Search

ObjectivesTo obtain more powerful assessment of the prognostic value of fractional flow reserveCT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFRCT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD).MethodsWe searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserveCT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as ‘all-cause mortality (ACM) or myocardial infarction (MI)’ at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint.ResultsFive studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFRCT>0.80% and 1.4% (47/3334) with FFRCT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFRCT ≤0.80 versus patients with FFRCT >0.80. Each 0.10-unit FFRCT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), pConclusionsThe 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFRCT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFRCT numerical value was inversely associated with outcomes.

BACKGROUND Myocardial perfusion imaging (MPI) and fractional flow reserve (FFR) are established approaches to the assessment of myocardial ischemia. Recently, various FFR cutoff values were proposed, but the diagnostic accuracy of MPI in identifying positive FFR using various cutoff values is not well established.Methods and Results:We retrospectively studied 273 patients who underwent stress MPI and FFR within a 3-month period. Results for FFR were obtained from 218 left anterior descending artery (LAD) lesions and 207 non-LAD lesions. Stress MPI and FFR demonstrated a good correlation in the detection of myocardial ischemia. However, the positive predictive value (PPV) of FFR for detecting MPI-positive lesions at the optimal FFR thresholds was insufficient (44% for LAD and 65% for non-LAD lesions). This was caused by a sharp drop in PPV at an FFR threshold of 0.7 or more. Notably, 41% of the lesions with normal MPI demonstrated FFRs

This study sought to evaluate the prognostic impact of plaque morphology and coronary physiology on outcomes after medical treatment or percutaneous coronary intervention (PCI).Although fractional flow reserve (FFR) is currently best practice, morphological characteristics of coronary artery disease also contribute to outcomes.A total of 872 vessels in 538 patients were evaluated by invasive FFR and coronary computed tomography angiography. High-risk attributes (HRA) were defined as high-risk physiological attribute (invasive FFR ≤0.8) and high-risk morphological attributes including: 1) local plaque burden (minimum lumen area 4 mmThe mean FFR was 0.88 ± 0.08, and PCI was performed in 239 vessels. The primary outcome occurred in 54 vessels (6.2%). All high-risk morphological attributes were associated with the increased risk of adverse outcomes after adjustment for FFR ≤0.8 and demonstrated direct prognostic effect not mediated by FFR ≤0.8. The 5-year event risk proportionally increased as the number of HRA increased (p for trend 0.001) with lower risk in the PCI group than the medical treatment group in vessels with 1 or 2 HRA (9.7% vs. 14.7%), but not in vessels with either 0 or ≥3 HRA. Of the vessels with pre-procedural FFR ≤0.8, ischemia relief by PCI (pre-PCI FFR ≤0.8 and post-PCI FFR0.8) significantly reduced vessel-oriented composite outcome risk compared with medical treatment alone in vessels with 0 or 1 high-risk morphological attributes (hazard ratio: 0.33; 95% confidence interval: 0.12 to 0.93; p = 0.035), but the risk reduction was attenuated in vessels with ≥2 high-risk morphological attributes.High-risk morphological attributes offered additive prognostic value to coronary physiology and may optimize selection of treatment strategies by adding to FFR-based risk predictions (CCTA-FFR Registry for Development of Comprehensive Risk Prediction Model; NCT04037163).

