FFR, IVUS, Apples, Oranges, and Overcoming Conventional Wisdom: A review of basic concepts to guide everyday usage

Before we start, here’s my summary of and disclaimer for fractional flow reserve (FFR) and intravascular ultrasound (IVUS). I like FFR and IVUS. I favor FFR for physiologic lesion assessment, since IVUS is not designed to assess physiology. I favor IVUS for vessel sizing, and confirming stent expansion and strut apposition. I am on the speaker’s bureau for both FFR and IVUS companies, and teach about both techniques. I am entertained yet concerned with commonly spoken conventional wisdom regarding FFR and IVUS for everyday interventional cardiology. Conventional wisdom (CW) says, “If you want to stent, use IVUS; if you don’t, use FFR.” What’s wrong with this CW (besides being wrong)? CW describes ideas that are generally held to be true by the public or even some experts. CW may be only partly true or just plain wrong. CW is an obstacle to accepting new explanations or approaches despite new and highly credible information to the contrary. Some hold to CW to the point of absurd denial, repeating or embracing an outdated or incorrect view. The strength of this erroneous belief is due to the fact that CW is made of convenient and appealing ideas which are easy to accept without critical inspection. Eventually, CW will not match its holders’ reality and a new approach with evident benefit takes over. Some promoters of conventional wisdom in interventional cardiology would want you to believe that IVUS provides the same and even more information than FFR for lesion assessment. I recently saw an interpretation of this CW in the interventional cardiology marketplace, implying that FFR and IVUS are essentially the same tool. However, the conventional wisdom for this comparison is dead wrong. These two tools are apples and oranges, and as everyone knows, apples are not oranges. From this recent, troubling sighting of such a misleading expression of CW, I thought that this would be a good time to review the similarities and differences between FFR and IVUS. The First Question For coronary lesion assessment, the first question that should be asked and answered is, “Does this lesion limit blood flow and produce ischemia?” Said another way, the question can be: “Is the patient’s stenosis (usually of uncertain significance) responsible for the clinical syndrome?” If the answer is no, then stenting is of no value to the patient and introduces unneeded risk and cost. FFR – First Principles Fractional flow reserve (FFR) assesses flow across a stenosis and is based on 3 principles of coronary pressure and flow. The first is that aortic pressure is transmitted completely through normal coronary arteries without pressure loss even to the distal regions of the vessels. The second principle is that atherosclerotic narrowings inside the arteries produce resistance to blood flow, which is measured as a loss of pressure beyond the stenosis. The pressure drop across the stenosis increases with increasing flow rates. Lastly, a coronary stenosis has complex anatomic features, such as flow entrance angle, minimal lumen diameter, length of narrowing, shape of the orifice, exit angle and region of turbulence, which together form the resistance. More importantly, these anatomic factors are unknowable from the angiogram. This means that there is more to a stenosis than just minimal lumen diameter or area which produce a reduction in coronary flow (Figure 1). To measure the effect of the stenosis on blood flow, FFR is calculated by measuring the translesional pressure with a 0.014-inch pressure sensor guide wire. Let’s review the 4 steps to measuring FFR. First, zero the pressure wire to atmosphere outside the patient. Second, match the guide wire pressure to aortic pressure (guide catheter) near the coronary artery before crossing the stenosis. Third, pass the pressure guide wire across the lesion (10-20mm beyond the lesion is fine, but even 1mm beyond the narrowing will also work). Finally, turn on adenosine [either intravenous (IV) or intracoronary (IC), since the hyperemia, maximal flow response is equal between techniques]. FFR is the ratio of distal pressure (Pd) to aortic pressure (Pa) at hyperemia. FFR, Pd/Pa at hyperemia, has a normal value of 1 in all vessels under all conditions.1 Every FFR value below 1 is the percent reduction of normal flow. For