Median Fractional Flow Reserve Research Articles

Physiological disease pattern as assessed by PPGI in vessels with FFR and iFR discordance

Abstract Background Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree on the hemodynamic significance of a coronary lesion in≈20% of cases. It is unclear whether the physiological pattern of disease is an influencing factor for this. This study assessed whether the physiological pattern of coronary artery disease (CAD) as assessed by angiography derived pullback pressure gradient index (PPGI) influences discordance between FFR and iFR measurement. Methods and results This study is a centralized off-line analysis by an independent academic core laboratory (CORRIB Core lab) of a prospective cohort of 444 vessels with both pressure wire-instantaneous wave free ratio (PW-iFR) and pressure wire-fractional flow reserve (PW-FFR) measurements. The study population consisted of a patients presenting with chronic coronary syndrome and having at least one epicardial coronary artery lesion with a 40% to 90% diameter stenosis by visual assessment on invasive coronary angiography. Three-hundred and ninety vessels (355 patients; mean age, 68±10 years; 70% men) with combined FFR, iFR, QFR and angiography derived PPGI were included. QFR was calculated using the QAngio XA 3D 2.1 software package (Medis Medical Imaging System BV, Leiden, The Netherlands). PPGI was calculated using the QFR 2.1.38.2 Research Edition software package. Cut points for hemodynamic significance were FFR ≤0.80 and iFR ≤0.89, respectively. Vessels were classified into FFR+/iFR+ (n=103; 26.4%), FFR-/iFR+ (n=27; 6.9%), FFR+/iFR- (n=38; 9.7%), and FFR-/iFR- (n=222; 57%) groups.. Median FFR, iFR, and QFR were 0.84 (0.77-0.90), 0.92 (0.88-0.97), and 0.83 (0.73-0.90) respectively. FFR disagreed with iFR in 16.7% (65 of 390). The Median PPGI was 0.75 (0.67-0.85). Vessels with PPGI ≥0.75 was considered to have predominantly focal disease pattern and vessels with PPGI <0.75 was considered to have predominantly diffuse disease pattern. The physiological pattern of disease was classified according to the angiography derived pullback pressure gradient index (PPGI) as predominantly physiologically focal (n=209; 53.6%) or predominantly physiologically diffuse (n=181; 46.4%). The median PPGI was significantly lower in FFR-/iFR+ vessels as compared to FFR+/iFR- vessels [0.65(0.60-0.69) vs 0.82(0.75-0.85), p<0.001). The physiological pattern of disease was the influencing factor relating to FFR/iFR discordance: predominantly physiologically focal was significantly associated with FFR+/iFR- (76.3% [29 of 38]), and predominantly physiologically diffuse was significantly associated with FFR-/iFR+ (96.3% [26 of 27]; P<0.001 for pattern of disease between FFR+/iFR- and FFR-/iFR+ groups). Conclusions The physiological pattern of coronary artery disease was an important influencing factor for FFR/iFR discordance.

Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Coronary Artery Disease.

The Placebo-controlled Trial of Percutaneous Coronary Intervention for the Relief of Stable Angina (ORBITA-2) provided evidence for the role of percutaneous coronary intervention (PCI) for angina relief in stable coronary artery disease (CAD). Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are often used to guide PCI, however their ability to predict placebo-controlled angina improvement is unknown. Participants with angina, ischemia, and stable CAD were enrolled and antianginal medications were stopped. Participants reported angina episodes daily for 2 weeks using the ORBITA-app. At the research angiogram, FFR and iFR were measured. After sedation and auditory isolation, participants were randomized to PCI or placebo, before entering a 12-week blinded follow-up phase with daily angina reporting. The ability of FFR and iFR, analyzed as continuous variables, to predict the placebo-controlled effect of PCI, was tested using Bayesian proportional odds modelling. Invasive physiology data were available in 279 patients (140 PCI and 139 placebo). The median (IQR) age was 65 years (59.0 to 70.5) and 223 (79.9%) were male. Median FFR was 0.60 (0.46 to 0.73) and median iFR was 0.76 (0.50 to 0.86). The lower the FFR or iFR, the greater the placebo-controlled improvement with PCI across all endpoints. There was strong evidence that a patient with an FFR at the lower quartile would have a greater placebo-controlled improvement in angina symptom score with PCI than a patient at the upper quartile (FFR 0.46 vs. 0.73: OR 2.01, 95% CrI 1.79 to 2.26, Pr(Interaction)>99.9%). Similarly, there was strong evidence that a patient with an iFR at the lower quartile would have a greater placebo controlled improvement in angina symptom score with PCI than a patient with an iFR at the upper quartile (iFR 0.50 vs. 0.86: OR 2.13, 95% CrI 1.87 to 2.45, Pr(Interaction) >99.9%). The relationship between benefit and physiology was seen in both Rose angina and Rose nonangina. Physiological stenosis severity, as measured by FFR and iFR, predicts placebo-controlled angina relief from PCI. Invasive coronary physiology can be used to target PCI to those patients who are most likely to experience benefit.

