Gray-zone Fractional Flow Reserve Research Articles

Impact of intravascular ultrasound parameters on revascularization decision in grey zone fractional flow reserve: data from IRIS FFR registry

Abstract Background The optimal revascularization strategy for coronary stenosis with grey-zone fractional flow reserve (FFR) value (0.75-0.80) is still debated. This study investigated the prognostic impact of the lesion characteristics measured by intravascular ultrasound (IVUS) in grey-zone FFR. Methods A total of 734 native coronary stenoses with grey-zone FFR in 734 patients from the prospective multicenter IRIS-FFR registry were simultaneously evaluated by IVUS. The primary outcome was a composite of cardiac death, myocardial infarction and target vessel revascularization. Results Among the 734 patients, revascularization was deferred for 293 patients and performed for 441. During a median follow-up of 4.4 years, the primary outcome occurred in 31 (10.6%) patients in deferred group and 42 (9.5%) in performed group. With the best cut-off values of 2.62 mm2 (area under curve 0.64) and 75% (area under curve 0.63), respectively, the minimal lumen area (MLA) and plaque burden (PB) at the MLA site were significant predictors of the primary outcome in the deferred group, whereas they were not predictive in the performed group. Revascularization performed group showed lower incidence rate of the primary outcome than deferral group in 348 patients with smaller MLA (<2.62 mm2) and larger PB (>75%) (19.3% vs. 36.8%, hazard ratio 0.58, 95% confidence interval [CI] 0.34-0.91, P=0.017), whereas other patients showed similar incidence rate of primary outcome between two groups (15.7% vs. 19.8%, hazard ratio 0.78, 95% CI 0.47-1.31, P=0.35). Conclusions For coronary stenoses with grey-zone FFR and smaller MLA and larger PB measured by IVUS, revascularization was associated with better clinical outcomes than deferral. The incorporation of FFR and IVUS may improve the revascularization decision in native coronary stenoses with grey-zone FFR.

TCTAP A-061 Impact of Minimal Lumen Area Measured by Intravascular Ultrasound on Revascularization Decision in Grey Zone Fractional Flow Reserve: Data From IRIS FFR Registry

TCTAP A-061 Impact of Minimal Lumen Area Measured by Intravascular Ultrasound on Revascularization Decision in Grey Zone Fractional Flow Reserve: Data From IRIS FFR Registry

TCT-282 Impact of Minimal Lumen Area Measured by Intravascular Ultrasound on Revascularization Decision in Grey Zone Fractional Flow Reserve: Data From IRIS FFR Registry

TCT-282 Impact of Minimal Lumen Area Measured by Intravascular Ultrasound on Revascularization Decision in Grey Zone Fractional Flow Reserve: Data From IRIS FFR Registry

Relationship between fractional flow reserve and graft patency after coronary artery bypass grafting

Bypass for moderately stenosed coronary arteries may cause graft failure (string phenomenon or occlusion). We examined the effects of fractional flow reserve (FFR) on the efficacy of coronary artery bypass grafting (CABG) in preventing graft failure. Between January 2013 and December 2017, 48 patients underwent CABG after FFR was measured. Twenty-five grafts in 23 patients were evaluated for graft patency after the procedure. We studied stenosis of native coronary arteries, FFR, graft flow, graft patency, and the presence of pre-procedure and post-procedure myocardial ischemia. Three internal thoracic arteries showed the string sign, and two saphenous vein grafts showed occlusion. All target coronary arteries for these grafts had moderate (50-75%) stenosis. Of the 25 grafts, five failed, and 20 were successful. All grafts with the string sign had been bypassed for target coronary arteries with the gray-zone FFR value (0.75-0.80). No difference in graft flow was observed between the failed and successful grafts. Patients with graft failure had no postoperative myocardial ischemia in target areas despite graft condition. Internal thoracic artery graft for coronary arteries with the gray-zone FFR value may exhibit the string phenomenon. We believe that graft failure occurred because the target area had no ischemia before CABG. FFR is useful in pre-operative ischemic evaluation including scintigraphy and will influence the success of revascularization, including the selection of grafts.

Percutaneous coronary intervention versus medical therapy in patients with angina and grey-zone fractional flow reserve values: a randomised clinical trial

IntroductionThere is conflicting evidence regarding the benefits of percutaneous coronary intervention (PCI) in patients with grey zone fractional flow reserve (GZFFR artery) values (0.75–0.80). The prevalence of ischaemia is unknown....

Highlights From the Circulation Family of Journals.

Highlights From the Circulation Family of Journals.

