The Clinical and Economic Impact of Measuring Fractional Flow Reserve

What are the criteria you utilize to determine whether or not to use a pressure guidewire in a particular case? Visual estimation of the stenosis. As you know, patients with coronary artery disease don’t necessarily have one area that is severe. Typically, it’s diffuse disease involving multiple areas in the coronary tree. A good proportion of the time, the severity of one lesion versus the other is not obvious with visual estimation alone. When I am not comfortable in determining whether or not the stenosis is hemodynamically significant, I resort to a pressure guidewire. It adds about 10 minutes to the procedure. We use the PressureWire (Radi Medical Systems, Wilmington, MA). The DEFER trial, which was presented earlier this year with positive results, looked at elective PCI patients with stable chest pain and one lesion. Yet all types of complex, multi-vessel disease patients are seen in cath labs daily. Is it possible to extrapolate the trial data for more complex disease? Yes, and it is the same story with any new device or technology. The benefit of clinical trials is that they allow for the introduction of new technology that does something good for the patient. We use clinical trials to apply the technology to the general population. If we are going to wait for every subset of patients to be studied in a clinical trial, we won’t be able to take good care of our patients. It is not possible to study all types of patients by the use of randomized clinical trials and therefore it is impossible for us to get an answer for every subset of patients. In clinical practice, we have to use our judgment to generalize when possible, knowing that there are pitfalls and that the certain population we are generalizing to may not fall into this group that was studied. This is not something new. You have to use your clinical judgment as to when to use a new technology, like a pressure guidewire, in a subset of patients that has not been studied. So, I have been generalizing, like everybody, like with any device, and with success. I get a lot of input from using this technology to make better decisions. It has been very helpful. Could you share a recent complex case and describe how FFR measurement was incorporated? I actually had a patient last week, in his mid-50’s and diabetic. Two years ago, I placed stents in his right coronary artery and left circumflex, and he did well, but recently developed typical angina. A stress thallium showed antero-lateral and inferior ischemia. I proceeded with coronary angiography and to my surprise, the stents and the left anterior descending artery were fine. The only thing I could see was a tubular lesion in the left main. It did not strike me as severe. The left main was a long vessel and in its mid-portion there was a long area of some narrowing, but it did not look bad at all. I would estimate it to be in the 40% range, at worst. I could not find any other lesions to explain the typical symptoms of angina as well as the abnormalities in the stress thallium. I decided to quickly measure FFR by using the pressure guidewire. The patient had a resting gradient of about 20mm of mercury without adenosine, and with IV adenosine, his fractional flow reserve was 0.68, which is one of the worst I have ever seen (remember that a FFR of Without having measured FFR, what course might you have chosen? We would have scratched our heads a lot, and I probably would not have sent him to bypass surgery. I would have tried him on medical therapy, and if I’m lucky and he’s lucky, he wouldn’t drop dead on medical therapy because of left main disease. Probably medical therapy would not have worked and I would have ended up cathing him again, and eventually, would have sent him to surgery. Ultimately, I expedited good care for this patient by using a pressure guidewire. Do you think FFR measurement could be of use in acute myocardial infarction, where time is muscle? Around 80% of acute ST-elevation myocardial infarction patients will have a severe stenosis or a 100% occlusion, so there’s no need for a pressure guidewire. The lesion is obvious. About 10% of the time, the thrombus has resolved and the underlying stenosis may not necessarily be severe. In ST-elevation myocardial infarction (MI) in an acute setting, you can potentially benefit from a diagnostic FFR measurement. In the setting of a non ST-elevation MI, not necessarily acute, where the patient is stable, the rate of use of a pressure guidewire is probably the same as in the general population. The real question is what benefits the pressure guidewire would give us to assess the stent result, meaning to assess whether the stent deployment is optimal. There are some physicians who really believe in this type of use for the pressure guidewire, and use it to assess the stent result by using the functional assessment. At this point, I am not using a pressure guidewire to that extent. I use it mainly for diagnostic purposes. How does the information you receive by measuring stent deployment with a pressure guidewire differ from measuring it with intravascular ultrasound? As opposed to intravascular ultrasound, which like angiography is just another imaging modality, the pressure guidewire is a much more valuable tool that measures the functional severity of a residual in-stent narrowing due to suboptimal deployment or a significant stent edge dissection. The only advantage of intravascular ultrasound is that it shows stent strut malapposition