pre-PCI Fractional Flow Reserve Research Articles

Association of Coronary Computed Tomography-Defined Myocardial Bridge With Pre- and Post-Procedural Fractional Flow Reserve in Patients Undergoing Elective Percutaneous Coronary Intervention.

Myocardial bridge (MB) is a common coronary anomaly characterized by a tunneled course through the myocardium. Coronary computed tomography angiography (CCTA) can identify MB. The impact of MB detected by CCTA on coronary physiological parameters before and after percutaneous coronary intervention (PCI) is unknown.Methods and Results: We investigated 141 consecutive patients who underwent pre-PCI CCTA and fractional flow reserve (FFR)-guided elective PCI for de novo single proximal lesions in the left anterior descending artery (LAD). We compared clinical demographics and physiological parameters between patients with and without CCTA-defined MB. MB was identified in 46 (32.6%) patients using pre-PCI CCTA. The prevalence of diabetes was higher among patients with MB. Median post-PCI FFR values were significantly lower among patients with than without MB (0.82 [interquartile range 0.79-0.85] vs. 0.85 [interquartile range 0.82-0.89]; P=0.003), whereas pre-PCI FFR values were similar between the 2 groups. Multivariable linear regression analysis revealed that the presence of MB and greater left ventricular mass volume in the LAD territory were independently associated with lower post-PCI FFR values. Multivariable logistic regression analysis also revealed that the presence of MB and lower pre-PCI FFR values were independent predictors of post-PCI FFR values ≤0.80. CCTA-defined MB independently predicted both lower post-PCI FFR as a continuous variable and ischemic FFR as a categorical variable in patients undergoing elective PCI for LAD.

Association between myocardial bridge with transthoracic doppler echocardiography-defined physiological indices and fractional flow reserve before and after elective percutaneous coronary intervention

Abstract Background A myocardial bridge (MB) is a coronary variant in which an epicardial coronary artery courses through myocardium. MB can be identified by computed tomographic coronary angiography (CTCA) or invasive coronary angiography (ICA), which is known to be common in left anterior descending artery (LAD). Transthoracic Doppler echocardiography (TDE) noninvasively provides coronary flow information. Purpose We aimed to investigate the physiological impact of myocardial bridge on coronary flow dynamics assessed by adenosine-induced stress-TDE before and after elective percutaneous coronary intervention (PCI). Methods We examined 93 consecutive patients treated with fractional flow reserve (FFR)-guided elective PCI who underwent pre-PCI CTCA and pre- and post-PCI stress-TDE. We compared patient characteristics, angiographic, physiological data, and stress-TDE-defined coronary flow parameters in patients with versus without MB. Results We identified MB in 40 (43.0%) and 15 (16.1%) patients by CTCA and ICA, respectively. All MBs diagnosed by ICA were identified by CTCA. Longer MB was associated with the detectability by ICA. Older age and higher frequency of diabetes mellitus were observed in patients with CTCA-defined MB compared with those without. Pre-PCI FFR was similar in patients with versus without CTCA-defined MB (0.69 [0.61-0.73] vs. 0.69 [0.61-0.75], P=0.92), while post-PCI FFR was significantly lower in patients with versus without CTCA-defined MB (0.82 [0.78-0.86] vs. 0.84 [0.82-0.88], P=0.01). Pre- and Post- PCI hyperemic systolic peak flow velocity (SPV) by stress-TDE was higher in patients with versus without MB by CTCA (36 [26-43] m/s vs. 30 [23-34] m/s, P=0.03 and 38 [32-52] m/s vs. 33 [20-39] m/s, P=0.02, respectively). Pre-PCI hyperemic diastolic peak flow velocity (DPV) by stress-TDE was not significantly different between the 2 groups (49 [39-64] m/s vs. 45 [34-55] m/s, P=0.12), while post-PCI hyperemic DPV was higher in patients with versus without CTCA-defined MB (73 [60-85] m/s vs. 63 [50-81] m/s, P=0.03). Conclusion In patients undergoing elective PCI for LAD, a presence of CTCA-defined MB was associated with higher pre- and post-PCI hyperemic SPV and an acceleration of hyperemic DPV after the PCI. Impact of systolic compression by MB on hyperemic DPV at the distal segment accelerated by the treatment of upstream stenosis may lead to lower post-PCI FFR compared with patients without MB.