Mean Pressure Gradient and Fractional Flow Reserve at A Superficial Femoral Artery Dissection after Drug-Coated Balloon Angioplasty.

Residual dissection is a concern in endovascular treatment with a DCB, and there is limited knowledge of hemodynamics at a dissection lesion. Therefore, the objective of this study is to evaluate the mean pressure gradient (MPG) and fractional flow reserve (FFR) at a residual dissection after DCB angioplasty for the superficial femoral artery (SFA). A total of 59 cases with residual SFA dissection treated with DCB angioplasty at a single center were analyzed retrospectively. The dissection was classified into 6 types (A-F). The primary endpoints were MPG and FFR at a residual dissection lesion after DCB angioplasty, using evaluation with a pressure wire. The median lesion length was 70 (40-130) mm with 24% popliteal involvement, and 11 cases (18%) had chronic total occlusion. A completion angiogram revealed dissection of types A (n = 33, 56%), B (n = 18, 31%), C (n = 7, 12%), and D (n = 1, 2%). The median MPGs in type A, B, and C cases were 0 (0-2), 0 (0-4), and 3 (0-6) mmHg, with a significant lower in type C cases than in type A cases (A vs C, P = .021). The median FFRs in type A, B, and C cases of 1.0 (.98-1.00), 1.0 (.96-1.00), and .98 (.95-1.00) did not differ significantly among dissection types (A vs B, P = .86; A vs C, P = .055; B vs C, P = .15). This is the first report of hemodynamics at a SFA dissection. The results suggest that low-grade dissection (types A or B) does not affect MPG and FFR at a SFA lesion. This indicates that a bailout stent may be unnecessary for patients with dissection of types A or B. A further investigation is needed to determine whether a scaffold is required for a SFA lesion with type C dissection.

N-of-1 Trial of Angina Verification Before Percutaneous Coronary Intervention

BackgroundIn stable coronary artery disease, 30% to 60% of patients remain symptomatic despite successful revascularization. Perhaps not all symptoms reported by a patient with myocardial ischemia are, in fact, angina. ObjectivesThis study sought to determine whether independent symptom verification using a placebo-controlled ischemic stimulus could distinguish which patients achieve greatest symptom relief from percutaneous coronary intervention (PCI). MethodsORBITA-STAR was a multicenter, n-of-1, placebo-controlled study in patients undergoing single-vessel PCI for stable symptoms. Participants underwent 4 episodes (60 seconds each) of low-pressure balloon occlusion across their coronary stenosis, randomly paired with 4 episodes of placebo inflation. Following each episode, patients reported the similarity of the induced symptom in comparison with their usual symptom. The similarity score ranged from −10 (placebo replicated the symptom more than balloon occlusion) to +10 (balloon occlusion exactly replicated the symptom). The primary endpoint was the ability of the similarity score to predict symptom relief with PCI. ResultsFifty-one patients were recruited, aged 62.9 ± 8.6 years. The median fractional flow reserve was 0.68 (Q1-Q3: 0.57-0.79), and the instantaneous wave-free ratio was 0.80 (Q1-Q3: 0.48-0.89). The median similarity score was 3 (Q1-Q3: 0.875-5.25). The similarity score was a strong predictor of symptom improvement following PCI: a patient with an upper quartile similarity score of 5.25 was significantly more likely to have lower angina frequency at follow-up (OR: 8.01; 95% credible interval: 2.39-15.86) than a patient with a lower quartile similarity score of 0.875 (OR: 1.31; 95% credible interval: 0.71-1.99), Pr(difference) >99.9%. ConclusionsSimilarity score powerfully predicted symptom improvement from PCI. These data lay the foundation for independent symptom mapping to target PCI to those patients most likely to benefit. (Systematic Trial of Angina Assessment Before Revascularization [ORBITA-STAR]; NCT04280575)

Microvascular resistance reserve before and after PCI: A serial FFR and [15O] H2O PET study

