Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial.

BACKGROUND AND OBJECTIVES: Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions. METHODS: This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months. RESULTS: The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCA-FFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479). Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294). CONCLUSIONS: The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02673424.

Change in Pd/Pa: Clinical Implications for Predicting Future Cardiac Events at Deferred Coronary Lesions.

BACKGROUND: Cardiovascular events still occur at intermediate stenosis with fractional flow reserve (FFR) ≥0.81, underscoring the additional measure to evaluate this residual risk. A reduction in distal coronary artery pressure/aortic pressure (Pd/Pa) from baseline to hyperemia (ie, change in Pd/Pa) reflects lipidic burden within vessel walls. We hypothesized that this physiological measure might stratify the risk of future cardiac events at deferrable lesions. METHODS: Lesion- (899 intermediate lesions) and patient-based (899 deferred patients) analyses in those with FFR ≥0.81 were conducted to investigate the association between change in Pd/Pa and target lesion failure (TLF) and major adverse cardiac events at 7 years, respectively. RESULTS: The occurrence of TLF and major adverse cardiac events was 6.7% and 13.4%, respectively. The incidence of target lesion-related nonfatal myocardial infarction was 0.6%. Lesions with TLF had a greater change in Pd/Pa (0.11±0.03 versus 0.09±0.04; P=0.002), larger diameter stenosis (51.0±9.2% versus 46.4±12.4%; P=0.048), and smaller FFR (0.84 [0.82-0.87] versus 0.86 [0.83-0.90]; P=0.02). Change in Pd/Pa (per 0.01 increase) predicted TLF (odds ratio, 1.16 [95% CI, 1.05-1.28]; P=0.002) and major adverse cardiac event (odds ratio, 1.08 [95% CI, 1.01-1.16]; P=0.03). Lesions with change in Pd/Pa ≥0.10 had 2.94- and 1.85-fold greater likelihood of TLF (95% CI, 1.30-6.69; P=0.01) and major adverse cardiac event (95% CI, 1.08-3.17; P=0.03), respectively. Lesions with FFR ≤0.85 had a substantially higher likelihood of TLF when there is a change in Pd/Pa ≥0.10 (12.4% versus 2.9%; hazard ratio, 3.60 [95% CI, 1.01-12.80]; P=0.04). However, change in Pd/Pa did not affect TLF risk in lesions with FFR ≥0.86 (3.8% versus 3.7%; hazard ratio, 0.56 [95% CI, 0.06-5.62]; P=0.62). CONCLUSIONS: Despite deferrable FFR values, lesions and patients with a change in Pd/Pa ≥0.10 had higher cardiovascular risk. Change in Pd/Pa might help stratify lesion- and patient-level risks of future cardiac events in those with FFR ≥0.81.

Myocardial Blood Flow by Magnetic Resonance in Patients With Suspected Coronary Stenosis: Comparison to PET and Invasive Physiology.

BACKGROUND: Despite recent guideline recommendations, quantitative perfusion (QP) estimates of myocardial blood flow from cardiac magnetic resonance (CMR) have only been sparsely validated. Furthermore, the additional diagnostic value of utilizing QP in addition to the traditional visual expert interpretation of stress-perfusion CMR remains unknown. The aim was to investigate the correlation between myocardial blood flow measurements estimated by CMR, positron emission tomography, and invasive coronary thermodilution. The second aim is to investigate the diagnostic performance of CMR-QP to identify obstructive coronary artery disease (CAD). METHODS: Prospectively enrolled symptomatic patients with >50% diameter stenosis on computed tomography angiography underwent dual-bolus CMR and positron emission tomography with rest and adenosine-stress myocardial blood flow measurements. Subsequently, an invasive coronary angiography (ICA) with fractional flow reserve and thermodilution-based coronary flow reserve was performed. Obstructive CAD was defined as both anatomically severe (>70% diameter stenosis on quantitative coronary angiography) or hemodynamically obstructive (ICA with fractional flow reserve ≤0.80). RESULTS: About 359 patients completed all investigations. Myocardial blood flow and reserve measurements correlated weakly between estimates from CMR-QP, positron emission tomography, and ICA-coronary flow reserve (r<0.40 for all comparisons). In the diagnosis of anatomically severe CAD, the interpretation of CMR-QP by an expert reader improved the sensitivity in comparison to visual analysis alone (82% versus 88% [P=0.03]) without compromising specificity (77% versus 74% [P=0.28]). In the diagnosis of hemodynamically obstructive CAD, the accuracy was only moderate for a visual expert read and remained unchanged when additional CMR-QP measurements were interpreted. CONCLUSIONS: CMR-QP correlates weakly to myocardial blood flow measurements by other modalities but improves diagnosis of anatomically severe CAD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481712.

