Discrepancy in Diagnosing Coronary Artery Occluded Lesion: CT-Derived Fractional Flow Reserve (FFRCT) Versus Invasive Coronary Angiography.

Coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (FFRCT) findings demonstrate high diagnostic accuracy, aligning consistently with invasive coronary angiography (ICA), the gold standard diagnostic technique for coronary artery disease. The differential diagnosis of total versus subtotal coronary occlusion is crucial in determining the appropriate treatment strategy. Subtotal coronary occlusions composed of vulnerable tissue can sometimes present as total coronary occlusions on ICA. This presentation can be inconsistent with findings from CCTA and FFRCT. This case report presents discrepant findings between CCTA, which indicated subtotal coronary occlusion, and ICA, which suggested total coronary occlusion. The stenotic lesion, filled with vulnerable tissue (low-attenuation plaque volume: 20.3 mm3 and intermediate-attenuation plaque volume: 71.6 mm3), could be dilated with a vasodilator during maximal hyperemia. This dilation facilitated the acquisition of CCTA and FFRCT images. We were able to diagnose subtotal coronary occlusion and identify the overall anatomical structure of the vessels prior to percutaneous coronary intervention (PCI). This allowed us to perform a successful and uncomplicated PCI.

Prognostic Value of Poststenting Fractional Flow Reserve After Imaging-Guided Optimal Stenting.

BACKGROUND: Prognostic value of poststenting fractional flow reserve (FFR) remains uncertain in patients undergoing an imaging-guided optimal stenting strategy. OBJECTIVES: The authors evaluated the prognostic value of poststenting FFR according to the intracoronary imaging-guided lesion preparation, stent sizing, and postdilation (iPSP) strategy to optimize stent outcomes. METHODS: Poststenting FFR assessment was performed in 1,108 lesions in 1,005 patients from the IRIS-FFR registry. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization at 5 years. RESULTS: At the index procedure, 326 lesions (29.4%) were treated using all 3 parts of the iPSP strategy. In the overall population, poststenting FFR was significantly associated with the risk of TVF at 5 years (per 0.01 increase of FFR, adjusted HR [aHR]: 0.94; 95% CI: 0.90-0.98; P = 0.004). Significant interaction was detected between poststenting FFR and the iPSP strategy on the risk of TVF at 5 years (P = 0.045 for interaction). In the iPSP group, poststenting FFR was not associated with the risk of TVF at 5 years (per 0.01 increase of FFR, aHR: 1.00; 95% CI: 0.96-1.05; P = 0.95), whereas a significant association between poststenting FFR and TVF at 5 years was observed in the no iPSP group (per 0.01 increase of FFR, aHR: 0.94; 95% CI: 0.90-0.99; P = 0.009). CONCLUSIONS: Poststenting FFR showed a significant association with cardiac events. However, its prognostic value appeared to be limited after the application of an imaging-guided optimal stenting strategy.

A randomised multicentre study of angiography- versus physiologyguided percutaneous coronary intervention in patients with coronary artery disease undergoing TAVI: design and rationale of the FAITAVI trial.

The treatment of coronary artery disease (CAD) in patients with severe aortic valve stenosis (AVS) eligible for transcatheter aortic valve implantation (TAVI) is not supported by clinical evidence, and the role of physiology over anatomy as well as the timing of coronary intervention are not defined. FAITAVI (ClinicalTrials.gov: NCT03360591) is a nationwide prospective, open-label, multicentre, randomised controlled study comparing the angiography-guided versus the physiology-guided coronary revascularisation strategy in patients with combined significant CAD and severe AVS undergoing TAVI. Significant CAD will be defined as coronary stenosis ≥50%, as assessed by visual estimation in vessels ≥2.5 mm. Physiology will be tested by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). The study will be conducted at 15 sites in Italy. In the angiography arm, percutaneous coronary intervention (PCI) will be performed either before TAVI, during the TAVI procedure - before or after the valve implantation - or within 1 month±5 days of the valve implantation, left to the operator's decision. In the physiology arm, FFR and iFR will be performed before TAVI, and PCI will be indicated for FFR ≤0.80, otherwise the intervention will be deferred. In case of borderline values (0.81-0.85), FFR and iFR will be repeated after TAVI, with PCI performed when needed. With a sample size of 320 patients, the study is powered to evaluate the primary endpoint (a composite of death, myocardial infarction, stroke, major bleeding, or ischaemia-driven target vessel revascularisation). TAVI indication, strategy and medical treatment will be the same in both groups. After discharge, patients will be contacted at 1, 6, 12 and 24 months after the procedure to assess their general clinical status, and at 12 months for the occurrence of events included in the primary and secondary endpoints. FAITAVI is the first randomised clinical trial to investigate "optimal" percutaneous coronary intervention associated with TAVI in patients with severe AVS and CAD.

