Discordance Between Resting and Hyperemic Indices of Coronary Stenosis Severity

Fractional flow reserve (FFR) is the ratio of distal coronary pressure to aortic pressure (Pd/Pa) across a stenosis measured during maximal hyperemia, most commonly achieved by the intracoronary or intravenous administration of adenosine. Multiple studies have demonstrated that FFR-guided revascularization improves clinical outcomes compared with angiographic guidance alone. This has resulted in a class 1 recommendation from the European Society of Cardiology (ESC) and a class 2a recommendation from the American College of Cardiology/ American Heart Association for the use of FFR. Despite this, there has only been limited adoption of FFR into routine clinical practice. Some observers have suggested that this is because of the need to induce maximal hyperemia to measure FFR and have consequently studied and promoted the use of resting (nonhyperemic) indices of stenosis severity including Pd/Pa and the instantaneous wave-free ratio (iFR) which through utilization of a patented algorithm measures the trans-stenotic pressure ratio in the so-called wave-free period of diastole. Initially, it was proposed that iFR could be used for decision making using a dichotomous cutoff value in a similar fashion to FFR. In the ADVISE registry (Adenosine Vasodilator Independent Stenosis Evaluation Study; NCT01118481) (n=339 stenoses), an iFR value of ≤0.89 provided 80% agreement with the widely used FFR cutoff value of ≤0.80. Background—Distal coronary to aortic pressure ratio (Pd/Pa) and instantaneous wave-free ratio (iFR) are indices of functional significance of a coronary stenosis measured without hyperemia. It has been suggested that iFR has superior diagnostic accuracy to Pd/Pa when compared with fractional flow reserve (FFR). We hypothesized that in comparison with FFR, revascularization decisions based on either binary cutoff values for iFR and Pd/Pa or hybrid strategies incorporating iFR or Pd/Pa will result in similar levels of disagreement. Methods and Results—This is a prospective study in consecutive patients undergoing FFR for clinical indications using proprietary software to calculate iFR. We measured Pd/Pa, iFR, FFR, and hyperemic iFR. Diagnostic accuracy versus FFR ≤0.80 was calculated using binary cutoff values of ≤0.90 for iFR and ≤0.92 for Pd/Pa, and adenosine zones for iFR of 0.86 to 0.93 and Pd/Pa of 0.87 to 0.94 in the hybrid strategy. One hundred ninety-seven patients with 257 stenoses (mean diameter stenosis 48%) were studied. Using binary cutoffs, diagnostic accuracy was similar for iFR and resting Pd/ Pa with misclassification rates of 21% versus 20.2% (P=0.85). In the hybrid analysis, 54% of iFR cases and 53% of Pd/ Pa cases were outside the adenosine zone and rates of misclassification were 9.4% versus 11.9% (P=0.55). Conclusions—Binary cutoff values for iFR and Pd/Pa result in misclassification of 1 in 5 lesions. Using a hybrid strategy, approximately half of the patients do not receive adenosine, but 1 in 10 lesions are still misclassified. The use of nonhyperemic indices of stenosis severity cannot be recommended for decision making in the catheterization laboratory. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02377310. (Circ Cardiovasc Interv. 2016;9:e004016. DOI: 10.1161/CIRCINTERVENTIONS.116.004016.)