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The mechanism of the fractional flow reserve (FFR) difference according to sex has not been clearly understood.This study sought to evaluate sex differences in coronary stenosis, plaque characteristics, and left ventricular (LV) mass and their implications for physiological significance.This was a post hoc analysis of a pooled population of multicenter, international prospective cohorts. Patients (166 women and 489 men) underwent coronary computed tomography angiography (CCTA) within 90 days before invasive FFR measurements were included. The minimal lumen area, percent of plaque burden, whole vessel plaque volume by composition, high-risk plaque characteristics, and LV mass were analyzed from CCTA images.Among 1,188 vessels analyzed, the FFR value was higher in women than that in men (0.85 ± 0.13 vs 0.82 ± 0.14;Higher FFR values for the same stenosis severity in women can be explained by fewer high-risk plaque characteristics and smaller myocardial mass in women than that in men. (CCTA-FFR Registry for Risk Prediction; NCT04037163).

Background: There is great degree of interobserver variability in the visual angiographic assessment of left main coronary disease (LMCD). Fractional flow reserve and intravascular ultrasound are often used in this setting. The use of instantaneous wave-free ratio (iFR) for evaluation of LMCD has not been well studied. The aim of this study is to evaluate the use of iFR in the assessment of angiographically intermediate LMCD. Methods: This is an international multicenter retrospective observational study of patients who underwent both iFR and intravascular ultrasound evaluation for angiographically intermediate LMCD. An independent core laboratory performed blinded off-line analysis of all intravascular ultrasound data. A minimum lumen area of 6 mm 2 was used as the cutoff for significant disease. Results: One hundred twenty-five patients (mean age, 68.4±9.5 years, 84.8% male) were included in this analysis. Receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area 2 with an area under the curve of 0.77 (77% sensitivity, 66% specificity; P 2 with an area under the curve of 0.84 (70% sensitivity, 84% specificity; P Conclusions: In this study, in patients with intermediate LMCD, iFR of ≤0.89 correlates with intravascular ultrasound minimum lumen area 2 regardless of body surface area. The current study supports the use of iFR for the evaluation of intermediate LMCD.

Background Stent thrombosis (ST) after drug‐eluting stent (DES) implantation remains a life‐threatening complication. Recurrent ST (RST) is not a rare phenomenon, potentially contributing to high mortality after the index ST events. However, little evidence is available about the incidence, risk factors, and clinical outcomes of definite RST after DES thrombosis. Methods and Results From REAL‐ST (Retrospective Multicenter Registry of ST After First‐ and Second‐ Generation DES Implantation), this study evaluated 595 patients with definite ST (first‐generation DES thrombosis, n=314; second‐generation DES thrombosis, n=281). During a median follow‐up of 31 months, we identified 32 patients with definite RST after first‐generation DES thrombosis (n=18) and second‐generation DES thrombosis (n=15). Cumulative incidence of RST was 4.5% and 6.0% at 1 and 5 years, respectively, which did not significantly differ between first‐generation DES thrombosis and second‐generation DES thrombosis. Independent predictors of definite RST were early ST (hazard ratio [HR], 2.38; 95% CI, 1.06–5.35 [ P =0.035]) and multivessel ST (HR, 3.47; 95% CI, 1.03–11.7 [ P =0.044]). Definite RST was associated with a 2.8‐fold increased risk of mortality (adjusted HR, 2.78; 95% CI, 1.35–5.73 [ P =0.006]). Conclusions Cumulative incidence of definite RST did not significantly differ between first‐generation DES thrombosis and second‐generation DES thrombosis. Early ST and multivessel ST were risk factors of definite RST. Definite RST significantly increased mortality after DES thrombosis, highlighting the clinical importance of preventing RST to improve outcomes of patients with ST. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: UMIN000025181.

OBJECTIVE: To evaluate the diagnostic performance of quantitative flow ratio (QFR) related to fractional flow reserve (FFR) and resting distal-to-aortic pressure ratio (resting Pd/Pa) concordance.BACKGROUND: QFR is a method for computation of FFR based on standard coronary angiography. It is unclear how QFR is performed in patients with discordance between FFR and resting pressure ratios (distal-to-aortic pressure ratio [Pd/Pa]).MATERIALS AND METHODS: The main comparison was the diagnostic performance of QFR with FFR as reference stratified by correspondence between FFR and resting Pd/Pa. Secondary outcome measures included distribution of clinical or procedural characteristics stratified by FFR and resting Pd/Pa correspondence.RESULTS: Four prospective studies matched the inclusion criteria. Analysis was performed on patient level data reaching a total of 759 patients and 887 vessels with paired FFR, QFR, and resting Pd/Pa. Median FFR was 0.85 (IQR: 0.77-0.90). Diagnostic accuracy of QFR with FFR as reference was higher if FFR corresponded to resting Pd/Pa: accuracy 90% (95% CI: 88-92) versus 72% (95% CI: 64-80), p CONCLUSION: Diagnostic performance of QFR with FFR as reference is reduced for lesions with discordant FFR (≤0.80) and resting Pd/Pa (≤0.92) measurements.

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) was eagerly awaited study in the field of ischemic heart disease. Following the presentation and publication of ISCHEMIA, multiple opinions and viewpoints get complicated. The ongoing debates have been including the relevance of coronary revascularization, noninvasive diagnostic methods, and invasive ischemic testing in patients with stable ischemic heart disease (SIHD). Prior to ISCHEMIA, observational studies indicated the potential of coronary revascularization for improving clinical outcomes, while the randomized Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial did not support the plausible concept. Although the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 2 trial implied the superiority of percutaneous coronary intervention over medical therapy alone, the clinical relevance of coronary revascularization to improve outcomes and quality of life has been questioned. As a consequence, the ISCHEMIA trial did not demonstrate clear benefits in reducing clinical events but showed antianginal effects of revascularization. This landmark trial also suggested the difficulties of noninvasive ischemia testing rather than computed tomography angiography. Despite the complex results, the ISCHEMIA trial may simplify the clinical indications of coronary revascularization in patients with SIHD. Future publications from the ISCHEMIA trial and debates on the results will sharpen our thinking and understanding.

