An Overview of Computational Coronary Physiology Technologies Based on Medical Imaging and Artificial Intelligence.

This article reviews four new technologies for assessment of coronary hemodynamics based on medical imaging and artificial intelligence, including quantitative flow ratio (QFR), optical flow ratio (OFR), computational fractional flow reserve (CT-FFR) and artificial intelligence (AI)-based instantaneous wave-free ratio (iFR). These technologies use medical imaging such as coronary angiography, computed tomography angiography (CTA), and optical coherence tomography (OCT), to reconstruct three-dimensional vascular models through artificial intelligence algorithms, simulate and calculate hemodynamic parameters in the coronary arteries, and achieve non-invasive and rapid assessment of the functional significance of coronary stenosis. This article details the working principles, advantages such as non-invasiveness, efficiency, accuracy, limitations such as image dependency, and assumption restrictions, of each technology. It also compares and analyzes the image dependency, calculation accuracy, calculation speed, and operation simplicity, of the four technologies. The results show that these technologies are highly consistent with the traditional invasive wire method, and shows distinct advantages in terms of accuracy, reliability, convenience and cost-effectiveness, but there are also factors that affect accuracy. The results of this review demonstrates that AI-based iFR technology is currently one of the most promising technologies. The main challenges and directions for future development are also discussed. These technologies bring new ideas for the non-invasive assessment of coronary artery disease, and are expected to promote the technological progress in this field.

Instantaneous wave free ratio vs. fractional flow reserve and 5-year mortality: iFR SWEDEHEART and DEFINE FLAIR.

BACKGROUND AND AIMS: Guidelines recommend revascularization of intermediate epicardial artery stenosis to be guided by evidence of ischaemia. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are equally recommended. Individual 5-year results of two major randomized trials comparing FFR with iFR-guided revascularization suggested increased all-cause mortality following iFR-guided revascularization. The aim of this study was a study-level meta-analysis of the 5-year outcome data in iFR-SWEDEHEART (NCT02166736) and DEFINE-FLAIR (NCT02053038). METHODS: Composite of major adverse cardiovascular events (MACE) and its individual components [all-cause death, myocardial infarction (MI), and unplanned revascularisation] were analysed. Raw Kaplan-Meier estimates, numbers at risk, and number of events were extracted at 5-year follow-up and analysed using the ipdfc package (Stata version 18, StataCorp, College Station, TX, USA). RESULTS: In total, iFR and FFR-guided revascularization was performed in 2254 and 2257 patients, respectively. Revascularization was more often deferred in the iFR group [n = 1128 (50.0%)] vs. the FFR group [n = 1021 (45.2%); P = .001]. In the iFR-guided group, the number of deaths, MACE, unplanned revascularization, and MI was 188 (8.3%), 484 (21.5%), 235 (10.4%), and 123 (5.5%) vs. 143 (6.3%), 420 (18.6%), 241 (10.7%), and 123 (5.4%) in the FFR group. Hazard ratio [95% confidence interval (CI)] estimates for MACE were 1.18 [1.04; 1.34], all-cause mortality 1.34 [1.08; 1.67], unplanned revascularization 0.99 [0.83; 1.19], and MI 1.02 [0.80; 1.32]. CONCLUSIONS: Five-year all-cause mortality and MACE rates were increased with revascularization guided by iFR compared to FFR. Rates of unplanned revascularization and MI were equal in the two groups.

Comparison of quantitative flow ratio with instantaneous wave-free ratio and resting full-cycle ratio during daily routine in the catheterization laboratory.

