By Michael H. Crawford, MD
Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco
Dr. Crawford reports no financial relationships relevant to this field of study.
SYNOPSIS: Analysis of ST transients in aVR during exercise ECG testing can provide additional diagnostic information in patients suspected of having ischemic heart disease. ST elevation in aVR with exercise also is predictive of major adverse cardiac events.
SOURCE: Wagener M, Abacherli R, Honegger U, et al. Diagnostic and prognostic value of lead aVR during exercise testing in patients suspected of having myocardial ischemia. Am J Cardiol 2017;119:959-966.
The diagnostic and prognostic value of ST segment changes in ECG lead aVR during exercise testing is controversial. Thus, investigators from Basal, Switzerland, studied 1,596 patients with suspected ischemic heart disease by upright bicycle exercise with rest/stress nuclear myocardial perfusion imaging. Patients were excluded who had depolarization abnormalities on ECG that would impair the interpretation of ST segment changes, including bundle branch blocks or nonspecific QRS widening > 120 ms. The presence of myocardial ischemia was based on the interpretation of the perfusion scans combined with coronary angiography when available (26%). Medications that could influence the results of the test were held for 24-48 hours. Automated digital interpretations of the ECG were supplemented by a manual interpretation using standard criteria. ST segment analysis was performed at the J point plus 40, 60, or 80 ms. The interpretation time points were at rest, at peak exercise, and at two minutes of recovery. The primary prognostic endpoint was a combination of death, myocardial infarction (MI), or coronary artery revascularization during two years of follow-up.
Evidence of ischemia was found in 470 patients (29%) and these patients exhibited more ST elevation in aVR and ST depression in V5 than those without ischemia (P < 0.001). The diagnostic accuracy by the area under the receiver operating curve (AUC) was highest at two minutes of recovery and similar in aVR and V5 (0.62 vs. 0.58, respectively; P = 0.08 for the difference). However, for detection of left anterior descending (LAD) ischemia, aVR was slightly better (odds ratio [OR], 0.62 vs. 0.60, respectively; P = 0.046). A multivariate model that corrected for age, sex, clinical factors, and manual interpretation showed that ST elevation in aVR contributed independent diagnostic information, whereas V5 changes did not (OR, 1.7; 95% confidence interval, 1.2-2.4; P = 0.003). During a median follow-up of 15 months, the primary endpoint occurred in 293 patients (254 revascularization, 44 MI, 47 deaths). ST elevation in aVR and depression in V5 both contributed independent prognostic information (OR, 1.4 and 1.3, respectively). The authors concluded that ST elevations in aVR contribute independent diagnostic information and predict outcomes in patients undergoing exercise stress testing for suspected myocardial ischemia.
COMMENTARY
Since the identification that ST elevation in aVR alone can identify ST elevation MI due to left main or ostial LAD disease, there has been interest in using aVR in exercise stress testing. Previous studies have suggested its value for this purpose, but these studies were small or suffered the selection bias of a coronary angiographic gold standard. This study was conducted in a more real-world population, using nuclear perfusion imaging backed up by coronary angiography, when available. The study showed that ST elevation in aVR was at least as good as ST depression in V5 for detecting ischemia and slightly better at detecting LAD ischemia. This probably is because aVR, especially when used with truncal placement of the limb leads, as occurs often with exercise testing, lies along the same long axis plane of the LV as V5. Other studies have shown that 90% of the ST segment depression seen on a 12-lead ECG with exercise is captured in V4-6, so it is not surprising that aVR can augment the detection of ST changes, but not by much. Also, it is comforting that changes in ST transients in aVR predict outcomes as well as V5 and so are unlikely to markedly increase false-positive studies. In fact, in this study, after considering aVR, the sensitivity of the exercise ECG for ischemia was 26% and specificity was 91%, so false-negative studies are the bigger issue.
There are some caveats to this study that should be considered. The main analysis of ST transients was conducted by computer, which resulted in decision cutpoints in the tenths of millimeters. Also, the most accurate diagnostic and predictive measurements occurred at two minutes of recovery and the J point plus 80 ms. Many labs use peak exercise and measure ST transients closer to the J point. Additionally, in the real world, all the exercise test findings are used to reach a final working diagnosis. When these investigators compared all the exercise test findings in a multivariate model for diagnosing ischemia, the manual ECG interpretation was best (OR, 3.8), followed by exercise-induced angina (OR, 2.8), ST change in aVR (OR, 1.7), and being female (OR, 0.35).
Another issue is the use of upright bicycle stress testing, which is not the dominant exercise testing method in the United States. It is well known that many patients experience leg fatigue with cycle tests before they develop minimal oxygen uptake. Consequently, bicycle tests can be less sensitive than treadmill exercise for ischemia detection.
This study supports the recommendation of the 2013 American Heart Association scientific statement on exercise testing, which encourages the inclusion of aVR in the ECG analysis. However, until someone conducts large, non-selective studies with treadmill exercise, we will not know its true value.
Analysis of ST transients in aVR during exercise ECG testing can provide additional diagnostic information in patients suspected of having ischemic heart disease.
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