It has been found that the assessment of coronary artery lesions using the fractional flow reserve and instantaneous flow reserve measurements reduces the incidence of further cardiovascular events. Here, we investigated differences in the coronary flow velocity and resistance within the analysis interval between the instantaneous flow reserve (iFR) and the intracoronary electrocardiogram (IC-ECG)-triggered distal/aortic pressure (Pd/Pa) ratio (ICE-T). Thirty-three consecutive patients with stenoses that required coronary flow measurement were enrolled. ICE-T was defined as the average Pd/Pa ratio in the period corresponding to the isoelectric line of the IC-ECG. The index value, flow velocity, and intracoronary resistance during the analysis intervals of the iFR and ICE-T, both at rest and under hyperemia, were compared. The index value and intracoronary resistance of the ICE-T were found to be significantly lower, while the flow velocity was significantly higher, than those of the iFR (P

Background: CT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFR CT) is a safe alternative to invasive coronary angiography. A negative FFR CT has been shown to have low cardiac event rates compared to those with a positive FFR CT. However, the clinical utility of FFR CT according to age is not known. Methods: Patients’ in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry, were stratified into those ≥65 or CT on clinical decision-making, as assessed by patient age, was determined by evaluating patient management using CTA results alone, followed by site investigators submitting a report on the treatment plan based upon the newly provided FFR CT data. Outcomes at 1-year post CTA were assessed, including major adverse cardiovascular events (myocardial infarction, all-cause mortality or unplanned hospitalization for ACS leading to revascularisation) and total revascularisation. Positive FFR CT was deemed to be ≤ 0.8. Results: FFR CT was calculated in 1849 (40.6%) subjects aged CT strata for subjects above and below the age of 65. MACE and revascularisation rates were not significantly different for those ≥ or CT positivity or stenosis severity CT result, and anatomical stenosis ≥50%, those ≥ and CT and treatment (CABG, PCI, medical therapy), indicated a statistically significant, but small increase in the odds of a MACE event with increasing age (OR 1.04, 95% CI 1.006–1.08, p = 0.02). Amongst patients with a FFR CT > 0.80, there was no effect of age on the odds of revascularisation. Conclusion: The findings of this study point to a low risk of MACE events or need for revascularisation in those aged ≥ or CT>0.80, despite the higher incidence of anatomic obstructive CAD in those ≥65 years. The findings show the clinical usefulness and outcomes of FFR CT are largely constant regardless of age.

Coronary physiological assessment using fractional flow reserve or nonhyperemic pressure ratios has become a standard of care for patients with coronary atherosclerotic disease. However, most evidence has focused on the pre-interventional use of physiological assessment to aid revascularization decision-making, whereas post-interventional physiological assessment has not been well established. Although evidence for supporting the role of post-interventional physiological assessment to optimize immediate revascularization results and long-term prognosis has been reported, a more thorough understanding of these data is crucial in incorporating post-interventional physiological assessment into daily practice. Recent scientific efforts have also focused on the potential role of pre-interventional fractional flow reserve or nonhyperemic pressure ratio pullback tracings to characterize patterns of coronary atherosclerotic disease to better predict post-interventional physiological outcomes, and thereby identify the appropriate revascularization target. Pre-interventional pullback tracings with dedicated post-processing methods can provide characterization of focal versus diffuse disease or major gradient versus minor gradient stenosis, which would result in different post-interventional physiological results. This review provides a comprehensive look at the current evidence regarding the evolving role of physiological assessment as a functional optimization tool for the entire process of revascularization, and not merely as a pre-interventional tool for revascularization decision-making.

Background: Ultrasonic flow ratio (UFR) is a novel method for fast computation of fractional flow reserve (FFR) from intravascular ultrasound images. The objective of this study is to evaluate the diagnostic performance of UFR using wire-based FFR as the reference. Methods: Post hoc computation of UFR was performed in consecutive patients with both intravascular ultrasound and FFR measurement in a core lab while the analysts were blinded to FFR. Results: A total of 167 paired comparisons between UFR and FFR from 94 patients were obtained. Median FFR was 0.80 (interquartile range, 0.68–0.89) and 50.3% had a FFR≤0.80. Median UFR was 0.81 (interquartile range, 0.69–0.91), and UFR showed strong correlation with FFR ( r =0.87; P P P =0.48), prior myocardial infarction ( P =0.29), and imaging catheters ( P =0.22). Intraobserver and interobserver variability of UFR analysis was 0.00±0.03 and 0.01±0.03, respectively. Median UFR analysis time was 102 (interquartile range, 87–122) seconds. Conclusions: UFR had a strong correlation and good agreement with FFR. The fast computational time and excellent analysis reproducibility of UFR bears the potential of a wider adoption of integration of coronary imaging and physiology in the catheterization laboratory.

Background: The ADVANCE registry is a large prospective study of outcomes and resource utilization in patients undergoing coronary computed tomography angiography (CCTA) and CT-based fractional flow reserve (FFRCT). As experience with new technologies and practices develops over time, we investigated temporal changes in the use of FFRCT within the ADVANCE registry. Methods: 5083 patients with coronary artery disease (CAD) on CCTA were prospectively enrolled in the ADVANCE registry and were divided into 3 equally sized cohorts based on the temporal order of enrollment per site. Demographics, CCTA and FFRCT findings, and clinical outcomes through 1-year follow-up, were recorded and compared between tertiles. Results: The number of patients with a ≥70% stenosis on CCTA was similar over time (33.6%, 30.9%, and 33.8% for cohort 1–3). The rate of positive FFRCT ≤0.80 was higher for cohorts 2 (67.3%) and 3 (74.6%) than for cohort 1 (57.1%, p < 0.001). Invasive FFR rates decreased from 25.8% to 22.4% between cohort 1 and 3 (p = 0.023). Moreover, patients with a FFRCT ≤0.80 were less frequently referred for invasive coronary angiography (ICA) (from 62.9% to 52.9%, p < 0.001), and underwent fewer revascularizations between cohort 1 and 3 (from 41.9% to 32.0%, p < 0.001). The prevalence of major events was low (1.2%) and similar between cohorts. Conclusions: Growing experience with FFRCT improved the likelihood of identifying hemodynamically significant CAD and safely reduced the need for ICA and revascularization in patients with anatomically significant disease even in the instance of an abnormal FFRCT.