Ticagrelor induces ischaemic preconditioning in coronary artery disease

Abstract Ticagrelor is a reversibly P2Y12 antagonist used in patient undergoing coronary interventions, able to block adenosine re-uptake through inhibition of ENT-1 cotransporter. The increased levels of adenosine are responsible for some of its side effects (dyspnea, bradycardia), but adenosine bioavailability increase could also provide beneficial effects. We sought to investigate whether ticagrelor, as compared to clopidogrel, could enhance ischemic preconditioning in patients with stable CAD undergoing PCI. Methods and results The "Ticagrelor and preconditioning in patients with stable coronary artery disease (TAPER-S)" trial was a prospective, randomized 1:1, blinded end-point trial enrolling stable patients with CAD requiring fractional flow reserve (FFR)-guided PCI. Ischemic preconditioning was assessed by measuring the ST-segment elevation at intracoronary ECG during a two-step sequential coronary balloon inflation (2 minutes each, with a 5-minute interval) in the reference vessel. The primary endpoint of the study was the comparison of the delta (difference in millimeters) of ST-segment elevation extent at first and second coronary balloon inflations between ticagrelor and clopidogrel arms. Secondary endpoints were: 1) changes in coronary flow reserve (CFR), index of mcrovascular resistance (IMR), and FFR measured in the index vessel before and at the end of PCI; 2) difference in anginal pain (measured with VAS) during inflations. Also, lab tests with assessment of adenosine serum concentration and ENT-1 expression were conducted at baseline and after index procedure. The study was stopped by the DSMB after two thirds (n=53) of the patients qualifying for the primary endpoint were enrolled. Indeed, an independent statistical report evaluating the blinded results at a pre-specified interim analysis found a statistically significant difference in primary endpoint between the groups. The primary endpoint was significantly higher with ticagrelor as compared to clopidogrel (p < 0.0001). Ticagrelor group was also associated with lower extent of chest pain during coronary balloon inflations (p=0.04), wheras no difference was observed in the delta between pre and post PCI values of FFR (p=0.70), CFR (p=0.72) or IMR (p=0.72). Among lab tests, ticagrelor administration promoted a statistically significant increase in adenosine serum concentration when compared with clopidogrel group, while ENT-1 expression was not different. Conclusions Ticagrelor induces ischemic preconditioning among patients with stable CAD undergoing PCI and reduces intraprocedural anginal pain. Adenosine bioavailability was confirmed to be increased in ticagrelor-treated patients. However, since ENT-1 expression was proved not to be different between groups and all patients in this study underwent adenosine infusion during pre-PCI FFR, our results suggest ticagrelor can further induce ischemic preconditioning via non-adenosine mediated mechanisms.

Impact of myocardial bridge defined by computed tomographic coronary angiography on fractional flow reserve after elective percutaneous coronary intervention

Abstract Background Myocardial bridge (MB) is a common anomaly of epicardial coronary artery that courses through myocardium. MB can be identified by computed tomographic coronary angiography (CTCA) or invasive coronary angiography (ICA). However, its relevance to coronary physiological parameters remains unknown. Purpose This observational study aimed to explore how MBs affect physiological parameters in patients with chronic coronary syndrome before and after revascularization. Methods We investigated 172 consecutive patients who underwent preprocedural CTCA and elective fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) in left anterior descending artery (LAD). We compared patient characteristics, angiographic, and pre- and post-PCI physiological parameters in patients with versus without MB. Results We identified MB in 70 (40.7%) and 23 (13.3%) patients by CTCA and ICA, respectively. CTCA detected the presence of MB with a sensitivity of 100% and a specificity of 33% when ICA-defined MB was regarded as a reference standard. Longer MB (adjusted odds ratio 1.18 [95% confidence interval 1.05-1.33], P < 0.01) and smaller left ventricular myocardial mass volume in whole LAD territory (adjusted odds ratio 0.93 [95% confidence interval 0.89-0.98], P<0.01) were associated with ICA detectability of MB. Older age and higher frequency of diabetes mellitus were observed in patients with MB compared with those without MB. Pre-PCI FFR values were not associated with a presence of MB regardless of either CTCA- or ICA-defined MB. On the other hand, post-PCI FFR values were significantly lower in patients with versus without MB by CTCA (0.82 [0.80-0.86] vs. 0.86 [0.82-0.89], P<0.01), while no significant difference was observed in post-PCI FFR between patients with and without ICA-defined MB (0.82 [0.81-0.84 vs. 0.84 [0.80-0.88], P=0.08). Multivariable linear regression analysis revealed that a presence of CTCA-defined long MB (≥25mm) (adjusted β coefficient = -0.040, P<0.01) and greater myocardial mass volume in whole LAD territory (adjusted β coefficient = -0.0004, P<0.01) were independently associated with lower post-PCI FFR. Conclusion A presence of MB was an independent predictor of lower post-PCI FFR after successful and elective PCI for LAD.

Machine-learning-based prediction of fractional flow reserve after percutaneous coronary intervention

Background and aimsPost-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) reflects residual atherosclerotic burden and is associated with future events. How much post-PCI FFR can be predicted based on baseline basic information and the clinical relevance have not been investigated. MethodsWe compiled a multicenter registry of patients undergoing pre- and post-PCI FFR. Machine-learning (ML) algorithms were designed to predict post-PCI FFR levels from baseline demographics, quantitative coronary angiography, and pre-PCI FFR. FFR deviation was defined as actual minus ML-predicted post-PCI FFR levels, and its association with incident target vessel failure (TVF) was evaluated. ResultsMedian (IQR) pre- and post-PCI FFR values were 0.71 (0.61, 0.77) and 0.88 (0.84, 0.93), respectively. The Spearman correlation coefficient of the actual and predicted post-PCI FFR was 0.54 (95% CI: 0.52, 0.57). FFR deviation was non-linearly associated with incident TVF (HR [95% CI] with Q3 as reference: 1.65 [1.14, 2.39] in Q1, 1.42 [0.98, 2.08] in Q2, 0.81 [0.53, 1.26] in Q4, and 1.04 [0.69, 1.56] in Q5). A model with polynomial function of continuous FFR deviation indicated increasing TVF risk for FFR deviation ≤0 but plateau risk with FFR deviation >0. ConclusionsAn ML-based algorithm using baseline data moderately predicted post-PCI FFR. The deviation of post-PCI FFR from the predicted value was associated with higher vessel-oriented event.

