessary referrals for invasive coronary angiography (ICA). We determined the clinical factors that were independently associated with a TMT FP result. Methods: We analyzed a cohort of patients referred for ICA for stable coronary artery disease diagnosis, based on clinical judgment and a TMT positive for ischemia, in a single tertiary-care center (2006-2011). Traditional and nontraditional coronary artery disease risk factors, modified Framingham risk score, symptoms, pre-test (TMT) probability of OCAD, left ventricular ejection fraction and ICA results were assessed. OCAD was defined as any luminal narrowing ≥70%, or ≥50% for the left main artery. A FP TMT result was defined as an ischemic response (2006 TMT European Society of Cardiology guidelines) and no OCAD. The predictors of a FP result were determined by the chi-square, exact Fisher and t-student tests when appropriate, and multivariate analysis (logistic regression). The discriminatory power for a FP result, of a model based on those predictive factors, was assessed by the area under the ROC curve (AUC) analysis. Results: 1243 patients were included: 65.2±9.9 years, 63.0% male, mean 10-year Framingham risk 17.8%; 51.1% typical angina and 20.1% atypical angina; 65.4% high pre-test probability of OCAD; 4.3% depressed left ventricular ejection fraction (<55%). Globally, 51.6% of TMT were FP results. The factors independently associated with a FP TMT were: absence of severe angina (OR 22.0, 95% CI 5.3-91.2), presence of atypical angina (OR 17.3, 95% CI 9.4-31.6), absence of angina (OR 3.8, 95% CI 2.9-5.2), female gender (OR 2.4, 95% CI 1.8-3.3), non-smoking (OR 2.1, 95% CI 1.4-3.0), absence of diabetes (OR 1.5, 95% CI 1.1-2.0) and younger age (OR 1.1, 95% CI 1.0-1.1), (all p<0.05). A model considering these factors together had good discriminatory power for predicting a FP result: AUC 0.80, 95% CI 0.78-0.83. Conclusions: Half of positive TMT were FP in a population of patients referred for ICA following clinical judgment and a TMT positive for ischemia. When analyzed together, the absence of angina/severe angina, the presence of atypical angina, female gender, non-smoking, absence of diabetes and younger age have good power for discriminating a FP result. These parameters should be given more relevance in order to avoid some unnecessary referrals for ICA.

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