Background Physiology-guided treatment strategy improves clinical outcomes of patients with coronary artery disease. However, it has not been fully evaluated whether such guideline-based strategy is useful for patients with diffuse coronary artery disease as well, which is known to be one of the major factors affecting morbidity and mortality. Purpose The aim of this study was to clarify clinical outcomes of patients with diffuse coronary artery disease whose treatment strategy was based on coronary physiology. Methods From an international multicentre registry of iFR-pullback, consecutive 1067 patients (1185 vessels) with stable angina were included in whom coronary lesions were deferred or revascularized according to the iFR cutoff: 0.89. The physiological pattern of disease was classified according to the iFR-pullback recording as predominantly physiologically diffuse (n=463) or predominantly physiologically focal (n=722). Major adverse cardiovascular events (MACEs), defined as a composite of cardiac death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization during follow-up period, were compared between diffuse and focal groups, in both deferred and revascularized groups, respectively. Results Mean age was 67.1±10.7 years and 75.8% of patients were men. Median iFR was 0.88 (interquartile range: 0.80 to 0.92). At a median follow-up period of 18 months, no significant differences in MACEs were found between diffuse and focal groups, in both iFR-based deferred and revascularized groups. In the deferred group (n=480), MACEs occurred in 6.9% patients (15/217) in the diffuse group and 8.0% patients (21/263) in the focal group (p=0.44). In the revascularized group (n=705), MACEs occurred in 8.9% patients (22/246) in the diffuse group and 7.2% patients (33/459) in the focal group (p=0.49). Conclusions Despite potentially higher risks in patients with diffuse coronary artery disease, clinical outcomes of those patients were comparable to those of patients without diffuse disease, as long as treatment strategy was based on the physiology guidance, which is globally recommended by international guidelines. Funding Acknowledgement Type of funding source: None

Background The safety of deferral of revascularization based on instantaneous wave-free ratio (iFR) is established in randomized controlled trials. However, there is little data regarding long-term outcomes after deferral of revascularization based on iFR in real-world practice. Purpose We sought to assess clinical outcomes after deferral of revascularization based on iFR in clinical practice as compared with those based on fractional flow reserve (FFR). Methods This is a post hoc analysis of the J-CONFIRM registry (long-term outcomes of Japanese patients with deferral of coronary intervention based on fractional flow reserve in multicenter registry), in which 1262 patients with 1447 lesions deferred the revascularization based on FFR. Of these, both FFR and iFR were measured in 399 patients with 452 lesions. The patients were classified into the two groups: the iFR group (iFR >0.89; 308 patients with 348 lesions) and the FFR group (FFR >0.80; 740 patients with 855 lesions). The primary study endpoint was the 3-year target vessel failure (TVF) including cardiac death, target-vessel related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). Results Mean iFR was 0.96±0.04 in the iFR group. Mean FFR was significantly lower in the iFR group than in the FFR group (0.87±0.05 vs. 0.89±0.05, p=0.002). The iFR group included 35 lesions (11.4%) with FFR ≤0.80. At 3 years, the rate of TVF on a lesion basis were not significantly different between the iFR and FFR groups (8.8% vs. 6.1%, p=0.10), whereas CDTVR rate was significantly higher in the iFR group than in the FFR group (8.5% vs. 5.3%, p=0.044). Cardiac death and TVMI on a patient basis rarely occurred in both groups during the 3-year follow-up (0.33% vs. 0.77%, p=0.47; 0.66% vs. 0.56%, p=0.85, respectively). Conclusion At 3 years, TVF rate in deferred lesions was numerically higher in the iFR group than in the FFR group, driven by a higher rate of CDTVR. However, cardiac death and TVMI was very rare in both groups, highlighting the safety of both iFR- and FFR-based deferral of revascularization in daily practice. Funding Acknowledgement Type of funding source: None

Background The trial collected prospective data from physiology measurements of borderline lesions in five Czech, one Japan and one Argentinian cathlabs. The main purposes were to analyze diagnostic agreement between FFR (fractional flow reserve) and iFR (instantaneous wave free ratio) examinations and to find possible explanations for discrepant results. Methods FFR and iFR examinations were analyzed using Philips-Volcano console and coronary flow reserve (CFR) was analyzed by using Combomap machine Philips-Volcano. Hyperemia for FFR and CFR measurements was induced by intracoronary administration of adenosine. We used CFR as a truth for comparison between FFR and iFR, because CFR has higher impact on patients prognosis than pressures indices. Results Data were collected from February 2016 to June 2019 and the database includes 1.789 examinations from 1.492 patients (282 of them, 15.8%, with ACS). CFR were measured in 343 lesions in 293 patients. (ACS 31.2%). Overall correlation between FFR and iFR is high (R=0.86 p Conclusion The FFR/iFR discrepancy occurred in almost one quarter of examinations. Correlation between CFR and iFR is better than between CFR and FFR. High flow is probably one of the main reason for FFRp/iFRn type of discrepancy. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Czech Health Research Council

Aims This study aimed to determine the effects of a proprotein convertase subtilisin-kexin type 9 inhibitor (PCSK9i) on coronary plaque volume and lipid components in patients with a history of coronary artery disease (CAD). Methods and results This prospective, open-label, single-centre study analysed non-culprit coronary segments using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) at baseline and follow-up angiography. Following changes in the lipid-lowering treatment based on the most recent guideline, the enrolled subjects were divided into two groups: treatment with PCSK9i and statins (PCSK9i: 21 patients and 40 segments) and statins only (control: 32 patients and 50 segments). The absolute and percent LDL-C reductions were significantly greater in the PCSK9i group than in the control group (between group difference: 59.3 mg/dL and 46.4%; P Conclusion The lipid component of non-culprit coronary plaques was significantly decreased by PCSK9i. The effects of statin combined with PCSK9i might be attributed to the stabilization and regression of residual vulnerable coronary plaques in patients with CAD.