Three-Year Outcomes With Fractional Flow Reserve-Guided or Angiography-Guided Multivessel Percutaneous Coronary Intervention for Myocardial Infarction.

BACKGROUND: In patients with multivessel disease with successful primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, the FLOWER-MI trial (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of noninfarct-related artery lesions regarding the 1-year risk of death from any cause, myocardial infarction, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up. METHODS: In this multicenter trial, we randomly assigned patients with ST-segment-elevation myocardial infarction and multivessel disease with successful percutaneous coronary intervention of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577). RESULTS: After 3 years, a primary outcome event occurred in 52 of 498 patients (9.40%) in the FFR-guided group and in 44 of 502 patients (8.17%) in the angiography-guided group (hazard ratio, 1.19 [95% CI, 0.79-1.77]; P=0.4). Death occurred in 22 patients (4.00%) in the FFR-guided group and in 23 (4.32%) in the angiography-guided group (hazard ratio, 0.96 [95% CI, 0.53-1.71]); nonfatal myocardial infarction in 23 (4.13%) and 14 (2.56%), respectively (hazard ratio, 1.63 [95% CI, 0.84-3.16]); and unplanned hospitalization leading to urgent revascularization in 21 (3.83%) and 18 (3.36%; hazard ratio, 1.15 [95% CI, 0.61-2.16]), respectively. CONCLUSIONS: Although event rates in the trial were lower than expected, in patients with ST-segment-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization up to 3 years. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954.

Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

BACKGROUND: The Murray law-based quantitative flow ratio (µFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of µFR and the safety of deferring non-IRA lesions with µFR >0.80 in the setting of AMI. METHODS: µFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of µFR was compared with QFR and FFR. Patients were classified by the non-IRA µFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. RESULTS: µFR and QFR analyses were feasible in 443 patients (552 lesions). µFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (µFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with µFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). CONCLUSIONS: In patients with multivessel AMI, µFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with µFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Prognostic Value of Microvascular Resistance Reserve Measured Immediately After PCI in Stable Coronary Artery Disease.

BACKGROUND: Microvascular resistance reserve (MRR) has been proposed as a specific metric to quantify coronary microvascular function. The long-term prognostic value of MRR measured in stable patients immediately after percutaneous coronary intervention (PCI) is unknown. This study sought to determine the prognostic value of MRR measured immediately after PCI in patients with stable coronary artery disease. METHODS: This study included 502 patients with stable coronary artery disease who underwent elective PCI and coronary physiological measurements, including pressure and flow estimation using a bolus thermodilution method after PCI. MRR was calculated as coronary flow reserve divided by fractional flow reserve times the ratio of mean aortic pressure at rest to that at maximal hyperemia induced by hyperemic agents. An abnormal MRR was defined as ≤2.5. Major adverse cardiac events (MACEs) were defined as a composite of all-cause mortality, any myocardial infarction, and target-vessel revascularization. RESULTS: During a median follow-up of 3.4 years, the cumulative MACE rate was significantly higher in the abnormal MRR group (12.5 versus 8.3 per 100 patient-years; hazard ratio 1.53 [95% CI, 1.10-2.11]; P<0.001). A higher all-cause mortality rate primarily drove this difference. On multivariable analysis, a higher MRR value was independently associated with lower MACE and lower mortality. When comparing 4 subgroups according to MRR and the index of microcirculatory resistance, patients with both abnormal MRR and index of microcirculatory resistance (≥25) had the highest MACE rate. CONCLUSIONS: An abnormal MRR measured immediately after PCI in patients with stable coronary artery disease is an independent predictor of MACE, particularly all-cause mortality.

