Summary
Fractional flow reserve (FFR) is emerging as a useful clinical tool for assessing the functional significance of coronary atherosclerosis. As opposed to anatomical approaches, physiological measurements (particularly pressure-derived FFR) assess the function of the coronary circulation and offer the possibility of ‘ad hoc’ treatment. The use of FFR is still limited in France because there is no financial support. The present review will focus on coronary pressure-derived FFR.
Résumé
La mesure de la réserve coronaire ou fractional flow reserve (FFR) est un outil très utile pour évaluer le caractère fonctionnel des lésions coronaires. Contrairement à l’approche anatomique, l’évaluation physiologique (et notamment la FFR) permet de déterminer directement en salle de cathétérisme si une sténose est hémodynamiquement significative. Cette sténose peut alors être traitée dans le même temps. L’utilisation de la FFR en France est encore limitée en raison de l’absence de remboursement. Cet article est une revue des outils de physiologie coronaire et s’intéresse plus particulièrement à la FFR.
Introduction
The goal of any treatment is to improve patients’ prognosis and/or symptoms. Accordingly, the goal of any diagnostic tool is to guide decision-making, to apply optimal treatment to individual patients. Any diagnostic tool not fulfilling these requirements should not be used in patients. FFR is emerging as a useful technique for the assessment of coronary artery stenosis. FFR evaluates the functional significance of coronary artery stenosis and helps interventional cardiologists with ‘on the spot’ decision-making . This is especially relevant when a coronary angiogram shows mild-to-moderate coronary atheroma. The usefulness of FFR is also further clinically validated in complex bifurcation lesions, ostial stenoses, multivessel disease and left main stenoses . As opposed to anatomical approaches, physiological measurements (particularly pressure-derived FFR) assess the function of the coronary circulation and offer the possibility of ‘ad hoc’ treatment . The use of this tool is still limited in France because there is no financial support. The present review will focus on coronary pressure-derived FFR.
Coronary circulation
To comprehend the concept of FFR, the coronary circulation can be viewed as a two-compartment model. The first compartment consists of large epicardial vessels (> 400 microns), which are also referred to as ‘conductance vessels’ because they have minimal resistance to blood flow. Therefore, the pressure in the distal part of a healthy human coronary artery should be equal to central aortic pressure. The second compartment consists of arteries smaller than 400 microns, or ‘resistive vessels’ ( Fig. 1 ). Myocardial flow is controlled predominantly by resistive vessels.
Physiological indices of the coronary circulation
In the next few paragraphs, we will discuss some of the relevant indices of coronary physiology that can be used to estimate coronary circulatory function as a guide to clinical decision-making. FFR is the best validated of all of these physiological indices. In the first part of this section, we will briefly describe the other indices before focusing on FFR.
Coronary flow reserve
CFR is defined as the ratio of hyperaemic blood flow (Q max) to resting myocardial blood flow (Q rest) (i. e. CFR = Q max/Q rest). The normal value for CFR is still not well defined and normal values differ from study to study . There is some consensus of opinion, however, suggesting that a value > 4 should be considered as normal, which means that microvascular resistance can decrease by a factor of 4 . As absolute myocardial flow is not easy to determine, surrogate markers of flow are commonly used, such as flow velocities assessed by the Doppler Wire (FloWire, Volcano Inc., Rancho Cordova, CA, USA) or Tmn assessed by the PressureWire (Saint Jude Medical Systems Inc., Uppsala, Sweden). Regardless of the method used to measure CFR, this technique has several limitations: resting flow is highly variable; there is considerable spatial heterogeneity of flow velocity distal to an epicardial stenosis; hyperaemic flow is directly dependent on systemic blood pressure; the hyperaemic and resting measurements are performed simultaneously not successively; and CFR is not specific for an epicardial stenosis, as the CFR value depends on both epicardial vessels and microcirculation. When CFR is low, it is impossible to distinguish whether this value is related to an epicardial artery stenosis alone, microcirculatory dysfunction alone or a combination of both. Owing to these limitations, CFR is not used routinely in clinical practice to assess the haemodynamic significance of a coronary stenosis and has limited value in clinical decision-making.
