Fractional Flow Reserve Pullback Research Articles

Rationale and design of the pullback pressure gradient (PPG) global registry

Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum. The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR. This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least one lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events. Recruitment is ongoing and is expected to be completed in the second half of 2023. This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the pre-procedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes. gov Identifier: NCT04789317.

Validation of Segmental Post-PCI Physiological Gradients With IVUS-Detected Focal Lesions and Stent Underexpansion

BackgroundSegmental postpercutaneous coronary intervention (PCI) pressure gradients may detect residual disease and potential targets for optimization. However, universal definitions of relevant segmental gradients are lacking. ObjectivesThis study sought to evaluate the diagnostic performance of post-PCI fractional flow reserve (FFR), distal coronary pressure-to-aortic pressure ratio (Pd/Pa), and diastolic pressure ratio (dPR) gradients to detect residual focal lesions and stent underexpansion as observed by intravascular ultrasound (IVUS). MethodsPatients from the IVUS-guided optimization arm of the FFR REACT (FFR-guided PCI Optimization Directed by High-Definition IVUS Versus Standard of Care) trial with complete IVUS and FFR pullback data were included. Patients with angiographically successful PCI and post-PCI FFR <0.90 underwent FFR, Pd/Pa, and IVUS pullbacks. dPR was calculated offline using dedicated software. Segmental pressure gradients (distal, in stent, and proximal) in segments ≥5 mm were evaluated against IVUS-detected residual disease (distal or proximal focal lesions and stent underexpansion). ResultsA total of 139 vessels were included (mean post-PCI FFR: 0.83 ± 0.05, range 0.56-0.89). Focal distal and proximal lesions were detected by IVUS in 23 (17.4%) of 132 and 14 (12.6%) of 111 vessels, respectively, whereas stent underexpansion was present in 86 (61.9%) vessels. Diagnostic ability of segmental FFR gradients to predict IVUS-detected distal and proximal lesions was moderate-to-good (area under the curve [AUC]: 0.69 and 0.84, respectively) and poor to moderate for segmental Pd/Pa and dPR gradients (AUC ranging from 0.58 to 0.69). In-stent gradients had no discriminative ability to detect stent underexpansion (FFR AUC: 0.52; Pd/Pa AUC: 0.54; dPR AUC: 0.55). ConclusionsIn patients with post-PCI FFR <0.90, segmental post-PCI pressure gradients have moderate discriminative ability to identify IVUS-detected focal lesions but no discriminative ability to identify IVUS-detected stent underexpansion.

Development, validation, and reproducibility of the pullback pressure gradient (PPG) derived from manual fractional flow reserve pullbacks.

Fractional flow reserve (FFR) pullbacks assess the location and magnitude of pressure drops along the coronary artery. The pullback pressure gradient (PPG) quantifies the FFR pullback curve and provides a numeric expression of focal versus diffuse coronary artery disease. This study aims (1) to validate the PPG using manual FFR pullbacks compared with motorized FFR pullbacks as a reference; and (2) to determine the intra- and interoperator reproducibility of the PPG derived from manual FFR pullbacks.Patients with stable coronary artery disease and an FFR ≤ 0.80 were included. All patients underwent FFR pullback evaluation either with a motorized device or manually, depending on the study cohort. The agreement of the PPG between repeated pullbacks was assessed using the Bland-Altman method. Overall, 116 FFR pullback maneuvers (96 manual and 20 motorized) were analyzed. There was excellent agreement between the PPG derived from manual and motorized pullbacks (mean difference -0.01 ± 0.07, 95% limits of agreement [LOA] -0.14 to 0.12). The intra- and interoperator reproducibility of PPG derived from manual pullbacks were excellent (mean difference <0.01, 95% LOA -0.11 to 0.12, and mean difference <0.01, 95% LOA -0.12 to 0.11, respectively). The duration of the pullback maneuver did not impact the reproducibility of the PPG (r = 0.12, 95% CI: -0.29 to 0.49, p = 0.567).Manual pullbacks allow for an accurate PPG calculation. The inter- and intraoperator reproducibility of PPG derived from manual pullbacks were excellent.