Background and aimsMicrovascular Resistance Reserve (MRR) has recently been introduced as a microvasculature-specific index and hypothesized to be independent of coronary stenosis. The aim of this study was to investigate the change of MRR after percutaneous coronary intervention (PCI). MethodsIn this post-hoc analysis from the PACIFC trials, symptomatic patients underwent [15O]H2O positron emission tomography (PET) and invasive fractional flow reserve (FFR) before and after revascularization. Coronary flow reserve (CFR) from PET and invasive FFR were used to calculate MRR. ResultsAmong 52 patients (87 % male, age 59.4 ± 9.4 years), 61 vessels with a median FFR of 0.71 (95 % confidence interval: 0.55 to 0.74) and a mean MRR of 3.80 ± 1.23 were included. Following PCI, FFR, hyperemic myocardial blood flow (hMBF) and CFR increased significantly (all p-values ≤0.001). MRR remained unchanged after PCI (3.80 ± 1.23 before PCI versus 3.60 ± 0.97 after PCI; p=0.23). In vessels with a pre-PCI, FFR ≤0.70 pre- and post-PCI MRR were 3.90 ± 1.30 and 3.73 ± 1.14 (p=0.56), respectively. Similar findings were observed for vessels with a FFR between 0.71 and 0.80 (pre-PCI MRR 3.70 ± 1.17 vs. post PCI MRR 3.48 ± 0.76, p=0.19). ConclusionsOur study indicates that MRR, assessed using a hybrid approach of PET and invasive FFR, is independent of the severity of epicardial stenosis. These findings suggest that MRR is a microvasculature-specific parameter.

A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina

BackgroundPercutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina.ResultsA total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group.ConclusionsAmong patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.)

Diagnostic performance of noninvasive computed tomography-derived fractional flow reserve in patients with severe aortic stenosis

Abstract Background Noninvasive fractional flow reserve derived from coronary computed tomography angiography (FFRct) is developed as a decision-making tool in daily clinical practice. However, its diagnostic performance has not been sufficiently explored in patients with severe aortic stenosis (AS). Purpose To identify the diagnostic performance of FFRct in patients with severe AS using invasive fractional flow reserve (FFR) as the reference standard. Methods This study was a retrospective observational that included consecutive patients with severe AS undergoing TAVI who had concomitant intermediate coronary artery stenosis based on preoperative invasive coronary angiography. Preoperative invasive FFR and CT data preoperatively before TAVI were prospectively collected. Results We analyzed the data of patients with severe AS demonstrating intermediate coronary artery stenosis and compared the FFRct values with the invasive FFR values. Among 93 patients (100 vessels), the median FFR and FFRct (Q1, Q3) were 0.85 (0.78, 0.90) and 0.83 (0.72, 0.88), respectively. The FFRct values significantly correlated with the FFR values (r = 0.57; p &amp;lt; 0.0001). The vessel-based analysis of the accuracy of FFRct showed a sensitivity of 90.3%, specificity of 73.9%, positive predictive value of 60.9%, and negative predictive value of 94.4%. Conclusions FFRct demonstrated a significant correlation with invasive FFR and a high negative predictive value in patients with severe AS. These findings suggest that FFRct would be a clinically beneficial noninvasive tool for excluding functional coronary artery stenosis in patients with severe AS.

Influence of sex on the functional assessment of myocardial ischemia.

Fractional flow reserve (FFR) and non-hyperemic resting pressure ratios, such as instantaneous wave-free ratio (iFR) and resting full-cycle ratio (RFR), are recommended for evaluating the significance of angiographically intermediate coronary stenoses. Despite their usefulness, approximately 20% of assessed lesions exhibit discordance between FFR and iFR/RFR. The role of sex in this discrepancy remains uncertain; thus, we aimed to investigate its impact on the discordance between FFR and iFR/RFR. We reviewed 417 consecutive intermediate stenotic lesions from 381 patients, stratified by sex and assessed with both FFR and iFR/RFR. FFR≤0.80 and iFR/RFR ≤0.89 were considered positive for ischemia. Among the 381 patients, 92 (24.1%) were women. Women were older, had lower estimated glomerular filtration rate (eGFR), a higher ejection fraction, and were more likely to have peripheral artery disease than men. Median FFR and iFR/RFR values were lower in men than in women (FFR 0.86 vs. 0.80; P < 0.001; iFR 0.92 vs. 0.90; P = 0.049). However, overall discordance prevalence was similar for both sexes (20.6% vs. 15.1%; P = 0.22). In men, eGFR, insulin-treated diabetes mellitus, and arterial hypertension were predictors of positive FFR | negative iFR/RFR discordance, while eGFR, insulin-treated diabetes mellitus, atrial fibrillation, and chronic obstructive pulmonary disease were predictors of negative FFR | positive iFR/RFR discordance. No factors associated with either discordance were identified in women. FFR and iFR/RFR results indicating significant ischemia were more common in men than women when assessing intermediate coronary stenoses. Nevertheless, sex did not predict discordant results.