Outcomes With Deferred Versus Performed Revascularization of Coronary Lesions With Gray-Zone Fractional Flow Reserve Values.

Management of coronary lesions with fractional flow reserve values in the gray zone (0.75-0.80) remains controversial due to conflicting data on the performance versus deferral of revascularization. We performed a systematic review and meta-analysis of 7 observational studies including 2683 patients that compared the outcomes of deferred versus performed revascularization of coronary lesions with gray-zone fractional flow reserve values. During a mean follow-up of 31±9 months, the incidence of major adverse cardiovascular events (12.54 % versus 11.25%; odds ratio [OR], 1.64 [95% CI, 0.78-3.44]; P=0.19, I2=84%), cardiac mortality (1.25% versus 0.72%; OR, 1.78 [95% CI, 0.58-5.46]; P=0.31, I2=18%), and myocardial infarction (1.28% versus 2.66%; OR, 0.79 [95% CI, 0.22-2.79]; P=0.71, I2=65%) was similar with deferral versus performance of revascularization in coronary lesions with gray-zone fractional flow reserve. Deferral of revascularization was associated with a higher incidence of target vessel revascularization (9.12% versus 5.78%; OR, 1.85 [95% CI, 1.03-3.33]; P=0.04, I2=62%). When the analysis was limited only to studies that used percutaneous coronary intervention for revascularization, deferred revascularization remained associated with a higher risk of target vessel revascularization (18% versus 7.3%; OR, 3.04 [95% CI, 1.53-6.02]; P<0.001) and was associated with a higher risk of major adverse cardiovascular event (23.2% versus 13.4%; OR, 3.38 [95% CI, 1.92-5.95]; P<0.001). In lesions with gray-zone fractional flow reserve, revascularization was associated with a similar incidence of major adverse cardiovascular event but a lower incidence of target vessel revascularization over a mean follow-up of approximately 2.5 years. URL: https://www.crd.york.ac.uk/prospero/. Unique identifier: CRD42019128076.

P5635Predictive ability of lipdic burden for FFR-derived physiological measures: insights from near-infrared spectroscopy imaging analysis

Abstract Background Fractional flow reserve (FFR) has enabled to physiologically assess the myocardial ischemia of coronary artery with intermediate stenosis. Mechanistically, not only the severity of coronary stenosis but also the extent of maximal vasodilatation within the entire coronary artery potentially affects this physiological measure. Since the accumulation of lipidic materials within vessel wall increases vascular stiffness via inducing endothelial dysfunction, the presence of lipidic atheroma burden may affect physiological measures. Purpose To investigate the association of FFR with lipidic coronary atheroma by near-infrared spectroscopy/intravascular ultrasound (NIRS/IVUS) imaging, which quantitatively visualize lipidic burden in vivo. Methods We analyzed 61 coronary arteries (LAD/RCA/LCX=52/5/4) with FFR≤0.80 in 59 stable coronary artery disease subjects receiving PCI. Following FFR measurement, NIRS/IVUS imaging was conducted to evaluate the extent of atheroma burden (maximum percent plaque area=max%PA) and lipidic materials (lipid core burden index within the entire vessel=LCBIvessel). The analyzed vessels were stratified according to FFR: definite FFR group (FFR≤0.74, n=34) and gray-zone FFR group (0.75≤FFR≤0.80, n=27). Results NIRS/IVUS imaging analysis (analyzed longitudinal length=77±7mm) was more likely to exhibit a significantly higher LCBIvessel and a larger max%PA in the definite FFR group (Table). Of note, FFR was significantly correlated to LCBIvessel (ρ=-0.299, p=0.02), but not max%PA (ρ=-0.255, p=0.07). Multivariate analysis demonstrated that an independent determinant of FFR≤0.74 was LCBIvessel [odds ratio (OR)=1.016, 95% confidential interval (CI)=1.002–1.031, p=0.02], but not max%PA [OR=1.084, 95% CI=0.994–1.182, p=0.07]. Area under the receiver-operating characteristic curve analysis elucidated that the addition of LCBIvessel to angiography- and IVUS-derived measures resulted in a significant improvement for detecting FFR≤0.74 (picture). Definite FFR Group (FFR≤0.74, n=34) Gray-zone FFR Group (0.75≤FFR≤0.80, n=27) p value Fractional flow reserve (FFR) 0.68±0.05 0.78±0.02 &lt;0.01 Percent diameter stenosis (%) 56.2±13.1 51.9±7.8 0.16 Maximum percent plaque area (max%PA, %) 84.3±6.9 79.9±7.2 0.01 Lipid core burden index within the entire vessel (LCBIvessel) 102.0±60.2 65.6±51.6 0.01 ROC analysis for detecting FFR≦0.74 Conclusion The propagation of lipidic burden associates with the physiological measures. The present findings indicate the possibility that vessel characteristics or instability may have influence for causing ischemia on the coronary artery.