BACKGROUND: Quantitative flow ratio (QFR) is a novel, software-based method to evaluate the physiology of coronary lesions. The aim of this study was to compare QFR with the established invasive measurements of coronary blood flow using instantaneous wave-free ratio (iFR) or resting full-cycle ratio (RFR) in daily cathlab routine. METHODS: 102 patients with stable coronary artery disease and a coronary stenosis of 40%-90% were simultaneously assessed with QFR and iFR or RFR. QFR-computation was performed by two certified experts using the appropriate software (QAngio XA 3D 3.2). RESULTS: QFR showed a significant correlation (r = 0.75, p < 0.001) to iFR and RFR. The area under the receiver curve for all measurements was 0.93 (95% confidence interval, 0.87-0.98) for QFR compared to iFR or RFR. QFR based assessment required less time with a median of 501 s (IQR 421-659 s) compared to iFR or RFR which required a median of 734 s to obtain the result (IQR 512-967 s; p < 0.001). The median use of contrast medium was similar with 21 mL (IQR 16-30 mL) for the QFR-based and 22 mL (IQR 15-35 mL) for the iFR- or RFR-based diagnostic. QFR diagnostic required less radiation. The median dose area product for QFR was 307cGycm2 (IQR 151-429 cGycm2 ) compared to 599 cGycm2 (IQR 345-1082 cGycm2 ) for iFR or RFR, p < 0.001. CONCLUSION: QFR measurements of coronary artery blood flow correlate with iFR or RFR measurements and are associated with shorter procedure times and reduced radiation dose.

Instantaneous wave free ratio value impact on left internal mammary artery graft patency.

OBJECTIVES: To assess whether instantaneous wave - free ratio (iFR) value is associated with left internal mammary artery (LIMA) graft failure at 12 months follow-up post coronary artery bypass graft (CABG). BACKGROUND: Data suggests bypass to a non-significant left anterior descending artery (LAD) lesion due to visual over-estimation may lead to LIMA graft failure. Implementing iFR may result in better arterial graft patency. METHODS: In iCABG (iFR guided CABG) study patients planned to undergo an isolated CABG procedure was prospectively enrolled and iFR was performed for LAD. Coronary computed tomography angiography was performed at 2 and 12 months follow-up. The primary endpoint of this study was to determine the rate of LIMA graft occlusion or hypoperfusion at 2 and 12-months follow-up. We considered a composite secondary endpoint of Major adverse cardiovascular and cerebrovascular event (MACCE) as a secondary outcome. RESULTS: In total 69 patients were included with no differences regarding age, sex and risk factors. At 2 months, 50 of LIMAs with pre-CABG iFR median 0.855 (0.785 - 0.892) were patent. Hypoperfusion was found in 8 LIMAs (median iFR 0.88 (0.842 - 0.90)). While, 7 LIMAs (median iFR 0.91 (0.88 - 0.96)) were occluded (p = 0.04). At 12 months, when iFR of LAD was >0.85: just 12 (31.6% out of all patent LIMAS) grafts were patent and 24 (100.0% out of all hypoperfused/occluded) grafts were hypoperfused or occluded (p < 0.001). In terms of MACCE, no difference (p = 1.0) was found between all 3 groups divided according to iFR value. CONCLUSIONS: Instantaneous wave - free ratio value above 0.85 in LAD is a powerful tool predicting LIMA graft failure at 1-year follow up period.

The Impact of Age on the Physiological Assessment of Borderline Coronary Stenoses.

Background and Objectives: Coronary angiography is the gold standard for diagnosing coronary artery disease (CAD). In the case of borderline changes, patients require further diagnosis through ischemia assessment via one of the recommended methods of invasive evaluation. This study aimed to assess whether clinical factors influence the risk of a positive result in invasive myocardial ischemia assessment and if these potential factors change with the patient's age and the consistency of ischemia assessment. Materials and Methods: Data were collected retrospectively on all consecutive patients hospitalized in the University Hospital in Krakow between 2020 and 2021, on whom physiological assessments of coronary circulation were performed. Patients were divided into two groups: patients aged 60 or younger and patients older than 60. Results: Despite the older patients having more risk factors for CAD, their physiological assessment results of borderline lesions were similar to those of the younger patients. Positive fractional flow reserve (FFR) assessments were obtained from almost 50% of vessels. In the younger patients, cigarette use and type 2 diabetes mellitus increased the risk of a positive FFR result by 3.5 and 2.5 times, respectively. In the older patients, male gender and peripheral vascular disease significantly increased the risk of a positive FFR by 2.5 and 2 times, respectively. Conclusions: Clinical characteristics of patients undergoing physiological assessment of borderline coronary stenosis varied significantly by age. Refining the definition of borderline lesions to include age, gender, and other factors may improve the identification of patients who would benefit from physiological assessment and coronary revascularization.