Background: Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) is an established tool for identifying lesion-specific ischemia that is now approved for use by the Japanese insurance system. However, current clinical reimbursement is strictly limited to institutions with designated appropriate use criteria (AUC). This study assessed differences in physicians' behavior (e.g., use and interpretation of FFRCT, final management) according to Japanese AUC and non-AUC site designation. Methods and Results: Of 5,083 patients in the ADVANCE Registry, 1,829 from Japan were enrolled in this study. Physicians' behavior after interrogating CCTA and FFRCT was analyzed separately according to AUC and non-AUC site designation. Compared with AUC sites, patients referred for FFRCT from non-AUC sites had a higher rate of negative FFRCT, less severe anatomic stenosis, and a slightly lower rate of management plan reclassification (51.2% vs. 61.3%), with near-identical utility in both groups. Actual care corresponded equally well to post-FFRCT plans in both groups. The likelihood of revascularization for positive or negative FFRCT was similar between the 2 groups. Importantly, AUC and non-AUC sites were equally unlikely to revascularize patients with negative FFRCT and stenosis >50% or patients with positive FFRCT and stenosis

To review the technical limitations of available pressure-wires, present the design evolution of a nitinol fiber-optic pressure wire and to summarize the First-in-Man (FIM) ODespite increasing use of physiology assessment of coronary lesions, several technical limitations persist. We present technical details, design evolution and early clinical results with a novel 0.014" nitinol fiber-optic based pressure-wire.The 0.014' OptoWire™ (Opsens Medical, Quebec, Canada) was designed to combine improved handling properties compared to standard pressure-wires and to offer extremely reliable pressure recording and transmission due to fiber-optic properties compared to piezo-electric sensors and electrical wires. In vitro assessment showed that OptoWire™ steerability, pushability and torquability properties were closer to regular PCI wires than standard electrical pressure wires. In the First-in-Man OThe novel 0.014" fiber-optic OptoWire™ provides superior wire handling with reduced risk of pressure drift allowing reliable pre- and post-PCI physiology assessment.

Objectives The goal of this study was to investigate the association of stenosis and plaque features with myocardial ischemia and their prognostic implications. Background Various anatomic, functional, and morphological attributes of coronary artery disease (CAD) have been independently explored to define ischemia and prognosis. Methods A total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography were analyzed. Stenosis and plaque features of the target lesion and vessel were evaluated by an independent core laboratory. Relevant features associated with low FFR (≤0.80) were identified by using machine learning, and their predictability of 5-year risk of vessel-oriented composite outcome, including cardiac death, target vessel myocardial infarction, or target vessel revascularization, were evaluated. Results The mean percent diameter stenosis and invasive FFR were 48.5 ± 17.4% and 0.81 ± 0.14, respectively. Machine learning interrogation identified 6 clusters for low FFR, and the most relevant feature from each cluster was minimum lumen area, percent atheroma volume, fibrofatty and necrotic core volume, plaque volume, proximal left anterior descending coronary artery lesion, and remodeling index (in order of importance). These 6 features showed predictability for low FFR (area under the receiver-operating characteristic curve: 0.797). The risk of 5-year vessel-oriented composite outcome increased with every increment of the number of 6 relevant features, and it had incremental prognostic value over percent diameter stenosis and FFR (area under the receiver-operating characteristic curve: 0.706 vs. 0.611; p = 0.031). Conclusions Six functionally relevant features, including minimum lumen area, percent atheroma volume, fibrofatty and necrotic core volume, plaque volume, proximal left anterior descending coronary artery lesion, and remodeling index, help define the presence of myocardial ischemia and provide better prognostication in patients with CAD. (CCTA-FFR Registry for Risk Prediction; NCT04037163 )

The aim of this study was to investigate the accuracy of pre-percutaneous coronary intervention (PCI) predicted nonhyperemic pressure ratios (NHPRs) with actual post-PCI NHPRs and to assess the efficacy of PCI strategy using pre-PCI NHPR pullback.Predicting the functional results of PCI is feasible using pre-PCI longitudinal vessel interrogation with the instantaneous wave-free ratio (iFR), a pressure-based, adenosine-free NHPR. However, the reliability of novel NHPRs (resting full-cycle ratio [RFR] and diastolic pressure ratio [dPR]) for this purpose remains uncertain.In this prospective, multicenter, randomized controlled trial, vessels were randomly assigned to receive pre-PCI iFR, RFR, or dPR pullback (50 vessels each). The pre-PCI predicted NHPRs were compared with actual NHPRs after contemporary PCI using intravascular imaging. The number and the total length of treated lesions were compared between NHPR pullback-guided and angiography-guided strategies.The predicted NHPRs were strongly correlated with actual NHPRs: iFR, r = 0.83 (95% confidence interval: 0.72 to 0.90; p 0.001); RFR, r = 0.84 (95% confidence interval: 0.73 to 0.91; p 0.001), and dPR, r = 0.84 (95% confidence interval: 0.73 to 0.91; p 0.001). The number and the total length of treated lesions were lower with the NHPR pullback strategy than with the angiography-guided strategy, leading to physiological improvement.Predicting functional PCI results on the basis of pre-procedural RFR and dPR pullbacks yields similar results to iFR. Compared with an angiography-guided strategy, a pullback-guided PCI strategy with any of the 3 NHPRs reduced the number and the total length of treated lesions. (Study to Examine Correlation Between Predictive Value and Post PCI Value of iFR, RFR and dPR; UMIN000033534).