Deferral Versus Performance of Revascularization for Coronary Stenosis With Grey Zone Fractional Flow Reserve Values: A Systematic Review and Meta-Analysis.

We searched PubMed, EMBASE, Cochrane Library, and Web of Science for studies using fractional flow reserve (FFR) to determine whether revascularization should be performed or deferred for patients with coronary stenosis and grey zone FFR. Meta-analysis was performed using the generic inverse variance method, and hazard ratios (HR) were synthesized with a random-effects model. Of 2766 records, 7 nonrandomized studies including 2683 patients were selected. The pooled results demonstrated, during a median follow-up of 32 months, that revascularization significantly reduced the risk of major adverse cardiac events (MACE; 7 studies: HR [95% confidence interval, CI]: 0.65 [0.45-0.93], P = .02) and target vessel revascularization (TVR; 4 studies: HR [95% CI]: 0.52 [0.36-0.76], P < .01). Whereas revascularization was not significantly superior in terms of all-cause death (3 studies: HR [95% CI]: 0.56 [0.26-1.22], P = .14), cardiac death (2 studies: HR [95% CI]: 0.57 [0.16-2.01], P = .38), myocardial infarction (MI; 4 studies: HR [95% CI]: 1.03 [0.26-4.03]), and all-cause death or MI (3 studies: HR [95% CI]: 0.66 [0.20-2.19], P = .50). Therefore, revascularization appeared to be superior to deferral for patients with grey zone FFR in MACE and TVR, while hard end points did not show such significance. This work was registered in PROSPERO (CRD42019118432).

Optimal Treatment Strategy for Coronary Artery Stenoses with Grey Zone Fractional Flow Reserve Values. A Systematic Review and Meta-Analysis.

We conducted a review and meta-analysis of published data to compare revascularization to deferral strategy for coronary lesions with grey zone fractional flow reserve (FFR). Optimal treatment for coronary stenoses with FFR values between 0.75 and 0.80, the so-called grey zone, remains a matter of debate. We included all studies evaluating revascularization versus deferral for lesions with grey zone FFR. The primary outcome was study-defined major adverse cardiac events (MACE). Secondary outcomes were the composite of death or MI and target vessel revascularization (TVR). A total of 2362 patients were included, of whom 1181 underwent revascularization (revascularization group) and 1181 received medical treatment only (deferral group). After a mean follow-up period of 2.4 years, no difference was found for the primary outcome of the study-defined MACE between the two groups [RR = 1.33 (0.73-2.44), p = 0.35]. In addition, there was no difference for the secondary outcomes of death or MI and TVR between the two groups [RR = 1.39 (0.56-3.47), p = 0.48 and RR = 1.49 (0.89-2.51), p = 0.13, respectively]. In this meta-analysis revascularization of coronary stenoses with grey zone FFR showed no advantage over a deferral strategy in terms of study-defined MACE. Case by case judgment should be implemented to guide treatment in this special subset of patients.

Gray zone fractional flow reserve 0.81–0.85 is associated with an increased risk of cardio-vascular events

Fractional Flow Reserve (FFR) is a widely accepted prognostic tool to estimate the risk of myocardial ischemia in coronary stenosis. Values above 0.80 are considered as an indication for medical therapy only. Whether intermediate values ranging from 0.81 to 0.85 are associated with an increase cardio-vascular (CV) risk is unknown. In a prospective study, 91 patients with FFR > 0.80 were enrolled and followed up for at least 1 year. Clinical outcomes of the subgroup with FFR > 0.85 ( N = 67) were compared with those of the subgroup with intermediate values of 0.81–0.85 ( N = 24). The outcome was a composite of cardio-vascular death/myocardial infarction/CV hospitalization/target lesion revascularization. There was significant difference in baseline demographic data or medical therapy between the two groups ( Table 1 ). The average follow-up is 2.505 ± 0.6 years. We observed a significantly higher number of events in patients with FFR between 0.81 and 0.85 than in those with FFR > 0.85. These events occurred respectively in 45.9% and 13.4% of patients ( P = 0.01) and were mostly the result of revascularizations and CV hospitalizations ( Fig. 1 ). FFR values in the gray zone of 0.81–0.85 are correlated with an increased CV risk compared to FFR values > 0.85. Appropriately powered trials are needed to assess the potential benefit of revascularization in this subset of patients.