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.

Evaluation of Instantaneous Wave-Free Ratio and Fractional Flow Reserve in Severe Aortic Valve Stenosis.

BACKGROUND: The optimal functional evaluation of coronary artery stenosis in patients with severe aortic stenosis (AS) has not been established. The objective of the study was to evaluate the instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) in patients with and without severe AS. METHODS: We retrospectively investigated 395 lesions in 293 patients with severe AS and 2257 lesions in 1882 patients without severe AS between 2010 and 2022 from a subgroup of the Interventional Cardiology Research In-Cooperation Society FFR Registry. All patients had FFR values, and iFR was analyzed post hoc using dedicated software only in lesions with adequate resting pressure curves (311 lesions in patients with severe AS and 2257 lesions in patients with nonsevere AS). RESULTS: The incidence of iFR ≤0.89 was 66.6% and 31.8% (P<0.001), while the incidence of FFR ≤0.80 was 45.3% and 43.9% (P=0.60) in the severe AS group and the nonsevere AS group, respectively. In the severe AS group, most lesions (95.2%) with iFR >0.89 had FFR >0.80, while 36.2% of lesions with iFR ≤0.89 had FFR >0.80. During a median follow-up of 2 years, FFR ≤0.80 was significantly associated with deferred lesion failure (adjusted hazard ratio, 2.71 [95% CI, 1.08-6.80]; P=0.034), while iFR ≤0.89 showed no prognostic value (adjusted hazard ratio, 1.31 [95% CI, 0.47-3.60]; P=0.60) in the severe AS group. Lesions with iFR ≤0.89 and FFR >0.80, in particular, were not associated with a higher rate of deferred lesion failure at 3 years compared with lesions with iFR >0.89 (15.4% versus 17.0%; P=0.58). CONCLUSIONS: This study suggested that FFR appears to be less affected by the presence of severe AS and is more associated with prognosis. iFR may overestimate the functional severity of coronary artery disease without prognostic significance, yet it can be useful for excluding significant stenosis in patients with severe AS.

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.

Optical Coherence Tomography-Based Functional Stenosis Assessment: FUSION-A Prospective Multicenter Trial.

BACKGROUND: Intravascular imaging and intracoronary physiology may both be used to guide and optimize percutaneous coronary intervention; however, they are rarely used together. The virtual flow reserve (VFR) is an optical coherence tomography (OCT)-based model of fractional flow reserve (FFR) facilitating the assessment of the physiological significance of coronary lesions. We aimed to validate the VFR assessment of intermediate coronary artery stenoses. METHODS: FUSION (Validation of OCT-Based Functional Diagnosis of Coronary Stenosis) was a multicenter, prospective, observational study comparing OCT-derived VFR to invasive FFR. VFR was mathematically derived from a lumped parameter flow model based on 3-dimensional lumen morphology. Patients undergoing coronary angiography with intermediate angiographic stenosis (40%-90%) requiring physiological assessment were enrolled. Investigational sites were blinded to the VFR analysis, and all OCT and FFR data were reviewed by an independent core laboratory. The coprimary end points were the sensitivity and specificity of VFR against FFR as the reference standard, each of which was tested against prespecified performance goals. RESULTS: After core laboratory review, 266 vessels in 224 patients from 25 US centers were included in the analysis. The mean angiographic diameter stenosis was 65.5%±14.9%, and the mean FFR was 0.83±0.11. Overall accuracy, sensitivity, and specificity of VFR versus FFR using a binary cutoff point of 0.80 were 82.0%, 80.4%, and 82.9%, respectively. The 97.5% lower confidence bound met the prespecified performance goal for sensitivity (71.6% versus 70%; P=0.01) and specificity (76.6% versus 75%; P=0.01). The area under the curve was 0.88 (95% CI, 0.84-0.92; P<0.0001). CONCLUSIONS: OCT-derived VFR demonstrates high sensitivity and specificity for predicting invasive FFR. Integrating high-resolution intravascular imaging with imaging-derived physiology may provide synergistic benefits as an adjunct to percutaneous coronary intervention. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04356027.