CT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFRPatients' in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry, were stratified into those ≥65 or65 years of age. The impact of FFRFFRThe findings of this study point to a low risk of MACE events or need for revascularisation in those aged ​≥ ​or65 with a FFR

Evidence supporting the use of coronary physiology as an adjunct to coronary angiography to guide percutaneous coronary interventions has accumulated over the past 25 years. The fractional flow reserve has dominated this evolving physiological guidance of coronary intervention and its use is supported by large clinical outcome trials. However, despite clinical practice guidelines advocating its use in most patients with coronary stenosis who are eligible for coronary intervention, the uptake of a physiology-guided approach remains limited. The use of non-hyperaemic coronary pressure measurements to guide coronary interventions was introduced in an attempt to simplify the routine application of coronary physiology-guided intervention in daily practice. Over the past decade, a large scientific effort has focused on the development of several non-hyperaemic pressure ratios. In this Review, we detail the basic principles of coronary physiology in non-hyperaemic conditions, the rationale for the use of non-hyperaemic coronary pressure measurements for stenosis evaluation, the current evidence base for the available non-hyperaemic coronary pressure ratios, the basis for the discordance between non-hyperaemic coronary pressure ratios and fractional flow reserve, and the potential advantages of these new parameters over fractional flow reserve.

Objectives The aim of this study was to assess the long-term clinical outcomes of patients with left main coronary artery (LM) stenosis in whom treatment strategy was based on the instantaneous wave-free ratio (iFR). Background The overall safety of iFR to guide revascularization decision making in patients with stable coronary artery disease has been established. However, no study has examined the safety of deferral of revascularization of LM disease on the basis of iFR. Methods This multicenter observational study included 314 patients in whom LM stenosis was deferred (n = 163 [51.9%]) or revascularized (n = 151 [48.1%]) according to the iFR cutoff ≤0.89. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were each individual component of the primary endpoint and also cardiac death. Results At a median follow-up period of 30 months, the primary endpoint occurred in 15 patients (9.2%) in the deferred group and 22 patients (14.6%) in the revascularized group (hazard ratio: 1.45; 95% confidence interval: 0.75 to 2.81; p = 0.26), indicating no evidence of a significant difference between the 2 groups. For the secondary endpoints, findings in the iFR-based deferral and revascularization groups were as follows: all-cause death, 3.7% versus 4.6%; cardiac death, 1.2% versus 2.0%; nonfatal myocardial infarction, 2.5% versus 5.3%; and target lesion revascularization, 4.3% versus 5.3% (p > 0.05 for all). Conclusions Deferral of revascularization of LM stenosis on the basis of iFR appears to be safe, with similar long-term outcomes to those in patients in whom LM revascularization was performed according to iFR values.

Background: The safety of fractional flow reserve (FFR)-based deferral of revascularization remains to be fully established in real-world practice. We sought to assess clinical outcomes after deferral of revascularization based on FFR. Methods: The J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry) prospectively enrolled 1263 patients with 1447 lesions in whom revascularization was deferred based on FFR at 28 Japanese centers. The primary study end point was the cumulative 2-year incidence of target vessel failure, including cardiac death, target-vessel related myocardial infarction, and clinically driven target vessel revascularization. Results: The mean FFR was 0.86±0.06. At 2 years, the target vessel failure rate was 5.5% in deferred lesions, mainly driven by a high rate of clinically driven target vessel revascularization (5.2%), and significantly increased with decreasing FFR, especially in the proximal location. Cardiac death and target-vessel related myocardial infarction rarely occurred during the 2-year follow-up (0.41% and 0.41%, respectively). Independent predictors of 2-year target vessel failure were FFR value (per 0.01 decrease; hazard ratio [HR] 1.07 [95% CI, 1.04–1.11], P P P =0.003), hemodialysis (HR, 2.90 [95% CI, 1.11–7.58]; P =0.03), and right coronary artery lesion (HR, 1.78 [95% CI, 1.02–3.11], P =0.042). Conclusions: The J-CONFIRM registry demonstrated the 2-year target vessel failure rate was 5.5% in deferred lesions, highlighting the safety of FFR-based deferral of revascularization in daily practice. Clinical Trial Registration: URL: http://www.umin.ac.jp . Unique identifier: UMIN000014473.

In this document, the background, concept, and current evidence are briefly summarized. The focus is on the clinical application of physiological lesion assessment from a practical standpoint for facilities that do not have ample experience. Finally, the characteristics of new resting indexes are summarized.

Background This study compared the diagnostic value of myocardial perfusion imaging (MPI) between the rest-stress 99 mTc-tetrofosmin protocol (Tc/Tc protocol) and simultaneous acquisition rest 99 mTc-tetrofosmin/stress 201Tl dual-isotope protocol (SDI protocol) with a semiconductor camera.Methods and Results: We retrospectively studied 147 patients who underwent stress MPI using a cadmium-zinc-telluride camera and invasive coronary angiography within a 3-month interval. The Tc/Tc and SDI protocols were used in 59 and 88 patients, respectively. The sensitivity, specificity, and accuracy of the summed difference score in per-patient analysis were 56%, 85%, and 69%, respectively, for the Tc/Tc protocol and 89%, 82%, and 85%, respectively, for the SDI protocol. The area under the receiver operating characteristic curve was significantly better for the SDI than Tc/Tc protocol for the left anterior descending artery (0.836 vs. 0.674; P=0.0380), the left circumflex artery (0.754 vs. 0.599; P=0.0441), and in per-patient analysis (0.875 vs. 0.707; P=0.0135). There was no significant difference in the diagnostic accuracy of the summed stress score for any vessel or in per-patient analysis between the 2 protocols. Conclusions The SDI protocol had a higher diagnostic accuracy for the detection of coronary ischemia than the Tc/Tc protocol.