The Influence of Microcirculatory Dysfunction on the Resting Full Cycle Ratio Compared to Fractional Flow Reserve

BackgroundThe relation between the resting full cycle ratio (RFR) and fractional flow reserve (FFR) is not fully understood. This study aims to investigate the influence of coronary microvascular dysfunction, assessed by the index of microvascular resistance (IMR), on RFR compared to FFR in patients undergoing functional assessment for coronary stenosis. Materials and methodsTwo-hundred patients with borderline stenosis underwent functional assessment of RFR, FFR, coronary flow reserve (CFR) and IMR. Retriever operator curve analysis was performed to assess the diagnostic value of RFR in patients with (IMR ≥ 24) and (IMR < 24). ResultsMedian RFR did not differ significantly in patients with IMR ≥ 24 compared to patients with IMR < 24: 0.89 (interquartile range (IQR) 0.84, 0.95) vs. 0.90 (IQR 0.84, 0.92), p = 0.29). FFR was significantly higher in patients with IMR ≥ 24 compared to patients with IMR < 24: median FFR 0.85 (IQR (0.76, 0.92)) vs. 0.82 (IQR 0.73, 0.86), p = 0.009, and median CFR was significantly lower 1.80 (IQR 1.40, 2.55) vs. 2.70 (IQR 1.80, 3.95), p < 0.001. The diagnostic value of RFR was high (Area under the curve (AUC) 0.89 95 % Confidence Interval: [0.85, 0.93]) and AUC did not differ between patients with IMR ≥ 24 compared to patients with IMR < 24: 0.89 vs. 0.90, p = 0.89. An overall optimal cut off of 0.88 was identified. The cut off did not differ significantly between patients with IMR ≥ 24 compared to patients with IMR < 24: 0.88 vs. 0.90, p = 0.397. ConclusionIn patients with coronary borderline stenosis, the coronary microvascular function did not influence on the cut off values or AUC of RFR compared to FFR.

Comparison between the diagnostic performance of vessel fractional flow reserve and nonhyperemic pressure ratio for functionally significant coronary stenosis severity as assessed by fractional flow reserve.

Fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs) have been widely used to assess the functional severity of coronary stenosis. However, their measurement requires using a pressure wire, making their use in all patients difficult. The recently developed vessel fractional flow reserve (vFFR), derived from three-dimensional quantitative coronary angiography, is expected to serve as a surrogate for pressure wire assessment. This retrospective study was conducted on patients with intermediate coronary stenosis who underwent FFR and NHPR measurements. The vFFR and NHPR values were compared for diagnosing coronary stenosis as defined by an FFR of ≤0.80, and the number of patients not requiring wire-based assessment was estimated. In a total of 90 lesions from 74 patients (median [SD] age 75 [12] years; men 80%), the median FFR was 0.78 (0.72-0.84), and 57% of these lesions (N = 51) exhibited an FFR of ≤0.80. vFFR provided high discrimination for coronary stenosis (area under the curve 0.80, 95% confidence interval0.70-0.90), which was comparable to that of NHPRs (p = 0.42). High diagnostic accuracy was consistently observed across a variety of clinical presentations (i.e., old age, diabetes, target coronary artery, and left ventricular hypertrophy) (pinteraction > 0.05). In total, 55 lesions (61%) demonstrated positive or negative likelihood of coronary stenosis when vFFR was <0.73 (specificity 90%) or >0.87 (sensitivity 88%), respectively. vFFR demonstrated excellent diagnostic performance for detecting functionally significant coronary stenosis as evaluated by FFR. vFFR may be used as a surrogate for pressure wire assessment.

Diagnostic accuracy of angiography-based vessel fractional flow reserve after chronic coronary total occlusion recanalization

Abstract Background Angiography-Based Vessel FFR (vFFR) demonstrated a strong correlation with invasive fractional flow reserve (FFR) in both a pre- and post-percutaneous coronary intervention (PCI) setting. However, the role of vFFR and its correlation with post-PCI FFR in chronic coronary occlusion (CTO) has not been evaluated yet. We sought to investigate the diagnostic performance of post-PCI vFFR with post-PCI FFR as a reference in patients undergoing successful CTO PCI. Methods Between March 2016 and September 2019, a total of 80 patients from the FFR-SEARCH and FFR REACT studies underwent successful CTO recanalization [1,2]). A total of 50 patients (median age 66 (IQR: 56–74) years, 76% were male) were eligible for the analysis. Median FFR was 0.89 (IQR: 0.84–0.94) while median vFFR was 0.91 (IQR: 0.85–0.94). Suboptimal physiological results, defined as FFR and vFFR &amp;lt;0.90, were identified in 26 (52%) and in 21 (42%) patients, respectively. A strong correlation (r=0.79) was found between vFFR and FFR with a mean bias of 0.013±0.051. Receiver-operating characteristics curve analysis revealed an excellent accuracy of vFFR in predicting FFR &amp;lt;0.90 (AUC: 0.97; 95% CI: 0.93–1.00). Conclusion vFFR shows a good agreement with FFR and a high diagnostic accuracy for FFR ≤0.90 in patients undergoing successful PCI of a CTO lesion. Funding Acknowledgement Type of funding sources: None.