Comparison of machine learning-based CT fractional flow reserve with cardiac MR perfusion mapping for ischemia diagnosis in stable coronary artery disease.

OBJECTIVES: To compare the diagnostic performance of machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and cardiac magnetic resonance (MR) perfusion mapping for functional assessment of coronary stenosis. METHODS: Between October 2020 and March 2022, consecutive participants with stable coronary artery disease (CAD) were prospectively enrolled and underwent coronary CTA, cardiac MR, and invasive fractional flow reserve (FFR) within 2 weeks. Cardiac MR perfusion analysis was quantified by stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). Hemodynamically significant stenosis was defined as FFR ≤ 0.8 or > 90% stenosis on invasive coronary angiography (ICA). The diagnostic performance of CT-FFR, MBF, and MPR was compared, using invasive FFR as a reference. RESULTS: The study protocol was completed in 110 participants (mean age, 62 years ± 8; 73 men), and hemodynamically significant stenosis was detected in 36 (33%). Among the quantitative perfusion indices, MPR had the largest area under receiver operating characteristic curve (AUC) (0.90) for identifying hemodynamically significant stenosis, which is in comparison with ML-based CT-FFR on the vessel level (AUC 0.89, p = 0.71), with comparable sensitivity (89% vs 79%, p = 0.20), specificity (87% vs 84%, p = 0.48), and accuracy (88% vs 83%, p = 0.24). However, MPR outperformed ML-based CT-FFR on the patient level (AUC 0.96 vs 0.86, p = 0.03), with improved specificity (95% vs 82%, p = 0.01) and accuracy (95% vs 81%, p < 0.01). CONCLUSION: ML-based CT-FFR and quantitative cardiac MR showed comparable diagnostic performance in detecting vessel-specific hemodynamically significant stenosis, whereas quantitative perfusion mapping had a favorable performance in per-patient analysis. CLINICAL RELEVANCE STATEMENT: ML-based CT-FFR and MPR derived from cardiac MR performed well in diagnosing vessel-specific hemodynamically significant stenosis, both of which showed no statistical discrepancy with each other. KEY POINTS: • Both machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and quantitative perfusion cardiac MR performed well in the detection of hemodynamically significant stenosis. • Compared with stress myocardial blood flow (MBF) from quantitative perfusion cardiac MR, myocardial perfusion reserve (MPR) provided higher diagnostic performance for detecting hemodynamically significant coronary artery stenosis. • ML-based CT-FFR and MPR from quantitative cardiac MR perfusion yielded similar diagnostic performance in assessing vessel-specific hemodynamically significant stenosis, whereas MPR had a favorable performance in per-patient analysis.

Advanced CT measures of coronary artery disease with intermediate stenosis in patients with severe aortic valve stenosis.