Fractional Flow Reserve-Guided Stent Optimisation in Focal and Diffuse Coronary Artery Disease.

Assessing coronary physiology after stent implantation facilitates the optimisation of percutaneous coronary intervention (PCI). Coronary artery disease (CAD) patterns can be characterised by the pullback pressure gradient (PPG) index. The impact of focal vs. diffuse disease on physiology-guided incremental optimisation strategy (PIOS) is unknown. This is a sub-study of the TARGET-FFR randomized clinical trial (NCT03259815). The study protocol directed that optimisation be attempted for patients in the PIOS arm when post-PCI FFR was <0.90. Overall, 114 patients (n = 61 PIOS and 53 controls) with both pre-PCI fractional flow reserve (FFR) pullbacks and post-PCI FFR were included. A PPG ≥ 0.74 defined focal CAD. The PPG correlated significantly with post-PCI FFR (r = 0.43; 95% CI 0.26 to 0.57; p-value < 0.001) and normalised delta FFR (r = 0.49; 95% CI 0.34 to 0.62; p-value < 0.001). PIOS was more frequently applied to vessels with diffuse CAD (6% focal vs. 42% diffuse; p-value = 0.006). In patients randomized to PIOS, those with focal disease achieved higher post-PCI FFR than patients with diffuse CAD (0.93 ± 0.05 vs. 0.83 ± 0.07, p < 0.001). There was a significant interaction between CAD patterns and the randomisation arm for post-PCI FFR (p-value for interaction = 0.004). Physiology-guided stent optimisation was applied more frequently to vessels with diffuse disease; however, patients with focal CAD at baseline achieved higher post-PCI FFR.

Angina After Percutaneous Coronary Intervention: Patient and Procedural Predictors.

Twenty percent to 40% of patients are affected by angina after percutaneous coronary intervention (PCI), which is associated with anxiety, depression, impaired physical function, and reduced quality of life. Understanding patient and procedural factors associated with post-PCI angina may inform alternative approaches to treatment. Two hundred thirty patients undergoing PCI completed the Seattle Angina Questionnaire (SAQ-7) and European quality of life-5 dimension-5 level (EQ-5D-5L) questionnaires at baseline and 3 months post-PCI. Patients received blinded intracoronary physiology assessments before and after stenting. A post hoc analysis was performed to compare clinical and procedural characteristics among patients with and without post-PCI angina (defined by follow-up SAQ-angina frequency score <100). Eighty-eight of 230 patients (38.3%) reported angina 3 months post-PCI and had a higher incidence of active smoking, atrial fibrillation, and history of previous myocardial infarction or PCI. Compared with patients with no angina at follow-up, they had lower baseline SAQ summary scores (69.48±24.12 versus 50.20±22.59, P<0.001) and EQ-5D-5L health index scores (0.84±0.15 versus 0.69±0.22, P<0.001). Pre-PCI fractional flow reserve (FFR) was lower among patients who had no post-PCI angina (0.56±0.15 versus 0.62±0.13, P=0.003). Percentage change in FFR after PCI had a moderate correlation with angina frequency score at follow-up (r=0.36, P<0.0001). Patients with post-PCI angina had less improvement in FFR (43.1±33.5% versus 67.0±50.7%, P<0.001). There were no between-group differences in post-PCI FFR, coronary flow reserve, or corrected index of microcirculatory resistance. Patients with post-PCI angina had lower SAQ-summary scores (64.01±22 versus 95.16±8.72, P≤0.001) and EQ-5D-5L index scores (0.69±0.26 versus 0.91±0.17, P≤0.001) at follow-up. Larger improvements in FFR following PCI were associated with less angina and better quality of life at follow-up. In patients with stable symptoms, intracoronary physiology assessment can inform expectations of angina relief and quality of life improvement after stenting and thereby help to determine the appropriateness of PCI. URL: https://www. gov; Unique identifier: NCT03259815.

Clinical Implications of Fractional Flow Reserve Measured Immediately After Percutaneous Coronary Intervention.