Triglyceride to high-density lipoprotein cholesterol ratio associated with long-term adverse clinical outcomes in patients deferred revascularization following fractional flow reserve.

BACKGROUND: Guidelines on coronary intermediate lesions strongly recommend deferred revascularization after detecting a normal fractional flow reserve (FFR). Researches about triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) on cardiovascular diseases has also been well conducted. However, the association of TG/HDL-C and long-term adverse clinical outcomes remains unknown for patients deferred revascularization following FFR. METHODS: This study retrospectively included 374 coronary artery disease (CAD) patients with non-significant coronary lesions diagnosed by coronary angiography (CAG) and FFR. The main outcome measure was the combination of major adverse cardiovascular and cerebrovascular events (MACCEs). All patients were categorized into three subgroups in terms of TG/HDL-C tertiles (T1 < 0.96, 0.96 ≤ T2 < 1.58, T3 ≥ 1.58). Three different Cox regression models were utilized to reveal the association between TG/HDL-C and prevalence of MACCEs. RESULTS: 47 MACCEs were recorded throughout a median monitoring period of 6.6 years. The Kaplan-Meier survival curves showed a higher MACCEs rate occurred in the higher TG/HDL-C group (5.6% vs. 12.9% vs. 19.4%, log-rank P < 0.01). After adjustment, patients in T3 suffered a 2.6-fold risk compared to the T1 group (T3 vs. T1: HR 2.55, 95% CI 1.05-6.21, P = 0.038; T2 vs. T1: HR 1.71, 95% CI 0.65-4.49, P = 0.075; P for trend = 0.001). The restricted cubic spline (RCS) analysis demonstrated that the HR for MACCEs rose as TG/HDL-C increased. Both the receiver operating characteristic (ROC) and time-dependent ROC proved the excellent predictive ability of TG/HDL-C. CONCLUSION: The study illustrates that TG/HDL-C correlates with the risk of MACCEs in CAD patients deferred revascularization following FFR. TG/HDL-C could serve as a dependable predictor of cardiovascular events over the long term in this population.

Chemokine Fractalkine and Non-Obstructive Coronary Artery Disease-Is There a Link?

Non-obstructive coronary artery disease (NO-CAD) constitutes a heterogeneous group of conditions collectively characterized by less than 50% narrowing in at least one major coronary artery with a fractional flow reserve (FFR) of ≤0.80 observed in coronary angiography. The pathogenesis and progression of NO-CAD are still not fully understood, however, inflammatory processes, particularly atherosclerosis and microvascular dysfunction are known to play a major role in it. Chemokine fractalkine (FKN/CX3CL1) is inherently linked to these processes. FKN/CX3CL1 functions predominantly as a chemoattractant for immune cells, facilitating their transmigration through the vessel wall and inhibiting their apoptosis. Its concentrations correlate positively with major cardiovascular risk factors. Moreover, promising preliminary results have shown that FKN/CX3CL1 receptor inhibitor (KAND567) administered in the population of patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), inhibits the adverse reaction of the immune system that causes hyperinflammation. Whereas the link between FKN/CX3CL1 and NO-CAD appears evident, further studies are necessary to unveil this complex relationship. In this review, we critically overview the current data on FKN/CX3CL1 in the context of NO-CAD and present the novel clinical implications of the unique structure and function of FKN/CX3CL1 as a compound which distinctively contributes to the pathomechanism of this condition.

FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction.

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).

Selective Use of CT Fractional Flow at a Large Academic Medical Center: Insights from Clinical Implementation after 1 Year of Practice.

