Off Script: PCI of the Future? Let’s Break Down the Border Between Physiology and Anatomy

One of the most game-changing trials at TCT 2019 offered a hint of the potential of OCT to improve PCI outcomes beyond FFR.

Off Script: PCI of the Future? Let’s Break Down the Border Between Physiology and Anatomy

SAN FRANCISCO, CA— It’s been 2 weeks since the close of TCT 2019 and in the wake of all the hustle and bustle of a packed meeting, I’ve had a chance to look back and reflect on the presentations I saw. For me, the most provocative and potentially game-changing trial was saved—in true TCT fashion (remember ORBITA?)—for the final late-breaking trial session. This saw the unveiling of the 13-month results of FORZA, an imperfect, yet audacious Italian trial that dared to pitch the almost impenetrable physiological FFR threshold for PCI revascularization of 0.80 against intravascular imaging using OCT and an anatomical, plaque-based revascularization criteria, derived from first principles.

Over 20 years of careful, iterative, hard endpoint-based trial designs, the intracoronary physiology-based techniques of FFR and iFR have firmly established a role in predicting which patients are likely to benefit from revascularization with PCI on a per-vessel basis. Despite being a huge fan of intracoronary physiology in clinical practice, I have always felt somewhat unsettled by several issues in its use to guide revascularization.

The first is the tendency of cardiologists, guidelines, and payers to characterize (wrongly) our choices as black and white: patients either have “ischemia and legitimate symptoms” or “no ischemia and those symptoms are not coming from your heart.” This dichotomy is built around the border walls that serve as the established thresholds for FFR (≤0.80) and for iFR (≤0.89). Randomized trials by their nature need hard decision thresholds, but these often fail to account for the biological complexity of a living, breathing human. Is it not possible that a 60% proximal LAD lesion with an iFR value of 0.91 in a large LAD supplying most of the heart is responsible for your patient’s typical anginal symptoms and can predict risk? Given all that is known about the linear relationship between decreasing FFR and adverse events, the slope of which seems to pay no heed to the thresholds, would it be not reasonable to consider this patient for revascularization? We have learned much from the marriage, or co-registration, of physiology and anatomy, with trials such as DEFINE-PCI showing us the importance of asking where exactly this fall in threshold is in the vessel and the potential clinical implications of the pattern of the gradient: diffuse or focal. A single threshold does not capture how much myocardium is at risk downstream and it cannot also tell us how much a stent will improve this ischemia.

The second important issue is an obvious conceptual gap in basing revascularization on physiology alone. It has been clearly established that a large proportion of acute coronary syndrome stems from anatomical factors—namely, vulnerable plaques that rupture with sudden, occlusive consequences. These sleeping volcanoes are not necessarily physiologically significant. As we inch towards the dream of The Perfect Stent which carries no clinical cost to implant, remains patent, retains all normal vasomotor function, keeps side branches open, and poses no thrombotic threat, the time may come when the correct answer will be to cage off all atherosclerosis before it has a chance to grow into the lumen or rupture. The cardiovascular event rates in the “negative” arms of the FFR and iFR trials were not zero (for example, at 5 years, 21% of patients in FAME 2 deferred from PCI based on a negative FFR underwent urgent revascularization versus 6% of patients in the FFR-positive group, who were revascularized with PCI). I have certainly seen patients over the years return with acute events in the exact lesions in which I had obtained “negative” FFR and iFR measurements.

The design of FORZA, a randomized, nonblinded study led by Francesco Burzotta, MD, PhD, and Antonio Maria Leone, MD (Università Cattolica del Sacro Cuore, Rome, Italy), somehow bypassed current guidelines around the management of intermediate lesions and pitted the traditional FFR criteria of ≤ 0.80 against OCT with new, reasonable anatomical criteria to determine the need for revascularization (area stenosis 75% or 50% to 75% area stenosis with MLA < 2.5 mm2  or plaque rupture). Importantly, both groups then underwent optimization of PCI with their respective initially assigned intracoronary modality. The rate of PCI based on OCT criteria was significantly higher (51% in the OCT group vs 29% in the FFR group), which suggests that many stents were likely placed in “FFR-negative” patients. Amazingly, despite this fundamental strategy shift, OCT was shown at 13 months to be superior with regards to the primary endpoint of a composite of MACE or significant angina (15% in the FFR group and 8% in the OCT group). This difference was not driven by any one component and all endpoints trended in favor of OCT.

While far from conclusive, these findings should allow us to push the door open a little further when it comes to anatomy-based revascularization. FORZA in no way diminishes physiology-guided revascularization, and it reminds us of the need to respect our fundamental first principles—namely, that our enemies are atherosclerosis and vulnerable plaque. My gut tells me there will come a day when the best strategy for deciding revascularization will involve a combination of co-registration-based physiology and intracoronary-imaged plaque burden, coupled with a strong culture of appropriate imaging-based lesion preparation. The same combination of post-PCI co-registered physiology and stent optimization by intracoronary imaging will likely then be required to ensure the best final outcomes.

We have come a long way from the days of relying on angiography alone, but we still have far to go.

Off Script is a first-person blog written by leading voices in the field of cardiology. It does not reflect the editorial position of TCTMD.

Kwan S Lee, MD is an Associate Professor of Medicine at the Sarver Heart Center, University of Arizona.  As interventional…

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