Objectives: The aim of this study was to assess clinical outcomes after combined pressure and flow assessment of coronary lesions. Background: Although fractional flow reserve (FFR) remains the invasive reference standard for revascularization, approximately 40% of stenoses have discordant coronary flow reserve (CFR). Optimal treatment for these disagreements remains unclear. Methods: A total of 455 subjects with 668 lesions were enrolled from 12 sites in 6 countries. Only lesions with reduced FFR and CFR underwent revascularization; all other combinations received initial medical therapy. Results: Fourteen percent of lesions had FFR ≤0.8 but CFR ≥2.0 while 23% of lesions had FFR >0.8 but CFR 0.8 and CFR ≥2.0 (6.2% event rate) exceeded the prespecified +10% noninferiority margin (P = 0.090). Target vessel failure models using both continuous FFR and continuous CFR found that only higher FFR was associated with reduced target vessel failure (Cox P = 0.007) after initial medical treatment. Central core laboratory review accepted 69.8% of all tracings with mean differences of 0.8 and CFR ≥2.0. These results do not support using invasive CFR ≥2.0 to defer revascularization for lesions with reduced FFR if the patient would otherwise be a candidate on the basis of the entire clinical scenario and treatment preference.

Background: In the resting conditions, narrowing the window of coronary pressure measurements from the whole cardiac cycle to diastole improves diagnostic performance of coronary pressure–derived physiological index. However, whether this also applies to the hyperemic conditions has not yet been thoroughly evaluated. Objectives: The purpose of this study was to assess whether diastolic fractional flow reserve (diastolic FFR) has better diagnostic performance in identifying ischemia-causing coronary lesions than conventional FFR in a prospective, multicenter, and independent core laboratory–based environment. Methods: In this prospective multicenter registry at 29 Japanese centers, we compared the diagnostic performance of FFR, diastolic FFR, resting distal to aortic coronary pressure (Pd/Pa), and diastolic pressure ratio (dPR) using myocardial perfusion scintigraphy (MPS) as the reference standard in 378 patients with single-vessel coronary disease. Results: Inducible myocardial ischemia was found on MPS in the relevant myocardial territory of the target vessel in 85 patients (22%). In the receiver-operating curve analyses, diastolic FFR had comparable area under the curve (AUC) compared with FFR (AUCdiastolic FFR: 0.66; 95% confidence interval [CI]: 0.58-0.73, vs AUCFFR: 0.66; 95% CI: 0.58-0.74, P = 0.624). FFR and diastolic FFR showed significantly larger AUCs than resting Pd/Pa (0.62; 95% CI: 0.54-0.70; P = 0.033 and P = 0.046) but did not show significantly larger AUCs than dPR (0.62; 95% CI: 0.55-0.70; P = 0.102 and P = 0.113). Conclusions: Diastolic FFR showed a similar diagnostic performance to FFR as compared with MPS. This result reaffirms the use of FFR as the most accurate invasive physiological lesion assessment. (Diagnostic accuracy of diastolic fractional flow reserve (d-FFR) for functional evaluation of coronary stenosis; UMIN000015906)

The physiological pattern of coronary artery disease as determined by pressure-wire (PW)-pullback is important for decision-making of revascularization and risk stratification of patients. However, it remains unclear whether inter-observer differences in interpreting PW-pullback data are subject to the expertise of physicians. This study sought to investigate the subjectivity of this assessment among non-experts. Expert interventional cardiologists classified 545 PW-pullback traces into physiologically focal or physiologically diffuse disease pattern. Defining expert-consensus as the reference standard, we evaluated ten non-expert doctors’ classification performance. Observers were stratified equally by two ways: (i) years of experience as interventional cardiologists (middle-level vs. junior-level) and (ii) volume of institutions where they belonged to (high-volume center vs. low-volume center). When judged against the expert-consensus, the agreement of non-expert observers in assessing physiological pattern of disease (focal or diffuse) ranged from 69.1 to 85.0% (p for heterogeneity

