Daubert MA, et al. JAMA Intern Med. 2020;doi:10.1001/jamainternmed.2019.6958.

Daubert MA, et al. JAMA Intern Med. 2020;doi:10.1001/jamainternmed.2019.6958.

Patients with positive ECG results and normal stress echocardiography had a slightly increased risk for adverse cardiac events, according to a study published in JAMA Internal Medicine.

“These findings add significantly to the current knowledge base,” Melissa A. Daubert, MD, associate professor of medicine at Duke University School of Medicine, member in the Duke Clinical Research Institute and Cardiology Today Next Gen Innovator, told Healio. “First, this study has identified an ‘at-risk’ population that is commonly encountered in clinical practice, but has been underrecognized and not well characterized. Second, previous studies have been either too small or too short in duration to definitively differentiate +ECG/–Echo patients from –ECG/–Echo patients, and thus until now, these populations have been considered to have an equivalent prognosis with a similar benign clinical trajectory. This study demonstrates that patients with +ECG/–Echo are at higher risk for adverse outcomes.”

Researchers analyzed data from 15,077 patients (mean age, 52 years; 41% men) who were free from CAD who underwent exercise stress echocardiography between January 2000 and February 2014. The primary outcome was a composite endpoint of major adverse cardiac events, defined as MI, all-cause death, coronary revascularization and hospitalization for unstable angina. Secondary endpoints were defined as downstream testing and individual adverse event rates.

Of the patients in the study, 85.5% had a negative ECG and negative echocardiography, 8.5% had positive ECG and negative echocardiography and 6% had positive echocardiography.

During a median follow-up of 7.3 years, the composite endpoint occurred in 8.5% of patients with a negative ECG and negative echocardiography, 14.6% of those with a positive ECG and negative echocardiography and 37.4% of patients with positive echocardiography. In addition, death occurred in 4.8% of patients with a negative ECG and negative echocardiography, 5.9% of those with a positive ECG and negative echocardiography and 11.2% of patients with positive echocardiography. MI was observed in 2.2% of patients with a negative ECG and negative echocardiography, 3.6% of those with a positive ECG and negative echocardiography and 8.7% of patients with positive echocardiography.

Adding stress ECG findings to exercise and clinical data resulted in incremental prognostic value, according to the study.

The least downstream testing was performed in patients with a negative ECG and negative echocardiography (2.3%), followed by those with a positive ECG and negative echocardiography (12.8%) and patients with positive echocardiography (33.6%; P < .001).

“We have identified a population with increased cardiac risk that until now were not well defined and unknowingly grouped with a lower-risk cohort, which obscured the prognostic significance of +ECG/–Echo,” Daubert said in an interview. “These findings have ramifications for the dissemination of clinical results. ... By recognizing that +ECG/–Echo patients are at increased cardiac risk, there is an opportunity to intervene and potentially decrease adverse outcomes in this population.” – by Darlene Dobkowski

Melissa A. Daubert, MD, can be reached at Duke Clinical Research Institute, 200 Morris St., Durham, NC 27701; email: melissa.daubert@duke.edu.

Disclosures: Daubert reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

This is an important study, as traditionally we have suggested that a positive ECG and negative echocardiography were false positives and indicative of a benign prognosis. This study suggests this group has a worse (albeit slightly worse) prognosis than those with completely normal studies. These patients are also at baseline higher risk than those with a negative ECG and negative echocardiography regardless, as they are older and have worse risk factor profiles (hyperlipidemia and hypertension). They also had worse exercise performance and more deconditioning than the negative ECG and negative echocardiography group.

This also points out that the echocardiography itself has limitations in terms of sensitivity. This is most likely due to the fact that wall motion abnormalities are further along the ischemic cascade than ECG changes, and thus it takes more ischemia to elicit wall motion abnormalities on echocardiography. In general, imaging studies that assess perfusion (SPECT, PET, MRI) are more sensitive than echocardiography, as abnormal perfusion is also earlier on the ischemic cascade, which explains this, at least in part.

This will change how I report stress echocardiography, as I will call attention to the positive ECG even in the setting of normal stress echocardiography.

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