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In intermediate lesions, angiographic measures of stenosis severity greater than 50% are at odds with the conventional fractional flow reserve (FFR) value for predicting ischemia in about one-third of cases, according to findings from a large series published online March 18, 2014, ahead of print in the European Heart Journal. Moreover, the disagreement is exacerbated by certain patient and lesion characteristics and is most critical in left main stenoses.

Bernard De Bruyne, MD, PhD, and colleagues from the Cardiovascular Center Aalst (Aalst, Belgium), analyzed data on 4,086 coronary stenoses from 2,986 unselected patients with at least 1 stable lesion of intermediate angiographic severity (30-70% stenosis). All patients underwent both QCA and FFR in at least 1 stenosis at their institution between September 1999 and December 2011.

For the entire cohort, the median FFR value was 0.82, angiographic diameter stenosis was 48%, and minimal lumen diameter (MLD) was 1.40 mm.

Overall Correlation ‘Modest’

Overall, the correlation between diameter stenosis and FFR was modest, albeit significant (-0.38; 95% CI -0.41 to -0.36; P < 0.001), with marked scatter around the regression line. A diameter stenosis ≥ 50% correctly identified a positive FFR value (≤ 0.80, indicating ischemia requiring revascularization) with a sensitivity of 61% (95% CI 59-63%), specificity of 67% (95% CI 65-69%), and diagnostic accuracy (AUC) of 0.64 (95% CI 0.56-0.72). There was also a relationship between MLD and FFR (AUC 0.45; 95% CI 0.42-0.47; P < 0.001), with a large scattering of the data.

When the data were analyzed according to patient characteristics, 2 traits diminished the ability of 50% diameter stenosis to predict significant FFR:

• Male vs female gender (OR 2.916 vs OR 4.071; P for interaction = 0.017)
• Diabetes vs no diabetes (OR 2.589 vs OR 3.808; P for interaction = 0.005)

At the same diameter stenosis threshold, different anatomical settings based on location (LAD, circumflex, or RCA), supplied territory (left main vs distal), lesion length (≤ 12 mm vs ≥ 20 mm), and vessel size (small, intermediate, or large) showed marked variations in sensitivity (range 35-74%) and specificity (range 58-76%), resulting in discordance in 35% of all cases. In particular, diagnostic accuracy was lowest in left main disease (AUC 0.53 (95% CI 0.43-0.62).

Interestingly, the overall diagnostic performance of angiography declined when the diameter stenosis cutoff was set at 70% rather than 50% (P = 0.004). Youden’s index (a measure in which the sum of sensitivity and specificity is maximized) from 50% diameter to 70% diameter decreased from 0.28 to 0.11 for the overall population and showed an absolute decrease of 0.16 ± 0.05 in various anatomical subsets.

The optimal cutoff values for diameter stenosis to predict ischemia (FFR ≤ 0.80) varied markedly across vessel segments supplying different myocardial territories, with the lowest value for left main location, while the overall diagnostic accuracy was similarly low for all locations (table 1).

Table 1. Diagnostic Power of Percent Diameter Stenosis by Lesion Location

 
“[T]he present data confirm that in comparison with FFR, [coronary angiography] underestimates or overestimates physiologic stenosis severity in a large proportion of angiographically intermediate stenoses that may trigger inappropriate decisions about revascularization,” the authors state.

LM Finding New, Critical

By this time, the existence of discrepancies between angiographic- and FFR-based predictions of ischemia is “no surprise,” Morton J. Kern, MD, of the University of California, Irvine (Irvine, CA), told TCTMD in a telephone interview. “The new wrinkle in this study is the fact that among the sections of the coronary arteries looked at, the left main shows the biggest discordance. Stenosis diameters of 50% or less can be [functionally] significant, whereas it is commonly thought that this is not the case. It emphasizes that this is a more critical clinical [territory].”

However, “the spread of data across other coronary segments is remarkable as well,” he added. “For example, when you look at a low [diameter stenosis] percentage for the LAD, it’s almost a 50-50 [split] as to whether you’re above or below an FFR value of 0.8.”

A key factor in such discordance is the volume of blood flow to the muscle mass served by the artery, Dr. Kern said, explaining that “a smaller narrowing can be more significant in lesions supplying large myocardial territories.”

James K. Min, MD, of Weill Cornell Medical College (New York, NY), agreed that underestimation of left main disease by the standard cutoff for diameter stenosis is a key finding of the study. “Patients who have ischemic left main disease are at high risk for future adverse events, and for us to be able to better identify those patients using this hemodynamic method is critical,” he noted in a telephone interview with TCTMD.

The advantage of FFR is that it isolates ischemia to the particular stenosis, Dr. Min observed. “That differs from traditional measures of myocardial perfusion imaging, which simply represent a combined metric of epicardial coronary stenosis and microvascular disease. FFR allows us to hone in on what we can treat interventionally, [namely] the stenosis that causes the flow limitation.”

Dr. Min observed that “this is the largest study [comparing angiographic and FFR lesion assessments] that has ever been performed. It covers the period from the early introduction of FFR to its current state, and I think the consistency in demonstrating the [benefit of FFR] over time is very important.”

Dr. Kern noted that although the study is largely a reiteration of previous findings, “it can take a long time for [a clinician] to become a believer [in the importance of FFR].” Dr. Min added that the somewhat slow uptake of FFR is probably due to multiple factors including considerations of efficiency of work flow and concerns about reimbursement.

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