Clinical and Prognostic Impact From Objective Analysis of Post-Angioplasty Fractional FlowReserve Pullback.

This study sought to evaluate clinical implications of the residual fractional flow reserve (FFR) gradient after angiographically successful percutaneous coronary intervention (PCI). Recent studies have demonstrated FFR measured after PCI is associated with clinical outcome after PCI. Although post-PCI FFR pull back tracings provide clinically relevant information on the residual FFR gradient, there are no objective criteria for assessing post-PCI FFR pull back tracings. A total of 492 patients who underwent angiographically successful PCI and post-PCI FFR measurement with pull back tracings were analyzed. The presence of the major residual FFR gradient after PCI was assessed by both conventional visual interpretation of the pull back tracings and objective analysis using the instantaneous FFR gradient per unit time (dFFR(t)/dt) with a cutoff value of dFFR(t)/dt≥0.035. Classification agreement between 2 independent operators for the presence of the major residual FFR gradient was compared before and after providing dFFR(t)/dt results. Target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 2 years, was compared according to the presence of the major residual FFR gradient. Among the study population, 33.9% had the major residual FFR gradient defined by dFFR(t)/dt. The classification agreement between operators' assessments for the major residual FFR gradient increased with dFFR(t)/dt results compared with conventional visual assessment (Cohen's kappa=0.633 to 0.819; P< 0.001; intraclass correlation coefficient: 0.776 to 0.901; P< 0.001). Patients with major residual FFR gradient were associated with a higher risk of TVF at 2 years than those without major residual FFR gradient (9.0% vs 2.2%; P< 0.001). Inclusion of the major residual FFR gradient to a clinical prediction model significantly increased discrimination and reclassification ability (C-index=0.539 vs 0.771; P = 0.006; net reclassification improvement=0.668; P = 0.007; integrated discrimination improvement =0.033; P = 0.017) for TVF at 2 years. The presence of the major residual FFR gradient was independently associated with TVF at 2 years, regardless of post-PCI FFR or percent FFR increase (adjusted hazard ratio: 3.930; 95% confidence interval: 1.353-11.420; P = 0.012). Objective analysis of post-PCI FFR pull back tracings using dFFR(t)/dt improved classification agreement on the presence of the major residual FFR gradient among operators. Presence of the major residual FFR gradient defined by dFFR(t)/dt after angiographically successful PCI was independently associated with an increased risk of TVF at 2 years. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship with Post-PCI Clinical Outcomes [Algorithm-PCI]; NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [COE-PERSPECTIVE]; NCT01873560).

Hyperemic hemodynamic characteristics of serial coronary lesions assessed by pullback pressure gradients

To characterize hemodynamics of serial coronary stenoses using fractional flow reserve (FFR) pullbacks and the pullback pressure gradients (PPG) index. The cross-talk between stenoses within the same coronary artery makes the prediction of the functional contribution of each lesion challenging. One-hundred seventeen patients undergoing coronary angiography for stable angina were prospectively recruited. Serial lesions were defined as two or more narrowings with visual diameter stenosis >50% on conventional angiography. Motorized FFR pullback tracings were obtained at 1 mm/s. Pullbacks were visually adjudicated as presenting two, one, and no focal pressure drops. The pattern of disease (i.e., focal or diffuse) was quantified using the PPG index. Twenty-five vessels presented serial lesions (mean PPG 0.48 ± 0.17). Two, one or no focal pressure drops were observed in 40% (n= 10; PPG 0.59 ± 0.17), 52% (n= 13; PPG 0.44 ± 0.12) and 8% of cases (n= 2; PPG 0.27 ± 0.01; p-value=0.01). Distal FFR was similar between vessels with two, one and no focal pressure drops in the pullback curve (p-value=0.27). The PPG index independently predicted the presence of two focal pressure drops in the pullback curve (p= 0.04). FFR pullbacks in serial coronary lesions exhibit three distinct functional patterns. High PPG was associated with pullback curves presenting two pressure drops. The PPG provides a quantitative assessment of the pattern of coronary artery disease in cases with serial lesions and might be useful to assess the appropriateness of percutaneous revascularization.