The diagnostic value of left-anterior-descending artery velocity assessed by transthoracic Doppler echocardiography for microvascular dysfunction in stenotic left-anterior-descending artery

Abstract Background Index of microcirculatory resistance (IMR) has been used as a clinical measure of microvascular function. Transthoracic Doppler echocardiography (TDE) can provide information on the functional status of coronary artery circulation. This study aims to assess the diagnostic value of left-anterior-descending artery (LAD) flow velocity by TDE for microvascular dysfunction. Methods Consecutive patients who were scheduled for elective percutaneous coronary intervention (PCI) for LAD lesions were prospectively enrolled in the single tertiary-care center between April 2020 and July 2021. Pre-PCI LAD diastolic peak velocity (DPV) by TDE at rest and hyperemia were measured. By invasive coronary angiography, quantitative coronary angiography and invasive wire-based physiological indices including fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) were measured. Results A total of 104 patients were studied. Median FFR and IMR values were 0.70 (0.60–0.74) and 20.68 (14.92–31.69), respectively. No significant relationship was observed between FFR and IMR. The prevalence of microvascular dysfunction defined as IMR≥25 was 39.4%. Basal DPV was 25 (20–33) cm/sec, and hyperemic DPV was 51 (41–67) cm/sec. In lesions with IMR≥25, reference diameter (RD) was significantly greater [2.63 (2.22–3.19) mm vs 2.39 (2.09–2.66) mm, p=0.019], basal DPV was lower [26 (18–29) cm/sec vs 29 (22–37) cm/sec, p=0.022)] and hyperemic DPV was lower [49 (19–54) cm/sec vs 56 (42–70) cm/sec, p=0.023] compared to lesions with IMR&amp;lt;25. ROC analysis showed basal DPV and RD are significant predictors of IMR≥25 [basal DPV: AUC 0.633 (0.525–0.742), best cutoff 29cm/sec RD: AUC 0.636 (0.523–0.750), best cutoff 2.84mm]. Multivariable logistic regression analysis showed basal DPV&amp;lt;29cm/sec and RD&amp;gt;2.84mm are independent predictors for IMR≥25 [Odds ratio: 3.08 (1.22–7.78), p=0.017; odds ratio 4.40 (1.55–12.50), p=0.005]. Conclusion Basal DPV by non-invasive pre-PCI TDE and reference diameter can predict lesions with coexisting microvascular dysfunction in LAD territory with functionally significant lesions without the need of vasodilator-induced hyperemia and a wire-based invasive physiological measurement. Funding Acknowledgement Type of funding sources: None.

Differential impact of coronary revascularization on long-term clinical outcome according to coronary flow characteristics: analysis of the international ILIAS registry

Abstract Backgrounds Coronary pressure indices such as fractional flow reserve (FFR) are standard in guiding elective revascularization. However, considering additional coronary flow parameters could further individualize and optimize the decision on revascularization, especially in terms of the impact on prognosis. We aimed to investigate the potentially differential prognostic associations of elective PCI according to coronary flow properties represented by coronary flow reserve (CFR), coronary flow capacity (CFC) and baseline CFC (bCFC). Methods From the Inclusive invasive physiological assessment in angina syndromes (ILIAS) registry composed of 16 hospitals globally from 7 countries, patients with obstructive coronary artery disease who underwent invasive coronary physiological assessment were included (N=2370 vessels). We assessed effect measure modifications of the association of PCI and 5-year target vessel failure (TVF) according to CFR, CFC and bCFC either assessed by Doppler-technique or thermodilution-method in three models: conditional logistic regression, marginal structural model, and COX proportional hazard model. Reduced CFR, CFC and bCFC were defined as CFR&amp;lt;2.1, CFR&amp;lt;2.1 with hyperemic average peak flow velocity (APV)&amp;lt;33.8 cm/s, and CFR&amp;lt;2.1 with baseline APV&amp;gt;17.0 cm/s in Doppler-technique, respectively (Figure 1), and the corresponding percentiles in thermodilution-methods. All models were adjusted for FFR, the interaction between PCI and FFR, and other confounders. Results The mean age of the population was 63.3 years and there were 1322 (73.6%) males. Median FFR was 0.85 and PCI was performed in 600 (25.3%) vessels. Reduced CFR, CFC, and abnormal bCFC were defined in 988 (41.7%), 542 (22.9%), and 600 (25.3%) vessels, respectively. There were little overlaps in vessels with reduced CFC and abnormal bCFC. In univariate analyses, vessels with reduced CFC had worse outcomes compared with those with normal CFC if deferred (13.4% vs. 6.6%), whereas reduced CFC was associated with better prognosis if treated by PCI (9.5% vs. 11.3%). Significant effect measure modifications were observed by CFC either in odds ratio (P=0.0018), additive (P=0.029), and hazard ratio scale (P=0.0002) (Figure 2). Vessels with reduced CFC had, compared with those with normal CFC, higher adjusted absolute risk of 5-year TVF by 5.9 [0.1, 12] percent if deferred, but lower risk by 1.8 [−1.7, 5.3] percent if treated by PCI. CFR and bCFC were not significant effect modifiers in any scales. Similar associations were observed in per-patient analyses, whereas the findings were less robust. Conclusions We observed a beneficial impact of PCI on absolute risk of 5-year clinical outcomes in vessels with reduced CFC, and a detrimental effect in those with normal CFC. CFR and bCFC were not robust effect modifiers of PCI. Therefore, CFC, combined with FFR, could be potentially used to optimize the patient selection for elective PCI treatment. Funding Acknowledgement Type of funding sources: None.