to the vessel wall, a finding that can lead to subacute stent thrombosis, especially in the drug-eluting stent era. This finding, however, needs further clinical study. What economic impact have you seen with the ability to measure FFR? The economic benefits are very significant, in my opinion, although I have not studied actual dollar amounts systematically. Patients come in with chest pain syndrome and multiple cardiac risk factors, maybe a slight increase in troponin. The cath shows moderate lesions. Without a pressure guidewire, we would end up putting those patients in the hospital for an extra day or two, in order to do an adenosine stress thallium in order to assess the hemodynamic significance of that lesion. If the stress thallium is abnormal, we then bring the patient back in the cath lab and do an intervention. By using a pressure guidewire, you can make that decision at the time of catheterization itself. You can decide if the lesion is significant and fix it in the same procedure. If the lesion is not significant, the patient goes home the same day. You saved a significant amount of money by reducing the length of stay and eliminated the need for additional diagnostic functional studies. So I believe the economic impact would be significant. How do you explain to the patient if you find a lesion that appears occlusive but does not need to be stented according to the pressure guidewire? Well, if it looks bad, I don’t bother with a pressure guidewire. However, some physicians may think a lesion is severe, while others may not. Such a situation comes about only rarely. I would tend to believe the measurement results rather than rely on the visual estimation, which is not as accurate. You could say that for an interventionalist to leave a lesion alone that looks like it is blocking blood flow goes against his or her core nature. Can you talk about fighting against the occulo-stenotic reflex to focus on the evidence-based medicine behind FFR measurement? We, typically, as interventional cardiologists, have an occulo-stenotic reflex. We see a stenosis, we immediately put in stents or do angioplasty. But that’s not necessarily the right thing to do. With better medical therapy, with better anti-platelet therapy, with better lipid-lowering therapy, it looks like the need for intervention, especially when you couple this with a significant risk of stent thrombosis on the long-term, should be weighed significantly against proceeding with an intervention. If you have any reason not to proceed, such as the FFR not concurring with what you think the lesion is initially, then maybe you shouldn’t proceed with an intervention. Unfortunately, right now it is only a few people that think along those lines. To generalize this attitude to the greater community is going to take time, education and experience with the technology. Pressure guidewires are an excellent addition to our diagnostic armamentarium. I think they need to be used more often than they are at present, because the interventionalist is then equipped to make the right decision at the right time without delaying patient care. Sometimes it ends up that the interventionalist must stent even if the lesion does not appear too occlusive or vice versa. Physicians need to be better educated on how to use this technology and how to interpret the results. There are some pitfalls that the physicians and the cath lab technologists need to understand and avoid when interpreting the results. What are some of the pitfalls to avoid? There are techniques that physicians and cath lab technologists must learn regarding how to use a pressure guidewire. The benefit of any technology is as good as it can be correctly applied. The operators and the cath lab staff should be meticulous about properly calibrating the system and equalizing the guiding catheter and pressure wire while the cathter is in the aorta. The guiding catheter should be disengaged from the coronary ostium before measurement. Intravenous rather than intracoronary adenosine should be used since this allows for a much stable and accurate pressure gradient assessment. It also allows for pullback gradient measurement, an important step in ruling out diffuse disease that would not be a candidate for stent implantation. It is important to understand how to use a pressure guidewire and apply it correctly, because otherwise you are not going to benefit the patient. You will be participating as a speaker in an advanced user’s course for the PressureWire, taking place November 8-9. Yes, we have an advanced 2-day users course directed at those who already are using the PressureWire, but might benefit from advancing their skills in interpretation for those lesions that I mentioned previously, such as left main and multi-vessel disease, as well as pullbacks, etc. The course is being held at Tampa General Hospital. We’ll be showing cases with several lectures about different topics, but it will be mainly geared toward the users of the PressureWire who are interested in improving their experience in applying this technology. Dr. Matar can be contacted at fm@fciheart.com

1. Pijls NH, Van Gelder B, Van der Voort P et al. Fractional flow reserve. A useful index to evaluate the influence of an epicardial coronary stenosis on myocardial blood flow. Circulation 1995 Dec 1;92(11):3183-3193.

2. Pijls NH, van Schaardenburgh P, Manoharan G, et al. Percutaneous Intervention of Functionally Nonsignificant Stenosis, 5-Year Follow-Up of the DEFER Study. J Am Coll Cardiol 2007; 49: 2105-2111.