What Is the Long-Term Outcome of Lesions Deferred Using FFR/iFR?

The presence of inducible ischemia is an essential prerequisite to obtain clinical benefits from revascularization through angioplasty. In that sense, the measurement of fractional flow reserve (FFR) is the gold standard as regards invasive methods assessing the functional significance of epicardial artery stenosis.

As opposed to FFR, the measurement of the instantaneous wave-free ratio (iFR) does not require hyperemia, which means that each of these indices may represent a different aspect of artery physiopathology.

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Two recently published large studies (DEFINE-FLAIR and iFR SWEDEHEART) measured and compared both indices, but they did not assess the clinical outcomes of lesions with discordant results in the two tests. In consequence, we lacked information enough to support the conclusion that both methods are equivalent.

From the 3V FFR-FRIENDS (3-Vessel Fractional Flow Reserve for the Assessment of Total Stenosis Burden and Its Clinical Impact in Patients With Coronary Artery Disease) study, 821 deferred lesions in 374 patients assessed with both methods were included in this study.

The primary endpoint was a composite of death, infarction, and ischemia-driven revascularization at 2 years.

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Lesions were classified according to FFR and iFR cutpoints into concordant normal (group 1: FFR >0.80 and iFR >0.89), high FFR and low iFR (group 2: FFR >0.80 and iFR ≤0.89), low FFR and high iFR (group 3: FFR ≤0.80 and iFR >0.89), and, finally, concordant abnormal (group 4: FFR ≤0.8 and iFR ≤0.89).

Deferred lesions despite FFR ≤0.80 and iFR ≤0.89 (group 4, concordant abnormal) showed significantly higher rates of 2-year events, compared with concordant normal lesions (7.2% in low FFR vs. 2.4% in high FFR; p < 0.001, and 8.1% in low iFR vs. 2.4% in high iFR; p < 0.001). Both indices were able to predict events as a continuous variable.

The discriminant ability for both indices was comparable (c-index 0.677 vs. 0.685; p = 0.857).

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Among all described groups classified according to FFR and iFR levels, only group 4 (concordant abnormal) showed a significantly higher number of events, compared with group 1, concordant normal (hazard ratio [HR]: 7.708; 95% confidence interval [CI]: 2.621 to 22.667; p < 0.001).

Conclusion

Both FFR and iFR were capable of predicting future events. Events increased only when both measurements resulted in an abnormal value. Discordant results between FFR and iFR were not associated with an increase in events.

Editorial

This is an extremely interesting study that seeds doubt on how to proceed with discordant lesions. Additionally, it might force us to perform both measurements for all lesions, which is highly unpractical. A reasonable course of action seems to be an initial assessment through iFR, which is faster and does not require adenosine hyperemia (thus saving time, money, and uncomfortable symptoms for the patient). If the result falls in a grey area such as ±0.03 from the cutpoint (between 0.86 and 0.92 iFR), use the adenosine and, under hyperemia, measure FFR and make an FFR-based decision. After all, this last method is the gold standard.

Another interesting piece of information that derives from this study is continuous event prediction, which means that FFR = 0.81 is not the same as FFR = 0.98 (although both values are considered normal in the classification). A patient with FFR = 0.81 is undoubtedly at higher risk than another with FFR = 0.98. In such cases, clinical criteria holds an undisputable importance that cannot be dimmed by a magic number resulting from a measurement.

Original title: Clinical Outcomes According to Fractional Flow Reserve or Instantaneous Wave-Free Ratio in Deferred Lesions.

Reference: Joo Myung Lee et al. J Am Coll Cardiol Intv 2017, article in press.

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