The purpose of the present study was to find the independent predictors of Fractional Flow Reserve (FFR) measured immediately after percutaneous coronary intervention with drug-eluting stent implantation (post-PCI FFR) and investigate if applying vessel-specific post-PCI FFR cut-off values to predict target vessel failure (TVF), a composite of cardiac death (CD), non-fatal myocardial infarction (MI) and target vessel revascularization (TVR), or a composite of CD and MI ameliorated its predictive power. Consecutive patients with post-PCI FFR measurement at our center between 2009 and 2021 were included in this analysis. A total of 434 patients with 500 vessels were included. Median pre-PCI FFR was 0.72 with no difference between LAD and non-LAD vessels. Median post-PCI FFR was 0.87. LAD location, male gender, smaller stent diameter, and lower pre-PCI FFR proved to be significant predictors of a lower post-PCI FFR. On a vessel-level, post-PCI FFR, stent length, and diabetes mellitus proved to be significant predictors of TVF and the composite of CD and MI. The best post-PCI FFR cut-off to predict TVF or a composite of CD and MI was 0.83 in the LAD and 0.91 in non-LAD vessels. LAD location is a predictor of a lower post-PCI FFR. Post-PCI FFR is an independent predictor of TVF as well as of the composite of CD and MI. No uniform target post-PCI FFR value exists; different cut-off values may have to be applied in LAD as opposed to non-LAD vessels.

Differential Improvement in Angina and Health-Related Quality of Life After PCI in Focal and Diffuse Coronary Artery Disease

BackgroundAn increase in fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is associated with improvement in angina. Coronary artery disease (CAD) patterns (focal vs diffuse) influence the FFR change after stenting and may predict angina relief. ObjectivesThe aim of this study was to investigate the differential improvement in patient-reported outcomes after PCI in focal and diffuse CAD as defined by the pullback pressure gradient (PPG). MethodsThis is a subanalysis of the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) randomized clinical trial. The 7-item Seattle Angina Questionnaire (SAQ-7) was administered at baseline and 3 months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks. The median PPG value was used to define focal and diffuse CAD. Residual angina was defined as an SAQ-7 score <100. ResultsA total of 103 patients were analyzed. There were no differences in the baseline characteristics between patients with focal and diffuse CAD. Focal disease had larger increases in FFR after PCI than patients with diffuse disease (0.30 ± 0.14 vs 0.19 ± 0.12; P < 0.001). Patients with focal disease who underwent PCI for focal CAD had significantly higher SAQ-7 summary scores at follow-up than those with diffuse CAD (87.1 ± 20.3 vs 75.6 ± 24.4; mean difference = 11.5 [95% CI: 2.8-20.3]; P = 0.01). After PCI, residual angina was present in 39.8% but was significantly less in those with treated focal CAD (27.5% vs 51.9%; P = 0.020). ConclusionsResidual angina after PCI was almost twice as common in patients with a low PPG (diffuse disease), whereas patients with a high PPG (focal disease) reported greater improvement in angina and quality of life. The baseline pattern of CAD can predict the likelihood of angina relief. (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve [TARGET-FFR]; NCT03259815)

Prediction of functional results of percutaneous coronary interventions with virtual stenting and quantitative flow ratio.

The clinical value of residual quantitative flow ratio (rQFR), a novel function of QFR technique, is unknown. We investigated the clinical value of rQFR, aimed to predict residual ischemia after virtual percutaneous coronary intervention (vPCI). This is a substudy of the COE-PERSPECTIVE registry, which investigated the prognostic value of post-PCI fractional flow reserve (FFR). From pre-PCI angiograms, QFR and rQFR were analyzed and their diagnostic performance was assessed at blinded fashion using pre-PCI FFR and post-PCI FFR as reference, respectively. The prognostic value of rQFR after vPCI was assessed according to vessel-oriented composite outcome (VOCO) at 2 years. We analyzed 274 patients (274 vessels) with FFR-based ischemic causing lesions (49%) from 555 screened patients. Pre-PCI QFR and FFR were 0.63 ± 0.10 and 0.66 ± 0.11 (R = 0.756, p < 0.001). rQFR after vPCI and FFR after real PCI were 0.93 ± 0.06 and 0.86 ± 0.07 (R = 0.528, p < 0.001). The mean difference between rQFR and post-PCI FFR was 0.068 (95% limit of agreement: -0.05 to 0.19). Diagnostic performance of rQFR to predict residual ischemia after PCI was good (area under the curve [AUC]: 0.856 [0.804-0.909], p < 0.001). rQFR predicted well the incidence of 2-year VOCO after index PCI (AUC: 0.712 [0.555-0.869], p = 0.041), being similar to that of actual post-PCI FFR (AUC: 0.691 [0.512-0.870], p = 0.061). rQFR ≤0.89 was associated with increased risk of 2-year VOCO (hazard ratio [HR]: 12.9 [2.32-71.3], p = 0.0035). This difference was mainly driven by a higher rate of target vessel revascularization (HR: 16.98 [2.33-123.29], p = 0.0051). rQFR estimated from pre-PCI angiography and virtual coronary stenting mildly overestimated functional benefit of PCI. However, it well predicted suboptimal functional result and long-term vessel-related clinical events. Influence of fractional flow reserve on the Clinical OutcomEs of PERcutaneouS Coronary Intervention (COE-PESPECTIVE) Registry, NCT01873560.

