Association Between Stress Testing-Induced Myocardial Ischemia and Clinical Events in Patients With Multivessel Coronary Artery Disease

Abstract

Importance: The long-term prognostic implications of myocardial ischemia documented during stress testing in patients with multivessel coronary artery disease (CAD) are unclear.

Objective: To assess whether documented stress testing-induced myocardial ischemia is associated with major adverse cardiovascular events or ventricular function changes in patients with stable multivessel CAD.

Design, setting, and participants: A prospective cohort study was conducted using data from a single-center randomized clinical trial (Medicine, Angioplasty, or Surgery Study [MASS] II) to examine the association of myocardial ischemia documented during stress testing at baseline with cardiovascular events and ventricular function changes during follow-up. Participants were previously randomized (May 1, 1995, to May 31, 2000) to medical therapy, percutaneous coronary intervention with bare metal stents, or coronary artery bypass grafting. Event-free survival was estimated by the Kaplan-Meier method, and multivariable Cox regression models were calculated to assess the association between ischemia and the primary composite end point. The vital status was determined on February 28, 2011. Data were analyzed from February 1, 2016, to April 1, 2017.

Main outcomes and measures: Cardiovascular events (overall mortality, myocardial infarction, and revascularization for refractory angina) were tracked from the time of randomization to the end of the 10-year follow-up (mean [SD] duration, 11.4 [4.3] years). Myocardial ischemia was assessed at baseline and at 1-year intervals by exercise stress testing, and ventricular function (left ventricular ejection fraction) was assessed by echocardiography at baseline and after 10 years. Patients with documented ischemia were compared with those without ischemia regarding the outcomes and changes in ventricular function.

Results: Of 611 participants, 535 underwent exercise stress testing at baseline: 270 with documented ischemia and 265 without. Of these 535 patients, 373 (69.7%) were men, and the mean (SD) age for the entire cohort was 59.7 (9.2) years. No association was found between the presence of ischemia at baseline and survival free of combined cardiovascular events (hazard ratio, 1.00; 95% CI, 0.80-1.27; P = .95) after multivariable adjustment that included CAD initial randomized treatments. In addition, among 320 patients who underwent echocardiographic evaluation, the slight decline in left ventricular ejection fraction after 10 years was similar in both groups (median [SD] difference, -4.9% [18.7%] vs -6.6% [20.0%], respectively, for groups with and without ischemia; P = .97).

Conclusions and relevance: In this study, regardless of the therapeutic strategy applied, the presence of documented myocardial ischemia did not appear to be associated with an increased occurrence of major adverse cardiovascular events or changes in ventricular function in patients with multivessel CAD during a long-term follow-up.

Figure 1.. Kaplan-Meier Curves for Survival Free of Cardiovascular Events According to Stress-Induced Ischemic Status at Baseline

HR indicates hazard ratio.

Figure 2.. Changes in Left Ventricular Ejection Fraction (LVEF) According to the Presence of Stress-Induced Ischemia

The delta LVEF (difference in reduction of LVEF) is calculated as 100 × [(LVEF at 10 years − LVEF at baseline)/LVEF at baseline]. The vertical line in the middle of each box indicates the median; left and right borders of the box, the interquartile ranges; whiskers, the maximum and minimum values excluding the outliers; and data points beyond the whiskers, outliers.