Latest From Ischemia: Worse Outcomes in Patients With Intermediate Left Main Disease on CCTA

Doug Brunk

June 01, 2020

Patients in the landmark ISCHEMIA trial with intermediate left main disease had a greater extent of coronary artery disease on invasive angiography, indicating greater atherosclerotic burden. They also had worse prognosis with a higher risk of cardiovascular events.

"Many times, we are looking at results as to whether patients have left main disease or not," Sripal Bangalore, MD, said during the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. "Here, we are showing that it's not black and white; there are shades of gray. If a patient has intermediate left main disease, the prognosis is worse. That's very important information we need to convey to our referrals also, because many times they may just look at the bottom line and say, 'there is no left main disease.' But here, we're seeing that even having intermediate left main disease has significantly worse prognosis. We need to take that seriously."

Prior studies show that patients with significant left main disease (LMD; defined as 50% or greater stenosis on coronary CT angiography [CCTA]) have a high risk of cardiovascular events and guidelines recommend revascularization to improve survival, said Dr. Bangalore, an interventional cardiologist at New York University Langone Health. However, the impact of intermediate LMD (defined as 25%-49% stenosis on CCTA) on outcomes is unclear.

Members of the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) research group randomized 5,179 participants to an initial invasive or conservative strategy. The main results showed that immediate revascularization in patients with stable ischemic heart disease provided no reduction in cardiovascular endpoints through 4 years of follow-up, compared with initial optimal medical therapy alone.

"Discordance" Revealed in Imaging Modalities

For the current analysis, named the ISCHEMIA Intermediate LM Substudy, those who underwent coronary CCTA comprise the LMD substudy cohort. The objective was to evaluate clinical and quality of life outcomes in patients with and without intermediate left main disease on coronary CT and to evaluate the impact of treatment strategy on those outcomes across subgroups.

At baseline, these patients were categorized into those with and without intermediate LMD as determined by a core lab. Patients with LMD of 50% or greater, those with prior coronary artery bypass graft surgery, and those with nonevaluable or missing data on LM stenosis were excluded.

Among the 3,913 ISCHEMIA participants who underwent CCTA, 3,699 satisfied the inclusion criteria. Of these patients, 962 (26%) had intermediate LMD and 2,737 (74%) did not.

The researchers observed no significant differences in baseline characteristics between patients with and without LMD. However, patients with intermediate LMD tended to be older, and a greater proportion had hypertension and diabetes. Stress test characteristics were also similar between patients with and without LMD. However, patients with intermediate LMD tended toward a greater severity of severe ischemia.

This was also true for anatomic disease on CCTA. A higher proportion of patients with intermediate LMD had triple-vessel disease (61%-62%, compared with 36%-40% along those without intermediate LMD). In addition, a higher proportion of patients with intermediate LMD had stenosis in the proximal left anterior artery descending (LAD) artery (65% vs. 39% among those without intermediate LMD).

On analysis limited to 1,846 patients who underwent invasive angiography treatment in the main ISCHEMIA trial, 7% of those who were categorized into the intermediate LMD group were found to have LMD disease of 50% or greater, compared with 1.4% of patients who were categorized as not having intermediate LMD. "This goes to show this discordance between the two modalities [CCTA and coronary angiography], and I think we have to be careful," said Dr. Bangalore, who also directs NYU Langone's Cardiac Catheterization Laboratory. "There may be patients with left main disease, even if the CCTA says it's not at 25%-29% [stenosis]."

The researchers found that, among patients who underwent invasive angiography, a greater proportion of those who were categorized into the LMD group had proximal LAD disease (43% vs. 33% among those who were categorized into the nonintermediate LMD group), triple-vessel disease (47% vs. 35%), a greater extent of coronary artery disease as denoted by a higher SYNTAX score (21 vs. 15), and a higher proportion underwent coronary artery bypass graft surgery (32% vs. 18%).

Intermediate LMD Linked to Worse Outcomes

After the researchers adjusted for baseline differences between the two groups in overall substudy cohort, they found that intermediate LMD severity was an independent predictor of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, and resuscitated cardiac arrest (hazard ratio, 1.31; P = .0123); cardiovascular death/MI/stroke (HR, 1.30; P = .0143); procedural primary MI (HR, 1.64; P = .0487); heart failure (HR, 2.06; P = .0239); and stroke (HR, 1.82, P = .0362)

"We then looked to see if there is a treatment difference, a treatment effect based on whether patients had intermediate LMD," Dr. Bangalore said. "Most of the P values were not significant. The results are very consistent with what we saw in the main analysis: not a significant difference between invasive and conservative strategy. We do see some differences, though. An invasive strategy was associated with a significantly higher risk of procedural MI [2.9% vs. 1.5%], but a significantly lower risk of nonprocedural MI [–6.4% vs. –2%]."

Dr. Bangalore added that there was significant benefit of the invasive strategy in reducing angina and improving quality of life based on the Seattle Angina Questionnaire-7. "This result was durable up to 48 months of follow-up, whether the patient had intermediate left main disease or not. These results were dependent on baseline angina status. The benefit of invasive strategy was mainly in patients who had daily, weekly, and monthly angina, and no benefit in patients with no angina; there was no interaction based on intermediate left main status."

Dr. Bangalore emphasized that the original ISCHEMIA trial excluded patients with severe left main disease by design. "But patients with intermediate left main disease in ISCHEMIA tended to have a greater extent of coronary artery disease, indicating greater atherosclerotic burden. I don't think that's any surprise. They had a worse prognosis with higher risk of cardiovascular events but similar quality of life, including angina-specific quality of life."

The key clinical message, he said, is that patients with intermediate LMD face an increased risk of cardiovascular events. "I think we have to be aggressive in trying to reduce their risk with medical therapy, etc.," he said. "If they are symptomatic, ISCHEMIA tells us that patients have two options. They can choose an invasive strategy, because clearly there is a benefit. You have a significant benefit at making you feel better and potentially reducing the risk of spontaneous MI over a period of time. Or, you can try medical therapy first. If you do see some left main disease, it's showing the general burden of atherosclerosis disease in those patients. I think that's the critical message, that we have to be very aggressive with these patients."

A Call for More Imaging Studies

An invited panelist, Timothy D. Henry, MD, said that the results of the ISCHEMIA substudy should stimulate further research. "With an intermediate lesion, clearly the interventional group did better, and it wasn't symptom related," said Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research and Education at the Christ Hospital in Cincinnati. "So even if you do medical therapy, you're not going to really find it out. In my mind, this should stimulate us to do more imaging of the left main that are moderate lesions, and follow this up as an independent study. I think this is a really important finding."

ISCHEMIA was supported by grants from the National Heart, Lung, and Blood Institute. Dr. Bangalore disclosed that he is a member of the advisory board and/or a board member for Meril, SMT, Pfizer, Amgen, Biotronik, and Abbott. He also is a consultant for Reata Pharmaceuticals.

SOURCE: Bangalore S et al. SCAI 2020, Abstract 11656.

This story originally appeared on


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: