Coronary flow reserve during dipyridamole stress echocardiography predicts mortality

Abstract OBJECTIVES: The goal of this study was to evaluate the ability of coronary flow reserve (CFR) over regional wall motion to predict mortality in patients with known or suspected coronary artery disease (CAD). BACKGROUND: CFR evaluated using pulsed Doppler echocardiography testing on left anterior descending artery is the state-of-the-art method during vasodilatory stress echocardiography. METHODS: In a prospective, multicenter, observational study, we evaluated 4,313 patients (2,532 men; mean age 65 ± 11 years) with known (n = 1,547) or suspected (n = 2,766) CAD who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echocardiography with CFR evaluation of left coronary descending artery (LAD) by Doppler. Overall mortality was the only endpoint analyzed. RESULTS: Stress echocardiography was positive for ischemia in 765 (18%) patients. Mean CFR was 2.35 ± 0.68. At individual patient analysis, 1,419 (33%) individuals had CFR <=2. During a median follow-up of 19 months (1st quartile 8; 3rd quartile 36), 146 patients died. The 4-year mortality was markedly higher in subjects with CFR <=2 than in those with CFR >2, both considering the group with ischemia (39% vs. 7%; p < 0.0001) and the group without ischemia at stress echocardiography (12% vs. 3%; p < 0.0001). At multivariable analysis, CFR on LAD <=2 (hazard ratio [HR]: 3.31; 95% confidence interval [CI]: 2.29 to 4.78; p < 0.0001), ischemia at stress echocardiography (HR: 2.40, 95% CI: 1.65 to 3.48, p < 0.0001), left bundle branch block (HR: 2.26, 95% CI: 1.50 to 3.41; p < 0.0001), age (HR: 1.08, 95% CI: 1.06-1.10; p < 0.0001), resting wall motion score index (HR: 3.52, 95% CI: 2.38 to 5.21; p < 0.0001), male sex (HR: 1.74, 95% CI: 1.12 to 2.52; p = 0.003), and diabetes mellitus (HR: 1.47, 95% CI: 1.03 to 2.08; p = 0.03) were independent predictors of mortality. CONCLUSIONS: CFR on LAD is a strong and independent indicator of mortality, conferring additional prognostic value over wall motion analysis in patients with known or suspected CAD. A negative result on stress echocardiography with a normal CFR confers an annual risk of death <1% in both patient groups.