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Revisiting the Optimal Fractional Flow Reserve and Instantaneous Wave-Free Ratio Thresholds for Predicting the Physiological Significance of Coronary Artery Disease.

ABSTRACT: BACKGROUND:There 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 RESULTS:Pd 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). CONCLUSIONS:Contemporary 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.

SUBMITTER: Modi BN

PROVIDER: S-EPMC6314449 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Revisiting the Optimal Fractional Flow Reserve and Instantaneous Wave-Free Ratio Thresholds for Predicting the Physiological Significance of Coronary Artery Disease.

Modi Bhavik N BN Rahman Haseeb H Kaier Thomas T Ryan Matthew M Williams Rupert R Briceno Natalia N Ellis Howard H Pavlidis Antonis A Redwood Simon S Clapp Brian B Perera Divaka D

Circulation. Cardiovascular interventions 20181201 12

<h4>Background</h4>There 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 ...[more]

PMID: 30562079

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Project description:Background Quantitative flow ratio ( QFR ) has a high diagnostic accuracy in assessing functional stenoses relevance, as judged by fractional flow reserve ( FFR ). However, its diagnostic performance has not been thoroughly evaluated using instantaneous wave-free ratio ( iFR ) or coronary flow reserve as the reference standard. This study sought to evaluate the diagnostic performance of QFR using other reference standards beyond FFR . Methods and Results We analyzed 182 patients (253 vessels) with stable ischemic heart disease and 82 patients (105 nonculprit vessels) with acute myocardial infarction in whom coronary stenoses were assessed with FFR , iFR, and coronary flow reserve. Contrast QFR analysis of interrogated vessels was performed in blinded fashion by a core laboratory, and its diagnostic performance was evaluated with respect to the other invasive physiological indices. Mean percentage diameter stenosis, FFR , iFR , coronary flow reserve, and QFR were 53.1±19.0%, 0.80±0.13, 0.88±0.12, 3.14±1.30, and 0.81±0.14, respectively. QFR showed higher correlation ( r=0.863 with FFR versus 0.740 with iFR , P<0.001), diagnostic accuracy (90.8% versus 81.3%, P<0.001), and discriminant function (area under the curve=0.953 versus 0.880, P<0.001) when FFR was used as a reference standard than when iFR was used as the reference standard. However, when coronary flow reserve was used as an independent reference standard, FFR , iFR , and QFR showed modest discriminant function (area under the curve=0.682, 0.765, and 0.677, respectively) and there were no significant differences in diagnostic accuracy among FFR , iFR , and QFR (65.4%, 70.6%, and 64.9%; all P values in pairwise comparisons >0.05, overall comparison P=0.061). Conclusions QFR has a high correlation and agreement with respect to both FFR and iFR , although it is better when FFR is used as the comparator. As a pressure-derived index not depending on wire or adenosine, QFR might be a promising tool for improving the adoption rate of physiology-based revascularization in clinical practice.

Project description:ObjectiveFractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive methods to assess the functional significance of intermediate severity coronary lesions. Both indexes have been extensively validated in clinical trials in guiding revascularisation in patients with stable ischaemic heart disease undergoing percutaneous coronary intervention (PCI) with improved clinical outcomes. However, the role of these tools in coronary artery bypass grafting (CABG) is less clear.MethodsA meta-analysis of randomised trials and observational studies was carried out to help in determining the optimal strategy for assessing lesion severity and selecting graft targets in patients undergoing CABG. Electronic searches were carried out on Embase, MEDLINE, and Web of Science. A group of four authors independently screened and then assessed the retrieved records. Cochrane's Risk of Bias and Robins-I tools were used for bias assessment. A survey was conducted among surgeons and cardiologists to describe current attitudes towards the preoperative use of functional coronary investigations in practice.ResultsClinical outcomes including mortality at 30 days, perioperative myocardial infarction, number of grafts, incidence of stroke, rate of further need for revascularisation, and patient-reported quality of life did not differ in CABG guided by functional testing from those guided by traditional angiography.The survey revealed that in half of the surgical and cardiology units functional assessment is performed in CABG patients; there is a general perception that functional testing has improved patient care and its use would clarify the role of moderate coronary lesions that often need multidisciplinary rediscussions; moderate stenosis are felt to be clinically relevant; and anatomical considerations need to be taken into account together with functional assessment.ConclusionsAt present, the evidence to support the routine use of functional testing in intermediate lesions for planning CABG is currently insufficient. The pooled data currently available do not show an increased risk in mortality, myocardial injury, and stroke in the FFR/iFR-guided group. Further trials with highly selected populations are needed to clarify the best strategy.Systematic review registrationClinicalTrials.gov, identifier (CRD42023414604).

Project description:Background The FiGARO (FFR versus iFR in Assessment of Hemodynamic Lesion Significance, and an Explanation of Their Discrepancies) trial is a prospective registry searching for predictors of fractional flow reserve/instantaneous wave-free ratio (FFR/iFR) discrepancy. Methods and Results FFR/iFR were analyzed using a Verrata wire, and coronary flow reserve was analyzed using a Combomap machine (both Philips-Volcano). The risk polymorphisms for endothelial nitric oxide synthase and for heme oxygenase-1 were analyzed. In total, 1884 FFR/iFR measurements from 1564 patients were included. The FFR/iFR discrepancy occurred in 393 measurements (20.9%): FFRp (positive)/iFRn (negative) type (264 lesions, 14.0%) and FFRn/iFRp (129 lesions, 6.8%) type. Coronary flow reserve was measured in 343 lesions, correlating better with iFR (R=0.56, P<0.0001) than FFR (R=0.36, P<0.0001). The coronary flow reserve value in FFRp/iFRn lesions (2.24±0.7) was significantly higher compared with both FFRp/iFRp (1.39±0.36), and FFRn/iFRn lesions (1.8±0.64, P<0.0001). Multivariable logistic regression analysis confirmed (1) sex, age, and lesion location in the right coronary artery as predictors for FFRp/iFRn discrepancy; and (2) hemoglobin level, smoking, and renal insufficiency as predictors for FFRn/iFRp discrepancy. The FFRn/iFRp type of discrepancy was significantly more frequent in patients with both risk types of polymorphisms (endothelial nitric oxide synthaser+heme oxygenase-1r): 8 patients (24.2%) compared with FFRp/iFRn type of discrepancy: 2 patients (5.9%), P=0.03. Conclusions Predictors for FFRp/iFRn discrepancy were sex, age, and location in the right coronary artery. Predictors for FFRn/iFRp were hemoglobin level, smoking, and renal insufficiency. The risk type of polymorphism in endothelial nitric oxide synthase and heme oxygenase-1 genes was more frequently found in patients with FFRn/iFRp type of discrepancy. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03033810.

Dataset Information

Revisiting the Optimal Fractional Flow Reserve and Instantaneous Wave-Free Ratio Thresholds for Predicting the Physiological Significance of Coronary Artery Disease.

Publications

Revisiting the Optimal Fractional Flow Reserve and Instantaneous Wave-Free Ratio Thresholds for Predicting the Physiological Significance of Coronary Artery Disease.

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