Clinical Outcomes of Deferred Lesions With Angiographically Insignificant Stenosis But Low Fractional Flow Reserve

Abstract

BackgroundData are limited regarding outcomes of deferred lesions in patients with angiographically insignificant stenosis but low fractional flow reserve (FFR). We investigated the natural history of angiographically insignificant stenosis with low FFR among patients who underwent routine 3‐vessel FFR measurement.Methods and ResultsFrom December 2011 to March 2014, 1136 patients with 3298 vessels underwent routine 3‐vessel FFR measurement (3V FFR‐FRIENDS study, ClinicalTrials.gov identifier NCT01621438), and this study analyzed the 2‐year clinical outcomes of 1024 patients with 2124 lesions with angiographically insignificant stenosis (percentage of diameter stenosis <50%), in which revascularization was deferred. All lesions were classified according to FFR values, using a cutoff of 0.80 (high FFR >0.80 versus low FFR ≤0.80). The primary end point was outcome of major adverse cardiovascular events (a composite of cardiac death, myocardial infarction, and ischemia‐driven revascularization) at 2 years. Mean angiographic percentage of diameter stenosis and FFR of total lesions were 32.5±10.3% and 0.91±0.08%, respectively. Among the total lesions with angiographically insignificant stenosis, 8.7% showed low FFR (185 lesions). The incidence of lesions with low FFR was 2.5%, 3.8%, 9.0%, and 15.1% in categories of percentage of diameter stenosis <20%, 20% to 30%, 30% to 40%, and 40% to 50%, respectively. At 2‐year follow‐up, the low‐FFR group showed a significantly higher risk of major adverse cardiovascular events compared with the high FFR group (3.3% versus 1.2%, hazard ratio: 3.371; 95% CI, 1.346–8.442; P=0.009). In multivariable analysis, low FFR was the most powerful independent predictor of future MACE in deferred lesions with angiographically insignificant stenosis (adjusted hazard ratio: 2.617; 95% CI, 1.026–6.679; P=0.044).ConclusionsIn deferred angiographically insignificant stenosis, lesions with low FFR showed significantly higher event rates than those with high FFR. FFR was an independent predictor of future major adverse cardiovascular events in lesions with angiographically insignificant stenosis.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01621438.

Fractional Flow Reserve in Angiographically Insignificant Stenoses: Unmasking the Lesion or Creating Disease?

“…In this issue of JAHA, a subgroup analysis from the 3-Vessel Fractional Flow Reserve for the Assessment of Total Stenosis Burden and its Clinical Impact in Patients With Coronary Artery Disease (3-Vessel FFR-FRIENDS) study provides novel insight into patient outcome data for low-FFR but angiographically insignificant lesions. 18 The majority of the findings by Lee et al are consistent with much of what we already know about FFR, namely, that low-FFR values can be generated in even mild stenoses and that these situations arise most frequently in left main stem and proximal left anterior descending artery lesions. In this patient population, however, in which a low-FFR value may have previously been rationalized away as an indirect sign of high flow and a healthy microcirculation, the (comparatively) unfavorable major adverse cardiac event (MACE) outcomes reported by Lee et al potentially imply an altogether different prognosis.…”

“…In this issue of JAHA , a subgroup analysis from the 3‐Vessel Fractional Flow Reserve for the Assessment of Total Stenosis Burden and its Clinical Impact in Patients With Coronary Artery Disease (3‐Vessel FFR‐FRIENDS) study provides novel insight into patient outcome data for low‐FFR but angiographically insignificant lesions . The majority of the findings by Lee et al are consistent with much of what we already know about FFR, namely, that low‐FFR values can be generated in even mild stenoses and that these situations arise most frequently in left main stem and proximal left anterior descending artery lesions.…”

The Interplay between Features of Plaque Vulnerability and Hemodynamic Relevance of Coronary Artery Stenoses

“…Our study consistently showed that a coronary stenosis with a normal FFR has a low likelihood of having plaques with high-risk features. Therefore, these aforementioned associations shown between plaque features of vulnerability and hemodynamic outcome can also help us understand why revascularization may be safely deferred in lesions with FFR >0.80 [38] and why the event rates were significantly higher in deferred angiographically insignificant lesions in stable CAD patients with low FFR than those with high FFR [39]. In this respect, the benefit of FFR-guided therapy may become evident, at least in part, based on its potential connection with plaque vulnerability/activity shown in both stable and unstable CAD patients in the current study.…”

Functional Approach for Coronary Artery Disease: Filling the Gap Between Evidence and Practice

“…In addition, FFR was an independent predictor of future clinical events in those lesions with angiographically insignificant stenosis. 33) In another substudy, patients with multi-vessel moderate CAD (FFR, 0.81–0.87) showed a comparable risk of clinical events with patients with functionally significant CAD. 34) …”