Correlation of FFR measured after DES implantation with clinical parameters and long-term clinical outcome

Abstract Introduction The role of fractional flow reserve (FFR) measured directly after drug eluting stent (DES) implantation (post-PCI FFR) is not clear in predicting major adverse cardiac events (MACE), and it is not known which clinical parameters affect post-PCI FFR. Aim We aimed to clarify the relationship between post-PCI FFR and clinical parameters, post-PCI FFR and long-term MACE and determine the best post-PCI FFR cut-off in MACE prediction. Method Patients who underwent post-PCI (DES) FFR measurement at our center between March 2009 and January 2021 were included. We examined the relationship between post-PCI FFR and gender, age, hypertension, diabetes mellitus, hyperlipidemia, indication (acute (ACS) vs. chronic coronary syndrome (CCS)), stent diameter, in-stent restenosis vs de novo lesion category, proximal vs. non-proximal lesion location, LAD (vs. non-LAD) location, and pre-PCI FFR. We sought to determine the correlation between post-PCI FFR and target vessel-related MACE (cardiovascular death (CVD), non-fatal myocardial infarction (MI), recurrent revascularization (TVR)). Optimal cut-off was determined by ROC curves. Results Post-PCI FFR measurement was performed in 500 coronary arteries of 434 patients. LAD location (0.86 vs. non-LAD 0.91, p&amp;lt;0.001), male gender (0.87 vs. 0.89, p=0.001), younger age (p=0.0215), smaller stent diameter (p=0.0028) and lower pre-PCI FFR (p=0.0006) proved to be independent predictors of lower post-PCI FFR, no other parameter showed a significant correlation with post-PCI FFR. During a median follow-up of 37 months, 24 CVD, 15 MI and 47 TVR occurred. Follow-up was complete in 96.2% of patients. There was a significant inverse correlation between post-PCI FFR and MACE (p&amp;lt;0.001). Diabetes mellitus (p=0.0024) and in-stent restenosis (0.0356) were also independent predictors of MACE. The best post-PCI FFR cut-off for the total patient population, LAD and non-LAD lesions were 0.83 (p&amp;lt;0.0001), 0.83 (p&amp;lt;0.0001), and 0.88 (p=0.0091), respectively. Conclusion LAD location, male gender, younger age, smaller stent diameter and lower pre-PCI FFR value result in lower post-PCI FFR. There is no significant difference between post-PCI FFR measured in ACS vs. CCS. FFR measured after PCI, diabetes mellitus and in-stent restenosis are significant predictors of MACE-free long-term survival. The best post-PCI FFR cut-off to predict MACE was 0.83 for the whole patient population and for LAD and 0.88 for non-LAD lesions. Funding Acknowledgement Type of funding sources: None.

Improvement in angina pectoris after percutaneous coronary interventions in focal and diffuse coronary artery disease

Abstract Objective To investigate the effect of PCI on patient-reported outcomes in focal and diffuse coronary artery disease (CAD) as defined by the pullback pressure gradient (PPG). Background Improvements in fractional flow reserve (FFR) following PCI are associated with freedom from angina. CAD patterns influence the FFR change after stenting. Therefore, CAD patterns might be essential to assess the likelihood of PCI success in terms of angina relief. Methods This is a sub-analysis of the TARGET-FFR randomized clinical trial (NCT03259815). The 7-item Seattle Angina Questionnaire (SAQ-7) and EuroQol five-level EQ-5D questionnaire (EQ-5D-5L) were administered at baseline and three months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks and the median PPG value was used to define focal and diffuse CAD. Results 103 patients (51 with focal and 52 with diffuse disease) were analyzed. There were no differences in baseline characteristics between patients with focal and diffuse CAD. Patients with focal disease had larger increases in FFR with PCI than those with diffuse disease (0.30±0.14 units vs 0.19±0.12 units, p&amp;lt;0.001). Patients who underwent PCI to focal CAD had significantly higher SAQ-7 summary scores at follow-up compared to those with diffuse CAD (87.1±20.3 vs. 75.6±24.4, mean difference 11.5 [95% CI 2.8 to 20.3], p=0.01). Following PCI, residual angina was present in 39.8% of all patients but was significantly lower among those with treated focal CAD (27.5% vs 51.9%, p-value=0.020). Conclusion Persistent angina after PCI was almost twice as common in patients with diffuse CAD as defined by the pre-PCI PPG. Patients with focal disease reported greater improvement in angina and quality of life with PCI. The likelihood of successful angina relief from PCI can be predicted by the baseline pattern of CAD. Funding Acknowledgement Type of funding sources: None.

Preprocedural transthoracic Doppler echocardiography to identify stenosis associated with increased coronary flow after revascularisation

The benefit of percutaneous coronary intervention (PCI) has been reported to be associated with functional stenosis severity defined by fractional flow reserve (FFR). This study aimed to investigate the predictive ability of preprocedural transthoracic Doppler echocardiography (TDE) for increased coronary flow. A total of 50 left anterior descending arteries (LAD) that underwent TDE examinations were analysed. Hyperaemic LAD diastolic peak velocity (hDPV) was used as a surrogate of volumetric coronary flow. The increase in coronary flow was evaluated by the metric of % hDPV-increase defined by 100× (post-PCI hDPV-pre-PCI hDPV)/pre-PCI hDPV. The two groups divided by the median value of % hDPV-increase were compared, and the determinants of a significant coronary flow increase defined as more than the median % hDPV-increase were explored. After PCI, FFR values improved in all cases. hDPV significantly increased from 53.0 to 76.0 mm/s (P < 0.01) and the median % hDPV-increase was 45%, while hDPV decreased in 10 patients. On multivariable analysis, pre-PCI FFR and hDPV were independent predictors of a significant coronary flow increase. Preprocedural TDE-derived hDPV provided significant improvement of identification of lesions that benefit from revascularisation with respect to significant coronary flow increase.