Culprit versus Complete Revascularization during the Initial Intervention in Patients with Acute Coronary Syndrome Using a Virtual Treatment Planning Tool: Results of a Single-Center Pilot Study.

Background and Objectives: The revascularization strategy for percutaneous coronary intervention (PCI) in patients with multivessel (MV) acute coronary syndrome (ACS) remains controversial. Certain gaps in the evidence are related to the optimal timing of non-culprit lesion revascularization and the utility of instantaneous wave-free ratio (iFR) in the management of MV ACS intervention. The major benefits of iFR utilization in MV ACS patients in one-stage complete revascularization are: (1) the possibility to virtually plan the PCI, both the location and the extension of the necessary stenting to achieve the prespecified final hemodynamic result; (2) the opportunity to validate the final hemodynamic result of the PCI, both in culprit artery and all non-culprit arteries and (3) the value of obliviating the uncomfortable, costly, time consuming and sometimes deleterious effects from Adenosine, as there is no requirement for administration. Thus, iFR use fosters the achievement of physiologically appropriate complete revascularization in MV ACS patients during acute hospitalization. Materials and Methods: This pilot study was aimed to test the feasibility of a randomized trial research protocol as well as to assess patient safety signals of co-registration iFR-guided one-stage complete revascularization compared with that of standard staged angiography-guided PCI in de novo patients with MV ACS. This was a single-center, prospective, randomized, open-label clinical trial consecutively screening patients with ACS for MV disease. The intervention strategy of interest was iFR-guided physiologically complete one-stage revascularization, in which the virtual PCI planning of non-culprit lesions and the intervention itself were performed in one stage directly following treatment of the culprit lesion and other critical stenosis of more than ninety percent. Seventeen patients were recruited and completed the 3-month follow-up. Results: Index PCI duration was significantly longer while the volume of contrast media delivered in index PCI was significantly greater in the iFR-guided group than in the angiography-guided group (119.4 ± 40.7 vs. 47 ± 15.5 min, p = 0.004; and 360 ± 97.9 vs. 192.5 ± 52.8 mL, p = 0.003). There were no significant differences in PCI-related major adverse cardiovascular events (MACE) between the groups during acute hospitalization and at 3-months follow-up. One-stage iFR-guided PCI requires fewer PCI attempts until complete revascularization than does angiography-guided staged PCI. Conclusions: Complete revascularization with the routine use of the virtual planning tool in one-stage iFR-guided PCI is a feasible practical strategy in an everyday Cath lab environment following the protocol designed for the study. No statistically significant safety signals were documented in the number of PCI related MACE during the 3-month follow-up.

Impact of stenosis resistance and coronary flow capacity on fractional flow reserve and instantaneous wave-free ratio discordance: a combined analysis of DEFINE-FLOW and IDEAL.

BACKGROUND: The pressure-derived parameters fractional flow reserve (FFR) and the emerging instantaneous wave-free ratio (iFR) are the most widely applied invasive coronary physiology indices to guide revascularisation. However, approximately 15-20% of intermediate stenoses show discordant FFR and iFR, and therapeutical consensus is lacking. AIMS: We sought to associate hyperaemic stenosis resistance index, coronary flow reserve (CFR) and coronary flow capacity (CFC) to FFR/iFR discordance. METHODS: We assessed pressure and flow measurements of 647 intermediate lesions (593 patients) of two multi-centre international studies. RESULTS: FFR and iFR were discordant in 15% of all lesions (97 out of 647). FFR+/iFR- lesions had similar hyperaemic average peak velocity (hAPV), CFR and CFC as FFR-/iFR- lesions, whereas FFR-/iFR+ lesions had similar hAPV, CFR and CFC as FFR+/iFR+ lesions (p > 0.05 for all). FFR+/iFR- lesions were associated with lower baseline stenosis resistance, but not hyperaemic stenosis resistance, compared with FFR-/iFR+ lesions (p < 0.001). CONCLUSIONS: Discordance with FFR+/iFR- is characterised by maximal flow values, CFR, and CFC patterns similar to FFR-/iFR- concordance that justifies conservative therapy. Discordance with FFR-/iFR+ on the other hand, is characterised by low flow values, CFR, and CFC patterns similar to iFR+/FFR+ concordance that may benefit from percutaneous coronary intervention.

