To evaluate borderline coronary lesions (a 40% to 70% obstruction), determining associated ischemia is paramount. For this purpose, pressure gradients are measured across the stenosis. These measurements can be hyperemic, such as the fractional flow reserve (FFR), or taken at rest, such as the instantaneous wave-free ratio (iFR).
According to the iFR-SWEDEHEART 5-year follow-up outcomes, both strategies have demonstrated effectiveness, as iFR is non-inferior to FFR. However, in different reports, these measurements have shown a correlation close to 80%. An altered reactivity of endothelial cells to vasoactive drugs might explain the observed discordance.
Whether this endothelial phenomenon can be caused by genetic polymorphisms of enzymes responsible for vasodilatation, such as endothelial nitric oxide synthase (eNOS) and heme oxygenase-1 (HO-1), is uncertain.
Building on this, the aim of this study was to analyze lesions and patients with discordant FFR and iFR measurements, and to determine whether polymorphism in the eNOS gene and in HO-1 influence coronary pressure and flow measurements.
Enrollment included patients with acute coronary syndrome (non-culprit vessel measurement) and chronic coronary syndromes in centers in the Czech Republic, Japan, and Argentina. FFR, IFR, and—in some cases—coronary flow reserve (CFR) were measured. Nitroglycerin 200 µg pre-measurement and adenosine 240 µg were systematically administered for pressure and flow measurements.
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Three groups of tests were classified according to positive or negative results: FFR/iFR concordance, FFRp/iFRn discordance, and FFRn/iFRp discordance.
A total of 1884 measurements from 1564 patients were analyzed; most measurements corresponded to the anterior descending artery (58%). FFR/iFR discordance was observed in 20.9% of the measurements, with FFRp/iFRn being the most frequent. In flow measurements, CFR correlated better with iFR (R = 0.56; p < 0.0001) than with FFR (R = 0.36; p <0.0001). When genetic analysis was conducted, eNOS and HO-1 polymorphisms showed no changes in FFR or IFR values.
Right coronary lesions presented a higher FFRp/iFRn index, which would indicate a distinctive coronary flow (absence of maximum flow in meso-diastole). In turn, this FFRp/iFRn discordance was observed in situations with indemnity of endothelial function, especially in young patients, and more frequently in men than in women.
The FFRn/iFRp discordance presented increased microvascular resistance (decreased CFR). These were generally older patients who suffered more frequently from chronic kidney disease. This discordance was more commonly observed in patients with eNOS and HO-1 polymorphism.
Conclusions
There was a 21% discordance between FFR and iFR measurements. FFRn/iFRp discordance is probably caused by a defective endothelial reaction to vasodilator drugs. Additionally, eNOS and HO-1 gene polymorphisms were more frequently observed in this group.
Dr. Omar Tupayachi.
Member of the Editorial Board of SOLACI.org.
Reference: Kovarnik, Tomas et al. “Fractional Flow Reserve Versus Instantaneous Wave-Free Ratio in Assessment of Lesion Hemodynamic Significance and Explanation of their Discrepancies. International, Multicenter and Prospective Trial: The FiGARO Study.” Journal of the American Heart Association vol. 11,9 (2022): e021490. doi:10.1161/JAHA.121.021490.
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