The study sought to investigate the prognostic implications of relative increase of fractional flow reserve (FFR) with PCI in combination with post-percutaneous coronary intervention (PCI) FFR.FFR, measured after PCI has been shown to possess prognostic implications. The relative increase of FFR with PCI can be determined by the interaction of baseline disease pattern, adequacy of PCI, and residual disease burden in a target vessel. However, the role of relative increase of FFR with PCI has not yet been evaluated.A total of 621 patients who underwent PCI using second-generation drug-eluting stents based on low pre-PCI FFR (≤0.80) and available post-PCI FFR were analyzed. The relative increase of FFR was calculated by %FFR increase with PCI ([post-PCI FFR - pre-PCI FFR]/pre-PCI FFR × 100). Patients were divided according to the optimal cutoff values of post-PCI FFR (0.84) and %FFR increase (≤15%). The primary outcome was target vessel failure (TVF) (a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization) at 2 years.Among the total population, 66.0% showed high post-PCI FFR (≥0.84) and 69.2% showed high %FFR increase (15%). Patients with low post-PCI FFR showed a higher risk of 2-year TVF than did those with high post-PCI FFR (9.1% vs. 2.6%; hazard ratio [HR]: 3.367; 95% confidence interval [CI]: 1.412 to 8.025; p = 0.006). Patients with low %FFR increase also showed a higher risk of 2-year TVF compared with those with high %FFR increase (9.2% vs. 3.0%; HR: 3.613; 95% CI: 1.543 to 8.458; p = 0.003). Among the high post-PCI FFR group, there were no significant differences in clinical outcomes according to %FFR increase. Conversely, among the low post-PCI FFR group, those with low %FFR increase showed a significantly higher risk of TVF than did those with high %FFR increase (14.3% vs. 4.1%; HR: 4.334; 95% CI: 1.205 to 15.594; p = 0.025). Percent FFR increase significantly increased discriminant and reclassification ability for the occurrence of TVF when added to a model with clinical risk factors and post-PCI FFR (C-index 0.783 vs. 0.734; relative integrated discrimination improvement 0.702; p = 0.009; category-free net reclassification index 0.479; p = 0.031).Percent FFR increase with PCI showed similar prognostic implications with post-PCI FFR. Adding the relative increase of FFR to post-PCI FFR would enable better discrimination of high-risk patients after stent implantation. (Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [PERSPECTIVE]; NCT01873560).

There has been no established echocardiographic parameter to accurately assess left ventricular (LV) relaxation. Impaired LV relaxation assessed by the time constant of LV pressure decline (Tau) is one of the major components of diastolic dysfunction. We sought to noninvasively estimate Tau (eTau) by speckle tracking echocardiography (STE) and to validate the eTau against Tau by catheterization. Tau was reported to be calculated using the isovolumic relaxation time (IVRT), LV end-systolic pressure, and left atrial (LA) pressure. We reported that pulmonary capillary wedge pressure (ePCWP) can be noninvasively and accurately estimated as 10.8 - 12.4 × Log (LA active emptying function/minimum LA volume index). Therefore, the eTau by STE is noninvasively calculated using the formula: eTau = IVRT / (ln 0.9 × systolic blood pressure-ln ePCWP). Echocardiographic parameters were measured just before catheterization in 110 patients with cardiac disease (age 72 ± 8). There was a good correlation between the eTau and Tau by catheterization (r = 0.69, p0.001), whereas IVRT and the e' had a poor correlation with Tau (r = 0.33 and -0.33, respectively). The sensitivity and specificity of the eTau to predict prolonged Tau (48 ms) was 77% and 91%, respectively, with area under curve of 0.87 using an optimal cutoff of 48 ms. Bland-Altman analysis revealed a good agreement between the eTau and Tau. In conclusion, this study demonstrated that the eTau by our noninvasive method has a good correlation with Tau obtained by cardiac catheterization. LV relaxation may be noninvasively and accurately estimated by STE.

Background Interventionists' experience and skills are essential factors for successful chronic total occlusion-percutaneous coronary intervention (CTO-PCI). However, the construction of theoretical strategy independent from interventionists' procedure may also improve it. We sought to assess the feasibility of CTO-PCI using an educational system supported by a single expert proctor. Methods A total of 160 patients underwent CTO-PCI between 2009 and 2016 at 92 Japanese centers in the Hands-on proctorship project. The CTO-PCI strategy was discussed with all participants and their specialists, before and during the procedure. We divided patients into 2 groups based on the CTO-PCI experience of their interventionist: (1) the less experienced group (CTO-PCI ≤ 50 cases, n = 65) and (2) the more experienced group (CTO-PCI > 50 cases, n = 95). Baseline characteristics, procedural complications, and clinical outcomes were compared between groups. Results No significant differences in patient age, sex, prevalence for coronary risk factors, and lesion complexity was observed between groups. The retrograde approach was used equivalently between groups (55.4% vs. 60.0%, p = 0.56), and procedural success rates were similar (96.9% vs. 90.5%, p = 0.12). The rate of proctor's bailout for recanalization were not frequent between groups (4.6% vs. 5.3%, p = 0.85). No procedure-related mortality was noted in either group. In addition, no significant differences in procedural cardiac complications, including coronary dissection, perforation, or tamponade, were observed between groups (10.8% vs. 14.7%, p = 0.47). Conclusions The expert-supported CTO-PCI maintained high success rates regardless of interventionists' experience. This highlights the importance of theoretical strategy for the management patients undergoing CTO-PCI.

