Paradigm Shifting: Clinical analysis impact of measuring fractional flow reserve

In The Clinical and Economic Impact of Measuring Fractional Flow Reserve, Dr. Matar has presented an insightful discussion on his use of physiologic measurements in his very busy clinical practice, specifically, the pressure-wire derived fractional flow reserve (FFR). It is worth noting that as an expert, experienced interventional cardiologist, his previous highly aggressive approach of just stent it to nearly all lesions has given way to a thoughtful and more objective approach of measure and decide. Dr. Matar elegantly discusses some of the major issues with regard to the clinically relevant aspects of using in-lab coronary physiology in his clinical decision-making. Addressing the key indicator for the use of FFR, i.e., the uncertainty regarding angiographic lesion significance, Dr. Matar uses this additional objective data to decide whether or not to give his patient drug-eluting stent. Although data supporting this approach has been available for more than 10 years, one of the most important and long-awaited studies has recently been published. As an extension to the original studies testing the appropriateness of stenting a non-functional stenosis, Pijls et al1 report on the 5-year follow up results of the DEFER study. In this study, 325 patients scheduled for percutaneous coronary intervention (PCI) of an intermediate stenosis were examined by FFR before intervention. If the FFR was above the ischemic threshold (> or = 0.75), patients were randomly assigned to: The Defer group (n=91, medical therapy without PCI); Or the Performance group (n=90, PCI despite a normal FFR and intermediate lesion). If the FFR was Reference group (n=144). Clinical follow-up for major adverse cardiac events over 5 years was then recorded. For the three groups, complete follow-up was obtained in 98% of patients. Event-free survival was not different between the Defer and Perform groups with 80 and 73% respectively (p=0.52), but was significantly worse in the Reference group, 63%; (p=0.03). With regard to cardiac death and acute myocardial infarction over a 5-year period, the Defer and Reference groups had rates of 3.7% and 7.9% respectively versus 15.7% for the Perform group, which was higher than either of the other two groups. The percentage of patients free from chest pain at follow-up was not different between the Defer and Perform groups. The data indicated that the 5-year outcome of deferring PCI for intermediate stenosis based on coronary physiology is excellent. The risk of cardiac death or infarction related to target stenosis was less than 1% per year and not decreased by stenting. The limitations for such a study included the non-universal use of drug-eluting stents and operator-selected use of clopidogrel, since this was not standard care over the study period. However, neither of these two factors changes the important clinical message that an intermediate lesion which is physiologically normal has a predictable clinical course, like that of any coronary atherosclerosis patient. Furthermore, these patients do not benefit by having a stent. In fact, such an approach, that of stenting all intermediate lesions, may do worse. Modifying risk factors and adequate medical treatment in such patients is of greater value than the mechanical intervention. It is also gratifying to know that acute coronary syndromes do not frequently occur at the site of non-significant stenoses in the DEFER study. The event rates reported reflect the universal effects of atherosclerotic plaque, not an individual lesion propensity for plaque rupture. Dr. Matar correctly indicates that according to current PCI guidelines, documented ischemia is one of the critical indications to perform PCI, especially in patients with atypical chest pain syndromes and intermediate lesions. Of special interest is that in patients with multi-vessel disease, nuclear perfusion imaging with sestamibi stress testing is less reliable for indicating the functional significance of individual stenoses and cannot reliably assist in the decision-making for the particular territories at risk. FFR can select specific ischemia-associated lesions. As Dr. Matar indicates, patients in the cath lab with multi-vessel disease are the greatest challenge for the interventionalist. FFR can sort out some complex decisions. Why FFR is not as widely used as it could be appears to be for reasons which are as diverse and complex as the PCI physicians. Nonetheless, FFR can be easily incorporated into an interventional practice if the operator has a sufficient understanding of the limitations of angiography, stress testing in multi-vessel disease, and by deciding to put the clinical impact of inappropriate stenting ahead of any economic impact associated with procedure performance. FFR does impart considerable economic saving to laboratory and hospital. An old dictum in stenting was when in doubt, just stent it, but this was before the time of our appreciation of the downsides of drug-eluting stents. Now with the rare but catastrophic DES-related complications, the paradigm shift to when in doubt, check the lesion before drug-eluting stenting appears to be sage advice. It is my and Dr. Matar’s belief that the use of FFR in clinical practice should be a routine part of the interventionalist toolbox. Dr. Matar’s discussion of this practice focuses our thinking about being a complete interventionalist.

1. Pijls N, 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.