Traditionally, the functional evaluation of coronary stenoses is performed through measurement of the fractional flow reserve (FFR) during hyperemia induced by adenosine or adenosine triphosphate (ATP). However, contraindications, adverse effects, and the risk of vascular injury associated with these agents have prompted the development of alternative indices — both hyperemic and non-hyperemic — and, more recently, angiographic ones.
The main objective of this review was to analyze the diagnostic accuracy and clinical outcomes of various functional indices alternative to FFR. Secondary objectives included the comparison of adverse effects, hyperemic characteristics, clinical applicability, and prognostic impact during follow-up.
A comprehensive literature review was conducted, including randomized trials, meta-analyses, and multicenter registries. The analysis encompassed the principal hyperemic agents (papaverine, adenosine, ATP, nitroprusside, regadenoson, nicorandil, nicardipine), non-hyperemic pressure ratios (iFR, resting Pd/Pa, dPR, RFR, DFR, dPRmicro, cRR), and angiographic indices (FFRv, QFR, angio-FFR, caFFR, accuFFRangio, μQFR). Most trials included between 150 and 3,825 patients, with standardized cut-off values of FFR ≤ 0.80 or iFR ≤ 0.89 to define significant ischemia.
Among the hyperemic agents, papaverine proved the most potent, though associated with a risk of ventricular arrhythmias. Adenosine and ATP demonstrated equivalent diagnostic performance and remain the reference agents (p > 0.05 vs. FFR). Nicorandil and sodium nitroprusside showed comparable efficacy with a lower incidence of adverse effects (atrioventricular block < 5%), whereas regadenoson and nicardipine displayed less consistency and higher cost.
Among the non-hyperemic pressure ratios (NHPRs), iFR showed 79–88% concordance with FFR across three studies (n = 1,259). In the DEFINE-FLAIR (n = 2,492) and iFR-SWEDEHEART (n = 2,037) trials, iFR-guided revascularization was non-inferior to FFR-guided strategies for the composite endpoint of death, myocardial infarction, or revascularization at 1- and 5-year follow-up (MACE 18.6% vs. 16.8%; p = 0.63). Patients with post-PCI iFR values ≥ 0.95 had a significantly reduced combined risk of cardiac death, myocardial infarction, or repeat revascularization at 1 year. Other NHPRs (Pd/Pa = 0.91, dPR, RFR, DFR) demonstrated diagnostic accuracies > 93% with no significant differences in clinical outcomes.
Angiographic indices — which require neither pressure wire nor hyperemia — yielded promising results. The vascular fractional flow reserve (FFRv) achieved 90% diagnostic accuracy in the FAST II study (n = 334), and values ≤ 0.93 were associated with a higher risk of target-vessel failure (TVF) at 5 years (n = 748). The quantitative flow ratio (QFR) showed an overall accuracy of 87%, and in the FAVOR III China trial (n = 3,825), QFR-guided strategy significantly reduced the composite endpoint of death, myocardial infarction, or revascularization (5.8% vs. 8.8%; p < 0.001). Both angio-FFR and caFFR demonstrated accuracies > 93% and comparable safety when deferring PCI, while μQFR identified a higher risk of TVF (29.2% vs. 10.8%; p < 0.05) when values were < 0.8.
Conclusion
FFR remains the reference standard for guiding percutaneous coronary intervention (PCI). However, current evidence supports the use of alternative indices. iFR provides equivalent long-term outcomes with reduced procedural time and greater patient comfort, while angiographic indices are emerging as reliable, non-hyperemic, and non-invasive options with high diagnostic precision and favorable prognostic correlation.
Original Title: Functional assessment of coronary stenosis: alternative hyperemic, nonhyperemic, and angiographic indexes.
Reference: Federico Vergni et al. REC: Interventional Cardiology, 2024;6(3):224-234.
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