Discordance between fractional flow reserve and instantaneous wave-free ratio in patients with severe aortic stenosis: A retrospective cohort study

BackgroundDiscordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) occurs in approximately 20 % of cases. However, no studies have reported the discordance in patients with severe aortic stenosis (AS). We aimed to evaluate the diagnostic discordance between FFR and iFR in patients with severe AS. MethodsWe examined 140 consecutive patients with severe AS (164 intermediate coronary artery stenosis vessels). FFR and iFR were calculated in four quadrants based on threshold FFR and iFR values of ≤0.8 and ≤0.89, respectively (Group 1: iFR >0.89, FFR >0.80; Group 2: iFR ≤0.89, FFR >0.80; Group 3: iFR >0.89, FFR ≤0.80; and Group 4: iFR ≤0.89, FFR ≤0.80). Concordant groups were Groups 1 and 4, and discordant groups were Groups 2 and 3. Positive and negative discordant groups were Groups 3 and 2, respectively. ResultsThe median (Q1, Q3) FFR and iFR were 0.84 (0.76, 0.88) and 0.85 (0.76, 0.91), respectively. Discordance was observed in 48 vessels (29.3 %). In the discordant group, negative discordance (Group 2: iFR ≤0.89 and FFR >0.80) was predominant (45 cases, 93.6 %). Multivariate analysis showed that the left anterior descending artery [odds ratio (OR), 3.88; 95 % confidence interval (CI): 1.54–9.79, p = 0.004] and peak velocity ≥5.0 m/s (OR, 3.21; 95%CI: 1.36–7.57, p = 0.008) were independently associated with negative discordance (FFR >0.8 and iFR ≤0.89). ConclusionsIn patients with severe AS, discordance between FFR and iFR was predominantly negative and observed in 29.3 % of vessels. The left anterior descending artery and peak velocity ≥5.0 m/s were independently associated with negative discordance.

Differential Impact of Coronary Revascularization on Long-Term Clinical Outcome According to Coronary Flow Characteristics: Analysis of the International ILIAS Registry

Coronary pressure indices such as fractional flow reserve are the standard for guiding elective revascularization. However, considering additional coronary flow parameters could further individualize and optimize the decision on revascularization. We aimed to investigate the potentially differential prognostic associations of elective percutaneous coronary intervention (PCI) according to coronary flow properties represented by coronary flow reserve (CFR), coronary flow capacity (CFC), and baseline CFC (bCFC). From the ILIAS Registry (Inclusive Invasive Physiological Assessment in Angina Syndromes) composed of 16 hospitals globally from 7 countries, patients with obstructive coronary artery disease who underwent invasive coronary physiological assessment were included (N=2370 vessels). We assessed effect measure modifications of the association of PCI and 5-year target vessel failure according to CFR, CFC, and bCFC either assessed by Doppler-technique or thermodilution-method. The mean age of the population was 63.3 years, and there were 1322 (73.6%) males. Median fractional flow reserve was 0.85, and PCI was performed in 600 (25.3%) vessels. Reduced CFR, CFC, and abnormal bCFC were defined in 988 (41.7%), 542 (22.9%), and 600 (25.3%) vessels, respectively. Significant effect measure modifications were observed by CFC either in odds ratio (P=0.0018), additive (P=0.029), and hazard ratio scale (P=0.0002). The absolute risk of 5-year target-vessel failure was higher if treated by PCI in vessels with normal CFC by 1.8 (-1.7 to 5.3) percent, while that was lower by -5.9 (-12 to -0.1) percent in those with reduced CFC. CFR and bCFC were not significant effect modifiers in any scales. Similar associations were observed in per-patient analyses, whereas the findings were less robust. We observed qualitative effect measure modification of PCI and 5-year clinical outcomes according to CFC status in additive scale. CFR and bCFC were not robust effect modifiers. Therefore, CFC could be potentially used to optimize the patient selection for elective PCI treatment combined with fractional flow reserve.

