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An intravascular ultrasound (IVUS)-derived cutpoint appears to be a reliable measure for determining which intermediate left main lesions require revascularization, according to data published in the July 19, 2011, issue of the Journal of the American College of Cardiology. The study was prompted in part by the well-known limitations of angiography in the left main coronary artery, an observation confirmed by the findings.

The main results of the multicenter study, known as LITRO, originally were presented in September 2010 at the annual Transcatheter Cardiovascular Therapeutics symposium in Washington, DC.

A team led by Jose M. de la Torre Hernandez, MD, PhD, of Marqués de Valdecilla University Hospital (Santander, Spain), prospectively studied 354 patients with suspected or confirmed CAD who underwent angiography at 22 Spanish centers in 2007 and were found to have intermediate left main lesions (25%-60% visual stenosis). IVUS imaging was also performed in all patients.

IVUS Threshold Set for Revascularization

Operators were strongly encouraged to leave untreated lesions that were determined to have a minimum lumen area (MLA) of at least 6 mm² and to revascularize those with a smaller MLA. In fact, the great majority of patients were managed according to protocol: Among patients whose MLA was above the cutoff (n = 186), revascularization was deferred in 96.2%, while it was performed in 90.5% of those whose MLA fell below the recommended threshold (n = 168).

The 2 groups had similar clinical characteristics, but revascularized patients had significantly more bifurcations, diffuse disease, calcification, and overall more significant lesions, but less ostial disease.

Little correlation was observed between the degree of angiographic stenosis and MLA, with stenosis levels scattered widely within both MLA groups (those above and below the cutoff). In fact, one-third of patients whose MLA measurements were below the cutoff had angiographic stenosis of less than 30%, while in 43% of patients with angiographic stenosis over 50%, the MLA was larger than 6 mm²).

At 2-year follow-up, the deferred and treated groups had similarly high rates of survival free from cardiac death and from adverse events (cardiac death, MI, and clinically driven revascularization; table 1).

Table 1. Outcomes at 2 Years

 
In the deferred group, 12 patients died, 4 from cardiac causes. Of the latter, all had an MLA less than 8 mm² and 3 were elderly (> 75 years) with LV dysfunction and high-risk predictors. In addition, 8 patients required revascularization, but in no case due to acute MI. In the overall deferred group, there were no significant clinical, angiographic, or IVUS differences between those who did or did not undergo revascularization.

During follow-up of the low-MLA group, 2 patients died of cardiac causes, 3 had MIs, and 4 underwent left main revascularization. In the group that did not receive revascularization despite low MLAs, rates of cardiac death-free survival and event-free survival were considerably lower than in the deferred group (86% vs. 97.7%; P = 0.04 and 62.5% vs. 87.3%; P = 0.02, respectively).

Angiography Unreliable in the Left Main

The authors note that the diffuse nature of left main disease and the shortness of the left main artery make angiographic stenosis a less reliable guide to revascularization in this location than in other sites in the coronary tree.

The authors acknowledge that their findings come with certain caveats. For example, because the study was not randomized, the strength of its conclusion may be compromised by the differing baseline characteristics between the deferred and revascularized groups. Another limitation is that a small percentage of patients were not treated according to the recommended strategy.

IVUS Criterion Consistent Across Studies

In a telephone interview with TCTMD, Massoud A. Leesar, MD, of the University of Cincinnati (Cincinnati, OH), said the study is the largest yet to look at methods of determining the significance of left main stenosis, and it essentially corroborates his earlier research showing a strong correlation between the gold standard FFR of 0.75 and an MLA of 5.9 in terms of diagnostic accuracy (Jasti V, et al. Circulation. 2004;110:2831-2836).

John McBarron Hodgson, MD, of the Geisinger Health System (Wilkes-Barre, PA), added that the MLA cutpoints identified have been very consistent. “This is the latest of 4 or 5 papers now, and they all show the same thing: an MLA of about 6,” he told TCTMD in a telephone interview. “And [physiologically] it seems to make sense.”

