Usefulness of Fractional Flow Reserve Guidance for Percutaneous Coronary Intervention in Acute Myocardial Infarction

Recent trends mean that intracoronary stents are now implanted in as many as 80% of percutaneous coronary interventions (PCI). The usefulness of stents as a treatment for acute myocardial infarction (AMI) has also been well-documented, as has their efficacy in the treatment of thrombotic lesions.1,2 However, when stenting in the setting of AMI, the fact that antiplatelet therapy is not always an option prior to intervention means that consideration must be made for the heightened risk of thrombosis and acute reocclusion.3–5 In addition, considering the increased costs involved with stenting, there is an important debate still to be had as to whether or not stents are truly indicated for all lesion types. Against this background, one method that we have adopted at our institution, when assessing whether or not it is safe not to stent, is the use of a pressure guidewire, which has been reported to be useful for evaluating coronary circulation6 and is a simple and accurate method for evaluating lesion-specific stenosis severity.7 In this prospective study, we used a pressure guidewire and an established cut-off value for fractional flow reserve (FFR) to determine whether stenting should be conducted, and then investigated the usefulness of this parameter as a tool for guiding stent implantation, in terms of patient outcomes and reduced cost-effectiveness. Methods Patient population. Our patient population consisted of 77 PCI patients (77 lesions) out of 117 consecutive patients admitted to the Kawasaki Social Insurance Hospital between January and December 1998 and diagnosed with first-time AMI, in whom adequate wave patterns could be obtained using a pressure guidewire (JoMetrics Wavewire™; JoMed, Rancho Cordova, California) after conventional balloon angioplasty. Our control group consisted of 77 patients (78 lesions) who underwent conventional stent implantation at our institution in 1997. Coronary intervention was performed via the femoral approach using 8 French (Fr) guiding catheters. Patients were given 5,000 units of intravenous heparin at the time of sheath insertion. First, coronary angiography was used to visualize the non-infarct-related arteries, including any lesions in other vessels and the collaterals. The infarct-related vessel was then visualized to evaluate the site and degree of occlusion. The lesion was crossed with a 0.0014´´ guidewire and a balloon catheter was inserted over the wire. The guidewire was then replaced with a 0.0014´´ WaveWire. Preprocedural coronary pressure across the lesion was measured and a value for FFR was obtained. The pressure guidewire was then replaced once more with a PTCA balloon catheter and the occluded site was dilated with a balloon catheter. Dilation continued until residual stenosis was reduced to = 300 seconds. Angiographic findings were analyzed using the CMS quantitative analysis system (QCA-CMS, Version 3.0; Medis, The Netherlands) to evaluate stenosis severity and lesion morphology. Images were taken from the angle that suggested greatest stenosis severity, and the tip of the catheter was used for absolute calibration. The coronary arteries were analyzed with the CMS Vascular Analysis system to determine percent diameter stenosis (%DS) and minimum luminal diameter (MLD). The angiographic criteria used for determining the success of coronary intervention were TIMI grade 3 blood flow and residual stenosis = 50% diameter stenosis at this time. The number of balloon catheters and stents used in all patients was also carefully recorded, in order to investigate the cost efficiency of percutaneous transluminal coronary angioplasty and hospitalization across the full range of the patient population. Long-term prognosis was based on the 700-day long-term survival rate determined using the Kaplan-Meier method from data obtained by questionnaire and telephone interview (response rate, 97%). Numerical values are expressed as means ± standard deviation values, with the student’s t-test used for continuous variables. The different patient groups were compared using non-parametric tests (Chi-square and Fischer’s exact tests) and p-values Patient baseline characteristics (Tables 1 and 2). Lesions were divided into 2 groups: thirty-seven lesions with FFR >= 0.94 following direct PTCA which did not undergo stenting (FFR-PTCA group) and 40 lesions with FFR Stenting strategy (Table 3). The Multi-Link stent was the most commonly used, in 32/40 patients (80%) of the FFR-stent group and 53/78 patients (68%) of the control group. There were no significant differences in terms of the frequency of predilatation, dilatation pressure or stent size in the 2 stented cohorts. Change in %DS (Figures 1 and 2). There were no significant differences in %DS between the FFR-guided patients and the controls prior to the procedures, but %DS tended to be greater in the FFR-guided patients post-procedure (23 ± 10% for the FFR-guided group versus 14 ± 14% for the control group) and prior to discharge (45 ± 18% for the FFR-guided group versus 34 ± 17% for the control group). Pre-procedural MLD was virtually the same in both groups, but tended to be smaller in the FFR-guided patients post-procedure (2.2 ± 0.5 mm for the FFR-guided group versus 2.6 ± 0.3 mm for the control group) and prior to discharge (1.5 ± 0.6 mm for the FFR-guided group versus 2.0 ± 0.5 mm for the control group). Reocclusion and restenosis rates (Figures 3 and 4). The acute post-procedural reocclusion rate was 0% in both the FFR-guided groups and the controls. Reocclusion rates at discharge were 1.7% for the FFR-guided patients and 0% for the controls, while restenosis at discharge was 5.1% for the FFR-guided patients and 0% for the controls. Looking only at patients in whom FFR was used to determine the endpoint of intervention, the acute post-procedural reocclusion