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 Physiology-guided percutaneous coronary intervention (PCI) has demonstrated to improve clinical outcomes. Previous trials showed the agreement between iFR and FFR is approximately 80%, however the details of discordance pattern remain to be elucidated. Methods We retrospectively reviewed 1024 consecutive intermediate stenotic lesions for which functional evaluation using both iFR and FFR were performed between January 2015 and June 2016. The lesions were classified into 4 groups according to iFR and FFR concordance [(iFR+/FFR+) and (iFR-/FFR-)] or discordance [(iFR+/FFR-) and (iFR-/FFR+)]. Results Our study evaluated 451 lesions, 264 lesions (58.5%) from men and 187 lesions (41.5%) from women. iFR was similar between women and men, however FFR was significantly higher in women than men. The rate of discordance between iFR and FFR was 21.3% (iFR+/FFR- 12.4% and iFR-/FFR+ 8.9%) in overall cohort. The prevalence of overall concordance and discordance were similar between men and women, however iFR+/FFR- discordance was significantly higher in women (17.1% vs. 9.1%) whereas iFR-/FFR+ discordance was significantly higher in men (11.3% vs. 4.8%). In multivariable analysis, female sex and older age were significantly associated with iFR+/FFR- discordance (odds ratio 1.88 and 1.48, respectively). Conversely, younger age, higher stenosis, and concomitant chronic total occlusion were independent predictors for iFR-/FFR+ discordance (odds ratio 0.67, 1.82, and 4.32, respectively). Conclusions Despite similar prevalence of overall concordance and discordance between men and women, iFR+/FFR- discordance was higher in women and iFR-/FFR+ discordance was higher in men. Multivariable analysis showed female sex to be independent predictor of iFR+/FFR- discordance.

Background: The effect of symptoms on clinical outcomes after deferral of revascularization based on fractional flow reserve (FFR) remains poorly understood. Methods and Results: From the J-CONFIRM (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter) Registry, this study evaluated 1,215 patients with stable coronary artery disease, including symptomatic and asymptomatic patients (n=571 and 644, respectively). The primary endpoint was the cumulative 2-year incidence of target vessel failure (TVF), including cardiac death, target vessel-related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). An inverse probability weighted analysis was performed to adjust for the differences in baseline clinical characteristics between the 2 groups. At 2 years, the TVF rate did not differ significantly between symptomatic and asymptomatic patients (6.5% vs. 4.9%, respectively; P=0.15) or between symptomatic and asymptomatic patients with lesions with an FFR ≤0.80 (8.0% vs. 12.3%, respectively; P=0.20). Conversely, symptomatic patients showed significantly higher rates of TVF (6.2% vs. 3.3%; P=0.01) and CDTVR (6.2% vs. 3.1%; P=0.009) than asymptomatic patients, regardless of negative FFR values (>0.80). Conclusions: Despite negative FFR values, symptomatic patients were at higher risk of TVF than asymptomatic patients, driven primarily by a higher rate of CDTVR. Conversely, those with a positive FFR were likely to develop TVF regardless of their symptoms.

Objectives 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. Background 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. Methods 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. Results The predicted NHPRs were strongly correlated with actual NHPRs: iFR, r = 0.83 (95% confidence interval: 0.72 to 0.90; p Conclusions 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 )

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.

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

The diastolic pressure ratio (dPR) and resting full-cycle ratio (RFR) are considered to be almost identical to the instantaneous wave-free ratio (iFR) in the retrospective analysis of pooled data. The aim of this study was to investigate the direct comparison of iFR and these new resting indexes in real world practice. Two pressure wires were inserted and placed in the distal part of the same coronary artery. The measurement of the iFR and the other resting indexes was performed simultaneously. A total of 54 lesions from 23 patients were subject to physiological study. In 49 lesions, iFR and other resting indexes were also measured in hyperemic conditions. The general correlation between iFR and other resting indexes was excellent in both resting and hyperemic conditions (r2 = 0.99; mean difference − 0.001 ± 0.021; p