BACKGROUND: Coronary artery disease (CAD) and severe aortic valve stenosis (AS) frequently coexist. While pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) allows to rule out obstructive CAD, interpreting hemodynamic significance of intermediate stenoses is challenging. This study investigates the incremental value of CT-derived fractional flow reserve (CT-FFR), quantitative coronary plaque characteristics (e.g., stenosis degree, plaque volume, and composition), and peri-coronary adipose tissue (PCAT) density to detect hemodynamically significant lesions among those with AS and CAD. MATERIALS AND METHODS: We included patients with severe AS and intermediate coronary lesions (20-80% diameter stenosis) who underwent pre-TAVR CTA and invasive coronary angiogram (ICA) with resting full-cycle ratio (RFR) assessment between 08/16 and 04/22. CTA image analysis included assessment of CT-FFR, quantitative coronary plaque analysis, and PCAT density. Coronary lesions with RFR ≤ 0.89 indicated hemodynamic significance as reference standard. RESULTS: Overall, 87 patients (age 77.9 ± 7.4 years, 38% female) with 95 intermediate coronary artery lesions were included. CT-FFR showed good discriminatory capacity (area under receiver operator curve (AUC) = 0.89, 95% confidence interval (CI) 0.81-0.96, p < 0.001) to identify hemodynamically significant lesions, superior to anatomical assessment, plaque morphology, and PCAT density. Plaque composition and PCAT density did not differ between lesions with and without hemodynamic significance. Univariable and multivariable analyses revealed CT-FFR as the only predictor for functionally significant lesions (odds ratio 1.28 (95% CI 1.17-1.43), p < 0.001). Overall, CT-FFR ≤ 0.80 showed diagnostic accuracy, sensitivity, and specificity of 88.4% (95%CI 80.2-94.1), 78.5% (95%CI 63.2-89.7), and 96.2% (95%CI 87.0-99.5), respectively. CONCLUSION: CT-FFR was superior to CT anatomical, plaque morphology, and PCAT assessment to detect functionally significant stenoses in patients with severe AS. CLINICAL RELEVANCE STATEMENT: CT-derived fractional flow reserve in patients with severe aortic valve stenosis may be a useful tool for non-invasive hemodynamic assessment of intermediate coronary lesions, while CT anatomical, plaque morphology, and peri-coronary adipose tissue assessment have no incremental or additional benefit. These findings might help to reduce pre-transcatheter aortic valve replacement invasive coronary angiogram. KEY POINTS: • Interpreting the hemodynamic significance of intermediate coronary stenoses is challenging in pre-transcatheter aortic valve replacement CT. • CT-derived fractional flow reserve (CT-FFR) has a good discriminatory capacity in the identification of hemodynamically significant coronary lesions. • CT-derived anatomical, plaque morphology, and peri-coronary adipose tissue assessment did not improve the diagnostic capability of CT-FFR in the hemodynamic assessment of intermediate coronary stenoses.

A multicenter study on the prognostic value of SPECT myocardial blood flow quantitative technique in patients with intermediate stenoses of coronary arteries / 中华核医学与分子影像杂志

Objective:To investigate the prognostic value of myocardial flow reserve (MFR) measured by SPECT myocardial blood flow (MBF) quantitative technique in patients with intermediate stenoses of coronary arteries.Methods:From September 2019 to May 2021, patients with intermediate stenoses (50% to 80%) identified by invasive coronary angiography in Fuwai Hospital, Chinese Academy of Medical Sciences, Fuwai Center China Cardiovascular Hospital, and TEDA International Cardiovascular Hospital were prospectively included. All patients underwent a one-day rest/stress SPECT myocardial perfusion imaging (MPI) and SPECT MBF quantification. The radioactivity distribution of each segment of the MPI bullseye polar maps were obtained according to the standard 5-point method to obtain the summed stress score (SSS) and the summed difference score (SDS) to determine the existence of abnormality. ROC curve analysis was used to obtain the optimal prognostic cut-off value for MFR. The primary endpoint was defined as cardiovascular endpoint events. Survival and prognostic analyses were conducted by Kaplan-Meier method and Cox proportional hazard models. The difference of AUCs was analyzed by Delong test.Results:A total of 314 patients (194 males, 120 females; age (59.4±8.6) years) were enrolled. Over a median follow-up duration of 754 (range: 628-914) d, 54 patients had endpoint events. ROC curve showed that the prediction ability of MFR was significantly better than that of conventional MPI (AUCs: 0.713 and 0.512; z=3.76, P<0.001). The optimal prognostic cut-off value for MFR to predict endpoint events in patients with intermediate stenoses was 2.04. Cox multivariate analysis showed that MFR (hazard ratio ( HR)=0.434, 95% CI: 0.282-0.669, P<0.001) was an independent predictor of endpoint events in patients with intermediate stenoses. Kaplan-Meier survival analysis showed that the prevalence of endpoint events in patients with MFR≤2.04 was significantly higher than that in patients with MFR>2.04 (25.4%(43/169) vs 7.6%(11/145); χ2=21.27, P<0.001). Conclusion:The MFR measured by SPECT MBF quantitative technique has an independent predictive value for cardiovascular endpoint events in patients with intermediate stenoses.