Differential Prognostic Implications of Pre- and Post-Stent Fractional Flow Reserve in Patients Undergoing Percutaneous Coronary Intervention.

The influence of pre-intervention coronary physiologic status on outcomes post percutaneous coronary intervention (PCI) is not well known. We sought to investigate the prognostic implications of pre-PCI fractional flow reserve (FFR) combined with post-PCI FFR. A total of 1,479 PCI patients with pre-and post-PCI FFR data were analyzed. The patients were classified according to the median values of pre-PCI FFR (0.71) and post-PCI FFR (0.88). The primary outcome was target vessel failure (TVF) at 2 years. The risk of TVF was higher in the low pre-PCI FFR group than in the high pre-PCI FFR group (hazard ratio, 1.82; 95% confidence interval, 1.15-2.87; p=0.011). In 4 group comparisons, the cumulative incidences of TVF at 2 years were 3.8%, 4.1%, 4.8%, and 10.2% in the high pre-/high post-, low pre-/high post-, high pre-/low post-, and low pre-/low post-PCI FFR groups, respectively. The risk of TVF was the highest in the low pre-/low post-PCI FFR group among the groups (p values for comparisons <0.05). In addition, the high pre-/low post-PCI FFR group presented a comparable risk of TVF with the high post-PCI FFR groups (p values for comparison >0.05). When the prognostic value of the post-PCI FFR was evaluated according to the pre-PCI FFR, the risk of TVF significantly decreased with an increase in post-PCI FFR in the low pre-PCI FFR group, but not in the high pre-PCI FFR group. Pre-PCI FFR was associated with clinical outcomes after PCI, and the prognostic value of post-PCI FFR differed according to the pre-PCI FFR. ClinicalTrials.gov Identifier: NCT04012281.

Effect of Coronary Disease Characteristics on Prognostic Relevance of Residual Ischemia After Stent Implantation

Objectives: We investigated the influence of coronary disease characteristics on prognostic implications of residual ischemia after coronary stent implantation.Methods: This study included 1,476 patients with drug-eluting stent implantation and available pre- and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) measurements. Residual ischemia was defined as post-PCI FFR ≤ 0.80. Coronary disease characteristics with significant interaction hazard ratios (HRs) for clinical outcomes with residual ischemia were defined as interaction characteristics with residual ischemia (ICwRI). The primary outcome was target vessel failure (TVF)—a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization—at 2 years.Results: The mean pre- and post-PCI FFR were 0.68 ± 0.11 and 0.87 ± 0.07, respectively. During the median follow-up duration of 2.0 years, the cumulative incidence of TVF was 6.1%. The 203 vessels (13.8%) with residual ischemia had higher risks of TVF compared to that for post-PCI FFR >0.80 (P < 0.001). ICwRI with a significant interaction HR with residual ischemia included pre-PCI SYNTAX score >17 and pre-PCI FFR ≤ 0.62. Each ICwRI had a direct prognostic effect not mediated by residual ischemia. The association between an increased TVF risk and residual ischemia was significant in patients with 0 or 1 ICwRI [hazard ratio (HR) 3.25, 95% confidence interval (CI) 1.90–5.57, P < 0.001] but not in those with 2 ICwRI (HR 0.47, 95% CI 0.14–1.64, P = 0.24). Among patients with post-PCI FFR >0.80, those with 2 ICwRI showed similar TVF risks to those with residual ischemia (HR 1.55, 95% CI 0.79–3.02, P = 0.20).Conclusions: Coronary disease characteristics including pre-PCI SYNTAX score and pre-PCI FFR affected the prognostic implications of residual ischemia. The prognostic relevance of residual ischemia was attenuated in patients with multiple interacting characteristics.

Abstract 8984: Prediction of Functional Results of Percutaneous Coronary Interventions With Virtual Stenting and Quantitative Flow Ratio