Discrepancy between plaque vulnerability and functional severity of angiographically intermediate coronary artery lesions.

This study sought to investigate the relationship between physiological severity and plaque vulnerability of intermediate coronary artery stenoses as assessed by fractional flow reserve (FFR) and near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). We included vessels where both FFR and NIRS-IVUS were performed. A positive FFR was defined as FFR ≤ 0.80. Lipid core burden index of the entire target vessel (TV-LCBI), maximum LCBI in 4mm (maxLCBI4mm), and maximum plaque burden (PB) were evaluated using NIRS-IVUS. A vulnerable plaque was defined as a lipid-rich plaque (maxLCBI4mm ≥ 400) with large PB (≥ 70%). A total of 59 vessels of 45 patients were included. Median FFR value was 0.75 [interquartile 0.72, 0.82]. An FFR value of ≤ 0.80 was observed in 42 vessels (71%). TV-LCBI (correlation coefficient [CC] = -0.331, p = 0.011), lesion length (CC = -0.350, p = 0.007), and PB (CC = -0.230, p = 0.080) negatively correlated with FFR value, while maxLCBI4mm did not (CC = -0.156, p = 0.24). The prevalence of vulnerable plaques (26.2% vs. 29.4%, p > 0.99) and mean TV-LCBI, maxLCBI4mm, and PB values were not significantly different between the vessels with FFR ≤ 0.80 and those with FFR > 0.80. In multivariable logistic models, diabetes mellitus (p = 0.003) and hemoglobin A1c (p = 0.012) were associated with the presence of a vulnerable plaque. In conclusion,the results of the present study suggested that FFR may reflect total lipid burden but not necessarily plaque vulnerability. In patients with coronary artery disease and a high likelihood of rapid atherosclerosis progression, such as diabetes mellitus patients, assessing plaque vulnerability in addition to the functional severity of coronary artery lesions may help stratify better the risk of future events.

Angiographic predictors of coronary hemodynamics.

Aims: Assess the correlation between diameter stenosis, lesion length, location, diffuse coronary disease and with fractional flow reserve (FFR). Methods/Results: We performed quantitative coronary analysis analysis on 384 lesions with stable coronary artery disease undergoing FFR assessment. Vessels were 59.1% left anterior descending artery (LAD), 16.1% left circumflex artery and 14.8% right coronary artery. Median diameter stenosis was 58% ± 2.5 and median lesion length was 10 mm ± 7.36. 21% of vessels were diffusely diseased. Lesions were 33.6% proximal, 44% mid-vessel and 12% distal. Median FFR was 0.85. Diameter stenosis correlated with lower FFR (p < 0.005, odds ratio [OR]: 2.4 [95% CI: 0.99-5.63]). There was no association between lesion length, location, number of proximal side branches and FFR. Vessels with diffuse disease had a nonsignificant trend for lower FFR (0.84 vs 0.85, p = 0.375, OR: 1.26 [95% CI: 0.76-2.09]). LAD lesions had significantly lower FFR compared with non-LAD (p < 0.001, OR: 2.55 [95% CI: 1.61-4.04]); including left circumflex artery and right coronary artery lesions (p = 0.001, OR: 3.4 [95% CI: 1.7-6.9]) and p = 0.02, OR: 2.55 [95% CI: 1.17-4.34]). Conclusion: FFR is not related to lesion length, location or number of proximal branches.

Diagnostic agreement of quantitative flow ratio with fractional flow reserve in a Latin-American population.