Purpose This special report outlines a retrospective observational study of CT fractional flow reserve (CT-FFR) analysis using dual-source coronary CT angiography (CTA) scans performed without heart rate control and its impact on clinical outcomes. Materials and Methods All patients who underwent clinically indicated coronary CTA between August 2020 and August 2021 were included in this retrospective observational study. Scans were performed in the late systolic to early diastolic period without heart rate control and analyzed at the interpreting physician's discretion. Demographics, coronary CTA features, and rates of invasive coronary angiography (ICA), percutaneous coronary intervention (PCI), myocardial infarction, and all-cause death at 3 months were assessed by chart review. Results During the study period, 3098 patients underwent coronary CTA, of whom 113 with coronary bypass grafting were excluded. Of the remaining 2985 patients, 292 (9.7%) were referred for CT-FFR analysis. Two studies (0.7%) were rejected from CT-FFR analysis, and six (2.1%) analyses did not evaluate the lesion of concern. A total of 160 patients (56.3%) had CT-FFR greater than 0.80. Among patients with significant stenosis at coronary CTA, patients who underwent CT-FFR analysis presented with lower rates of ICA (74.5% vs 25.5%, P = .04) and PCI (78.9% vs 21.1%, P = .05). Conclusion CT-FFR was implemented in patients not requiring heart rate control by using dual-source coronary CTA acquisition and showed the potential to decrease rates of ICA and PCI without compromising safety in patients with significant stenosis and an average heart rate of 65 beats per minute. Keywords: Angiography, CT, CT-Angiography, Fractional Flow Reserve, Cardiac, Heart, Arteriosclerosis Supplemental material is available for this article. © RSNA, 2024.

Feasibility and Diagnostic Performance of Functional SYNTAX Score Derived From Dynamic CT Myocardial Perfusion Imaging.

BACKGROUND: Computed tomography (CT) fractional flow reserve (FFR)-derived functional SYNTAX score (FSSCT-FFR) is a valuable method for guiding treatment strategy in patients with multivessel coronary artery disease. Dynamic CT myocardial perfusion imaging (CT-MPI) demonstrates higher diagnostic accuracy than CT-FFR in identifying hemodynamically significant coronary artery disease. We aimed to evaluate the feasibility of CT-MPI-derived FSS (FSSCT-MPI) with reference to invasive FSS. METHODS: In this retrospective study, patients with multivessel coronary artery disease who underwent dynamic CT-MPI+ coronary CT angiography and invasive coronary angiography or FFR within 4 weeks were consecutively included. Invasive (FSSinvasive) and noninvasive FSS (FSSCT-MPI and FSSCT-FFR) were calculated by an online calculator, which assigned points to lesions with hemodynamic significance (defined as FFRinvasive ≤0.80, invasive coronary angiography diameter stenosis ≥90%, CT-FFR ≤0.80, and myocardial ischemia on CT-MPI). Weighted κ value and net reclassification index were calculated to determine the consistency and incremental discriminatory power of FSSCT-MPI. Receiver operating characteristic curve analysis was used for the comparison of FSSCT-MPI and FSSCT-FFR in detecting intermediate- to high-risk patients. RESULTS: A total of 119 patients (96 men; 64.6±10.6 years) with 305 obstructive lesions were included. The average FSSCT-MPI, FSSCT-FFR, and FSSinvasive were 15.58±13.03, 16.18±13.30, and 13.11±12.22, respectively. The agreement on risk classification based on the FSSCT-MPI tertiles was good (weighted κ, 0.808). With reference to FSSinvasive, FSSCT-MPI correctly reclassified 27 (22.7%) patients from the intermediate- to high SYNTAX score group to the low-score group (net reclassification index, 0.30; P<0.001). In patients with severe calcification, FSSCT-MPI had better diagnostic value than FSSCT-FFR in detecting intermediate- to high-risk patients when compared with FSSinvasive (area under the curve, 0.976 versus 0.884; P<0.001). CONCLUSIONS: Noninvasive FSS derived from CT-MPI is feasible and has strong concordance with FSSinvasive. It allows accurate categorization of FSS in patients with multivessel coronary artery disease, in particular with severe calcification.

Triglyceride glucose index is associated with functional coronary artery stenosis in hypertensive patients.