Objectives This study sought to assess the diagnostic performance of FFRangio (CathWorks, Kfar Saba, Israel), an angiogram-derived fractional flow reserve (FFR) technology. Background Despite practice guidelines recommendations, the use of coronary physiologic assessment in daily practice remains low for patients undergoing coronary angiography. Angiogram-derived FFR technologies have the potential to promote the integration of physiologic assessment in daily practice. Methods The study performed an analysis of pooled patient- and lesion-level data from 5 prospective cohort studies that examined the diagnostic performance of FFRangio compared with the reference standard wire-based FFR. Results A total of 700 lesions from 588 patients were analyzed. Mean age was 65 years, 71% were men, and 40% presented with acute coronary syndromes. Mean FFR and FFRangio were 0.81 ± 0.12 and 0.81 ± 0.11, with 31.6% and 31.4% of lesions were in the 0.75 to 0.85 range, respectively. When using a binary cutoff FFR value of 0.80, FFRangio showed a sensitivity of 91%, a specificity of 94%, and a diagnostic accuracy of 93%. The mean difference between FFR and FFRangio was 0.00 ± 0.12. The correlation coefficient between FFR and FFRangio was 0.83 (p Conclusions In the largest reported cohort examining the performance of angiogram-derived FFR technology, FFRangio showed excellent diagnostic performance, which was robust and consistent across all patient and lesion subgroups. Additional studies are needed allow FFRangio and fulfill its potential expand the implementation of functional assessment of coronary lesions in routine clinical practice.

Objectives The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFRCT) with downstream care and clinical outcomes. Background Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes. Methods Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFRCT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured. Results At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFRCT ≤0.80 and in 89 (5.60%) with an FFRCT >0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p 0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFRCT ≤0.80 compared with 10 (0.60%) patients with an FFRCT >0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFRCT ≤0.80 compared with patients with an FFRCT >0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01). Conclusions The 1-year outcomes from the ADVANCE FFRCT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFRCT compared with patients with abnormal FFRCT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679)

Background: The role of change in fractional flow reserve derived from CT (FFRCT) across coronary stenoses (ΔFFRCT) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown. Objectives: To investigate the incremental value of ΔFFRCT in predicting early revascularization and improving efficiency of catheter laboratory utilization. Materials: Patients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFRCT was measured 2 ​cm distal to stenosis. ΔFFRCT was manually measured as the difference of FFRCT across visible stenosis. Results: Of 4730 patients (66 ​± ​10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFRCT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26–1.35]; p ​< ​0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFRCT. Among the 3 models (model 1: risk factors ​+ ​stenosis type and location ​+ ​CAD-RADS; model 2: model 1 ​+ ​FFRCT; model 3: model 2 ​+ ​ΔFFRCT), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86–0.88] vs 0.85 [0.84–0.86]; p ​< ​0.001), with the greatest incremental value for FFRCT 0.71–0.80. ΔFFRCT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFRCT ≤0.8, a diagnostic strategy incorporating ΔFFRCT >0.13, would potentially reduce ICA by 32.2% (1638–1110, p ​< ​0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%. Conclusions: ΔFFRCT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFRCT, particularly for those with FFRCT 0.71–0.80. ΔFFRCT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization.

Background Immune status in the tumor microenvironment is an important determinant of cancer progression and patient prognosis. Although a higher immune activity is often associated with a better prognosis, this trend is not absolute and differs across cancer types. We aimed to give insights into why some cancers do not show better survival despite higher immunity by assessing the relationship between different biological factors, including cytotoxicity, and patient prognosis in various cancer types using RNA-seq data collected by The Cancer Genome Atlas. Results Results showed that a higher immune activity was associated with worse overall survival in patients with uveal melanoma and low-grade glioma, which are cancers of immune-privileged sites. In these cancers, epithelial or endothelial mesenchymal transition and inflammatory state as well as immune activation had a notable negative correlation with patient survival. Further analysis using additional single-cell data of uveal melanoma and glioma revealed that epithelial or endothelial mesenchymal transition was mainly induced in retinal pigment cells or endothelial cells that comprise the blood-retinal and blood-brain barriers, which are unique structures of the eye and central nervous system, respectively. Inflammation was mainly promoted by macrophages, and their infiltration increased significantly in response to immune activation. Furthermore, we found the expression of inflammatory chemokines, particularly CCL5, was strongly correlated with immune activity and associated with poor survival, particularly in these cancers, suggesting that these inflammatory mediators are potential molecular targets for therapeutics. Conclusions In uveal melanoma and low-grade glioma, inflammation from macrophages and epithelial or endothelial mesenchymal transition are particularly associated with a poor prognosis. This implies that they loosen the structures of the blood barrier and impair homeostasis and further recruit immune cells, which could result in a feedback loop of additional inflammatory effects leading to runaway conditions.

