Optimal Application of Fractional Flow Reserve to Assess Serial Coronary Artery Disease: A 3D‐Printed Experimental Study With Clinical Validation

Abstract

Background Assessing the physiological significance of stenoses with coexistent serial disease is prone to error. We aimed to use 3‐dimensional‐printing to characterize serial stenosis interplay and to derive and validate a mathematical solution to predict true stenosis significance in serial disease. Methods and Results Fifty‐two 3‐dimensional‐printed serial disease phantoms were physiologically assessed by pressure‐wire pullback (Δ FFR app ) and compared with phantoms with the stenosis in isolation (Δ FFR true ). Mathematical models to minimize error in predicting FFR true , the FFR in the vessel where the stenosis is present in isolation, were subsequently developed using 32 phantoms and validated in another 20 and also a clinical cohort of 30 patients with serial disease. Δ FFR app underestimated Δ FFR true in 88% of phantoms, with underestimation proportional to total FFR . Discrepancy as a proportion of Δ FFR true was 17.1% (absolute difference 0.036±0.048), which improved to 2.9% (0.006±0.023) using our model. In the clinical cohort, discrepancy was 38.5% (0.05±0.04) with 13.3% of stenoses misclassified (using FFR <0.8 threshold). Using mathematical correction, this improved to 15.4% (0.02±0.03), with the proportion of misclassified stenoses falling to 6.7%. Conclusions Individual stenoses are considerably underestimated in serial disease, proportional to total FFR . We have shown within in vitro and clinical cohorts that this error is significantly improved using a mathematical correction model, incorporating routinely available pressure‐wire pullback data.

Physiological Pattern of Disease Assessed by Pressure-Wire Pullback Has an Influence on Fractional Flow Reserve/Instantaneous Wave-Free Ratio Discordance

“…17,18 Recent report demonstrated a simple predictive equation could accurately evaluate the component contributions of individual stenoses in serial lesions using FFR pullback, which might be helpful for determining the physiological pattern of disease in the future. 19 As a result, currently, classification of the physiological pattern of disease is operator dependent and thus prone to both intra and interoperator variability. Mindful of this, within the present study, each iFR pullback trace was judged by the consensus opinion of 3 expert interventional cardiologists who reviewed the pullback data together.…”

Clinical situations for which 3D printing is considered an appropriate representation or extension of data contained in a medical imaging examination: adult cardiac conditions

“…As such, there are minimal results for the use of 3D printed models for myocardial infarction. Several authors assess the feasibility of 3D printed models for studying coronary arterial flow dynamics, but the results were not directly applied to patient care [ 22 – 27 ]. There are several published case reports of 3D printed models used in procedural planning for coronary artery aneurysm and fistula repair [ 33 – 36 ].…”

How to select patients requiring coronary revascularisation using coronary physiology

“…33 To correct for some of this error, a simple equation to use with hyperemic pressure wire pullback has been derived with a 3-D printed model and validated in patients with serial disease to show a significant reduction error and stenosis misclassification. 32,33 Until novel FFR/iFR correction equations are studied further, we recommend making decisions based on the size of the step-up observed during hyperarmic or resting pressure wire pullback manoeuvres, both before and after PCI. The pullback should be done at a steady speed from the distal vessel, without stopping between stenoses, and should be performed even when a stenosis appears angiographically discrete, as there maybe be accompanying diffuse disease in the vessel that would affect the pressure gradient across a given stenosis.…”

“…The pullback should be done with knowledge that the accompanying disease is most commonly underestimated, and the extent of this underestimation is greater when there is a large cumulative pressure drop in the vessel. 32 Physiology in special scenarios: Acute coronary syndromes FFR has largely been validated for use in the stable coronary disease and its applicability in the acute setting is less clear. In the case of ST-elevation myocardial infarction (STEMI), impaired microcirculation in the infarction region has been shown to influence FFR measurements in the culprit vessel for up to 6 months after the event.…”

“…The reality, particularly within elderly and diabetic populations, is that serial and diffuse CAD is common. 31 As discussed in the section on physiological assessment of LMCA disease, it is unclear if physiological indices can reliably assess individual lesions in the commonly-encountered scenario of serial/diffuse coronary artery disease, with significant stenosis underestimation having been shown, even when relying on a pressure wire pullback method 32 (Figure 2).…”