TCT CONNECT-402 Automated Algorithm Using Pre-Intervention Fractional Flow Reserve Pullback Curve to Predict Post-Intervention Physiologic Results

TCT CONNECT-402 Automated Algorithm Using Pre-Intervention Fractional Flow Reserve Pullback Curve to Predict Post-Intervention Physiologic Results

Fractional Flow Reserve following Percutaneous Coronary Intervention.

Fractional flow reserve (FFR) is routinely used to determine lesion severity prior to percutaneous coronary intervention (PCI). However, there is an increasing recognition that FFR may also be useful following PCI to identify mechanisms leading to restenosis and the need for repeat revascularization. Post-PCI FFR is associated with the presence and severity of stent under-expansion and may help identify peri-stent-related complications. FFR pullback may also unmask other functionally significant lesions within the target vessel that were not appreciable on angiography. Recent studies have confirmed the prognostic utility of performing routine post-PCI FFR and suggest possible interventional targets that would improve stent durability. In this review, we detail the theoretical basis underlying post-PCI FFR, provide practical tips to facilitate measurement, and discuss the growing evidence supporting its use.

Searching into the invisible: hunting for present and future ischaemia with fractional flow reservepullback and wall shear stress.

Searching into the invisible: hunting for present and future ischaemia with fractional flow reservepullback and wall shear stress.

P855Evaluation of epicardial coronary resistance using computed tomography angiography

Abstract Background A Fractional flow reserve (FFR) pullback allows assessing the distribution of pressure loss along the vessel. FFR derived from CT (FFRCT) provides a virtual pullback curve that may also aid in the assessment of epicardial coronary resistance in the non-invasive setting. Purpose The present study aims to determine the accuracy of the virtual FFRCT pullback curve using a motorized invasive FFR pullback as reference in patients with stable coronary artery disease. Methods This is a single centre, prospective study of patients with stable coronary artery disease in whom FFRCT was performed as standard of care for non-invasive assessment. Patients referred to coronary angiography with clinically indicated invasive FFR measurement were included. FFRCT and invasive FFR values were extracted from coronary vessels every 1 mm to generate pullback curves. Invasive FFR pullbacks were acquired using a dedicated device at a speed of 1 mm/s. The area under the pullback curve (AUPC), defined as the sum of areas under the FFR pullback curve, was compared between FFRCT and invasive FFR pullbacks. Lesions were defined based on invasive angiography. FFR gradients in lesions and non-obstructive segments were defined as the difference between FFR values at the proximal and distal edge of the segments. FFR vessel gradient was defined as the difference between the most distal FFR value and the FFR at the ostium of the vessel. Mixed effect model was used to account for the correlation of FFR values within vessels. The agreement between FFRCT and FFR gradients was assessed using the Passing Bablok regression analysis and Bland-Altman methods at the vessel, lesion and non-obstructive level. Results A total of 3172 matched FFRCT and FFR values were obtained in 24 vessels. The correlation coefficient between FFRCT and FFR was 0.76 (95% CI 0.75 to 0.78; p&lt;0.001). The mean difference between the FFRCT and invasive FFR pullback values was 0.07 (LOA −0.11 to 0.24). AUPC was similar between FFRCT and invasive FFR (79.0±16.1 vs. 85.3±16.4, p=0.097); the mean slope of FFRCT pullback curve was steeper compared to invasive FFR (p&lt;0.001). The mean difference in lesion gradient was −0.07 (LOA −0.26 to 0.13) and −0.01 (LOA −0.06 to 0.05) in non-obstructive segments. There were no systematic or proportional differences between FFRCT and FFR gradients either in lesion or non-obstructive segments); however, vessel gradients were overestimated by FFRCT with a bias of −0.12 (LOA −0.35 to 0.12) driven by a higher mean difference in lesion gradients (−0.07; 95% CI −0.26 to 0.13). Conclusions The evaluation of epicardial coronary resistance using coronary CT angiography with FFRCT was feasible. FFRCT pullbacks were accurate in the assessment of lesion and non-obstructive gradients. FFRCT can identify the physiological pattern of coronary artery disease in the non-invasive setting.