Pathophysiological factors contributing to fractional flow reserve and instantaneous wave-free ratio discordance.

The diagnostic accuracy and clinical benefits of instantaneous wave-free ratio (iFR) compared to fractional flow reserve (FFR) have been well-established in the literature. Despite the advantages of non-hyperemic pressure indices, approximately 20% of iFR and FFR measurements are discordant. Efforts have been made to establish the mechanisms as well as identify causative factors that lead to such a discordance. Recent studies have identified many factors of discordance including sex differences, age differences, bradycardia, coronary artery stenosis location, elevated left ventricular end-diastolic pressure, and diastolic dysfunction. Additionally, discordance secondary to coronary artery microcirculation dysfunction, as seen in diabetics and patients on hemodialysis, has sparked interest amongst experts. As more interventional cardiologists are utilizing iFR independent of FFR to guide percutaneous coronary intervention an emphasis has been placed on identifying factors leading to discordance. The aim of this review is to outline recent studies that have identified factors of FFR and iFR discordance.

Instantaneous wave-free ratio for guiding treatment of nonculprit lesions in patients with acute coronary syndrome: A retrospective study.

BACKGROUND: The aim of this study was to analyze the feasibility of a physiological coronary evaluation with the instantaneous wave-free ratio (iFR) of nonculprit lesions in patients with acute coronary syndrome (ACS) successfully revascularized. METHODS: A multicenter registry including patients of four high-volume PCI centers with ACS and underwent successful revascularization of the culprit vessel and had other nonculprit lesions that were physiologically evaluated with the iFR between January 2017 and December 2019. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction, probable or definitive stent thrombosis and new revascularization (MACEs). RESULTS: A total of 356 patients with 472 nonculprit lesions were included. The mean age was 66 ± 11 years. The clinical presentation was ACS without persistent ST-segment elevation (NSTE-ACS) in 235 patients (66%) and ST-segment elevation myocardial infarction (STEMI) in 121 patients (34%). After a median follow-up period of 21 (14-30) months, the primary endpoint occurred in 32 patients (9%). There were no differences in outcomes regarding clinical presentation (NSTEMI vs. NSTE-ACS, 9.1 vs. 8.9%, padj  = 0.570) or iFR induced treatment strategy (patients with all lesions revascularized vs. patients with at least one lesion with an iFR > 0.89 deferred for revascularization, 10.5 vs. 8.4%, padj  = 0.476). CONCLUSIONS: The use of the iFR to guide percutaneous coronary intervention decision making in nonculprit lesions seems to be feasible, with an acceptable percentage of MACEs at the mid-term follow-up. Patients with deferred revascularization of lesions without physiological significance and patients undergoing complete revascularization had a similar risk of MACEs.

Coronary angiography-derived contrast fractional flow reserve.