Assessment of coronary artery lesions using the fractional flow reserve and instantaneous flow reserve (iFR) measurements has been found to reduce the incidence of further cardiovascular events. Here, we investigated differences in terms of coronary flow velocity and resistance within the analysis interval between the iFR and the intracoronary electrocardiogram (IC-ECG)-triggered distal/aortic pressure (Pd/Pa) ratio (ICE-T). We enrolled 23 consecutive patients (n = 33 stenoses) who required coronary flow measurements. ICE-T was defined as the average Pd/Pa ratio in the period corresponding to the isoelectric line of the IC-ECG. We compared the index value, flow velocity, and intracoronary resistance during the analysis intervals of the iFR and the ICE-T, both at rest and under hyperemia. ICE-T values and ICE-T intracoronary resistance were both found to be significantly lower, whereas flow velocity was significantly higher than those of the iFR at both rest and under hyperemia (P

Item does not contain fulltext OBJECTIVES: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies. BACKGROUND: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. METHODS: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. RESULTS: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 +/- 0.51 vs. 0.43 +/- 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 +/- 0.09 vs. 0.91 +/- 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 +/- 0.09 vs. 0.85 +/- 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). CONCLUSIONS: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038).

Objectives The aim of this study was to compare diagnostic performance between quantitative flow ratio (QFR) derived from coronary angiography and fractional flow reserve derived from computed tomography (FFRCT) using fractional flow reserve (FFR) as the reference standard. Background QFR and FFRCT are recently developed, less invasive techniques for functional assessment of coronary artery disease. Methods QFR, FFRCT, and FFR were measured in 152 patients (233 vessels) with stable coronary artery disease. Results QFR was highly correlated with FFR (r = 0.78; p Conclusions QFR and FFRCT showed significant correlation with FFR. Mismatches between QFR and FFR and between FFRCT and FFR were frequent.

Objective To assess the performance of angiography derived Fractional Flow Reserve (FFRangio) in multivessel disease (MVD) patients undergoing angiography. Background FFR is the reference standard for physiologic assessment of coronary stenosis and guidance of revascularization, especially in patients with MVD, yet it remains grossly underutilized. The non-wire based FFRangio performs well in non-MVD patients, but its accuracy in MVD is unknown. Methods A prospective clinical study was conducted at Gifu Heart Centre, Japan. Patients underwent physiologic assessment of all relevant coronary lesions using wire-based FFR (wbFFR) and FFRangio. Primary outcome was diagnostic performance (sensitivity, specificity, accuracy) for FFRangio with wbFFR as reference. Other outcomes were the correlation between wbFFR/FFRangio, time required for wbFFR/FFRangio measurements, and the effect of wbFFR/FFRangio on the reclassification of coronary disease severity. Results Fifty patients (118 lesions in total) were included. Mean age was 72 ± 9 years, 72% were male, 36% had triple vessel disease and the average SYNTAX score was 13. The mean measurement of wbFFR and FFRangio were 0.83 ± 0.12 and 0.81 ± 0.11, respectively. Accuracy, sensitivity and specificity for FFRangio were 92.3% (95% CI 79.1–98.4%), 92.4% (95% CI 84.3–97.2%) and 92.4% (95% CI 87.4–97.3%), respectively. Pearson's r between wbFFR and FFRangio was 0.83. FFRangio measurement was faster than wbFFR (9.6 ± 3.4 vs. 15.0 ± 8.9 min, p Conclusions In patients with MVD, FFRangio shows good correlation and excellent diagnostic performance compared to wbFFR, and measuring FFRangio is faster than wbFFR. These results highlight the potential clinical benefits of utilizing FFRangio among patients with MVD.