Comparison of clinical outcomes following percutaneous coronary intervention versus optimal medical therapy based on gray-zone fractional flow reserve in stable angina patients with intermediate coronary artery stenosis (COMFORTABLE prospective study): Study protocol for a multicenter randomized controlled trial

BackgroundEven in the current drug-eluting stent era, revascularization for coronary stenosis with fractional flow reserve (FFR) between 0.75 and 0.80, the so-called “gray zone,” is a matter of debate. Previous studies have reported conflicting results regarding outcomes of revascularization versus deferral for coronary stenosis when FFR values are in the gray zone, but these studies have had differing designs and populations. We therefore will investigate whether medical therapy plus percutaneous coronary intervention (PCI) is superior to medical therapy alone in reducing major cardiovascular events in patients presenting with coronary stenosis with gray zone FFR values.Methods/designThis is a prospective, multicenter, open-label, parallel group, randomized, controlled, superiority study. A total of 410 eligible participants will be recruited and randomized to either the medical therapy plus PCI group or the medical therapy alone group. The primary endpoint is 1-year major adverse cardiac events (MACEs), defined as a combined endpoint of all-cause death, nonfatal myocardial infarction (MI), or unplanned target vessel revascularization (TVR). Secondary endpoints include MACE at 2 and 5 years. Moreover, each individual component of the primary endpoint, cardiovascular death, target vessel-related and non-target vessel-related MI, all MI, clinically driven TVR or non-TVR, all revascularization, stent thrombosis, and angina symptom status will be evaluated at 1, 2, and 5 years.DiscussionThis is the first prospective, multicenter, randomized, controlled study to investigate the superiority of medical therapy plus PCI over medical therapy by itself in reducing major cardiovascular events in patients presenting with coronary stenosis with “gray zone” FFR values. The results will help interventional cardiologists in making revascularization decisions regarding coronary stenosis with gray zone FFR values.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry, UMIN000031526. Registered on 1 March 2018.

Yellow traffic lights and grey zone fractional flow reserve values: stop or go?

Yellow traffic lights and grey zone fractional flow reserve values: stop or go?

Coronary physiological assessment combining fractional flow reserve and index of microcirculatory resistance in patients undergoing elective percutaneous coronary intervention with grey zone fractional flow reserve.

The aim of this study is to investigate the association between fractional flow reserve (FFR) values and change in coronary physiological indices after elective percutaneous coronary intervention (PCI). Decision making for revascularization when FFR is 0.75-0.80 is controversial. A retrospective analysis was performed of 296 patients with stable angina pectoris who underwent physiological examinations before and after PCI. To investigate the differences of coronary flow improvement between territories with low-FFR (<0.75) and grey-zone FFR (0.75-0.80), serial changes in physiological indices including mean transit time (Tmn), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were compared between these two groups. Compared to low-FFR territories, grey-zone FFR territories showed significantly lower prevalence of Tmn shortening, CFR improvement, and decrease in IMR (Tmn shorting, 63.9% vs. 87.0%, P < .001; CFR improvement, 63.0% vs. 75.7%, P = .019; IMR decrease, 51.3% vs. 63.3%, P = .040) and lower extent of their absolute changes (Tmn shorting, 0.06 (-0.03 to 0.16) vs. 0.22 (0.07-0.45), P < .001; CFR improvement, 0.45 (-0.32 to 1.87) vs. 1.08 (0.02-2.44), P < .01; IMR decrease, 0.2 (-44.0 to 31.3) vs. 2.9 (-2.9 to 11.8), P = .022). Multivariate analysis showed that pre-PCI IMR predicted improved coronary flow profile in both groups, whereas pre-PCI FFR predicted increased coronary flow indices in low-FFR territories. Worsening of physiological indices after PCI was not uncommon in territories showing grey-zone FFR. Physiological assessment combining FFR and IMR may help identify patients who may benefit by PCI, particularly those in the grey zone.

TCT-375 Deferred Versus Performed Revascularization in Coronary Stenoses With Gray Zone Fractional Flow Reserve: Data From IRIS FFR Registry

The optimal cutoff of fractional flow reserve (FFR) for revascularization is in debate. We evaluated the prognosis of deferred and performed revascularization in coronary stenoses with gray zone FFR (0.75-0.80). From prospective IRIS-FFR registry, 1334 native coronary stenoses in 1334 patients with

P1751Integrated physiological assessment of increased coronary flow after elective percutaneous coronary intervention in patients with grey zone fractional flow reserve

P1751Integrated physiological assessment of increased coronary flow after elective percutaneous coronary intervention in patients with grey zone fractional flow reserve

Seven-year clinical outcomes of patients with moderate coronary artery stenosis after deferral of revascularization based on gray-zone fractional flow reserve.