The bloom dynamics of the raphidophycean flagellate, Chattonella antiqua during summer 2016 in the Yatsushiro Sea, Japan were studied using a hydrodynamic model and monitoring data after typhoon Namtheun passed. The bloom formed in the southern area of the Yatsushiro Sea. The bloom dynamics differed from the dynamics of the 2008–2010 Chattonella blooms, which initially formed in the northern area and subsequently expanded to the southern area by effects of tidal currents. In 2016, high DIN levels appeared in the period preceding the bloom after the passage of the typhoon and the bloom formed in the southern area. The high DIN levels did not originate from the deeper water within the Yatsushiro Sea by vertical mixing because of the low DIN in the water column prior to the typhoon. A hydrodynamic model was used in order to examine how the high DIN was supplied. Model results suggested that deep offshore water intruded onshore and through the Ushibuka Strait into the Yatsushiro Sea in the period preceding the bloom. This deep offshore water intrusion was controlled by an internal tide, typhoon-induced current and vertical mixing induced by tidal stirring. The internal tide and typhoon-induced current transported offshore water to the lower layer in the Ushibuka Strait, and subsequently tidal mixing transported nutrients to the euphotic zone in the Ushibuka Strait by vertical diffusion.

Aims There are limited data on the clinical implications of total physiologic atherosclerotic burden assessed by invasive physiologic studies in patients with coronary artery disease. We investigated the prognostic implications of total physiologic atherosclerotic burden assessed by total sum of fractional flow reserve (FFR) in three vessels (3V-FFR). Methods and results A total of 1136 patients underwent FFR measurement in three vessels (3V FFR-FRIENDS study, NCT01621438). The patients were classified into high and low 3V-FFR groups according to the median value of 3V-FFR (2.72). The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction and ischaemia-driven revascularization) at 2 years. Mean angiographic percent diameter stenosis and FFR were 43.7 ± 19.3% and 0.90 ± 0.08, respectively. There was a negative correlation between 3V-FFR and estimated 2-year MACE rate (P

Background Following the development of breakthrough techniques for percutaneous coronary intervention (PCI) in the treatment of chronic total occlusions (CTO), the initial success rate of PCI in CTO lesions (CTO-PCI) has improved; however, there are few reports regarding the effects of successful CTO revascularization on long-term mortality in Japan. The aim of this study was to compare the long-term clinical outcomes of patients with successful versus failed CTO recanalization and to identify related factors. Methods and results From all PCI procedures performed in our hospital between 2006 and 2013, CTO-PCIs were extracted and classified into two groups: PCI success (n = 656 patients) and PCI failure (n = 82 patients). Patients with successful procedures only on a second attempt, CTO-PCI in small branches, or CTOs in more than one vessel were excluded. Survival was determined from a telephone interview or the consultation history in the outpatient clinic. Initial angiographic success was achieved in 88.9% of the patients. A Kaplan–Meier plot with log-rank analysis showed that cumulative all-cause death was significantly lower in the success group than in the failure group (p = 0.0003; average follow-up duration in success group vs. failure group was 1531.3 ± 33.5 vs. 1565.3 ± 97.5 days, p = 0.7). Moreover, the rate of evident cardiac death was significantly lower in the success group than in the failure group (3.5% [23/656] vs. 15.9% [13/82], p Conclusions This study suggests that successful revascularization in patients with CTO improves their long-term clinical outcomes.

Fractional flow reserve (FFR) prior to percutaneous coronary intervention (PCI) is useful to guide treatment. Whether post-PCI FFR assessment might have clinical impact is controversial. The aim of this study is to evaluate the range of post-PCI FFR values and analyze the relationship between post-PCI FFR and clinical outcomes.We systematically searched the PubMed, EMBASE, and Cochrane Library databases with cross-referencing of articles reporting post-PCI FFR and correlating post-PCI FFR values and clinical outcomes. The outcomes of interest were the immediate post-PCI FFR values and the correlations between post-PCI FFR and the incidence of repeat intervention and major adverse cardiac events (MACE).From 1995 to 2015, a total of 105 studies (n = 7470) were included, with 46 studies reporting post-PCI FFR and 59 studies evaluating relationship between post-PCI and clinical outcomes up to 30 months after PCI. Overall, post-PCI FFR values demonstrated a normal distribution with a mean value of 0.90 ± 0.04. There was a positive correlation between the percentage of stent use and post-PCI FFR (P.0001). Meta-regression analysis indicated that higher post-PCI FFR values were associated with reduced rates of repeat intervention (P.0001) and MACE (P = .0013). A post-PCI FFR ≥0.90 was associated with significantly lower risk of repeat PCI (odds ratio 0.43, 95% CI 0.34-0.56, P.0001) and MACE (odds ratio 0.71, 95% CI 0.59-0.85, P = .0003).FFR measurement after PCI was associated with prognostic significance. Further investigation is required to assess the role of post-PCI FFR and validate cutoff values in contemporary clinical practice.

Despite the clinical importance of ischemia evaluation, obtaining fractional flow reserve (FFR) value has, heretofore, only been available during invasive cardiac catheterization. Although there is a clear linkage between morphology and physiology, a significant gap still exists. FFR derived from coronary computed tomography angiography (FFRCT) is a novel method of quantifying the hemodynamic significance of coronary artery stenoses by translating morphological information into hemodynamic data. Improved diagnostic performance of FFRCThas been repeatedly demonstrated in comparison with coronary computed tomography angiography alone with an invasive FFR reference standard. More recently, the potential benefit of this technology to safely defer non-indicated catheterizations and reduce healthcare costs has been established and indicates this technology may improve the management of patients with coronary artery disease. In this review, we summarize the scientific basis of FFRCTand evidence from clinical trials, provide illustrative examples of clinical applications, discuss potential limitations, and outline avenues for future research.