Quantitative flow ratio (QFR) is a recently proposed angiographic index that allows to assess the pressure loss in coronary arteries in a similar fashion as the fractional flow reserve (FFR). The purpose of this study was to evaluate the diagnostic performance of QFR as compared to FFR, in a Latin-American population of patients with suspected ischaemic heart disease. QFR was retrospectively derived from coronary angiograms. The association, diagnostic performance, and continuous agreement of fixed-flow QFR (fQFR) and contrast-flow QFR (cQFR) with FFR was assessed by continuous and dichotomous methods. 90 vessels form 66 patients were finally included. The study comprised coronary stenoses of intermediate severity, both angiographically (diameter stenosis: 46.6 ± 12.8%) and physiologically [median FFR = 0.83 (quartile 1-3, 0.76-0.89)]. The correlation of FFR with both fQFR [ρ = 0.841, (95% CI 0.767 to 0.893), p < 0.001] and cQFR [ρ = 0.833, (95% CI 0.755 to 0.887), p < 0.001] was strong. The diagnostic performance of cQFR was good [area under the ROC curve of 0.92 (95% CI 0.86 to 0.97, p < 0.001)], with 0.80 as the optimal cQFR cut-off against FFR ≤ 0.80. This 0.80 cQFR cut-off classified correctly 83.3% of total stenoses, with a sensitivity of 85.2% and specificity of 80.6%. QFR was strongly associated with FFR and exhibited a high diagnostic performance in this Latin-American population.

Computed tomography-derived characterisation of pericoronary,epicardial and paracardial adipose tissue and its association with myocardial ischemia as assessed by computed and invasive fractional flow

Abstract Introduction Increased pericoronary adipose tissue (PCAT) computed tomography (CT) attenuation derived from coronary CT angiography (CTA) around the right coronary artery (RCA) reflects coronary inflammation and relates to cardiac mortality. Purpose We aimed to investigate the yet unclear association between CT-derived characterisation of different cardiac adipose tissue compartments and the presence of myocardial ischemia as assessed by fractional flow reserve (FFR). Methods 133 stable individuals (64 years, 74% male) with coronary artery disease (CAD) underwent CTA including computed FFR (FFR-CT) measurement followed by invasive angiography with FFR (invasive FFR) assessment. The CT attenuation (HU) and volume (mm3) of PCAT were quantified around the RCA (10 to 50 mm from RCA ostium), the proximal 40 mm of the left anterior descending artery (LAD) and the circumflex artery (LCX) with the help of semi-automated software. The per patient PCAT CT attenuation was calculated as followed: (PCAT CT attenuation of RCA+LAD+LCX)/3. Quantification of epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT; all intrathoracic adipose tissue outside the pericardium) were performed in non-contrast cardiac CT data sets using a fully automated deep-learning based algorithm. Results Median FFR-CT was 0.86 [0.79, 0.91] and median invasive FFR was 0.87 [0.81, 0.93]. Patients with presence of myocardial ischemia (n=26) defined by a FFR-CT threshold of ≤0.75 showed a significant higher PCAT CT attenuation of RCA (−75.1 HU vs. −81.1 HU, p=0.011) and per patient (−74.5 HU vs. −77.7 HU, p=0.045) than individuals without myocardial ischemia (n=107). In multivariable analysis adjusted for age, BMI, gender and traditional risk factors, both RCA and per patient PCAT CT attenuation were significant predictors of myocardial ischemia as assessed by FFRCT ≤0.75. Between individuals with myocardial ischemia compared to individuals without myocardial ischemia there was no significant difference neither in the volume and CT attenuation of EAT and PAT nor in the PCAT volume of RCA, LAD, LCX and per patient PCAT volume. Conclusions Our observations suggest that PCAT CT attenuation instead of PCAT volume, EAT and PAT measures might be associated with the presence of myocardial ischemia as assessed by FFR. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Heart Foundation e.V.

Physiological significance of pericoronary inflammation in epicardial functional stenosis and global coronary flow reserve

Both fractional flow reserve (FFR) and global coronary flow reserve (g-CFR) provide prognostic information in patients with stable coronary artery disease (CAD). Inflammation plays a vital role in impaired endothelial dysfunction and atherosclerotic progression, potentially predicting cardiovascular mortality. This study aimed to evaluate the physiological significance of pericoronary adipose tissue inflammation assessed by CT attenuation (PCATA) in epicardial functional stenosis severity and g-CFR in patients with CAD. A total of 131 CAD patients with a single de novo epicardial coronary stenosis who underwent coronary CT-angiography (CCTA), phase-contrast cine-magnetic resonance imaging (PC-CMR) and FFR measurement were studied. PCATA was assessed using the mean CT attenuation value. G-CFR was obtained by quantifying absolute coronary sinus flow (ml/min/g) by PC-CMR at rest and during maximum hyperemia. Median FFR, g-CFR, and PCATA values were 0.75, 2.59, and − 71.3, respectively. Serum creatinine, NT-proBNP, left ventricular end-diastolic volume, and PCATA were independently associated with g-CFR. PCATA showed a significant incremental predictive efficacy for impaired g-CFR (< 2.0) when added to the clinical risk model. PCATA was significantly associated with g-CFR, independent of FFR. Our results suggest the pathophysiological mechanisms linking perivascular inflammation with g-CFR in CAD patients.