Introduction: The clinical value of residual quantitative flow ratio (rQFR), a novel function of QFR technique aimed to predict residual ischemia after virtual percutaneous coronary intervention (vPCI) is unknown. Hypothesis: We hypothesized rQFR well predict functional results after PCI. Methods: This is a sub-study of the COE-PERSPECTIVE registry, which investigated the prognostic value of post-PCI fractional flow reserve (FFR). From pre-PCI angiograms, QFR and rQFR were analyzed and their diagnostic performance was assessed at blinded fashion using pre-PCI FFR and post-PCI FFR as reference, respectively. The prognostic value of rQFR after vPCI was assessed according to vessel-oriented composite outcome (VOCO) (a composite of cardiac death, vessel-specific myocardial infarction, and vessel-specific revascularization) at 2 years. Results: Two hundred and seventy-four patients (274 vessels) with FFR-based ischemic causing lesions were analyzed. Pre-PCI QFR and FFR were 0.63±0.10 and 0.66±0.11 (R=0.756, p&lt;0.001). rQFR after vPCI and FFR after real PCI were 0.93±0.06 and 0.86±0.07 (R=0.528, p&lt;0.001). Diagnostic performance of rQFR to predict actual post-PCI FFR was good (area under the curve (AUC): 0.856 [0.804-0.909], p&lt;0.001). rQFR predicted well the incidence of 2-year VOCO after index PCI (AUC: 0.712 [0.555-0.869], p=0.041), being similar to that of actual post-PCI FFR (AUC: 0.691 [0.512-0.870], p=0.061). rQFR ≤0.89 was associated with increased risk of 2-year VOCO (hazard ratio: 12.9 [2.32-71.3], P=0.0035). Conclusions: Residual QFR estimated from pre-PCI angiography and virtual coronary stenting predicts procedural functional results and long-term vessel-related clinical events.

Effect of coronary disease characteristics on prognostic relevance of residual ischemia after stent implantation

Abstract Background Although residual ischemia after revascularization is an important predictor of future cardiovascular events, its sensitivity and specificity to predict clinical events were relatively low, and data on which coronary disease characteristics affect prognostic implications of residual ischemia are limited. Purpose We aimed to investigate the influence of coronary disease characteristics on prognostic implications of residual ischemia after percutaneous coronary intervention (PCI). Methods This study included 1,476 patients with drug-eluting stent implantation and available pre- and post-PCI fractional flow reserve (FFR) measurements from the international post-PCI FFR registry (NCT04012281). Residual ischemia was defined as post-PCI FFR ≤0.80. Coronary disease characteristics with significant interaction hazard ratios (HRs) for clinical outcomes with residual ischemia were defined as interaction characteristics with residual ischemia (ICwRI). The primary outcome was target vessel failure (TVF)–a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization–at 2 years. Results The mean pre- and post-PCI FFR were 0.68±0.11 and 0.87±0.07, respectively. The 203 vessels (13.8%) with residual ischemia had higher risks of TVF compared to that for post-PCI FFR &amp;gt;0.80 (HR 2.45, 95% confidence interval [CI] 1.50–4.00, P&amp;lt;0.001). Among pre- and post-PCI angiographic characteristics, ICwRI with a significant interaction HR with residual ischemia (P&amp;lt;0.10) included lesion length ≥40 mm, pre-PCI SYNTAX score &amp;gt;17, and pre-PCI FFR ≤0.62 (Table). Each ICwRI had a direct prognostic effect not mediated by residual ischemia in mediation analysis. The association between an increased TVF risk and residual ischemia differed according to the number of ICwRI (p-for-interaction &amp;lt;0.001). It was significant in patients with 0 or 1 ICwRI (HR 3.48, 95% CI 2.01–6.00, P&amp;lt;0.001) but not in those with ≥2 ICwRI (HR 0.60, 95% CI 0.18–2.03, P=0.41) (Figure A). Compared to the residual ischemia group, patients without residual ischemia and those with 0 or 1 ICwRI showed a significantly lower risk of TVF (HR 0.32, 95% CI 0.19–0.54, P&amp;lt;0.001), but those with ≥2 ICwRI had a similar risk of TVF as the residual ischemia group (HR 1.08, 95% CI 0.57–2.01, P=0.819) (Figure B). The prognostic impact of ≥2 ICwRI in patients without residual ischemia was consistent in all subgroups with different clinical characteristics. Conclusions Coronary disease characteristics including lesion length, SYNTAX score, and pre-PCI FFR affected the prognostic implications of residual ischemia. This prognostic relevance was attenuated in patients with multiple interacting characteristics. Therefore, comprehensive assessment of coronary disease characteristics with post-procedural coronary physiology can help better risk stratification and appropriate treatment planning after revascularization. Funding Acknowledgement Type of funding sources: None.

High-Risk Morphological and Physiological Coronary Disease Attributes as Outcome Markers After Medical Treatment and Revascularization

