Exercise electrocardiography for pre-test assessment of the likelihood of coronary artery disease.

Objectives: To develop a tool including exercise electrocardiography (ExECG) for patient-specific clinical likelihood estimation of patients with suspected obstructive coronary artery disease (CAD).
Methods: An ExECG-weighted clinical likelihood (ExECG-CL) model was developed in a training cohort of patients with suspected obstructive CAD undergoing ExECG. Next, the ExECG-CL model was applied in a CAD validation cohort undergoing ExECG and clinically driven invasive coronary angiography and a prognosis validation cohort and compared with the risk factor-weighted clinical likelihood (RF-CL) model for obstructive CAD discrimination and prognostication, respectively.In the CAD validation cohort, obstructive CAD was defined as >50% diameter stenosis on invasive coronary angiography. For prognosis, the endpoint was non-fatal myocardial infarction and death.
Results: The training cohort consisted of 1214 patients (mean age 57 years, 57% males). In the CAD (N=408; mean age 55 years, 53% males) and prognosis validation (N=3283; mean age 57 years, 57% males) cohorts, 11.8% patients had obstructive CAD and 4.4% met the endpoint. In the CAD validation cohort, discrimination of obstructive CAD was similar between the ExECG-CL and RF-CL models: area under the receiver-operating characteristic curves 83.1% (95% CIs 77.5% to 88.7%) versus 80.7% (95% CI 74.6% to 86.8%), p=0.14. In the ExECG-CL model, more patients had very low (≤5%) clinical likelihood of obstructive CAD compared with the RF-CL (42.2% vs 36.0%, p<0.01) where obstructive CAD prevalence and event risk remained low.
Conclusions: ExECG incorporated into a clinical likelihood model improves reclassification of patients to a very low clinical likelihood group with very low prevalence of obstructive CAD and favourable prognosis.
Competing Interests: Competing interests: SES and MB acknowledge support from Acarix in form of an institutional research grant. MB discloses advisory board participation for NOVO Nordisk, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Sanofi, and Acarix outside of submitted work. SES is a part-time consultant and minor shareholders in Acarix. JK discloses speaker fees from GE Healthcare, Merck, Lundbeck, Boehringer-Ingelheim, Bayer and Pfizer and study protocol consultant fees from GE Healthcare and AstraZeneca outside of submitted work. KN acknowledges support from the NIH (NIH R01- HL141712; NIH R01 - HL146754), and reports unrestricted institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc, Novartis unrelated to this work, consulting for Siemens Medical Solutions USA and Novartis, and equity in Lumen Therapeutics.
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