Diagnostic Accuracy of a Precision Medicine Blood Test for Assessing Obstructive Coronary Artery Disease in Nondiabetic Patients with Newly-Diagnosed Heart Failure with Reduced Ejection Fraction - A Pilot Study

Abstract

IntroductionIn patients with newly-diagnosed heart failure with reduced ejection fraction (HFrEF), current guidelines recommend ischemic workup to rule out the presence of coronary artery disease (CAD), as revascularization in patients with left ventricular systolic dysfunction associated with obstructive CAD is strongly associated with improved survival. This ischemic work-up is based initially on non-invasive testing and, if indicated, invasive coronary angiography (ICA). While non-invasive testing is limited by its low diagnostic yield, ICA exposes patients to radiation, IV contrast and procedural complications. An age- and sex- specific gene expression score (ASGES) generated from precision medicine blood test has been previously validated in two large, prospective, multicenter trials to have a high sensitivity and negative predictive value in the assessment of obstructive CAD in nondiabetic patients with normal left ventricular systolic function who present with chest pain and associated symptoms who subsequently underwent ICA. Its utility for the assessment of obstructive CAD in nondiabetic patients who have symptoms arising from new-onset HFrEF has yet to be studied.HypothesisThe ASGES will have a high sensitivity and negative predictive value for predicting obstructive CAD in nondiabetic patients with newly-diagnosed HFrEF.MethodsWe enrolled 57 consecutive nondiabetic patients (median age 50.5 years, 63% males) who presented acutely to our institution with symptoms associated with new-onset HFrEF from February 2016 to February 2018. Patients underwent ICA as part of their ischemic workup before they were enrolled in our study. Whole blood samples were drawn during or within two weeks after ICA and sent to a central laboratory for generation of gene expression scores. The laboratory personnel were blinded to the patient's disease status per ICA. ASGES were then correlated with ICA results.ResultsGene expression scores were generated in 88% of patients (50 of 57 patients). The prevalence of obstructive CAD (defined as >70% stenosis in any of the major epicardial coronary arteries) was 20%. At a pre-specified cut-off of <15, the ASGES had a sensitivity, specificity, positive and negative predictive value of 90%, 50%, 31% and 95% respectively when compared to ICA in the detection of obstructive CAD.ConclusionsASGES has an excellent sensitivity and negative predictive value for predicting obstructive CAD in nondiabetic patients with newly-diagnosed HFrEF. In patients with newly-diagnosed heart failure with reduced ejection fraction (HFrEF), current guidelines recommend ischemic workup to rule out the presence of coronary artery disease (CAD), as revascularization in patients with left ventricular systolic dysfunction associated with obstructive CAD is strongly associated with improved survival. This ischemic work-up is based initially on non-invasive testing and, if indicated, invasive coronary angiography (ICA). While non-invasive testing is limited by its low diagnostic yield, ICA exposes patients to radiation, IV contrast and procedural complications. An age- and sex- specific gene expression score (ASGES) generated from precision medicine blood test has been previously validated in two large, prospective, multicenter trials to have a high sensitivity and negative predictive value in the assessment of obstructive CAD in nondiabetic patients with normal left ventricular systolic function who present with chest pain and associated symptoms who subsequently underwent ICA. Its utility for the assessment of obstructive CAD in nondiabetic patients who have symptoms arising from new-onset HFrEF has yet to be studied. The ASGES will have a high sensitivity and negative predictive value for predicting obstructive CAD in nondiabetic patients with newly-diagnosed HFrEF. We enrolled 57 consecutive nondiabetic patients (median age 50.5 years, 63% males) who presented acutely to our institution with symptoms associated with new-onset HFrEF from February 2016 to February 2018. Patients underwent ICA as part of their ischemic workup before they were enrolled in our study. Whole blood samples were drawn during or within two weeks after ICA and sent to a central laboratory for generation of gene expression scores. The laboratory personnel were blinded to the patient's disease status per ICA. ASGES were then correlated with ICA results. Gene expression scores were generated in 88% of patients (50 of 57 patients). The prevalence of obstructive CAD (defined as >70% stenosis in any of the major epicardial coronary arteries) was 20%. At a pre-specified cut-off of <15, the ASGES had a sensitivity, specificity, positive and negative predictive value of 90%, 50%, 31% and 95% respectively when compared to ICA in the detection of obstructive CAD. ASGES has an excellent sensitivity and negative predictive value for predicting obstructive CAD in nondiabetic patients with newly-diagnosed HFrEF.