example, if aortic pressure is 100mmHg, distal pressure 75mmHg at hyperemia, FFR then equals 0.75 and is translated as: this artery transmits 75% of expected normal artery flow. This simplified formula of FFR has been validated against clinical stress testing and long term (5-year) outcomes.2,3 FFR values of 0.80 are associated with low event rates in patients who have intermediate lesions managed medically without stenting. The FAME study3 has convincingly demonstrated the superiority of FFR-guided multi-vessel percutaneous coronary intervention (PCI) over the conventional, angiographically-guided PCI. IVUS – Dimensions for decisions Intravascular ultrasound (IVUS) imaging provides a picture from within a coronary artery showing the vessel wall, plaque and lumen in precise detail with resolution to 150 microns. IVUS use is based on one critical principle, which is angiography cannot accurately show the sizes (dimensions) or composition of coronary arteries and luminal narrowings. This information is critical to stent size selection and implantation, as well as selection of devices to treat calcified stenoses. The IVUS advantage over angiography for determining when a stent is correctly sized, fully expanded and struts apposed to the vessel wall is indisputable. To obtain IVUS images, the 2-3 French (Fr) monorail catheter is flushed and connected to the imaging cable, which is plugged into the display monitor. The catheter is then advanced over an angioplasty guide wire already in the artery beyond the stenosis. Then while recording the IVUS images, the catheter is pulled back (either manually or by a pullback device). The catheter is removed from the vessel and the images reviewed and measured for vessel, lumen and plaque areas and diameters. The most common measurements are minimal lumen and reference vessel diameters and areas (Figure 2). Stent size is based on reference vessel size. The identification of stent apposition by IVUS was a major advance in interventional cardiology, associated with superior stent outcomes, reduced abrupt closure, and lower restenosis rates. Can IVUS substitute for FFR? Some operators use the IVUS minimal lumen area of a stenosis of Dr. Kern can be contacted at: mortonkern005@hotmail.com References 1. Pijls NHJ, DeBruyne B, Peels K, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med 1996; 334:1703–1708. 2. Kern MJ, Samady H. Current concepts of integrated coronary physiology in the cath lab. J Am Coll Cardiol 2010;55:173–185. 3. Tonino PAL, DeBruyne B, Pijls NHJ, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:3:213-224. 4. Takagi A, Tsurumi Y, Ishii Y, et al. Clinical potential of intravascular ultrasound for physiological assessment of coronary stenosis: relationship between quantitative ultrasound tomography and pressure-derived fracational flow reserve. Circulation 1999;100(3):250-255. 5. Briguor C, Anzuini A, Airoldi F, et al. Intravascular ultrasound criteria for the assessment of the functional significance of intermediate coronary artery stenoses and comparison with fractional flow reserve. Am J Cardiol 2001;87:136-141. 6. Rodés-Cabau J, Candell-Riera J, Angel J, et al. Relation of myocardial perfusion defects and nonsignificant coronary lesions by angiography with insights from intravascular ultrasound and coronary pressure measurements. Am J Cardiol 2005;96;12:1621-1626. 7. Abizaid AS, Mintz GS, Abizaid A, et al. One-year follow-up after intravascular ultrasound assessment of moderate left main coronary artery disease in patients with ambiguous angiograms. J Am Coll Cardiol 1999 Sep;34(3):707-715. 8. Fassa AA, Wagatsuma K, Higano ST, et al. Intravascular ultrasound-guided treatment for angiographically indeterminate left main coronary artery disease: a long-term follow-up study. J Am Coll Cardiol 2005 Jan 18;45(2):204-211. 9. Russo RJ, Wong SC, Marchant D, et al. Abstract 2467: Is left main angiographic lesion location predictive of a significant stenosis by intravascular ultrasound and the need for revascularization? Observations from the Left Main IVUS registry. Circulation 2006; 114: II-508 10. Abizaid AS, Mintz GS, Mehran R, et al. Long-term follow-up after percutaneous transluminal coronary angioplasty was not performed based on intravascular ultrasound findings: importance of lumen dimensions. Circulation 1999 Jul 20;100(3):256-261.

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