Fully automated pixel-wise quantitative CMR-myocardial perfusion with CMR-coronary angiography to detect hemodynamically significant coronary artery disease.

OBJECTIVES: We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). METHODS: A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. RESULTS: Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). CONCLUSIONS: Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. KEY POINTS: • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.

Real world impact of added FFR-CT to coronary CT angiography on clinical decision-making and patient prognosis - IMPACT FFR study.

OBJECTIVES: The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). METHODS: This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan-Meier curves were used to visualize the occurrence of safety outcomes over time. RESULTS: A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p < 0.001 for all three options). The revascularization rate after ICA was similar between groups (p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). CONCLUSION: Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. KEY POINTS: • Previous studies have shown that computed tomography-derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.

Validity and Diagnostic Performance of Computing Fractional Flow Reserve From 2-Dimensional Coronary Angiography Images.

BACKGROUND: Measurement of fractional flow reserve (FFR) is the gold standard for determining the physiologic significance of coronary artery stenosis, but newer software programs can calculate the FFR from 2-dimensional angiography images. METHODS: A retrospective analysis was conducted using the records of patients with intermediate coronary stenoses who had undergone adenosine FFR (aFFR). To calculate the computed FFR, a software program used simulated coronary blood flow using computational geometry constructed using at least 2 patient-specific angiographic images. Two cardiologists reviewed the angiograms and determined the computational FFR independently. Intraobserver variability was measured using κ analysis and the intraclass correlation coefficient. The correlation coefficient and Bland-Altman plots were used to assess the agreement between the calculated FFR and the aFFR. RESULTS: A total of 146 patients were included, with 95 men and 51 women, with a mean (SD) age of 61.1 (9.5) y. The mean (SD) aFFR was 0.847 (0.072), and 41 patients (27.0%) had an aFFR of 0.80 or less. There was a strong intraobserver correlation between the computational FFRs (r = 0.808; P < .001; κ = 0.806; P < .001). There was also a strong correlation between aFFR and computational FFR (r = 0.820; P < .001) and good agreement on the Bland-Altman plot. The computational FFR had a high sensitivity (95.1%) and specificity (90.1%) for detecting an aFFR of 0.80 or less. CONCLUSION: A novel software program provides a feasible method of calculating FFR from coronary angiography images without resorting to pharmacologically induced hyperemia.