rate was 0% in both the FFR-PTCA group and the FFR-stent group, with rates at discharge of 4.7% for the FFR-PTCA group and 0% for the FFR-stent group. Restenosis rates just prior to discharge were 9.5% for the FFR-PTCA group versus 2.7% for the FFR-stent group. These differences did not reach statistical significance. In-hospital complications. There was no incidence of in-hospital coronary artery bypass graft surgery (CABG) or cardiac death in either the FFR-guided or non-FFR guided patients. Balloons used (Figure 5). Significantly more balloons were used in the control group (1.8 ± 0.5) than in the FFR-guided patients (1.3 ± 0.6; p Long-term survival (Figure 7). There were no differences between the groups in long-term survival rates at 700 days by the Kaplan-Meier method (90% for the FFR-guided group versus 89% for the control group). Discussion In the present study, we used the FFR cut-off value of 0.94 as the endpoint for conventional balloon angioplasty for AMI. For patients with FFR >= 0.94 after direct PTCA, coronary intervention was considered complete, while patients with FFR FFR cut-off value. A value of 0.94 was selected as the cut-off point for FFR in the present study. Bech et al.15 advocate an FFR of 0.90 or higher as the endpoint for conventional balloon angioplasty. In their study, patients at or above this cut-off point had a significantly better prognosis than those below, with a 6-month restenosis rate of 12% and an event-free survival rate of 88% after two years (versus 59%). An FFR of 0.94 has been proposed as the endpoint for stent implantation.16 Takeuchi et al.17 reported that FFR was as useful in patients with old myocardial infarction (OMI) as in patients without OMI. In their study, OMI patients had a mean FFR of 0.78, which was not significantly different from the 0.76 of the non-OMI subjects. In the Takeuchi study, mean FFR after stenting was 0.89, but in this study we adopted a cut-off of 0.94 after balloon angioplasty alone as a reasonable way of guaranteeing a stent-like result. In another study, Caymaz et al.18 reported that infarct-related arteries had a higher FFRmyo (0.78) than non-infarct related vessels (0.63) prior to intervention and emphasized the need for care when interpreting FFRmyo values prior to balloon angioplasty. However, after balloon angioplasty, FFRmyo in both infarct-related and non-infarct related vessels was the same (0.89%), demonstrating that the presence of an infarction is no obstacle to setting an endpoint for intervention. Initial success rate. In our study, the procedural success rate for FFR-guided intervention was 100%. The endpoint for intervention was reached by PTCA alone in 48% of subjects. The remaining 52% of patients (40/77) had FFR In-hospital prognosis. FFR is reported to be a useful clinical tool for predicting restenosis, since there is a good correlation between the severity of chronic stenosis, the hyperemic pressure gradient and FFRmyo in elective PTCA.19 This study constitutes a comparison of FFR-guided intervention patients and a stent-only group in an unstable pathological state, namely acute myocardial infarction. It is not altogether surprising that in-hospital reocclusion rates do not differ significantly between the groups (1.7% versus 0%, respectively). In-hospital mortality rates (0% in both groups) were also excellent, as was long-term survival. In other words, stent-like acute results were achieved with PTCA-alone using FFR guidance for intervention, resulting in clinical outcomes comparable to stenting alone. In the Doppler Endpoint Stenting International Investigation (DESTINI) Study20 using the Doppler guidewire, the interventional endpoint of a coronary flow reserve (CFR) of 2.0 was used in a similar way to determine whether stents should be implanted. Similar to the present study, the results for the CFR-guided intervention group were found to be comparable to those for subjects who underwent primary stenting without CFR guidance. Although there have been no studies to our knowledge into FFR-guided intervention, fractional flow reserve more closely reflects the functional significance of epicardial coronary artery stenosis than coronary flow reserve, and may therefore be more useful as an endpoint for intervention. Cost-effectiveness. As coronary interventional procedures become increasingly common, attention has rightly shifted to the cost of treatment.21 Reducing the overall cost of medical treatment not only lessens the financial burden on the patient, but is also desirable from a national perspective. The increasing use of stenting in coronary intervention, however, is likely to lead to a further increase in overall costs, especially with the development of the new drug-eluting stents, which are expected to be even more expensive. In this study, the fact that our use of FFR guidance for intervention enables us to achieve stent-like results with conventional balloon angioplasty, and therefore reduce the number of stents used as well as the number of balloons used for post-dilatation, suggests that FFR guidance can be a useful strategy for improving cost-efficiency. Its impact on the overall cost of hospitalization suggests it may be an effective way of reducing medical expenditures. Study limitations. Our study has a number of limitations. First is the relatively small number of study patients; further collaborative studies with a larger number of subjects are required to confirm our findings. Another is the fact that our subjects were acute myocardial infarction patients, which is a special disease state involving intervention that may differ from standard practice. Also, a relatively large number of patients admitted for acute myocardial infarction in the trial period had to be excluded from the study either because of difficulty obtaining adequate FFR readings or for other reasons, which means that our study population may not truly be a representative sample.