BACKGROUND: Based on coronary angiography and mean aortic pressure, a specially designed computational flow dynamics (CFD) method is proposed to determine contrast fractional flow reserve (cFFR) without using invasive pressure wire. This substudy assessed diagnostic performance of coronary angiography-derived cFFR in catheterization laboratory, based on a previous multicenter trial for online assessment of coronary angiography-derived FFR (caFFR). METHODS: Patients with diagnosis of stable angina pectoris or unstable angina pectoris were enrolled in six centers. Wire-based FFR was measured in coronary arteries with 30-90% diameter stenosis. Offline angiography-derived cFFR was computed in blinded fashion against the wire-based FFR and caFFR at an independent core laboratory. RESULTS: A total of 330 patients were enrolled to fulfill inclusion/exclusion criteria from June 26 to December 18, 2018. Offline angiography-derived cFFR and wire-based FFR results were compared in 328 interrogated vessels. The statistical analysis showed the highest diagnostic accuracy of 89.0 and 86.6% for angiography-derived cFFR with a cutoff value of 0.94 and 0.93 against the wire-based FFR with a cutoff value of 0.80 and 0.75, respectively. The corresponding sensitivity and specificity were 92.2 and 87.3% for the cutoff value of 0.94 and 80.0 and 88.4% for the cutoff value of 0.93, which are similar to those against the caFFR. The receiver-operating curve has area under the curve of 0.951 and 0.972 for the wire-based FFR with the cutoff value of 0.80 and 0.75, respectively. CONCLUSIONS: Coronary angiography-derived cFFR showed higher accuracy, sensitivity, and specificity against wired-based FFR and caFFR. Hence, angiography-derived cFFR could enhance the hemodynamic assessment of coronary lesions.

Instantaneous wave-free ratio-guided revascularization of nonculprit lesions in STEMI patients with multivessel coronary disease: The WAVE registry.

BACKGROUND: Complete revascularization (CR) of nonculprit lesions (NCL) is strongly recommended in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), but no definitive evidence is available regarding which diagnostic strategy should be preferred. Instantaneous wave-free ratio (iFR) has never been investigated in this setting. We aimed to describe clinical outcomes of a cohort of patients undergoing iFR-guided CR. METHODS: Following primary percutaneous coronary intervention (PCI), consecutive patients with STEMI and intermediate NCL were enrolled and destinated to an iFR-guided CR. NCL with iFR ≤ 0.89 underwent PCI while NCL with iFR > 0.89 were deferred. The primary endpoint was NC target lesion failure (NC-TLF) and the secondary endpoint was major adverse cardiovascular events (MACE), at 1-year follow-up. RESULTS: Overall, 209 patients were enrolled (ischemic iFR = 83; nonischemic iFR = 126). Patients with ischemic iFR showed a higher prevalence of traditional cardiovascular risk factors and angiographically determined three-vessel disease. In the entire cohort, NC-TLF and MACE occurred in 6.7% and 10.5% of patients, respectively. Compared to the deferred group, patients with ischemic iFR experienced significantly higher rates of both NC-TLF (3.2% vs. 12.1%; p = 0.021) and MACE (7.1% vs. 16.9%; p = 0.041). These results were mostly driven by increased rates of NC-TLF PCI and further revascularizations in this latter group, while no differences were evident in terms of nonfatal myocardial infarction or death. At multivariable analysis, the strongest predictor of MACE was symptom onset to balloon time (HR = 1.17 [95% CI: 1.04-1.31], p = 0.008). CONCLUSIONS: In our study enrolling STEMI patients with MVD, iFR assessment was feasible and safe. PCI-deferring according to iFR evaluation of NCL was associated with low rates of adverse events. Further randomized studies are needed to investigate the effectiveness of iFR-guided revascularization compared to current practice in this setting.

Performance of quantitative flow ratio in patients with aortic stenosis undergoing transcatheter aortic valve implantation.

OBJECTIVES: This study aims to evaluate the diagnostic performance of quantitative flow ratio (QFR) pre transcatheter aortic valve implantation (TAVI) in patients with aortic valve stenosis (AS) and coronary artery disease (CAD). Post-TAVI fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) was used as reference. BACKGROUND: CAD is prevalent in patients with AS, but the hemodynamics of AS confounds evaluation using pressure wire-based assessments. QFR might be less sensitive to the presence of AS thereby allowing for CAD evaluation before aortic valve replacement. Further, QFR does not require the use of pressure wire and therefore has the potential for reducing costs and complications related to insertion of a coronary pressure wire. METHODS: The diagnostic performance of QFR in coronary angiograms from 28 patients undergoing TAVI was evaluated. In all patients, both FFR and iFR were measured pre- and immediately post-TAVI while QFR was measured pre-TAVI. RESULTS: Using post-TAVI FFR and iFR as reference the diagnostic accuracy of pre-TAVI QFR were 83% (95%CI; 68-97) and 52% (95%CI; 30-74) p = .008, respectively. CONCLUSIONS: Pre-TAVI QFR showed a good diagnostic performance using post-TAVI FFR as reference. QFR could become a wire-free, safe, and quick way of evaluating CAD in patients with severe AS undergoing TAVI.

