Specific Pharmacological Profile of A 2A Adenosine Receptor Predicts Reduced Fractional Flow Reserve in Patients With Suspected Coronary Artery Disease

Franck Paganelli (1, 2) , Noémie Resseguier (3) , Marion Marlinge (1) , Marc Laine (2) , Fabrice Malergue (1) , Nathalie Kipson (1) , Pauline Armangau (2) , Nicolas Pezzoli (4) , François Kerbaul (5) , Laurent Bonello (2, 1) , Giovanna Mottola (1) , Emmanuel Fenouillet (1) , Régis Guieu (1) , Jean Ruf (1)

1 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
2 Service de cardiologie [Hôpital Nord - APHM]
3 CEReSS - Centre d'études et de recherche sur les services de santé et la qualité de vie
4 Hôpital Nord [CHU - APHM]
5 DS-ACI / UMR MD2 - Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques

Background: The rapid and reliable exclusion of myocardial revascularization is a major unmet clinical need in patients with suspected coronary artery disease (CAD) and non‐contributive electrocardiography and troponin. Non‐invasive tests have high rates of false positives and negatives, and there is no biomarker to assess myocardial ischemia. The presence of spare adenosine A2A receptors (A2AR)—characterized by a high dissociation constant/half maximal effective concentration (KD/EC50) ratio—expressed on peripheral blood mononuclear cells (PBMC) has been associated with ischemia during exercise stress testing in patients with CAD. In this work, we investigated the diagnostic accuracy of spare A2AR versus fractional flow reserve (FFR) in patients with suspected CAD. Methods and Results: Sixty patients with suspected CAD, but non‐contributive electrocardiography and troponin, were consecutively enrolled in this prospective study. The binding (KD), functional response (cyclic adenosine monophosphate [cAMP] production; EC50) on PBMC A2AR were compared with FFR results. Patients were divided into 3 groups: 17 (group 1) with normal coronary angiography (n=13) or stenosis <20% (n=4); 21 with CAD and non‐significant FFR (group 2); and 22 with CAD and significant FFR (group 3). Median KD/EC50 was 6‐fold higher in group 3 (4.20; interquartile range: 2.81–5.00) than group 2 (0.66; interquartile range: 0.47–1.25) and 7‐fold higher than group 1 (0.60; interquartile range: 0.30–0.66). Conclusions: In patients with suspected CAD and non‐contributive electrocardiography and troponin, the absence of spare A2AR on PBMC may help to rule out myocardial ischemia.

Keywords: adenosine receptor; coronary artery disease; diagnosis

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Human health and pathology; Cardiology and cardiovascular system; Life Sciences [q-bio]; Pharmaceutical sciences; Pharmacology

Franck Paganelli, Noémie Resseguier, Marion Marlinge, Marc Laine, Fabrice Malergue, et al.. Specific Pharmacological Profile of A 2A Adenosine Receptor Predicts Reduced Fractional Flow Reserve in Patients With Suspected Coronary Artery Disease. Journal of the American Heart Association, 2018, 7 (8), pp.444-446. ⟨10.1161/JAHA.117.008290⟩. ⟨hal-01855307⟩