Relationship between adenosine A2a receptor polymorphism rs5751876 and fractional flow reserve during percutaneous coronary intervention.

ABSTRACT

Fractional flow reserve (FFR) assessed during adenosine-induced maximal hyperemia has emerged as a useful tool for the guidance of percutaneous coronary interventions (PCI). However, interindividual variability in the response to adenosine has been claimed as a major limitation to the use of adenosine for the measurement of FFR, carrying the risk of underestimating the severity of coronary stenoses, with potential negative prognostic consequences. Genetic variants of the adenosine receptor A2a (ADORA2A gene), located in the coronary circulation, have been involved in the modulation of the hyperemic response to adenosine. However, no study has so far evaluated the impact of the single nucleotide polymorphism rs5751876 of ADORA2A on the measurement of FFR in patients undergoing percutaneous coronary intervention that was, therefore, the aim of our study. We included patients undergoing coronary angiography and FFR assessment for intermediate (40-70%) coronary lesions. FFR measurement was performed by pressure-recording guidewire (Prime Wire, Volcano), after induction of hyperemia with intracoronary boli of adenosine (from 60 to 1440 µg, with dose doubling at each step). Restriction fragment length polymorphism (RFLP) analysis was performed to assess the presence of rs5751876 C>T polymorphism of ADORA2a receptor. We included 204 patients undergoing FFR measurement of 231 coronary lesions. A total of 134 patients carried the polymorphism (T allele), of whom 41 (30.6%) in homozygosis (T/T).Main clinical and angiographic features did not differ according to ADORA2A genotype. The rs5751876 C>T polymorphism did not affect mean FFR values (p = 0.91), the percentage of positive FFR (p = 0.54) and the duration of maximal hyperemia. However, the time to recovery to baseline FFR values was more prolonged among the T-allele carriers as compared to wild-type patients (p = 0.04). Based on these results, in patients with intermediate coronary stenoses undergoing FFR assessment with adenosine, the polymorphism rs5751876 of ADORA2A does not affect the peak hyperemic response to adenosine and the results of FFR. However, a more prolonged effect of adenosine was observed in T-carriers.