Diagnostic performance of deep learning and computational fluid dynamics-based instantaneous wave-free ratio derived from computed tomography angiography.

BACKGROUND AND OBJECTIVES: Both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are widely used to evaluate ischemia-causing coronary lesions. A new method of CT-iFR, namely AccuiFRct, for calculating iFR based on deep learning and computational fluid dynamics (CFD) using coronary computed tomography angiography (CCTA) has been proposed. In this study, the diagnostic performance of AccuiFRct was thoroughly assessed using iFR as the reference standard. METHODS: Data of a total of 36 consecutive patients with 36 vessels from a single-center who underwent CCTA, invasive FFR, and iFR were retrospectively analyzed. The CT-derived iFR values were computed using a novel deep learning and CFD-based model. RESULTS: Mean values of FFR and iFR were 0.80 ± 0.10 and 0.91 ± 0.06, respectively. AccuiFRct was well correlated with FFR and iFR (correlation coefficients, 0.67 and 0.68, respectively). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of AccuiFRct ≤ 0.89 for predicting FFR ≤ 0.80 were 78%, 73%, 81%, 73%, and 81%, respectively. Those of AccuiFRct ≤ 0.89 for predicting iFR ≤ 0.89 were 81%, 73%, 86%, 79%, and 82%, respectively. AccuiFRct showed a similar discriminant function when FFR or iFR were used as reference standards. CONCLUSION: AccuiFRct could be a promising noninvasive tool for detection of ischemia-causing coronary stenosis, as well as facilitating in making reliable clinical decisions.

The reasons why fractional flow reserve and instantaneous wave-free ratio are similar using wave separation analysis.

BACKGROUND AND OBJECTIVES: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are the two most commonly used coronary indices of physiological stenosis severity based on pressure. To minimize the effect of wedge pressure (Pwedge), FFR is measured during hyperemia conditions, and iFR is calculated as the ratio of distal and aortic pressures (Pd/Pa) in the wave-free period. The goal of this study was to predict Pwedge using the backward wave (Pback) through wave separation analysis (WSA) and to reflect the effect of Pwedge on FFR and iFR to identify the relationship between the two indices. METHODS: An in vitro circulation system was constructed to calculate Pwedge. The measurements were performed in cases with stenosis percentages of 48, 71, and 88% and with hydrostatic pressures of 10 and 30 mmHg. Then, the correlation between Pback by WSA and Pwedge was calculated. In vivo coronary flow and pressure were simultaneously measured for 11 vessels in all patients. The FFR and iFR values were reconstructed as the ratios of forward wave at distal and proximal sites during hyperemia and at rest, respectively. RESULTS: Based on the in vitro results, the correlation between Pback and Pwedge was high (r = 0.990, p < 0.0001). In vivo results showed high correlations between FFR and reconstructed FFR (r = 0.992, p < 0.001) and between iFR and reconstructed iFR (r = 0.930, p < 0.001). CONCLUSIONS: Reconstructed FFR and iFR were in good agreement with conventional FFR and iFR. FFR and iFR can be expressed as the variation of trans-stenotic forward pressure, indicating that the two values are inferred from the same formula under different conditions.

Plaque characteristics on coronary CT angiography associated with the positive findings of fractional flow reserve and instantaneous wave-free ratio.

