The development of selective coronary angiography in the 1960s by Sones 1 offered a dramatic improvement in the management of ischaemic heart disease. However, decisions could only be made on ‘shadowgrams’ of coronary stenoses. Early invasive assessment of stenosis severity and coronary flow have been developed, based on the Doppler effect, using a piezoelectric crystal mounted at the tip of standard Sones catheters 2 or on intraluminal probes.3 However, partial obstruction of the coronary ostium by these devices limited their clinical use.
When Gruntzig performed his first percutaneous transluminal coronary angioplasty (PTCA) in 1977, the concept of physiological assessment of the results of percutaneous interventions (PCI) was already introduced. 4 The double-lumen dilatation catheters permitted balloon inflation on one side and the recording of the distal coronary pressure on the other side. Trans-stenotic pressure gradients were used to monitor the procedures – a residual trans-stenotic gradient less than 20mmHg was considered optimal. 5 However, with technical developments like the flexible-tipped guidewires introduced in the lumen, previously used to measure pressure, and the introduction of low-profile balloons, pressure recordings were more difficult to perform. Moreover, the relations between the measured pressure gradient, the diameter stenosis and the lesion length were imprecisely known, and were dependent on the presence of the catheter itself in the stenosis. 6 With the development of parameters to assess the functional significance of a stenosis from its geometry, 7 it was considered that the available anatomical information was sufficient. Nowadays, the angiogram is still considered by most physicians to be the ‘gold standard’ for defining coronary anatomy. However, its resolution is limited and numerous confounding factors (vessel tortuosity, overlap of structures, etc.) result in a marked disparity between the apparent severity of a lesion and its physiological effect. 8-10
Principles of Doppler Velocimetry
An observer moving towards a sound source will hear a tone with higher frequency than when stationary and an observer moving away from the source will hear a tone of lower frequency. This change in frequency is called the Doppler effect. This principle is applied in practice by mounting a piezoelectric crystal that emits and receives high-frequency sounds on the tip of an intravascular catheter. The blood flow velocity alters the return frequency, causing the Doppler shift. Electronic circuits performing spectral analysis of the received signal allow continuous determination of the Doppler shift, and of blood flow velocity, based on the following Doppler equation:
V= ( F1 – F0 ) . C
V = velocity of blood flow
F0 = transmitting (transducer) frequency
F1 = returning frequency
C = constant: speed of sound in blood
φ = angle of incidence.
Maximum velocity can be recorded, provided the transducer beam is nearly parallel to blood flow (cos(φ)~1). With continuous-wave Doppler, the signal reflects all the flow velocities encountered by the exploring ultrasound beam. In contrast, a pulsed-wave Doppler permits determination of both magnitude and direction of the flow changes at a predetermined distance from the transducer. Intracoronary Doppler has several advantages for the assessment of the coronary circulation. Doppler flowmeters directly measure the red blood cell velocity continuously so that flow markers are not required. There is a direct relationship between velocity and volumetric flow, where blood flow = vessel cross-sectional area x mean flow velocity. The differences or changes in Doppler coronary flow velocities can therefore be used to represent changes in absolute coronary flow, provided the cross-sectional area remains constant. Intracoronary Doppler, however, also has several limitations. The method is extremely ‘space-dependent’ and may be affected by the stenosis geometry as well as by the intracoronary velocity profile.11 The angle existing between the piezoelectric crystal and the main stream of the blood is critical for the estimation of flow velocity.12 In addition, the sampling volume can be rather limited and does not necessarily represent the mean velocity of the bloodstream.2 Finally, the catheter itself changes the velocity profile in the arterial lumen and this velocity profile is not constant during the pulsatile flow condition of a cardiac cycle.13
Major epicardial coronary vessels contribute to the coronary vascular resistance, but they act primarily as conductance vessels, and most of the resistance to coronary blood flow arises from the intramural arterioles of less than 200 μm in diameter.14 Gould has demonstrated that the resting coronary flow does not decrease until there is a 90% diameter stenosis of the epicardial vessel. On the contrary, the maximum achievable flow begins to decrease when the per cent diameter stenosis exceeds 50%. The coronary flow reserve, defined as the ratio of coronary flow at maximum vasodilatation to the flow at rest, has been proposed as a measure of stenosis severity.15 The fractional flow reserve, in its simplified form computed as the ratio during full hyperemia of the pressure distal to a stenosis to the pressure proximal to it, evaluates the percentage of the maximal flow one would measure in that artery without the interrogated stenosis. These assumptions are derived from the complex haemodynamic principles regulating the coronary circulation. At rest, flow is independent from the driving pressure over a wide range (60–180mm Hg) of physiologic pressures, a phenomenon classically described as autoregulation of the coronary circulation. During maximal vasodilation, flow becomes linearly related to the driving pressure.16,17 The presence of a flow-limiting stenosis in a major epicardial vessel generates a pressure drop across the stenotic lesion that is the result of viscous and turbulent resistances, so that the driving pressure distal to the stenosis decreases non- linearly in response to the flow increase.18