Background: The triglyceride glucose (TyG) index is an effective method for determining insulin resistance (IR). Limited research has explored the connection between the TyG index and functionally significant stenosis in hypertensive patients. Furthermore, the connections between the TyG index, fat attenuation index (FAI) and atherosclerotic plaque characteristics are also worth exploring. Methods: The study screened 1622 hypertensive participants without coronary artery disease history who underwent coronary computed tomography angiography. The TyG index was calculated as ln (fasting glucose [mg/dL] * fasting TG [mg/dL]/2). Adverse plaque characteristics (HRPCs), high-risk plaques (HRPs), FAI, and CT-derived fractional flow reserve (FFRCT) were analyzed and measured for all patients. Functionally significant stenosis causing ischemia is defined as FFRCT ≤ 0.80. Two patient groups were created based on the FFRCT: the FFRCT < 0.80 group and the FFRCT > 0.80 group. In hypertensive patients, the association between the TyG index and FFRCT was examined applying a logistic regression model. Results: The TyG index was higher for people with FFRCT ≤ 0.80 contrast to those with FFRCT > 0.80. After controlling for additional confounding factors, the logistic regression model revealed a clear connection between the TyG index and FFRCT ≤ 0.80 (OR = 1.718, 95% CI 1.097-2.690, p = 0.018). The restricted cubic spline analysis displayed a nonlinear connection between the TyG index and FFRCT ≤ 0.80 (p for nonlinear = 0.001). The TyG index increased the fraction of individuals with HRPs and HRPCs, FAI raised, and FFRCT decreased (p < 0.05). The multivariate linear regression analysis illustrated a powerfulcorrelation between high TyG index levels and FAI, FFRCT, positive remodeling (PR), and low-attenuation plaque (LAPs) (standardized regression coefficients: 0.029 [p = 0.007], -0.051 [p < 0.001], 0.029 [p = 0.027], and 0.026 [p = 0.046], separately). Conclusion: In hypertensive patients, the TyG index showed an excellent association with a risk of FFRCT ≤ 0.80. Additionally, the TyG index was also linked to FAI, FFRCT, PR, and LAPs.

Diagnostic Performance of Angiography-Derived Quantitative Flow Ratio in Complex Coronary Lesions.

BACKGROUND: Quantitative flow ratio derived from computed tomography angiography (CT-QFR) and invasive coronary angiography (Murray law-based quantitative flow ratio [µQFR]) are novel approaches enabling rapid computation of fractional flow reserve without the use of pressure guidewires and vasodilators. However, the feasibility and diagnostic performance of both CT-QFR and µQFR in evaluating complex coronary lesions remain unclear. METHODS: Between September 2014 and September 2021, 240 patients with 30% to 90% coronary diameter stenosis who underwent both coronary computed tomography angiography and invasive coronary angiography with fractional flow reserve within 60 days were retrospectively enrolled. The diagnostic performance of CT-QFR and µQFR in detecting functional ischemia among all lesions, especially complex coronary lesions, was analyzed using fractional flow reserve as the reference standard. RESULTS: CT-QFR and µQFR analyses were performed on 309 and 289 vessels, respectively. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for CT-QFR in all lesions at the per-vessel level were 91% (with a 95% CI of 84%-96%), 92% (95% CI, 88%-95%), 83% (95% CI, 75%-90%), 96% (95% CI, 93%-98%), and 92% (95% CI, 88%-95%), with values for µQFR of 90% (95% CI, 81%-95%), 97% (95% CI, 93%-99%), 92% (95% CI, 84%-97%), 96% (95% CI, 92%-98%), and 94% (95% CI, 91%-97%), respectively. Among bifurcation, tandem, and moderate-to-severe calcified lesions, the diagnostic values of CT-QFR and µQFR showed great correlation and agreement with those of invasive fractional flow reserve, achieving an area under the receiver operating characteristic curve exceeding 0.9 for each complex lesion at the vessel level. Furthermore, the accuracies of CT-QFR and µQFR in the gray zone were 85% and 84%, respectively. CONCLUSIONS: Angiography-derived quantitative flow ratio (CT-QFR and µQFR) demonstrated remarkable diagnostic performance in complex coronary lesions, indicating its pivotal role in the management of patients with coronary artery disease.

Prognostic Implications of Microvascular Resistance Reserve in Symptomatic Patients With Intermediate Coronary Stenosis.