The range (0.75-0.80) of fractional flow reserve (FFR) is known as the gray zone. Although the FFR of 0.80 was recently adopted as the cutoff value for coronary revascularization, the long-term clinical outcomes of patients with angiographically moderate coronary artery stenosis (FFR: 0.75-0.80) remain unknown. The objective of the present study was to investigate the clinical outcomes of patients with angiographically moderate coronary artery stenosis, whose FFR was 0.75-0.80. One hundred and twenty consecutive patients, for whom coronary revascularization was deferred based on FFR, were categorized to groups I and II, in which 55 and 65 patients had FFRs of 0.75-0.80 and 0.81-0.85, respectively. Adverse cardiac events included all-cause death, cardiac death, myocardial infarction, coronary revascularization for the FFR-measured and -unmeasured arteries, congestive heart failure, and admission for chest symptoms. Patients were followed up for 7years after coronary angiography. Event-free survival rates of all adverse cardiac events were 73% in group I and 63% in group II (P=0.35) and those of adverse cardiac events related to the FFR-measured artery were 94 and 85% (P=0.08). Throughout the follow-up period, the medication rate of statins was significantly lower in group II than in group I (P=0.008). Seven-year clinical outcomes of patients with the gray-zone FFR were good. Furthermore, FFR-measured artery-related events in patients with the gray-zone FFR tended to occur less frequently than in patients with better FFR of 0.81-0.85. Optimal medical therapy is required for them, regardless of coronary stenosis severity and FFR.

TCTAP A-116 Long-term Outcome After Deferral of Revascularization in Patients with Intermediate Coronary Stenosis and Gray-zone Fractional Flow Reserve

TCTAP A-116 Long-term Outcome After Deferral of Revascularization in Patients with Intermediate Coronary Stenosis and Gray-zone Fractional Flow Reserve

TCT-610 Deferred Coronary Lesion With A Gray Zone Fractional Flow Reserve In Patients With Intermediate Stenosis Is At Higher Risk Of Future Coronary Events

Deferral of revascularization of an intermediate coronary stenosis with fractional flow reserve (FFR) ≧0.75 was reported to be safe. However, the FFR value range between 0.75 and 0.80 has been recognized as a gray zone. We hypothesized that outcomes after deferral of revascularization between

Carotid pain: report of six cases.

<h3>Introduction</h3> There is conflicting evidence regarding the benefits of percutaneous coronary intervention (PCI) in patients with grey zone fractional flow reserve (^GZFFR artery) values (0.75–0.80). The prevalence of ischaemia is unknown. We wished to define the prevalence of ischaemia in ^GZFFR artery and assess whether PCI is superior to optimal medical therapy (OMT) for angina control. <h3>Methods</h3> We enrolled 104 patients with angina with 1:1 randomisation to PCI or OMT. The artery was interrogated with a Doppler flow/pressure wire. Patients underwent Magnetic Resonance Imaging (MRI) with follow-up at 3 and 12 months. The primary outcome was angina status at 3 months using the Seattle Angina Questionnaire (SAQ). <h3>Results</h3> 104 patients (age 60±9 years), 79 (76%) males and 79 (76%) Left Anterior Descending (LAD) stenoses were randomised. Coronary physiology and SAQ were similar. Of 98 patients with stress perfusion MRI data, 17 (17%) had abnormal perfusion (≥2 segments with ≥25% ischaemia or ≥1 segment with ≥50% ischaemia) in the target ^GZFFR artery. Of 89 patients with invasive physiology data, 26 (28%) had coronary flow velocity reserve &lt;2.0 in the target ^GZFFR artery. After 3 months of follow-up, compared with patients treated with OMT only, patients treated by PCI and OMT had greater improvements in SAQ angina frequency (21 (28) vs 10 (23); p=0.026) and quality of life (24 (26) vs 11 (24); p=0.008) though these differences were no longer significant at 12 months. <h3>Conclusions</h3> Non-invasive evidence of major ischaemia is uncommon in patients with ^GZFFR artery. Compared with OMT alone, patients randomised to undergo PCI reported improved symptoms after 3 months but these differences were no longer significant after 12 months. <h3>Trial registration number</h3> NCT02425969.