The ongoing search for simplifying fractional flow reserve assessment: the role of contrast medium

The current knowledge on the pathophysiology of coronary artery stenosis stems from the seminal studies by Lance Gould, who first described the pressure/flow/resistance characteristics, defining the coronary flow reserve as the ratio between hyperaemic and basal flow [1]. From the beginning it was clear, indeed, that this technique had several major limitations, and therefore the concept of fractional flow reserve (FFR) was introduced. The FFR was defined as the ratio of two flows, calculated from two pressure values, obtained during maximal hyperaemia [2]. Consequently, the achievement of hyperaemia is the crucial prerequisite to assess FFR correctly. In this regard, the administration of intravenous (i.v.) adenosine is still considered the gold standard. Even so, the correct achievement of maximal hyperaemia has been acknowledged as one of the major challenges of this technique, leading to significant FFR underutilization worldwide [3].
Indeed, i.v. adenosine is perceived as a time-consuming, relatively expensive tool, relatively uncomfortable for the patient. In order to circumvent, at least partially, these limitations, the vast majority of interventional cardiologists prefers the intracoronary (i.c.) route of administration, even in highly skilled centres [4]. However, the most favourable dose of adenosine to be administered is still a matter of debate. Our group has previously demonstrated that only a high dose bolus of 600 µg of i.c. adenosine has an effect on FFR comparable to the i.v. route, but this is achieved at a higher risk of atrioventricular (AV) block [5]. For this reason, we suggested to perform increasing boli of i.c. adenosine up to 600 µg, switching to the i.v. route in case of AV block. Recently, Adjedj et al. suggested that the best combination of hyperaemia and safety could be achieved by injecting 200 µg of adenosine in the left coronary artery (LCA) and 100 µg in the right [6]. However, these doses are still associated with a significant rate of AV block without reaching maximal hyperaemia. If adenosine still has some drawbacks, other potentially valuable vasodilator agents do not perform better [7].
For these reasons, adenosine-free pressure-derived indices were proposed over the last years. In 2010 Mamas et al. proposed the simple resting Pd/Pa value to predict positivity of FFR. Pd/Pa was demonstrated to be significantly correlated with FFR and relatively accurate in predicting a positive FFR with an area under...


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