Developments of miniaturised pressure and Doppler transducers, mounted on 0.014-inch guide wires, have resolved the initial fluid dynamics problems of flow impediment. The clinical importance of the coronary flow reserve (CFR) distal to a stenosis, derived from Doppler recordings, or of the myocardial fractional flow reserve (FFRmyo), derived from pressure recordings, has been extensively demonstrated.19,20 The safety of not performing an angioplasty for intermediate stenoses without a functional significant severity assessed by flow or pressure measurements has also been demonstrated.21,22 Because CFR is the summed response of a two-component system, there is some uncertainty in accepting an abnormal CFR as the sole indicator of lesion significance. To increase confidence in CFR as a measure of lesion severity, a relative CFR (rCFR) can be determined as defined by Gould et al.15,23 rCVR is defined as the ratio of maximum flow in the coronary with stenosis (QS), to flow in a normal coronary without stenosis (QN). It was shown that rCFR is independent of the aortic pressure and rate pressure product, and was well suited to assess the physiological significance of coronary stenoses when an adjacent non-diseased coronary artery is available. For flow velocity studies, rCFR in the catheterisation laboratory is defined as the ratio of CFR target to CFR in an angiographically normal reference vessel (rCFR=(QS/Qbase)/(QN/Qbase)= CFRtarget/CFRreference), and assumes that basal flow in the two vessels is similar and, thus, mathematically resembles Gould’s derivation. The normal range for rCFR is 0.8-1.0.24–26
Following the American and European guidelines, a revascularisation procedure (percutaneous or surgical) is only justified in flow-limiting lesions inducing ischaemia, yet surveys demonstrated that only 29% of patients treated by PCI had a stress test performed prior to cardiac catheterisation.27 Intracoronary physiological assessments of coronary lesions and interventions ideally complement coronary lumenology and morphology, as assessed by angiography and intravascular ultrasound. However, they are currently largely underused, although their cost-effectiveness has been demonstrated.28
Another field of application of intracoronary Doppler is the evaluation of early stages of coronary athero- sclerosis, without the presence of an epicardial stenosis, but with a functional impairment of coronary vasodilator capacity and endothelial dysfunction.29,30 An endothelium-derived relaxing factor, identified as nitric oxide,31 modulates vascular tone in response to physiologic and pathologic stimuli. Endothelial damage, leading to a decreased formation or release of nitric oxide from its precursor L-arginine, or reduced penetration due to the presence of subendothelial intimal thickening, are possible explanations of the impairment of endothelium-mediated vasodilation observed in patients with systemic hypertension, hyper-cholesterolemia, diabetes mellitus and atherosclerosis.32–34 The presence of paradoxic vaso- constriction induced by acetylcholine has been shown in coronary patients at sites of severe stenosis or moderate wall irregularities35 and in angio-graphically normalsegments.36–38
Since atherosclerosis is a diffuse process, endothelial function can be assessed in either the coronary39 or peripheral arteries40 as the brachial vasodilatory responses to reactive hyperaemia (flow) correlate closely with coronary vasodilatory response to acetylcholine.41 Endothelial function testing can provide prognostic data. It was shown that a reduced flow-mediated dilatation in the brachial artery predicts cardiovascular events in patients with chest pain.42 Also, coronary artery endothelial dysfunction predicts cardiovascular events in patients with coronary atherosclerosis.43
Recent years have seen rapid advances in coronary Doppler and pressure probes technology and the development of new approaches to the interpretation of intracoronary haemodynamic measurements. A complex technique reserved to a few research laboratories has been transformed into a reliable diagnostic tool that can be used for the assessment of stenosis severity, for the evaluation of the results of coronary interventions and for the study of coronary circulation and endothelial function.
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- R F Wilson, D E Laughlin, P H Ackell, et al., Transluminal, subselective measurement of coronary artery blood flow velocity and vasodilator reserve in man, Circulation (1985), 72: p. 82.
- A R Grüntzig, A Senning and W E Siegenthaler, Nonoperative dilatation of coronary artery stenosis, N. Engl. J. Med. (1979), 301 (2): pp. 61–68.
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- K Gould, K Kelley and E Bolson, Experimental validation of quantitative coronary arteriography for determining pressure-flow characteristics of coronary stenosis, Circulation (1982), 66 (5): pp. 930–937.
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- D Miller, T Donohue, L Younis, R Bach, F Aguirre, M Wittry, et al., Correlation of pharmacological 99mTcsestamibi myocardial perfusion imaging with poststenotic coronary flow reserve in patients with angiographycally intermediate coronary artery stenoses, Circulation (1994), 89 (5): pp. 2,150–2,160.
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- G Porenta, H Schima, A Pentaris, S Tsangaris, D Moertl, P Probst, et al., Assessment of coronary stenoses by Doppler wires: a validation study using in vitro modeling and computer simulations, Ultrasound Med. Biol. (1999), 25 (5): pp. 793–801.
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