Abstract & Commentary
Synopsis: This registry analysis demonstrates that FFR after stent implantation has strong, independent predictive value with respect to clinical outcomes at 6 months.
Source: Pijls NHJ, et al. Circulation. 2002;105: 2950-2954.
The presence of a significant pressure gradient within a coronary artery during maximal coronary blood flow suggests the presence of inadequate coronary flow reserve, and hence, a functionally significant coronary obstruction. Determination of fractional flow reserve (FFR) using a pressure-sensing guidewire and induction of coronary hyperemia induced by a microcirculatory vasodilator such as adenosine is a useful and convenient method for evaluating the physiologic significance of a coronary stenosis in the cardiac catheterization laboratory. FFR is the ratio of the mean distal coronary pressure (Pd) measured by the pressure wire placed beyond a coronary stenosis, to the mean proximal coronary pressure (Pa) at the tip on the guiding catheter. FFR can be used to evaluate the functional significance of an angiographically intermediate lesion, with FFR < 0.75 showing good correlation with ischemia documented by perfusion imaging and FFR > 0.75 correlating with low event rates at 1 year. FFR has also been shown to be a useful alternative to intravascular ultrasound (IVUS) for assessing the adequacy of stent implantation. However, the use of FFR measurement in assessing or improving clinical outcomes after stent implantation has not been described.
Pijls and colleagues present a retrospective analysis of data obtained from the Fractional Flow Reserve (FFR) Post-Stent Registry. They sought to determine whether post-stent implantation FFR correlated with clinical outcomes, using the end point of major adverse cardiac events (MACE), including death, myocardial infarction (MI), or target vessel revascularization (TVR) during 6 months of follow-up. The study population included patients from 15 hospitals who underwent coronary stenting in which a pressure wire (Radi Medical Systems—Uppsala, Sweden) was used as a guidewire for any reason. The stent implantation procedures (including use of adjuvant medical therapy) were performed at the operator’s discretion per local routine. After each angiographically successful stent procedure (< 10% residual diameter stenosis by visual estimation), FFR was determined during peak hyperemia induced by intracoronary administration of adenosine, ATP or papaverine, or by intravenous administration of adenosine or ATP. Data were analyzed using FFR as a dichotomous variable (FFR > 0.95 vs £ 0.95, or FFR > 0.90 vs £ 0.90) and as a continuous variable divided into 5 groups (0.75-0.80, 0.81-0.85, 0.86-0.90, 0.91-0.95, and 0.96-1.0).
The registry included 750 patients and 6-month follow-up was complete in 744 patients (99.2%). Baseline characteristics demonstrated that this patient population was similar to the average PCI populations from other large studies. On average, 1.18 stents were used per patient, with a stented length of 17.3 ± 6.4 mm. Final FFR > 0.95 was achieved in 36%, and FFR > 0.90 was achieved in 68% of patients. Final FFR was < 0.75 in 11 patients (1.5%) suggesting that these stent procedures were "physiologically unsuccessful." During the 6 months of follow-up, 90 events occurred in 76 patients and included 5 deaths (0.7%), 19 MIs (2.6%), 12 bypass graft surgeries (1.6%), and 54 PCIs (7.3%). By univariate analysis, significant predictors of adverse events were final FFR (P < 0.01), smaller stent diameter (P = 0.023), and longer stent length (P = 0.032). When the data were analyzed using 5 categories for FFR, there was a significant inverse correlation between final FFR and total MACE (P £ 0.001), as well as death or MI (P < 0.01), and TVR (P < 0.001). Patients in the highest category (FFR = 0.95) had the lowest event rate (4.9%) and patients in the lowest category (FFR < 0.80) had the highest adverse event rate (28.5%). Using multivariate analysis, only final FFR category (P < 0.001) and length of stent (P < 0.01) were predictive of adverse events.
Pijls et al conclude that this registry analysis demonstrates that FFR after stent implantation has strong, independent predictive value with respect to clinical outcomes at 6 months. In their discussion, they describe potential explanations for the correlation between FFR and clinical outcomes. Lower postprocedural FFR might reflect inadequate stent expansion, abnormal residual shear stress, or significant disease in the unstented portions of the target vessel, all of which could contribute to a persistent hyperemic pressure gradient. Based on their previous work, Pijls et al stress the importance of truly maximal hyperemia in performing accurate FFR measurements, recommending intracoronary adenosine doses of ³ 30 mg for the right coronary artery and ³ 40 mg for the left coronary artery. They point out that while abnormal FFR is indicative of a suboptimal procedural result, it does not elucidate the mechanism of the problem, which might be revealed by IVUS examination. They acknowledge the limitations inherent in this registry analysis and suggest that a prospective study to determine whether additional intervention can improve a suboptimal FFR and improve patient outcomes would be useful.
Comment by Sarah M. Vernon, MD
In recent years, the interventionalist’s armamentarium has expanded to included an array of different stent designs and sizes on markedly improved delivery systems. In addition to allowing the operator to tackle increasing complex lesions and anatomy with good outcomes, this equipment has made the straightforward lesion a "slam-dunk" for the experienced interventionalist. In the interest of time and expense, these lesions can be treated using direct stenting (without predilitation), moderate pressure deployment (though most available stents are mounted on compliant or semi-compliant balloon delivery systems), and in some cases, without high pressure postdilitation (saving the expense of an additional balloon). These procedures are quick and easy, and often give an "occulostenotically" satisfying result (0% residual stenosis, TIMI 3 flow), at least angiographically. However, the question for each individual patient remains: Is this result as good as it can be? Or even good enough?
Postdeployment evaluation of a stented artery using IVUS can be a very enlightening (and sometimes sobering) experience. Results can look much less optimal (undersized or incompletely expanded stents, residual uncovered disease) when viewed from the inside out. However, in most cath labs, IVUS evaluation adds considerable time and expense to the procedure. The imaging catheters and equipment are expensive and good data interpretation takes considerable expertise. By contrast, physiologic evaluation using a pressure wire system is remarkably quick and easy to perform. In our laboratory, a pressure wire evaluation (we use the Endosonics system) adds only minutes to the procedure and can provide important diagnostic information (Is this lesion really tight? Which of these lesions is the "culprit"?), in addition to important feedback about the physiologic result when a PCI procedure is undertaken. The wires are easy to manipulate, the measurements are quick and extremely easy to make (the FFR is read from a console), and the procedure is extremely well tolerated by patients (even when high-dose intracoronary adenosine is given). When a PCI is deemed to be physiologically appropriate, the pressure wire can then be used as the guidewire for the intervention (if rota is not performed) and remains in place until the postprocedural physiologic assessment is complete.
Pijls et al provide data suggesting that an optimal physiologic result, as measured by postprocedural FFR, should be more important to the interventional operator (and to his or her patient) than another pretty picture. The pressure wire might tell us that our "slam-dunk" procedure is, in fact, not quite finished. A low FFR might suggest that perhaps this patient’s clinical outcome could be improved by a high-pressure postdilitation, or by looking to see what the problem is using IVUS, for example. This paper tells us that careful evaluation and optimization of our "physiologic" results might make a real difference for our patients. While the availability of coated stents is just around the corner, the revolution they herald will be incomplete if we lose sight of how to optimally deploy them.
Dr. Vernon is Assistant Professor of Medicine; Director, VAMC Cardiac Catheterization Laboratory, University of New Mexico Health Sciences Center, Albuquerque, NM.