BACKGROUND: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are useful in determining indications for revascularization of coronary artery disease (CAD). Although the discordance of FFR and iFR was noted in approximately 20%, this cause has not been well established. We investigated patient background and features on coronary CT angiography (CCTA) showing not only FFR- and iFR-positive findings but also discordance between FFR ≤ 0.8 and iFR ≤ 0.89. METHODS: Subjects were consecutively treated in 83 cases with 105 vessels in which stenosis of 30-90% was detected at one vessel of at least 2 mm or more in the major epicardial vessels and FFR and iFR was performed within subsequent 90 days, among suspected CAD which underwent CCTA. The factors affecting not only FFR- and iFR-positive findings, respectively, but also discordance between FFR and iFR was evaluated using logistic regression analysis on per-patient and per-vessel basis. RESULTS: FFR- and iFR-positive findings were observed in 42 vessels (40.0%) and 34 vessels (32.3%), respectively. Discordance between FFR ≤ 0.8 and iFR ≤ 0.89 was observed in 22 vessels (21.0%) of 21 patients. In multivariate logistic analysis, LAD (OR 3.55; 95%CI 1.20-11.71; p = 0.0217) and lumen volume/myocardial weight (L/M) ratio (OR 0.93; 0.86-0.99, p = 0.0290) were significant predictors for FFR-positive findings. For iFR-positive findings, LAD (OR 3.86; 95%CI 1.12-13.31; p = 0.0236) was only significant predictor. In FFR ≤ 0.8 and iFR > 0.89 group (15 vessels, 14.3%), positive remodeling (PR) (OR 5.03, 95%CI 1.23-20.48, p = 0.0205) was significant predictor. In FFR > 0.8 and iFR ≤ 0.89 group (7 vessels, 6.7%), there were no significant predictors. CONCLUSION: On CCTA characteristics, a relevant predictor for FFR-positive findings included low L/M ratio. PR was significant predictor in FFR-positive, iFR-negative patients among those with discordance between the FFR and iFR.

Functional assessment of intermediate coronary artery stenosis with 4-Fr catheters.

The 4-Fr catheter system is not recommended for invasive functional assessment of coronary artery stenosis, because it tends to distort the aortic waveform. This study aimed to identify the incidence of aortic waveform distortion and a feasible method for correct diagnosis of coronary artery stenosis with a 4-Fr catheter. We retrospectively investigated 178 lesions with intermediate coronary artery stenosis. Non-hyperemic distal coronary artery pressure (Pd) and aortic pressure (Pa) were measured with a 4-Fr diagnostic or 6-Fr guiding catheter before and after saline flush. The mean Pd/mean Pa (Pd/Pa) and instantaneous wave-free ratio (iFR) were calculated before and after flushing. We compared the effect of flushing on the changes in Pd/Pa and iFR between the 4-Fr diagnostic and 6-Fr guiding catheters. Using the 4-Fr diagnostic catheter, there was a significant decrease in incidence of aortic waveform distortion from 42.0% (47 lesions) before flushing to 1.8% (2 lesions) after flushing (p < 0.001); the incidence was only 3.0% before saline flush and decreased to 0% after saline flush when using the 6-Fr guiding catheter. The presence of aortic waveform distortion influenced the iFR when the 4-Fr system was used. Functional measurements with the 4-Fr diagnostic catheter require adequate saline flush to remove the influence of aortic waveform distortion.

[Coronary physiology in the catheter laboratory]. / Koronarphysiologie im Herzkatheterlabor.

The regulation of coronary flow is mainly located in the resistance vessels of the microcirculation, so that the functional relevance of a coronary stenosis arises from the interaction between the epicardial stenosis and the downstream microcirculation. These complex interactions are precisely detectable by physiological measurements, such as the instantaneous wave-free ratio (iwFR) or the fractional flow reserve (FFR). In contrast, the purely visual assessment of the coronary anatomy could lead to misinterpretation and possibly to incorrect revascularization decisions. Consequently, in the current guidelines on myocardial revascularization of the European Society of Cardiology (ESC) the measurement of iwFR and FFR has a class IA indication in intermediate stenoses with unclear hemodynamic relevance. Despite this clear recommendation, physiological measurements are not yet regularly used in the clinical routine. Besides the purely hemodynamic assessment, novel methods such as co-registration and coronary mapping can be used for virtual planning of percutaneous coronary interventions, especially in vessels with diffuse lesions and serial stenoses. Furthermore, invasive flow measurements are also helpful for risk stratification between conservative and interventional treatment of patients with acute coronary syndrome, where additional factors of flow limitation, such as coronary spasm, thrombus and acute disturbance of the microcirculation play an important role.