BACKGROUND: Microvascular resistance reserve (MRR) is a novel index reflecting coronary microcirculatory function, irrespective of epicardial coronary artery stenosis. There is limited evidence regarding whether MRR can be an independent prognostic tool in patients with stable ischemic heart disease (IHD). OBJECTIVES: The aim of this study was to evaluate clinical outcomes according to MRR in patients with stable IHD accompanied with or without significant epicardial coronary artery stenosis. METHODS: The present study included 547 consecutive patients undergoing systematic echocardiographic and invasive physiological assessment for suspected stable IHD. Significant epicardial coronary artery stenosis was defined as fractional flow reserve (FFR) ≤0.80. Coronary microvascular dysfunction (CMD) was defined as MRR ≤3.0. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure. RESULTS: Among the study group, 172 patients (31.4%) had FFR ≤0.80, and 200 patients (36.6%) had CMD defined by MRR ≤3.0. MRR showed no significant correlation with FFR (R = -0.031; P = 0.469), but it was significantly correlated with the index of microcirculatory resistance (R = -0.353; P < 0.001), N-terminal pro-B-type natriuretic peptide (R = -0.296; P < 0.001), left ventricular filling pressure (E/e' ratio) (R = -0.224; P < 0.001), and diastolic dysfunction grade (P < 0.001). During a median follow-up period of 3.3 years (Q1-Q3: 2.0-4.5 years), MRR was significantly associated with MACE risk (HR: 1.23 per 1-U decrease; 95% CI: 1.12-1.36; P < 0.001). CMD defined by MRR ≤3.0 was associated with an increased MACE risk for both FFR >0.80 (41.0% vs 26.0%; adjusted HR: 1.59; 95% CI: 1.07-2.35; P = 0.021) and FFR ≤0.80 (34.7% vs 14.8%; adjusted HR: 2.32; 95% CI: 1.12-4.82; P = 0.024). CONCLUSIONS: Decreased MRR was associated with the presence of cardiac diastolic dysfunction as well as increased left ventricular filling pressure. The presence of CMD defined by MRR was independently associated with the risk for a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure in patients with stable IHD, irrespective of significant epicardial coronary artery stenosis. (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function [DIAST-CMD]; NCT05058833).

Coronary Artery Disease Assessment via On-Site CT Fractional Flow Reserve in Patients Undergoing Transcatheter Aortic Valve Replacement.

Purpose To examine the clinical feasibility of workstation-based CT fractional flow reserve (CT-FFR) for coronary artery disease (CAD) evaluation during preprocedural planning in patients undergoing transcatheter aortic valve replacement (TAVR). Materials and Methods In this retrospective single-center study, 434 patients scheduled for TAVR between 2018 and 2020 were screened for study inclusion; a relevant proportion of patients (35.0% [152 of 434]) was not suitable for evaluation due to insufficient imaging properties. A total of 112 patients (mean age, 82.1 years ± 6.7 [SD]; 58 [52%] men) were included in the study. Invasive angiography findings, coronary CT angiography results, and Agatston score were acquired and compared with on-site CT-FFR computation for evaluation of CAD and prediction of major adverse cardiovascular events (MACE) within a 24-month follow-up. Results Hemodynamic relevant CAD, as suggested by CT-FFR of 0.80 or less, was found in 41 of 70 (59%) patients with stenosis of 50% or more. MACE occurred in 23 of 112 (20.5%) patients, from which 14 of 23 had stenoses with CT-FFR of 0.80 or less (hazard ratio [HR], 3.33; 95% CI: 1.56, 7.10; P = .002). CT-FFR remained a significant predictor of MACE after inclusion in a multivariable model with relevant covariables (HR, 2.89; 95% CI: 1.22, 6.86; P = .02). An Agatston score of 1000 Agatston units or more (HR, 2.25; 95% CI: 0.98, 5.21; P = .06) and stenoses of 50% or more determined via invasive angiography (HR, 0.94; 95% CI: 0.41, 2.17; P = .88) were not significant predictors of MACE. Conclusion Compared with conventional CAD markers, CT-FFR better predicted adverse outcomes after TAVR. A relevant portion of the screened cohort, however, was not suitable for CT-based CAD evaluation. Keywords: CT, Transcatheter Aortic Valve Implantation/Replacement (TAVI/TAVR), Cardiac, Coronary Arteries, Outcomes Analysis © RSNA, 2024 See also the commentary by Weir-McCall and Pugliese in this issue.

Interaction of AI-Enabled Quantitative Coronary Plaque Volumes on Coronary CT Angiography, FFRCT, and Clinical Outcomes: A Retrospective Analysis of the ADVANCE Registry.