Dr. Hodgson put the range of visual angiographic stenosis that qualifies as intermediate at somewhat larger than that used in the study. Anything in the range of 25% up to 80% could be significant or not depending on the size of the vessel, the length of the lesion, and whether or not it appears diffuse, he observed.

Several studies have now shown that if a patient’s MLA measures above the cutpoint of 6 mm², “then he is likely to do well with medical therapy or treatment of a different lesion,” Dr. Hodgson noted. On the other hand, he said, “nobody has randomized patients who fall below the cutpoint to treatment or no treatment to see which do better. There are certainly people who have a low cross sectional area and are very stable, and with good medical treatment they do great. So it’s not just a single [MLA] number.”

IVUS Rules Out, Not In

“I think the take-home message from these studies is that if you measure an intermediate lesion and it’s above the cutpoint, then it is generally okay to leave it alone. Below that, we have to use our clinical judgment. Just saying the left main is narrow by IVUS and therefore the patient needs surgery—there are no data for that,” he emphasized. In short, the cutpoint is “not a rule-in, it’s a rule-out,” he added. “If the MLA is below the cutpoint, you have to put it in context with everything else that’s going on.”

For example, Dr. Hodgson said, “if you’ve got a couple of lesions that are easy to stent and the left main is questionable—and you go in [with IVUS] and the left main [MLA] measures 8, then leave it alone and do the other lesions.”

However, Dr. Hodgson added that “there is a bit of a gray zone between 6 and 7.5.”  For example, diabetics represent a special case, he said, adding, “If a diabetic had clear [cardiac] symptoms and [an MLA of] 7, I would probably treat the lesion.” Moreover, he said, “whenever there is a question—the clinical scenario doesn’t make sense—we use FFR [to help sort it out].”

In a telephone interview with TCTMD, Jeffrey W. Moses, MD, of Weill Cornell Medical College (New York, NY), agreed with Dr. Hodgson’s assessment regarding lesions on both sides of the cutpoint: “The study makes a good case for deferring treatment of stenoses [with an MLA] above 6, but the cutpoint for a decision to revascularize is still unsettled,” he said. “Nothing bad happened to patients [who were treated because their MLA fell below 6]—in fact, they did pretty well. It’s just that we don’t know if [the investigators] had used a different cutpoint whether the [outcomes] curve would look the same.”

Many Left Main Stenoses May Be IVUS Bystanders

In addition, Dr. Moses was skeptical of the investigators’ claim to have evaluated patients with ‘intermediate’ left main lesions ‘prospectively,’ since the visual stenosis of the lesions in the study population averaged around 40%, with some as low as 25%.

“When you eyeball a lesion and call it intermediate, it’s usually in the 50% to 60% range,” he pointed out. “So I wonder how many of the lesions here were just bystanders in the context of other revascularization—lesions that a priori you wouldn’t investigate with IVUS. So this is not totally a prospective study in the sense that in all cases the left main was targeted upfront.”

The main message of the study is that if an angiogram shows borderline left main stenosis, “don’t rely on angiography, because it can fool you,” Dr. Leesar said, citing cases in which doctors have sent patients for bypass surgery of the left main, only to discover later that the lesion was not significant by IVUS criteria.

FFR may sometimes play a deciding role in borderline-low MLA lesions, Dr. Leesar indicated. “If you have an MLA in an isolated left main of, say, 5.5 and you want to be sure of its significance, FFR can be done,” he commented. “But the problem is that if you also have disease in other vessels—and here 70% of patients did—then FFR is not going to be accurate.”

Related Stories:

• IVUS Guidance May Improve Survival in Unprotected Left Main Disease
• FFR Beats Angiography in Guiding Left Main Disease Treatment
• IVUS Cannot Replace FFR But Can Help Rule Out Ischemia-Producing Stenoses