Physiologic Assessment of Coronary Stenosis: Current Status and Future Directions.

PURPOSE OF REVIEW: Percutaneous coronary intervention (PCI) is a commonly used treatment option in coronary artery disease (CAD). Reduced major adverse cardiovascular events (MACE) in those randomized to PCI compared to optimal medical therapy have been demonstrated only if it is performed for physiologically significant coronary lesions. Despite data demonstrating improved outcomes primarily in stable CAD and then acute settings, physiology-guided PCI remains underutilized. This review summarizes the evidence and commonly used methods for physiologic assessment of coronary stenosis. RECENT FINDINGS: Fractional flow reserve (FFR) is the gold standard for the analysis of lesion severity. Its use is limited by the need for adenosine, which adds time, complexity, and potential adverse effects. Non-hyperemic instantaneous wave-free ratio-guided revascularization and quantitative flow reserve ratio assessment both have shown safety and effectiveness with improved patient outcomes. Coronary physiological assessment solves the ambiguity of coronary angiography. Detecting physiologically significant stenoses is crucial to decide which lesion needs to be treated. Technological advances have led to the development of new assessment indices in addition to FFR.

Per-Vessel Level Analysis of Fractional Flow Reserve and Instantaneous Wave-Free Ratio Discordance　- Insights From the AJIP Registry.

BACKGROUND: The per-vessel level impact of physiological pattern of disease on the discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) has not been clarified.Methods and Results:Using the AJIP registry, vessels with FFR/iFR discordance (133/671 [19.8%]) were analyzed. In the left anterior descending artery (LAD), physiologically diffuse disease, as assessed by pressure-wire pullback, was associated with FFR-/iFR+ (83.3% [40/48]), while physiologically focal disease was associated with FFR+/iFR- (57.4% [31/54]), significantly (P<0.0001). These differences were not significant in non-LAD (P=0.17). CONCLUSIONS: The impact of physiological pattern of disease on FFR/iFR discordance is more pronounced in the LAD.

Effect of QTU prolongation on hyperemic instantaneous wave-free ratio value: a prospective single-center study.

We hypothesized that in patients with QT prolongation, resistance might not decrease in the wave-free period, because QTU prolongation cannot be detected by instantaneous wave-free ratio (iFR) analysis software. We investigated whether corrected QTU (QTUc) prolongation affects the hyperemic iFR value. Forty-two consecutive patients with intermediate stenosis (≥ 50%) in the left anterior descending coronary artery (LAD) were analyzed. Fractional flow reserve (FFR) and hyperemic iFR were simultaneously and continuously recorded with intravenous adenosine triphosphate (ATP) and papaverine infusions. In 17 patients with stenosis in the proximal LAD, coronary flow was measured. Patients were divided into two groups according to the median absolute deviation of the QTUc by ATP administration/QTUc by papaverine administration. FFR, hyperemic iFR, and flow data were compared between each stimulus and group. Moreover, influences of pressure and electrocardiogram parameters on differences in iFR values under ATP and papaverine administration were compared between the following two groups (group 1: the absolute difference of hyperemic iFR values between ATP and papaverine administration is ≤ 0.05; group 2: that is > 0.05). The paired t test and t test were used in analysis. Hyperemic iFR values of patients under the use of papaverine were lower than those of patients under the use of ATP when QTUc was more prolonged by papaverine administration than by ATP administration (ATP 0.74 ± 0.14, papaverine 0.71 ± 0.15, P = 0.025). No significant differences were observed in the FFR value and flow data between the groups. Regarding QTU, QTUc, and QTUc by ATP/QTUc by papaverine, significant differences were observed between group 1 and group 2. Pressure parameters did not induce significant differences. QTUc prolongation induced by papaverine was associated with lower hyperemic iFR values. An iFR-based assessment might lead to inappropriate treatment of patients with QTUc prolongation.