1. Saito S, Hosokawa J, Kim K, et al. Primary stent implantation without coumadin in acute myocardial infarction. J Am Coll Cardiol 1996;28:74–81. 2. May MR, Labinaz M, Beanlands RB, et al. Usefulness of intracoronary stenting in acute myocardial infarction. Am J Cardiol 1996;78:148–152. 3. Macaya C, Serruys PW, Ruygrok P, et al. Continued benefit of coronary stenting versus balloon angioplasty: One year clinical follow-up of the BENESTENT trial. J Am Coll Cardiol 1996;27:255–261. 4. Schomig A, Neumann FJ, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulation therapy after the placement of coronary artery stents. N Engl J Med 1996;334:1084–1089. 5. Antoniucci D, Valenti R, Buonamici P, et al. Direct angioplasty and stenting of the infarct-related artery in acute myocardial infarction. Am J Cardiol 1996;78:568–571. 6. Emmanuelson H, Dohnal M, Lamm C, Tenerz L. Initial experiences with a miniaturized pressure transducer during coronary angioplasty. Cathet Cardiovasc Diagn 1991;24:137–143. 7. De Bruyne B, Pijls NJH, Paulus WJ, et al. Trans-stenotic coronary pressure gradient measurements in humans: In vitro and in vivo evaluation of a new pressure-monitoring angioplasty guidewire. J Am Coll Cardiol 1993;22:119–126. 8. Pijls NJH, van-Son JA, Krikeeide RL, et al. Experimental basis of determining maximum coronary, myocardial and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation 1993;87:1354–1367. 9. Ahmad T, Webb JG, Carere RR, Dodeck A. Coronary stenting for acute myocardial infarction. Am J Cardiol 1995;76:77–80. 10. Kaul U, Agarwal R, Jain P, Wasir H. Safety and efficacy of intracoronary stenting for thrombus-containing lesions. Am J Cardiol 1996;77:425–427. 11. Stone GW, Brodie BR, Griffin JJ, et al., for the PAMI Study Group. Improved short-term outcomes of primary coronary stenting compared to primary balloon angioplasty in acute myocardial infarction at experienced centers. J Intervent Cardiol 1999;12:101–108. 12. Strauss BH, Escaned J, Foley DP, Di Mario C, et al. Technological considerations and practical limitations in the use of quantitative angiography during percutaneous coronary recanalization. Prog Cardiovasc Dis 1994;36:343–362. 13. Bertrand ME, Lablanche JM, Bauters C, et al. Discordant results of visual and quantitative estimates of stenosis severity before and after coronary angioplasty. Cathet Cardiovasc Diagn 1993;28:1–6. 14. Hanekamp CEE, Koolen JJ, Pijls NH, et al. Comparison of quantitative coronary angioplasty, intravascular ultrasound and coronary pressure measurement to assess optimum stent deployment. Circulation 1999;99:1015–1021. 15. Bech GJ, Pijls NH, Bruyne BD, et al. Usefulness of fractional flow reserve to predict clinical outcome after balloon angioplasty. Circulation 1999;99:883–888. 16. Pijls NH, Bruyne BD. Coronary Pressure. Kluwer Academic Publishers, The Netherlands. 1997: pp. 264–271. 17. Takeuchi M, Himeno E, Sonoda S, Nakashima Y. Measurement of myocardial fractional flow reserve during coronary angioplasty in patients with old myocardial infarction. Cathet Cardiovasc Diagn 1997;42:19–25. 18. Gaymaz O, Tezcan H, Fak S, et al. Measurement of myocardial fractional flow reserve during coronary angioplasty in infarct-related and non-infarct-related coronary artery lesions. J Invas Cardiol 2000;12:236–241. 19. Fujita H, Inoue N, Matsuo Y, et al. Fractional flow reserve (FFRmyo) after coronary intervention as a predictor of chronic restenosis. J Invas Cardiol 1999;11:527–535. 20. Cohen DJ, Taira D, Di Mario C, et al. In-hospital and 6-month follow-up costs of universal versus provisional stenting: Results from the DESTINI trial. Circulation 1998;98:499. 21. Ellis SG, Brown KJ, Ellert R, et al. Cost of cardiac care in the three years after coronary catheterization in a contained care system: Critical determinants and implications. J Am Coll Cardiol 1998;31:1306–1313.