Original title: Thinking Out of the Lumen: FFR Vs. Intravascular Imaging for MACE Prediction. Reference: Pedro R. Moreno et al. J Am Coll Cardiol, article in press.

Intravascular imaging studies have shown that the lesions most likely to produce coronary events usually have modest luminal stenosis, large cap burden and thin fibrous cap. These plaques will evolve into a significative stenosis in the event of an ACS. On the other hand, we see significantly obstructive but predominantly fibrotic plaques associated to chronic angina that call for revascularization but do not evolve into ACS. 

This is why plaque assessment should focus on identifying the risk of evolving into ACS rather than luminography or physiology. At this point, we should ask ourselves whether intravascular imaging associated to fractional flow reserve could be superior to FFR alone. 

The COURAGE study showed no difference between optimal medical treatment and PCI, with 20% and 19.5% event rate, respectively, introducing the idea that not all angiographycally obstructive lesions need revascularization. When it became clear that not all multiple vessels symptomatic patients need a better stratification, the FFR and the FAME study came along. This work showed that 37% of obstructive lesions had negative FFR. The alternative to PCI resulted in a 5% absolute reduction in death and infarction risk, and revascularization after a year. 

Following these ideas, the FAME II was designed to compare OMT alone vs. PCI plus OMT in positive FFR lesions. This last strategy was proved superior basically because of the lower rate of emergency revascularization (1.6% vs. 11.1%; p<0.001), but showed no difference in death or infarction rate. We should treat 10.5 lesions with positive FFR (NNT) for event prevention.

Conversely, all studies involving patients with ACS (PROSPECT, VIVA, PREDICT) treated culprit and angiographycally significant lesions before evaluating non culprit lesions with imaging. This is why recognizing the role of obstructive lesions in future events was impossible right from the start.

In the PROSPECT study, the average stenosis percentage of non-culprit lesions responsible of future events was 32 ± 21%. However, at second events, these lesions progressed to 65 ± 16%. 

When looking at lesion morphology, plaque volume comes as an independent predictor of clinical events, with increasing plaque burden, a thin fibrous cap and minimal lumen area of ≤ 4mm². The simultaneous presence of these 3 parameters was associated to an 18% event incidence at 3.4 years.

After FAME II, functional evaluation of lesions became standard: if negative, medical treatment was the best option and, if positive, the best course of action was PCI. However, less than 15% of lesions with positive FFR result in future events and even positive FFR lesions could regress with medical treatment.

This was the rationale behind the YELLOW study that randomized patients with multiple vessels and stable angina with high doses rosuvastatin vs. standard doses. After culprit lesion revascularization, the remaining obstructive lesions with positive FFR were evaluated with intravascular ultrasound. The result was lipid plaque regression and a tendency to improve FFR; however, there were no changes in fibrous plaques.

The optimal quality of OCT imaging can help detect plaque with high risk characteristics and may evolve to be the gold standard for quantification of the fibrous cap in-vivo. However, very few studies could properly assess the clinical impact of OCT. There is evidence of the clinical impact of FFR; but, is it safe to avoid angiography and revascularization of all negative FFR and severe lesions?

At least 3% of lesions with negative FFR in the FAME study resulted in events at 2.5 years and, in fact, the significant difference of FFR guided PCI dissolves when compared to conventional PCI at two years follow up (p=0.08).

This is where plaque composition plays an important role with only 0.7% events at 3 years for fibrous lesions vs. 2.7% for rich lipids lesions (p<0.001), this is obviously out of FFR reach.

Conclusion:

The study of patients with presumed stable chronic angina suggests that guided FFR PCI reduces revascularization in the short term. However, in the long term, some lesions can lead to events such as death or infarction. FFR was a great progress compared to conventional angiography, but cannot differentiate plaques with great positive remodeling and atheroma volume that are not necessarily obstructive at the moment of assessment but are associated to events at follow up.

Conventional angiography, functional compromise with FFR and IVUS and OCT imaging complement each other and help prevent future events. 

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