Although the presence of ischemia is a key prognostic factor in patients with coronary artery disease, the presence of high-risk plaque characteristics (HRPC) is also associated with increased risk of cardiovascular events. Limited data exist regarding the prognostic implications of combined information on physiological stenosis severity assessed by fractional flow reserve (FFR) and plaque vulnerability by coronary computed tomography angiography (CTA)-defined HRPC.The current study aimed to evaluate the: 1) association between physiological stenosis severity and coronary CTA-defined HRPC; and 2) prognostic implications of coronary CTA-defined HRPC according to physiological stenosis severity in patients with coronary artery disease.A total of 772 vessels (299 patients) evaluated by both coronary CTA and FFR were analyzed. The presence and number of HRPC (minimum lumen area 4 mmThe proportion of lesions with ≥3 HRPC was significantly decreased according to the increase in FFR values (58.6%, 46.5%, 36.8%, 15.7%, and 3.5% for FFR ≤0.60, 0.61 to ≤0.70, 0.71 to ≤0.80, 0.81 to ≤0.90, and0.90, respectively; overall p value 0.001). Both FFR and number of HRPC showed significant association with the estimated risk of VOCO (p = 0.008 and p = 0.023, respectively). In the FFR0.80 group, lesions with ≥3 HRPC showed significantly higher risk of VOCO than those with 3 HRPC (15.0% vs. 4.3%; hazard ratio: 3.964; 95% confidence interval: 1.451 to 10.828; p = 0.007). However, there was no significant difference in the risk of VOCO according to HRPC in the FFR ≤0.80 group. By multivariable analysis, the presence of ≥3 HRPC was independently associated with the risk of VOCO in the FFR0.80 group.Physiological stenosis severity and the number of HRPC were closely related, and both components had significant association with the risk of clinical events. However, the prognostic implication of HRPC was different according to FFR. Integration of both physiological stenosis severity and plaque vulnerability would provide better prognostic stratification of patients than either individual component alone, especially in patients with FFR0.80. (Clinical Implication of 3-vessel Fractional Flow Reserve [3V FFR-FRIENDS study]; NCT01621438).

Background: Coronary computed tomography angiography (cCTA)-derived fractional flow reserve (FFRCT) is a promising diagnostic method for the evaluation of coronary artery disease (CAD). However, clinical data regarding FFRCT in Japan are scarce, so we assessed the clinical impact of using FFRCT in a Japanese population. Methods and Results: The ADVANCE registry is an international prospective FFRCT registry of patients suspected of CAD. Of 5,083 patients, 1,829 subjects enrolled from Japan were analyzed. Demographics, symptoms, cCTA, FFRCT, treatment strategy, and 90-day major cardiovascular events (MACE) were assessed. Reclassification of treatment strategy between cCTA alone and cCTA+FFRCT occurred in 55.8% of site investigations and in 56.9% in the core laboratory analysis. Patients with positive FFR (FFRCT ≤0.80) were less likely to have non-obstructive disease on invasive coronary angiography than patients with negative FFR (FFRCT >0.80) (20.5% vs. 46.1%, P=0.0001). After FFRCT, 67.0% of patients with positive results underwent revascularization, whereas 96.1% of patients with negative FFRCT were medically treated. MACE occurred in 5 patients with positive FFRCT, but none occurred in patients with negative FFRCT within 90 days. Conclusions: In this Japanese population, FFRCT modified the treatment strategy in more than half of the patients. FFRCT showed potential for stratifying patients suspected of CAD properly into invasive or non-invasive management pathways.

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.

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.

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.

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

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.

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.

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.

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.

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

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