P853Guiding myocardial revascularization by computer assisted interpretation of FFR pullback curves: an agreement study with actual standard of care

Abstract Background Guidelines recommend hemodynamic/functional assessment to guide treatment decision making in stable coronary artery disease. A Fractional flow reserve (FFR) motorized pullback allows a reproducible assessment of the distribution of pressure drop generated by coronary artery disease along the vessel and may provide more relevant hemodynamic information than a single distal FFR value. Purpose We aimed to assess the agreement between the revascularization strategy guided by coronary angiogram and a single distal FFR value interpretation (standard of care, SOC), and a treatment recommendation by a fully automated analysis of pullback FFR curves by an in-house developed computer-based algorithm (CBA). Methods Pullback FFR curves were recorded under continuous intra-venous adenosine in patients with intermediate coronary stenosis by using a motorized device working at a speed of 1 mm/s (Volcano R 100) set to grip a pressure wire. A proprietary algorithm (JD, Mathematica v.11) was applied to: 1) assess the distal FFR on the last 5 mm of the curves, 2) discriminate a stepwise from a progressive decrease of FFR, 3) propose a treatment strategy between optimal medical treatment (OMT), PCI (including the number, length(s) and position(s) of the stent) or CABG, 4) evaluate the post PCI expected change in FFR. A concordance analysis between effective and CBA recommended treatment was performed. Only curves with distal FFR ≤0.85 were included into the analysis. If post PCI FFR was recorded, CBA predicted and measured post PCI FFR were compared. Results 50 vessels from 43 patients (75% LAD, 10% Cx, 15% RCA) with a distal FFR of 0.78±0.08 were assessed. A revascularization was performed in 29 vessels (24 PCI, 5 CABG). Post PCI FFR pullback was recorded in 11 vessels. Compared to SOC, a similar proportion of vessels was referred for revascularization by CBA (56 vs. 58% respectively, Chi2 0.041, p NS). Agreement between SOC and CBA, regarding the need of a revascularization, was observed in 76% of cases. Observed Cohen's Kappa coefficient for OMT, PCI or CABG revascularization strategy was 0.48 (CI 95%: 0.26–0.7). A mismatch between SOC and CBA strategy was observed in 30% (n=15) of vessels. A post hoc examination of FFR pullback curves showed that CBA decision might have been appropriate in 80% of these mismatches. Reclassification of treatment strategy by CBA was related to misinterpretation of one single FFR value (40%, n=6), incorrect detection of significant stepwise decrease in FFR (33%, n=5) and incorrect detection of progressive decrease in FFR (7%, n=1) by SOC approach. A mean bias of 0.01 (CI 95% −0.05–0.07) was observed between CBA predicted and measured post PCI FFR. Conclusion CBA recommended treatment differs from SOC treatment in almost 1/3 of vessels. CBA of FFR pullback curves offers new opportunity to guide myocardial revascularization stategy and warrants further prospective evaluation.

