Physiologic Severity of Diffuse Coronary Artery Disease

In this issue of Circulation ,1 Taqueti and colleagues report cardiovascular outcomes related to both noninvasive, global coronary flow reserve (CFR) and invasive angiographic stenosis severity. Approximately 60% of patients underwent either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 90 days of imaging, allowing study of how revascularization modifies outcomes. Because randomized, controlled trials of revascularization for stable coronary artery disease (CAD) have not demonstrated a significant and consistent reduction in mortality or nonfatal myocardial infarction (MI) compared with medical management,2 what possible message does this observational report tell us? The answer incorporates physiological severity as an emerging guide to treatment.Article see p 19Since the first reports of experimental stenosis 40 years ago3,4 developed the concept of CFR, clinical physiological management of coronary lesions has migrated to pressure-derived fractional flow reserve (FFR), essentially a relative CFR.5 Over the past 20 years, FFR has evolved from clinical correlations with noninvasive testing6 to 3 large randomized, controlled trials. First, deferral of percutaneous coronary intervention (DEFER) demonstrated no advantage to PCI over medical therapy for lesions with an intact FFR.7 Next, Fractional Flow Reserve versus Angiography For Multivessel Evaluation (FAME) compared angiographic- versus FFR-guided PCI and showed a reduction in composite events when using FFR.8 Finally, FAME 2 randomized low FFR lesions to either medical therapy or immediate PCI.9A recent meta-analysis of the FFR outcomes literature documented a continuous, inverse relation between the FFR value and risk of subsequent adverse events.10 The analysis also demonstrated a corresponding, continuous, inverse relation between physiological severity assessed with FFR and impact from revascularization, suggesting potentially greater benefit at lower values. Intriguingly, the same analysis also showed adverse events proportional to residual FFR after successful PCI, implying residual risk …