Relationship between coronary flow reserve by CZT SPECT and invasive coronary fractional flow reserve and its potential clinical value / 中华核医学与分子影像杂志

Objective:To evaluate the relationship between regional coronary flow reserve (CFR) obtained from cadmium-zinc-telluride SPECT(CZT SPECT) myocardial functional perfusion imaging (MFPI) and invasive fractional flow reserve (FFR) measured during coronary angiography (CAG) and its clinical value in guiding coronary interventions.Methods:Forty-two patients (30 males, 12 females, age (63.3±9.8) years) who completed CZT SPECT MFPI in the First Affiliated Hospital of Nanjing Medical University from June 2022 to September 2022 and underwent CAG within 3 months were included retrospectively. The concordance of CFR and FFR for diagnosing myocardial ischemia (CFR<2.0 and FFR<0.8) was calculated at the vascular level. The diagnostic efficacy of coronary stenosis≥70% for decreased myocardial blood flow (CFR<2.0) was calculated. Kappa test was used to analyze the data. Results:A total of 126 major coronary arteries were identified in 42 patients, of which 30(23.8%) had a CFR<2.0 by CZT SPECT and 33(26.2%) had stenosis≥70% in CAG. A total of 32 coronary vessels were performed with MFPI CFR and FFR measurements, of which 6 were both decreased and 21 were both normal, so the concordance rate was 84.4%(27/32)( Kappa=0.612, P<0.001). Among 33 coronary vessels with stenosis≥70%, 13 were with CFR≥2.0. Among 30 coronary vessels with CFR<2.0, 10 were with stenosis<70%. When using stenosis≥70% to diagnose CFR decreasing, the sensitivity was 66.7%(20/30), specificity was 86.5%(83/96), positive predictive value was 60.6%(20/33), negative predictive value was 89.2%(83/93), and accuracy was 81.7%(103/126). Conclusions:The concordance between CFR and FFR for the diagnosis of myocardial ischemia is good. Nearly 1/3 of the coronary arteries with decreased CFR have stenosis<70%, whereas nearly 40% of the coronary arteries with stenosis≥70% are not result in myocardial ischemia. Regional CFR determined by CZT SPECT may have potentially significant clinical value in the diagnosis of coronary artery disease and decision-making of coronary intervention.

Value of SPECT myocardial perfusion imaging and coronary flow reserve combined with coronary artery calcium score in the diagnosis of obstructive coronary artery disease / 中华核医学与分子影像杂志

Objective:To study the value of myocardial perfusion imaging (MPI) and coronary flow reserve (CFR) combined with coronary artery calcium score (CACS) in the diagnosis of obstructive coronary artery disease (CAD).Methods:From January 2019 to December 2020, 96 confirmed or suspective CAD patients (65 males, 31 females; age: 30-81 years) who completed rest/stress MPI, CFR and CACS defection in Fuwai Central China Cardiovascular Hospital were retrospectively analyzed. Coronary angiography (CAG) was used as the diagnostic standard to calculate the sensitivity and accuracy of MPI, CFR and MPI/CFR combined with CACS in the diagnosis of CAD. The χ2 test was used to compare the diagnostic efficiency of different methods. Results:The diagnostic sensitivity of MPI was 76.06%(54/71), and the accuracy was 75.00%(72/96), while the sensitivity increased to 97.18%(69/71; χ2=13.67, P<0.001) and the accuracy increased to 87.50%(84/96; χ2=4.92, P=0.020) with significant differences after combined with CACS. The sensitivity and accuracy of CFR were 91.55%(65/71)and 87.50%(84/96), which increased to 97.18%(69/71; χ2=2.12, P=0.137) and 89.58%(86/96; χ2=0.21, P=0.411) with no significant differences after combined with CACS. The sensitivity of MPI in the diagnosis of three-vessel CAD was 70.00%(21/30), which increased to 100%(30/30; χ2=7.75, P=0.004) after combined with CACS; while the sensitivity of MPI combined with CACS in the diagnosis of single-vessel and double-vessel CAD were not significantly improved ( χ2 values: 3.29, 1.51, P values: 0.114, 0.416). Conclusion:The combination of MPI and CACS can significantly improve the diagnostic efficiency of CAD, contributed by the improvement of the diagnostic sensitivity in three-vessel disease; whereas the diagnostic efficiency of CFR for CAD is not significantly improved after combined with CACS.