The ADVANCE registry is a large prospective study of outcomes and resource utilization in patients undergoing coronary computed tomography angiography (CCTA) and CT-based fractional flow reserve (FFR5083 patients with coronary artery disease (CAD) on CCTA were prospectively enrolled in the ADVANCE registry and were divided into 3 equally sized cohorts based on the temporal order of enrollment per site. Demographics, CCTA and FFRThe number of patients with a ≥70% stenosis on CCTA was similar over time (33.6%, 30.9%, and 33.8% for cohort 1-3). The rate of positive FFRGrowing experience with FFR

Noninvasive fractional flow reserve derived from coronary CT angiography (FFR CT) is increasingly used in patients with coronary artery disease as a gatekeeper to the catheterization laboratory. While there is emerging evidence of the clinical benefit of FFR CT in patients with moderate coronary disease as determined with coronary CT angiography, there has been less focus on interpretation, reporting, and integration of FFR CT results into routine clinical practice. Because FFR CT analysis provides a plethora of information regarding pressure and flow across the entire coronary tree, standardized criteria on interpretation and reporting of the FFR CT analysis result are of crucial importance both in context of the clinical adoption and in future research. This report represents expert opinion and recommendation on a standardized FFR CT interpretation and reporting approach.

Background Recently, some studies have highlighted proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors produce incremental low-density lipoprotein cholesterol (LDL-C) lowering effect. However, it is unknown whether the lipid composition of plaque changes is associated with serum LDL-C reduction due to PCSK9 inhibitors administration. Purpose The purpose of this study was to determine the effects of PCSK9 inhibitor (PCSK9i) on coronary plaque component in patients with a history of coronary artery disease (CAD) assessed by near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS). Methods A total of 67 non-culprit coronary segments were identified in 34 patients. These lesions were analyzed utilizing NIRS-IVUS at baseline and follow-up coronary angiography (CAG). The subjects were divided into two groups according to lipid-lowering treatment; administration of PCSK9i group (PCSK9i: 19 segments, 9 patients) and traditional statin treatment group (Control: 48 segments, 25 patients). The change of lipid-rich plaque distribution between baseline and follow-up NIRS-IVUS was defined as the change of maximal lipid core burden index (LCBI) score for each of the 4-mm longitudinal segments (maxLCBI4mm). Results Mean duration from baseline to follow-up CAG was 239.4±52.4 days in the PCSK9i group and 341.0±84.1 days in the Control group (p Figure 1 Conclusion Compared with traditional statin therapy, PCSK9i treatment resulted in a greater decrease in lipid component in non-culprit coronary plaques. Therefore, PCSK9i may be useful option in preventing from adverse coronary events for the patients with CAD.

Objectives We sought to evaluate the efficacy of plaque debulking by directional coronary atherectomy (DCA) before 2nd generation drug-eluting stent (DES) implantation for bifurcated coronary lesions. Background Percutaneous coronary intervention (PCI) for bifurcated lesions still remains complex and challenging in terms of restenosis or stent thrombosis regardless of whether simple or complex stenting used. Methods Patients with bifurcated lesions were enrolled in this prospective multicenter registry. Pre-2nd generation DES plaque debulking with a novel DCA was conducted. All patients were scheduled to perform a follow up (9–12 months) angiography (coronary angiography or coronary computed tomography). The primary end point was the target vessel failure (TVF) at follow-up. Secondary end points were procedure-related events and major adverse cardiac events at 1 year. Results A total of 77 patients with bifurcated lesions were enrolled. PCI with DCA was performed successfully in all without any major procedure-related event and only 1 case needed complex stenting. TVF rate at 9–12 months follow up was 3.9% (3 of 77) and those were all associated with revascularization of the target vessel. Restenosis was only observed at ostial of main-branch in 3cases. No death, no coronary artery bypass grafting, and no myocardial infarction were reported in the patients within the first year. Figure1 Conclusion DCA before 2nd generation DES implantation can possibly avoid complex stenting and provide a good mid-term outcome in patients with bifurcated lesions. Acknowledgement/Funding None

Background QFR and FFRCT are recently developed, less-invasive techniques for functional assessment of coronary artery disease. Objectives We compared the diagnostic performance between fractional flow reserve derived from computed tomography (FFRCT) and quantitative flow ratio (QFR) derived from coronary angiography, using FFR as the standard reference. Methods We measured FFRCT, QFR and FFR in 152 patients (233 vessels) with stable coronary artery disease. Results QFR was highly correlated with FFR (r=0.78, p Figure 1. Comparison of FFR ≤0.80 predictors Conclusions Both QFR and FFRCTpossessed the ability to accurately evaluate the functional severity of coronary stenosis.

Patients with acute coronary syndrome (ACS) face a substantial risk of future adverse cardiovascular events, including recurrent ACS ([1][1],[2][2]). Because this risk is partly attributable to lipid-rich vulnerable plaque, high-intensity statin therapy is recommended as a secondary prevention

Objectives: The objective was to evaluate the safety, feasibility, and accuracy of the jailed-pressure wire technique using a durable optical fiber-based pressure wire with high-pressure dilatation using a non-compliant balloon after main vessel stenting. Background: Fractional flow reserve (FFR) information can help interventionists determine whether they should treat a jailed-side branch (SB). However, re-crossing a pressure wire into a jailed-SB is sometimes technically difficult. Methods: Fifty-one consecutive lesions from 48 patients who underwent the jailed-pressure wire technique were retrospectively investigated. The primary endpoint was complication rate and secondary endpoints included success rate of FFR measurement, incidence of wire disruption, and final drift rate. The usability of FFR for percutaneous coronary intervention of coronary bifurcation lesion was also evaluated. Results: Median age of the patients was 69 years and 80.4% were men. The most frequent underlying disease was stable angina (70.6%) and 68.6% were type B2 lesions. Our main findings were: the procedure was performed successfully in all cases without any complications or wire disruption, FFR could be measured without significant final drift in 95.9% of cases, and FFR measurements helped interventionists determine whether to perform a final kissing balloon dilatation in 49.0% cases. Conclusions: The jailed-pressure wire technique using a durable optical fiber-based pressure wire with high-pressure post-dilatation maneuver was safe, feasible, and accurate.