ObjectivesThis study sought to evaluate the prognostic impact of plaque morphology and coronary physiology on outcomes after medical treatment or percutaneous coronary intervention (PCI). BackgroundAlthough fractional flow reserve (FFR) is currently best practice, morphological characteristics of coronary artery disease also contribute to outcomes. MethodsA total of 872 vessels in 538 patients were evaluated by invasive FFR and coronary computed tomography angiography. High-risk attributes (HRA) were defined as high-risk physiological attribute (invasive FFR ≤0.8) and high-risk morphological attributes including: 1) local plaque burden (minimum lumen area <4 mm2 and plaque burden ≥70%); 2) adverse plaque characteristics ≥2; and 3) global plaque burden (total plaque volume ≥306.5 mm3 and percent atheroma volume ≥32.2%). The primary outcome was the composite of revascularization, myocardial infarction, or cardiac death at 5 years. ResultsThe mean FFR was 0.88 ± 0.08, and PCI was performed in 239 vessels. The primary outcome occurred in 54 vessels (6.2%). All high-risk morphological attributes were associated with the increased risk of adverse outcomes after adjustment for FFR ≤0.8 and demonstrated direct prognostic effect not mediated by FFR ≤0.8. The 5-year event risk proportionally increased as the number of HRA increased (p for trend <0.001) with lower risk in the PCI group than the medical treatment group in vessels with 1 or 2 HRA (9.7% vs. 14.7%), but not in vessels with either 0 or ≥3 HRA. Of the vessels with pre-procedural FFR ≤0.8, ischemia relief by PCI (pre-PCI FFR ≤0.8 and post-PCI FFR >0.8) significantly reduced vessel-oriented composite outcome risk compared with medical treatment alone in vessels with 0 or 1 high-risk morphological attributes (hazard ratio: 0.33; 95% confidence interval: 0.12 to 0.93; p = 0.035), but the risk reduction was attenuated in vessels with ≥2 high-risk morphological attributes. ConclusionsHigh-risk morphological attributes offered additive prognostic value to coronary physiology and may optimize selection of treatment strategies by adding to FFR-based risk predictions (CCTA-FFR Registry for Development of Comprehensive Risk Prediction Model; NCT04037163)

FFR=1.0 flow changes after percutaneous coronary intervention

BackgroundThe present study investigated the relationships between physiological indices and increased coronary flow during percutaneous coronary intervention (PCI) using a novel index of “anticipated maximum flow” [AMF; theoretical coronary flow of fractional flow reserve (FFR) = 1]. FFR-guided PCI aims to increase coronary flow, whereas recent studies have reported that PCI does not necessarily increase coronary flow despite improvement in FFR. MethodsThis retrospective analysis was performed in 71 functionally significant lesions treated with elective PCI. AMF obtained by hyperemic average peak coronary flow velocity (h-APV) divided by FFR would not change after PCI given the constant microvascular resistance, which is the assumption of FFR as a surrogate of coronary flow. We evaluated the relationship between AMF and coronary flow during PCI. ResultsPost-PCI AMF was significantly different from pre-PCI AMF (p = 0.022), which impacted discordance between FFR improvement and change in coronary flow. Coronary flow increase >50% was associated with smaller minimum lumen diameter (p = 0.010), greater diameter stenosis (p = 0.003), lower pre-PCI FFR (p < 0.001), lower pre-PCI coronary flow reserve (p = 0.001), higher pre-PCI hyperemic stenosis resistance (p < 0.001), lower pre-PCI h-APV (p = 0.001), and lower pre-PCI AMF (p = 0.031). Pre-PCI AMF provided significant incremental predictive capability for coronary flow increase >50% when added to the clinical model including pre-PCI FFR. ConclusionPre-PCI AMF provided incremental ability to predict increased coronary flow after PCI and impacted the discordance between FFR improvement and increased coronary flow.

Prognostic value of pre-revascularization fractional flow reserve mediated by the post-revascularization level: a causal mediation analysis

Abstract Background The prognostic value of pre-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) can depend on that of the post-PCI FFR and their interaction. To correctly interpret the prognostic value of pre-PCI FFR, it is essential to understand to what extent the relationship between pre-PCI FFR and clinical outcome is explained by pre-PCI FFR-related post-PCI FFR. Purpose The aim of this study is to investigate the extent to which post-PCI FFR mediates the relationship between pre-PCI FFR and vessel-related outcomes using a global, multicenter collaboration registry. Methods Patient data from 4 global FFR registries were pooled and 1488 patients with pre-PCI FFR ≤0.80 were analyzed. The primary outcome was target vessel failure (TVF) during 2-years of follow-up. We evaluated the extent to which post-PCI FFR &amp;lt;0.90 mediated the association between pre-PCI FFR &amp;lt;0.75 and TVF employing a causal mediation analysis in a counterfactual framework. Results Among 1488 patients, the mean (standard deviation) age was 63.5 (9.9) years and 78% (1161 patients) were male. The median (IQR) pre-PCI and post-PCI FFR were 0.71 (0.62–0.76) and 0.88 (0.83–0.92), respectively. The direct effect of low pre-PCI FFR (&amp;lt;0.75) on TVF was significantly elevated (OR: 1.81, 95% CI: 1.03–3.18, p=0.038), and was not mediated by post-PCI FFR&amp;lt;0.90 (indirect effect, OR: 1.01, 95% CI: 0.98–1.05, p=0.39). In the model, post-PCI FFR explained only 2.2% of the association between pre-PCI FFR and TVF. The subgroup analysis implicated that the prognostic information of pre-PCI FFR was mainly for diffuse lesions. Conclusions The prognostic information of pre-PCI FFR did not greatly depend on the results of PCI assessed by post-PCI FFR. Pre-PCI FFR, as a prognostic marker, may mainly reflect the global atherosclerotic burden of the artery, not the extent of the modifiable epicardial stenosis, thus providing independent information from post-PCI FFR. Interpretation Funding Acknowledgement Type of funding source: None