Measurement of Hyperemic Pullback Pressure Gradients to Characterize Patterns of Coronary Atherosclerosis

BackgroundDiffuse atherosclerosis is commonly observed in angiographically normal segments in patients with stable coronary artery disease (CAD). The distribution of epicardial resistance along the vessel can be evaluated using coronary physiology. ObjectivesThe purpose of this study was to characterize the pathophysiological patterns of CAD using invasive pressure pullbacks during continuous hyperemia. MethodsIn this prospective, multicenter study of patients undergoing clinically-indicated coronary angiography due to stable angina, a pressure-wire pullback device was set at a speed of 1 mm/s. Based on coronary angiography and on the fractional flow reserve (FFR) pullback curve, the patterns of CAD were adjudicated as focal, diffuse, or a combination of both. The distribution of epicardial resistance was characterized using the hyperemic pullback pressure gradients (PPGs). The PPG index, a continuous metric based on the magnitude of pressure drop over 20 mm and on the extent of functional disease was computed to determine the pattern of CAD. Low PPG index indicates diffuse CAD. ResultsA total of 158 vessels (n = 117) were included. Overall, 984,813 FFR values were used to generate 100 FFR pullback curves. Using coronary physiology, 36% of the vessel disease patterns were reclassified compared to angiography. The median of maximal PPG over 20 mm was 0.083 (interquartile range: 0.063 to 0.118) FFR units, and the mean extent of functional disease was 39.3 ± 21.3 mm. The mean PPG index was 0.58 ± 0.18 and differentiated pathophysiological focal and diffuse disease (p < 0.001). ConclusionsPathophysiological patterns of CAD can be characterized by motorized hyperemic PPGs. The evaluation of the FFR pullback curve reclassified one-third of the vessels’ disease patterns compared with conventional angiography. The PPG index is a novel metric that quantifies the distribution of epicardial resistance and discriminates focal from diffuse CAD. (Physiological Patterns of Coronary Artery Disease; NCT03824600)

Usefulness of the trans-stent fractional flow reserve gradient for predicting clinical outcomes.

We evaluated the usefulness of a fractional flow reserve (FFR) gradient across the stent (ΔFFRstent ) for long-term clinical outcomes after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). The clinical meaning of a trans-stent pressure gradient after DES implantation has not been estimated adequately. FFR pull-back and intravascular ultrasound (IVUS) were performed after successful PCI in 135 left anterior descending artery lesions. ΔFFRstent was defined as the FFR gradient across the stent. The ΔFFRstent/length was defined as the ΔFFRstent value divided by the total stent length multiplied by 10. Major adverse cardiac events (MACEs) were the composite of all-cause death, target vessel-related myocardial infarction, and target lesion revascularization. Despite successful PCI, ΔFFRstent > 0 was observed in 98.5% of cases. ΔFFRstent ≥ 0.04 and ΔFFRstent/length ≥ 0.009 predicted suboptimal stenting defined as final minimal stent area < 5.5 mm2 . During 2,183 ± 898 days, the MACE-free survival rate was significantly lower in patients with ΔFFRstent ≥ 0.04 and ΔFFRstent/length ≥ 0.009 compared to those with lower values (69.6 vs. 93.4%, log-rank p = .031; 72.1 vs. 97.7%, log-rank p = .003, respectively). ΔFFRstent/length ≥ 0.009 (hazard ratio 10.1, p = .032) was an independent predictor of MACE. A trans-stent FFR gradient was frequently observed. ΔFFRstent and ΔFFRstent/length are related to long-term outcomes in DES-treated patients.

Fractional flow reserve guided percutaneous coronary intervention optimization directed by high-definition intravascular ultrasound versus standard of care: Rationale and study design of the prospective randomized FFR-REACT trial

