Stress tests unreliable at detecting left main disease in moderate/severe ischemia

Reuters Health - 03/03/2022 - Moderate to severe ischemia on non-invasive imaging or exercise stress tests has only limited ability to predict left main coronary artery stenosis of 50% or greater in patients with stable heart disease, according to a post hoc analysis of data from a large randomized trial.

Anatomical imaging is necessary to accurately identify left main disease (LMD) in this setting, the investigators say.

Because American and European guidelines recommend revascularization for all patients with left main artery stenosis of 50% or more, regardless of symptoms or associated ischemic burden, the international ISCHEMIA study design included CTA to rule out clinical LMD prior to randomization to medical therapy with or without intervention.

The researchers studied 5,146 participants who underwent computed tomography angiography (CTA) to rule out clinical left main disease (LMD), identifying 414 patients (8%) with positive findings of over 50% LMD.

Participants had stable cardiac symptoms and moderate to severe ischemia as confirmed by exercise stress testing, nuclear SPECT testing with exercise or lexiscan, or stress echocardiography with exercise or dobutamine.

Variables included ST depression, metabolic equivalents (METS) and heart rate (HR) achievement in exercise stress tests, and the number of infarcted and ischemic segments (including ischemia in the left anterior descending coronary artery with or without left circumflex coronary artery regions), summed differences on nuclear, and transient ischemic dilation (TID) on SPECT or stress echo.

"Among imaging and exercise parameters, after adjusting for clinical factors, significant predictors of LMD were older age, male sex, lack of prior myocardial infarction (MI), greater ST-depression, and lower peak METs on exercise tolerance tests and TID on stress echocardiography," Dr. Roxy Senior of Northwick Park Hospital, London, UK and colleagues reported in the Journal of the American College of Cardiology. Their incremental predictive value, however, was "modest."

No specific stress test was able to identify more than 50% of the patients with LMD, the researchers reported. Only stress echo showed a statistical benefit with moderate/severe anterior ischemia or TID. Sensitivity for LMD was 42.7% with TID and 44.9% with moderate or severe anterior ischemia; false positive rates were 26.1% and 32.2%, respectively.

"As stress echo is free of ionizing radiation and is better than nuclear in discriminating patients with and without LMD, this could be the functional test of choice," Dr. Senior told Reuters Health by email.

The discriminatory value of SPECT scans did not appear to be significant, Dr. Senior added, perhaps because 55% were lexiscans, which only simulate the effects of exercise on the heart.

Too few participants had LMD of at least 70% to allow for adequate evaluation of stress tests' ability to identify them.

"The simplest combination of clinical features that excluded LMD with more than 97.5% probability on average in an adequately sized subgroup was female sex with mild or moderate ischemia," Dr. Senior concluded. In all other groups (men, and women with severe ischemia), the prevalence of LMD was 8.9%.

When the ISCHEMIA trial data were initially presented, the median follow-up was 3.2 years. At first, there was an increased risk of MI in the invasive therapy group, driven mainly by peri-procedural infarction. By the two-year mark, the curves had crossed, with the conservative group of patients having excess MIs. At the conclusion of the study, there was no mortality difference.

Dr. Judith Hochman of NYU Langone, who presented the original results in 2019, told Reuters Health that interim findings from ISCHEMIA-EXTEND, still to be finalized, show "no divergence of mortality curves to date."

Presumably, the physicians who recruited participants for the ISCHEMIA trial did not encourage every patient who underwent a stress test to enroll. Whether those patients weren't enrolled because they had too much or too little disease, or because their doctors were concerned about having them randomized, is not known.

"We do not know how many patients with mild or no ischemia on non-invasive stress testing in a similar population would have had LMD," Dr. Waleed Kayani of Baylor College of Medicine in Houston, Texas and colleagues wrote in an accompanying editorial.

Patients with significant LMD on cardiac-CTA will need angiographic evaluation, often with incorporation of fractional flow reserve (and plaque morphology on ultrasound), the editorialists say. They add that computed tomography-derived fractional flow reserve may become useful in the future, but larger studies are needed.

"This study left us with future questions and reinforced that for now we need to do some kind of anatomical imaging (CTA or coronary angio) to definitively rule out left main stenosis," Dr. Kayani told Reuters Health.

In an earlier post hoc analysis, the ISCHEMIA researchers found that among 1,728 patients without LMD on CTA who later underwent cardiac catheterization, 2.9% had angiographic LMD.

Dr. Senior offered this message: "According to our data, those with moderate-severe ischemia will require anatomical testing to exclude LMD. As coronary CTA also misses about 3% of patients with angiographic LMD, the anatomical investigation of choice should be invasive coronary angiography."

SOURCE: https://bit.ly/35CSPcz and https://bit.ly/35ID97u Journal of the American College of Cardiology, online February 14, 2022.

By Austin Kutscher MD FACC



Posted on 3 March 20228 March 2022