Index of microvascular resistance
The resistance of a vascular system is defined as the ratio of the pressure gradient divided by the flow across that particular system. Accordingly, the resistance of the coronary microvascular compartment is equal to the ratio (Pd–Pv)/Q, where Pd is distal coronary arterial pressure and Pv is coronary venous pressure or right atrial pressure. In the coronary circulation, Pv is often almost negligible. Fearon et al. introduced the concept of IMR, considering that the Tmn during maximal hyperaemia is inversely proportional to hyperaemic flow.
Therefore, during maximal hyperaemia, IMR = Pd/1/Tmn = Pd × Tmn. IMR is specific for the microcirculation and is simple to obtain, as Pd and Tmn can be obtained simultaneously with the PressureWire. This technique has been well validated in animals and was recently used in the setting of acute coronary syndromes to predict clinical outcomes and assess the effect of treatment . Nevertheless, IMR is a novel index that needs further validation in clinical studies.
Fractional flow reserve
FFR is the ratio of maximal myocardial blood flow depending on a stenotic artery to maximal myocardial blood flow if that same artery were to be normal. In other words, it is a fraction of the maximal normal flow, assuming that these measurements are obtained when the microvasculature resistance is minimal and constant (maximal hyperaemia) .
FFR represents the extent to which maximal myocardial blood flow is limited by the presence of an epicardial stenosis. If FFR is 0.60, it means that maximal myocardial blood flow reaches only 60% of its normal value. Conversely, FFR provides the interventionist with the exact extent to which optimal stenting of the epicardial stenosis will increase maximal myocardial blood flow. An FFR of 0.60 implies that stenting the focal stenosis responsible for this abnormal FFR should bring FFR to 1.0, which represents an increase in maximal myocardial blood flow of 67%. In addition, FFR excludes the confounding influence of the microcirculation, changes in haemodynamics or contractility .
FFR is a ratio of two flows. It has been shown, however, that this ratio of two flows can be derived from two pressures (distal coronary pressure and aortic pressure), provided they are both measured during maximal hyperaemia. The theoretical explanation of this relationship between hyperaemic flows and hyperaemic pressures is displayed in Fig. 2 .
Fractional flow reserve: practicalities
Catheters
The use of diagnostic catheters is technically feasible . However, due to the higher levels of friction hampering wire manipulation, the smaller internal calibre prejudicing pressure measurements and the inability to perform ad hoc PCI using diagnostic catheters, the use of guiding catheters is recommended.
Wires
Two pressure wire systems are available on the market for measuring intracoronary pressure, namely the PressureWire (Saint Jude Medical Systems Inc., Uppsala, Sweden) and the Volcano WaveWire (Volcano Inc., Rancho Cordova, CA, USA). The sensor is located 30 mm from the tip, at the junction between the radiopaque and radiolucent portions. The last generations of these 0.014 inch wires have similar handling characteristics to most standard angioplasty guide wires.
Hyperaemia
To measure FFR, it is absolutely essential to achieve maximal vasodilatation of the two vascular compartments of the coronary circulation, namely the conductance arteries (epicardial) and the resistance arteries (microvasculature). The pharmacological agents most often used to induce hyperaemia are listed in Table 1 . A bolus of 200 mg isosorbide dinitrate (or any other form of intracoronary nitrate) abolishes any form of vasoconstriction of epicardial arteries. The pharmacological agents most often used to induce hyperaemia in resistance arteries are adenosine (via the intracoronary or intravenous routes) and papaverine. An adenosine dose of 50 μg as an intracoronary bolus or 140 μg/kg/min as an intravenous infusion has been demonstrated to induce hyperaemia similar to intracoronary papaverine . An example of a typical coronary pressure tracing during the administration of intracoronary bolus adenosine is shown in Fig. 3 .
| Drug | Delivery |
|---|---|
| Epicardial vasodilation | |
| Isosorbide dinitrate | ≥ 200 μg intracoronary bolus, ≥ 30 s before the first measurements |
| Microvascular vasodilation | |
| Adenosine or adenosine triphosphate | 140 μg/kg/min intravenously (preferably through a central venous line) |
| Adenosine or adenosine triphosphate | 50 μg (to 150 μg) intracoronary bolus |
| Papaverine | Intracoronary delivery: 12–16 mg in the right coronary artery; 16–20 mg in the left coronary artery |
| Nitroprusside | 0.6 μg/kg intracoronary bolus |
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