Post percutaneous coronary intervention (PCI) fractional flow reserve (FFR) is a significant predictor of major adverse cardiac events (MACE). The rationale for low post procedural FFR values often remains elusive based on angiographic findings alone, warranting further assessment using an FFR pullback or additional intravascular imaging. It is currently unknown if additional interventions intended to improve the PCI, decrease MACE rates. The FFR REACT trial is a prospective, single-center randomized controlled trial in which 290 patients with a post PCI FFR <0.90 will be randomized (1:1) to either standard of care (no additional intervention) or intravascular ultrasound (IVUS)-directed optimization of the FFR (treatment arm). Eligible patients are those treated with angiographically successful PCI for (un)stable angina or non-ST elevation myocardial infarction (MI). Assuming 45% of patients will have a post PCI FFR <0.90, approximately 640 patients undergoing PCI will need to be enrolled. Patients with a post PCI FFR ≥ 0.90 will be enrolled in a prospective registry. The primary end point is defined as a composite of cardiac death, target vessel MI and clinically driven target vessel revascularisation (target vessel failure) at 1 year. Secondary end points will consist of individual components of the primary end point, procedural success, stent thrombosis and correlations on clinical outcome, changes in post PCI Pd/Pa and FFR and IVUS derived dimensions. All patients will be followed for 3 years. The FFR-REACT trial is designed to explore the potential benefit of HD-IVUS-guided PCI optimization in patients with a post PCI FFR <0.90 (Dutch trial register: NTR6711).

In-stent fractional flow reserve variations and related optical coherence tomography findings: the FFR-OCT co-registration study.

We sought to assess in-stent variations in fractional flow reserve (FFR) in patients with previous percutaneous coronary intervention (PCI) and to associate any drop in FFR with findings by optical coherence tomography (OCT) imaging. Suboptimal post-PCI FFR values were previously associated with poor outcomes. It is not known to which extent in-stent pressure loss contributes to reduced FFR. In this single-arm observational study, 26 patients who previously underwent PCI with drug-eluting stent or scaffold implantation were enrolled. Motorized FFR pullback during continuous intravenous adenosine infusion and OCT assessments was performed. Post-PCI FFR < 0.94 was defined as suboptimal. At a median of 63 days after PCI (interquartile range: 59-64days), 18 out of 26 patients (72%) had suboptimal FFR. The in-stent drop in FFR was significantly higher in patients with suboptimal FFR vs. patients with optimal FFR (0.08 ± 0.07 vs. 0.01 ± 0.02, p < 0.001). Receiver operating characteristic curve analysis showed that an in-stent FFR variation of > 0.03 was associated with suboptimal FFR. In patients with suboptimal FFR, the OCT analyses revealed higher mean neointimal area (respectively: 1.06 ± 0.80 vs. 0.51 ± 0.23 mm2; p = 0.018) and higher neointimal thickness of covered struts (respectively 0.11 ± 0.07 vs. 0.06 ± 0.01mm; p = 0.021). Suboptimal FFR values following stent-implantation are mainly caused by significant in-stent pressure loss during hyperemia. This finding is associated to a larger neointimal proliferation.

Visualization of the improvement of myocardial perfusion after coronary intervention using motorized fractional flow reserve pullback curve

This study aimed to evaluate the feasibility and utility of using motorized pullback of the pressure guidewire to provide a graphic assessment and prediction of the benefits of coronary intervention. Fractional flow reserve (FFR) measurements were performed with motorized pullback imaging in 20 patients who underwent successful percutaneous coronary intervention (PCI) of the left anterior descending artery. Physiological lesion length (PLL) was calculated using frame counts to determine stent length. FFR area was calculated by integrating the FFR values recorded during pullback tracing (FFRarea). The percentage increase in FFR area (%FFRarea) was defined as the ratio of the difference between the pre- and post-intervention FFRarea to the total frame count. The average FFR values were enhanced following PCI, from 0.64 to 0.82, and the median value of the difference between pre- and post-interventional FFR values (D-FFR) and %FFRarea were 0.13 and 10.6%, respectively. The %FFRarea demonstrated a significant positive correlation with D-FFR (R2, 0.61; p < 0.01). PLL tended to be longer and the %FFRarea was smaller in lesions with a gradual pressure-drop pattern than those with an abrupt pressure-drop pattern (35.37 vs. 20.40 mm, p = 0.07; 5.78 vs. 16.21%, p < 0.05, respectively). Motorized pullback tracing was able to identify the extent and location of stenosis and help in appropriate stent implantation, in addition to visualizing and quantifying the improvement in FFR following PCI.