Quantitative assessment of right ventricular myocardial blood flow with SPECT in pulmonary hypertension animal models / 中华核医学与分子影像杂志

Objective:To explore the changes of right ventricular myocardial perfusion in pulmonary arterial hypertension (PAH) pig models with a quantitative analysis technique based on dynamic SPECT myocardial perfusion imaging, and analyze the relationship between myocardial blood flow, hemodynamics and right ventricular function.Methods:Eleven Chinese miniature pigs (all males, 6-8 months old) weighing 25-30 kg were selected. The PAH models were established by ligating the main pulmonary artery and embolizing the right lower pulmonary artery. After the models were established, dynamic myocardial perfusion imaging with one-day resting/adenosine stress 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT was performed, and the quantitative parameters of left and right ventricles were obtained, including stress myocardial blood flow (SMBF), rest myocardial blood flow (RMBF) and myocardial flow reserve (MFR: the ratio of stress to rest myocardial blood flow). Right heart catheterization was performed to evaluate the mean pulmonary arterial pressure (mPAP), and the right heart function index tricuspid annular plane systolic excursion (TAPSE) was measured by transthoracic echocardiography. According to TAPSE, animals were divided into right heart function preserved group ( n=5, TAPSE≥17 mm) and right heart dysfunction group ( n=4, TAPSE<17 mm). Pearson correlation analysis and the independent-sample t test were used for data analysis. Results:Nine experimental pig models were established with increased mPAP of (38.1 ± 11.6 ) mmHg (1 mmHg=0.133 kPa). Myocardial perfusion imaging showed clear radiotracer uptake in the right heart and myocardial hypertrophy. There was a significant positive correlation between right ventricular myocardial RMBF ((0.71±0.13) ml·min -1·g -1) and mPAP ( r=0.94, P< 0.001). The SMBF in the decreased right ventricular function group was significantly lower than that in the preserved right ventricular function group ((1.66±0.35) vs (2.24±0.30) ml·min -1·g -1;t=2.68, P=0.032). Conclusion:SPECT myocardial blood flow quantification can be used to evaluate the right ventricular myocardial blood flow in pig models of PAH.

Diagnostic value of subtraction based coronary CT fractional flow reserve for calcification-related hemodynamically significant stenosis / 中华老年心脑血管病杂志

Objective To investigate the diagnostic value of subtraction technique based coronary CT fractional flow reserve(CT-FFR)in detecting calcification-related hemodynamically signifi-cant stenosis.Methods A total of 22 patients(42 lesions)with known or suspected coronary ar-tery disease admitted in our hospital from March 2020 to March 2022 were recruited prospectively.Subtraction coronary computed tomography angiography(CCTA)was provided for the patients who were scheduled for invasive coronary angiography(ICA).CCTA image reconstruction algo-rithm was based on hybrid iterative reconstruction.FFR was detected in the patients with moder-ate-to-severe coronary stenosis caused by calcification.A FFR value ≤0.80 was defined as signifi-cant hemodynamic stenosis.With FFR as the reference standard,the diagnostic performance of CCTA,subtraction CCTA,CT-FFR,and subtraction CT-FFR in detecting calcification-related hemodynamically significant stenosis were evaluated.Results Lesion-based analysis showed that subtraction CT-FFR yielded the highest diagnostic performance among four groups of images,with a sensitivity,specificity,positive predictive value,negative predictive value and accuracy of 100.0％,62.1％,54.2％,100.0％and 73.8％,respectively,and an AUC value of 0.83.Patient-based analysis showed subtraction CT-FFR performed best in diagnostic performance,with a sensitivity,specificity,positive predictive value,negative predictive value and accuracy of 100.0％,33.3％,55.6％,100.0％and 63.6％,respectively,and an AUC value of 0.77.Conclusion Subtraction CT-FFR has the highest diagnostic performance for calcification-related hemodynamically signifi-cant stenosis,which expands the application of CT-FFR in severe calcification lesions,and is of good value in clinical application.