BACKGROUND: Luminal stenosis, computed tomography-derived fractional-flow reserve (FFRCT), and high-risk plaque features on coronary computed tomography angiography are all known to be associated with adverse clinical outcomes. The interactions between these variables, patient outcomes, and quantitative plaque volumes have not been previously described. METHODS: Patients with coronary computed tomography angiography (n=4430) and one-year outcome data from the international ADVANCE (Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care) registry underwent artificial intelligence-enabled quantitative coronary plaque analysis. Optimal cutoffs for coronary total plaque volume and each plaque subtype were derived using receiver-operator characteristic curve analysis. The resulting plaque volumes were adjusted for age, sex, hypertension, smoking status, type 2 diabetes, hyperlipidemia, luminal stenosis, distal FFRCT, and translesional delta-FFRCT. Median plaque volumes and optimal cutoffs for these adjusted variables were compared with major adverse cardiac events, late revascularization, a composite of the two, and cardiovascular death and myocardial infarction. RESULTS: At one year, 55 patients (1.2%) had experienced major adverse cardiac events, and 123 (2.8%) had undergone late revascularization (>90 days). Following adjustment for age, sex, risk factors, stenosis, and FFRCT, total plaque volume above the receiver-operator characteristic curve-derived optimal cutoff (total plaque volume >564 mm3) was associated with the major adverse cardiac event/late revascularization composite (adjusted hazard ratio, 1.515 [95% CI, 1.093-2.099]; P=0.0126), and both components. Total percent atheroma volume greater than the optimal cutoff was associated with both major adverse cardiac event/late revascularization (total percent atheroma volume >24.4%; hazard ratio, 2.046 [95% CI, 1.474-2.839]; P<0.0001) and cardiovascular death/myocardial infarction (total percent atheroma volume >37.17%, hazard ratio, 4.53 [95% CI, 1.943-10.576]; P=0.0005). Calcified, noncalcified, and low-attenuation percentage atheroma volumes above the optimal cutoff were associated with all adverse outcomes, although this relationship was not maintained for cardiovascular death/myocardial infarction in analyses stratified by median plaque volumes. CONCLUSIONS: Analysis of the ADVANCE registry using artificial intelligence-enabled quantitative plaque analysis shows that total plaque volume is associated with one-year adverse clinical events, with incremental predictive value over luminal stenosis or abnormal physiology by FFRCT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02499679.

Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging.

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. A total of 917 coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22 to 50] vs 29 [21 to 41], p <0.001) was significantly higher and QFR (0.92 [0.78 to 0.99] vs 0.97 [0.91 to 0.99], p <0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (area under the curve of receiver operating characteristic [AUCROC] 0.632 [95% confidence interval [CI] 0.589 to 0.674], p <0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669 to 0.784], p <0.0001, p Value for AUCROC comparison = 0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p Value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

Evaluation of models of sequestration flow in coronary arteries-Physiology versus anatomy?

BACKGROUND: Myocardial ischaemia results from insufficient coronary blood flow. Computed virtual fractional flow reserve (vFFR) allows quantification of proportional flow loss without the need for invasive pressure-wire testing. In the current study, we describe a novel, conductivity model of side branch flow, referred to as 'leak'. This leak model is a function of taper and local pressure, the latter of which may change radically when focal disease is present. This builds upon previous techniques, which either ignore side branch flow, or rely purely on anatomical factors. This study aimed to describe a new, conductivity model of side branch flow and compare this with established anatomical models. METHODS AND RESULTS: The novel technique was used to quantify vFFR, distal absolute flow (Qd) and microvascular resistance (CMVR) in 325 idealised 1D models of coronary arteries, modelled from invasive clinical data. Outputs were compared to an established anatomical model of flow. The conductivity model correlated and agreed with the reference model for vFFR (r = 0.895, p < 0.0001; ＋0.02, 95% CI 0.00 to ＋ 0.22), Qd (r = 0.959, p < 0.0001; -5.2 mL/min, 95% CI -52.2 to ＋13.0) and CMVR (r = 0.624, p < 0.0001; ＋50 Woods Units, 95% CI -325 to ＋2549). CONCLUSION: Agreement between the two techniques was closest for vFFR, with greater proportional differences seen for Qd and CMVR. The conductivity function assumes vessel taper was optimised for the healthy state and that CMVR was not affected by local disease. The latter may be addressed with further refinement of the technique or inferred from complementary image data. The conductivity technique may represent a refinement of current techniques for modelling coronary side-branch flow. Further work is needed to validate the technique against invasive clinical data.