Agreement between site and core lab interpretation was moderate (kappa 0.46; 95% CI 0.35-0.57). Among discordant studies, more studies were determined to be abnormal by site but normal by core lab (n=51) but a small number were determined to be abnormal by core lab and normal by site (n=15). On multivariate analysis, patient variables predictive of a discordant interpretation were […]. Echocardiographic variables predictive of a discordant interpretation were […]. Accreditation status of the study site was/was not predictive of discordant stress echo interpretation ().
Compared to those with agreement, patients with discordant interpretations were older (63.5 [8.3] vs 59.3 [8.0] years), had higher mean ASCVD score (16.6 vs 13.0), and were more likely to be treated with beta-blocker (35.0% vs 20.1%) (all p ≤0.01). There was no difference in body mass index, chest pain characteristics, or risk factors between the concordant and discordant groups (all p>0.05). Echo characteristics associated with discordance were limited image quality as determined by sites (19.6 vs 8.7%, p=0.02) and any wall motion abnormality at rest or stress (by territory: left anterior descending [53.0 vs 2.7%], circumflex [22.7 vs 1.4%], and right coronary [42.4 vs 1.9%]) (all p<0.01). Variables not associated with discordance included stress type (exercise vs pharmacologic) or echo contrast use (both p>0.05).

Factors associated with concordant and discordant interpretations

Outcome events

The overall event rate among stress echocardiogram patients in the PROMISE trial \cite{disease2015}was low. In the small number of SE patients who had a clinical outcome, those with discordant SE results were more likely to undergo referral for a second non-invasive test or coronary angiography. A discordant stress echo result was not associated with 90-day revascularization, cardiovascular death, myocardial infarction, all-cause death, and hospitalization for unstable angina.

Discussion

Our study showed that among outpatients with chest pain who underwent stress echocardiography for risk stratification, agreement between between site and core lab interpretation was poor, with positive results according to site interpretation that were normal according to core lab interpretation. Predictors of discrepancy between site and core lab interpretations were [...]. 
A substudy of the Global Registry of Acute Coronary Events (GRACE) registry found significant and clinically important discrepancies in local site and core laboratory interpretation of electrocardiograms in acute coronary syndrome patients \cite{Yan_2007}. Previous studies have shown that echocardiographer experience contributes to the diagnostic accuracy of stress echocardiogram interpretation and accuracy of interpretation improves with adequate training \cite{Picano_1991}. A smaller substudy of the ISCHEMIA trial \cite{health2015} cohort found agreement between local site and core lab interpretation of myocardial ischemia by stress echocardiogram in 81% of cases and similar for both exercise and pharmacologic stress tests. In cases of disagreement, the majority were adjudicated as no or mild ischemia by the core lab and more extensive ischemia by the local site \cite{Kataoka_2015}. Disagreement has been found to be greater in minor wall motion abnormalities \cite{Hoffmann_2002}. A multicenter study using stress echocardiograms from six institutions found an average kappa coefficient of 0.48 between institutions and percentage agreement was highest in cases of three-vessel disease or left anterior descending artery disease \cite{Peteiro_2006}.
In a small prospective study, interpretation of dobutamine stress echocardiography has been found to be affected by low image quality, a wall motion abnormality which is not severe, and a low peak rate-pressure product resulting in low inter-rater agreement \cite{Hoffmann1998}. Harmonic imaging has also improved interpreter agreement and studies with poor image quality have previously been noted to have more inter-observer variability \cite{Hoffmann_2002}.
Previous studies have found a suggestive clinical history to significantly bias interpretation of electrocardiograms among physicians \cite{van_den_Berge_2013}. Multiple previous studies have shown that cognitive bias is associated with therapeutic or management errors \cite{Saposnik_2016}.
Because stress echocardiography is a commonly used imaging modality to discriminate between cardiac and non-cardiac chest pain and has implications for patient management, features which may influence non-expert interpretation of stress echo is of clinical importance. Fortunately, the rate of discordance was low and the majority of cases with disagreement were due to a site positive result of ischemia with a core lab result of normal. While this may lead to an increased use of medical therapy and further testing, it is likely that functionally significant coronary artery disease is not being missed by non-expert sites. [Insert statement about specific variables that influenced discordance].