A recent observational cohort study compared the annualized rate of major adverse cardiac events (MACE) in patients with abnormal exercise electrocardiograms (+ECG) but normal stress echocardiograms (–Echo) to patients with normal exercise ECGs (–ECG) and normal stress echocardiograms (–Echo). According to this study, which of the following statements is MOST likely true of the annualized MACE event rate in the +ECG/–Echo group compared with the –ECG/–Echo group?

  • □ (A) It was similar.

  • □ (B) It was lower.

  • □ (C) It was higher.

Both exercise ECG and stress Echo are used in clinical practice to evaluate patients at risk for coronary artery disease (CAD). The absence of regional wall motion abnormalities with stress (negative stress Echo) portends a low risk of CAD. Conversely, a stress Echo that reveals regional wall motion abnormalities has been correlated with an increased risk of CAD. At times, patients will undergo exercise ECG before or in addition to stress Echo, and a fraction of patients will demonstrate ischemic ST segment changes on exercise ECG (+ECG) but no regional wall abnormalities on stress Echo (–Echo). Whether the prognosis of these patients is the same as those with negative ECG and negative stress Echo is uncertain. The authors of a recent study sought to establish the clinical importance of discordant stress testing (ie, +ECG/–Echo).

The study included 15,077 patients who underwent stress Echo from 2000 to 2014 at a single institution. Patients were included if they were suspected of having CAD and if they achieved at least 85% of target heart rate during stress Echo testing. Exclusion criteria included preexisting CAD, heart transplant, congenital heart disease, and abnormal resting Echo. In addition to stress Echo, patients underwent exercise ECG. The primary study outcome was MACE, which included death, myocardial infarction, revascularization, and unstable angina hospitalizations. Secondary study outcomes included individual adverse event rates and downstream testing, defined as any noninvasive testing or diagnostic coronary angiography performed in the year following the index stress Echo.

Of 15,077 patients, 12,893 (85.5%) had –ECG/–Echo, 1,286 (8.5%) had +ECG/–Echo, 521 (3.5%) had –ECG/+Echo, and 377 (2.5%) had +ECG/+Echo. Mean patient age was 52 years, and 6,228 patients (41.3%) were men. Compared with patients with –ECG/–Echo, patients with +ECG/–Echo were older and had more CAD risk factors. They also had lower resting heart rate and higher systolic blood pressure compared with those with –ECG/–Echo. Patients with +ECG/–Echo also achieved shorter exercise times and lower metabolic equivalents compared with those with –ECG/–Echo.

Patients with +ECG/–Echo were more likely to have downstream coronary angiography performed in the year following initial stress testing compared with patients with –ECG/–Echo (5.8% vs. 0.7%, respectively). In 33 of the 75 patients with +ECG/–Echo (44%) in whom coronary angiography was performed, significant CAD (50% or greater stenosis in at least one coronary artery) was identified.

A total of 142 patients with +ECG/–Echo (14.6%) experienced a MACE in the study follow-up period, and the absolute MACE rate was higher in short- and long-term follow up in this group compared with the –ECG/–Echo group. The annualized MACE event rate in patients with +ECG/–Echo was 1.72% while the event rate in those with –ECG/–Echo was 0.89%; after the 9.6-year follow-up, the rates were 15% and 8%, respectively.

This study is important in potentially identifying a group of patients at higher risk of cardiovascular morbidity and mortality on the basis of a positive stress ECG despite negative stress Echo. In reporting the results of testing, the authors recommend identifying a +ECG/–Echo exam as abnormal to highlight to the referring provider the increased cardiac risk associated with this result. Intervening in this patient group may offer the opportunity to improve short- and long-term cardiovascular outcomes.

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Answer: C