Reversible ischemia and outcome after adjustment for coronary artery disease severity: a multicenter stress-echocardiography registry

To assess the potential association of reversible ischemia and Doppler coronary flow velocity reserve in the left anterior descending coronary artery (CFVR-LAD) during stress echocardiography (SE) with all-cause mortality and nonfatal myocardial infarction, after correction for anatomic coronary artery disease (CAD) burden and other significant clinical variables.We selected 3191 patients (mean age 66 ± 12 years) from our multicenter SE registry, who underwent both high-dose dipyridamole SE (comprehensive of CFVR-LAD measurement) and coronary angiography within 2 months. All-cause mortality and nonfatal myocardial infarction (MI) were the primary end points. The association of the primary end point with ischemia severity and CFVR-LAD was assessed, after multivariable adjustment for all other significant clinical and imaging variables, including anatomic CAD severity by the modified Duke Prognostic Index. The primary end point occurred in 767 (24%) patients (death in 409 and nonfatal MI in 375 patients) during a median follow-up of 42 months. Multivariable Cox regression analyses indicated that, among other significant variables, anatomic CAD severity, reversible ischemia and CFVR-LAD were all independently associated with the primary end point; reversible ischemia was also associated with subsequent MI, while CFVR-LAD with mortality, independent of anatomic CAD severity.Our study suggests that reversible ischemia by wall motion assessment and CFVR-LAD on dipyridamole SE are independently associated with dismal outcome in patients with suspected or known stable CAD, even after accounting for angiographic anatomic CAD severity and also independently from which coronary artery is diseased.