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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.

SUBMITTER: Modi BN

PROVIDER: S-EPMC6474982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Amongst patients with suspected obstructive coronary artery disease (CAD), less than a third of patients have obstructive disease on invasive coronary angiography (ICA) and fewer still have flow-limiting obstructive disease as determined by invasive fractional flow reserve (FFR). FFR is a powerful tool in guiding revascularization of flow-limiting lesions which in turn improves clinical outcome in those with haemodynamically significant obstructive disease. However FFR is infrequently performed due to the cost, time and patient discomfort the procedure entails. Further advances in non-invasive imaging has allowed FFR to be derived non-invasively by applying computational fluid dynamic (CFD) modeling to the coronary computed tomography angiography (CCTA) dataset without the need to induce hyperemia or modify the standard CCTA acquisition protocol. FFR derived from CCTA has been shown to have excellent correlation with invasive FFR and remains diagnostically robust in presence of reduced signal-to-noise ratio (SNR), coronary calcification and motion artifact. More recently, new data have emerged evaluating the clinical impact of fractional flow reserve computed tomography (FFRCT) on the assessment and management of patients with stable chest pain. One such study is the Prospective LongitudinAl trial of FFRCT: Outcome and Resource IMpacts (PLATFORM) study which showed an improved patient selection for ICA using CCTA-FFRCT approach by increasing the likelihood of identifying obstructive CAD at ICA amongst those intended for invasive testing. CCTA-FFRCT may therefore serve as efficacious gatekeeper to ICA that enriches the ICA population. The utility of FFRCT has also helped deepened our understanding of CAD. Through CFD modeling, it is now recognized that there are mechanistic forces of wall shear stress (WSS) and axial plaque force acting on coronary plaques. This has created further interest in exploring the possible interplay between these mechanistic forces on the development of coronary plaque and vulnerability of these plaques to rupture.

Project description:BackgroundThere has been a gradual upward creep of revascularization thresholds for both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), before the clinical outcome trials for both indices. The increase in revascularization that has potentially resulted is at odds with increasing evidence questioning the benefits of revascularizing stable coronary disease. Using an independent invasive reference standard, this study primarily aimed to define optimal thresholds for FFR and iFR and also aimed to compare the performance of iFR, FFR, and resting distal coronary pressure (Pd)/central aortic pressure (Pa).Methods and resultsPd and Pa were measured in 75 patients undergoing coronary angiography±percutaneous coronary intervention with resting Pd/Pa, iFR, and FFR calculated. Doppler average peak flow velocity was simultaneously measured and hyperemic stenosis resistance calculated as hyperemic stenosis resistance=Pa-Pd/average peak flow velocity (using hyperemic stenosis resistance >0.80 mm Hg/cm per second as invasive reference standard). An FFR threshold of 0.75 had an optimum diagnostic accuracy (84%), whereas for iFR this was 0.86 (76%). At these thresholds, the discordance in classification between indices was 11%. The accuracy of contemporary thresholds (FFR, 0.80; iFR, 0.89) was significantly lower (78.7% and 65.3%, respectively) with a 25% rate of discordance. The optimal threshold for Pd/Pa was 0.88 (77.3% accuracy). When comparing indices at optimal thresholds, FFR showed the best diagnostic performance (area under the curve, 0.91 FFR versus 0.79 iFR and 0.77 Pd/Pa, P=0.002).ConclusionsContemporary thresholds provide suboptimal diagnostic accuracy compared with an FFR threshold of 0.75 and iFR threshold of 0.86 (cutoffs in derivation studies). Whether more rigorous thresholds would result in selecting populations gaining greater symptom and prognostic benefit needs assessing in future trials of physiology-guided revascularization.

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

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