Xinyang Hu

Optimal Intravascular Ultrasound Criteria for Defining the Functional Significance of Intermediate Coronary Stenosis: An International Multicenter Study

Objective: We aimed to assess the ideal cut-off value of minimal lumen area (MLA) by intravascular ultrasound (IVUS) and its diagnostic performance to predict ischemia, using a large-scale, pooled analysis. Methods: Eleven centers worldwide were invited to provide their clinical, IVUS and fractional flow reserve (FFR) data. A total of 881 lesions were enrolled. Results: Angiographic % diameter stenosis (r = -0.373, p < 0.0001) and IVUS MLA (r = 0.289, p < 0.0001) correlated with FFR. Best cut-off value (BCV) of IVUS MLA to define the functional significance (FFR <0.8) was 2.75 mm2 (AUC 0.646, 95% CI 0.609-0.684). When the diagnostic performance of IVUS MLA was tested according to the lesion location, BCV could be found only in lesions in the proximal artery and the mid-left anterior descending artery. Interestingly, Asians (n = 623) and Westerners (n = 258) showed different demographic and lesion characteristics as well as different BCVs to define ischemia. The BCV for the proximal/mid-left anterior descending artery lesions was 2.75 mm2 (AUC 0.688, 95% CI 0.635-0.742) in Asians and 3.0 mm2 (AUC 0.695, 95% CI 0.605-0.786) in Westerners. Conclusion: In this pooled analysis, an IVUS MLA of 2.75 mm2 was the BCV to define the functional significance of intermediate coronary stenosis. However, when IVUS MLA is used to determine the functional significance, both the lesion and patient characteristics should be considered.

Clinical implications of three-vessel fractional flow reserve measurement in patients with coronary artery disease

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 < 0.001). The patients in low 3V-FFR group showed a higher risk of 2-year MACE than those in the high 3V-FFR group [(7.1% vs. 3.8%, hazard ratio (HR) 2.205, 95% confidence interval (CI) 1.201-4.048, P = 0.011]. The higher 2-year MACE rate was mainly driven by the higher rate of ischaemia-driven revascularization in the low 3V-FFR group (6.2% vs. 2.7%, HR 2.568, 95% CI 1.283-5.140, P = 0.008). In a multivariable adjusted model, low 3V-FFR was an independent predictor of MACE (HR 2.031, 95% CI 1.078-3.830, P = 0.029). Conclusion Patients with high total physiologic atherosclerotic burden assessed by 3V-FFR showed higher risk of 2-year clinical events than those with low total physiologic atherosclerotic burden. The difference was mainly driven by ischaemia-driven revascularization for both functionally significant and insignificant lesions at baseline. Three-vessel FFR might be used as a prognostic indicator in patients with coronary artery disease. Clinical trial registration 3V FFR-FRIENDS study (https://clinicaltrials.gov/ct2/show/NCT01621438, NCT01621438).

Usefulness of combined intravascular ultrasound parameters to predict functional significance of coronary artery stenosis and determinants of mismatch.

AIMS Efficacy of combined intravascular ultrasound (IVUS) parameters in functional significance prediction and discrepancy between IVUS and fractional flow reserve (FFR) have not been well defined. This study therefore aimed to: 1) evaluate the diagnostic accuracy of combined IVUS parameters, namely minimal lumen area (MLA) and percent plaque burden (%PB), in functional significance prediction of coronary artery stenosis; and 2) define factors that affect the relation between FFR value and IVUS parameters. METHODS AND RESULTS At 11 international centres, IVUS and FFR measurements were concurrently performed in 945 major epicardial coronary artery lesions (886 patients). Functional significance was defined as FFR ≤0.8. MLA and FFR correlated weakly (r=0.289, p<0.001). Diagnostic accuracy of MLA ≤4.0 mm2, %PB >70% and their combination were 50%, 47% and 51%, respectively, with similar area under the curve (AUC) of 0.561, 0.511 and 0.516, respectively. The best cut-off values (BCV) were MLA ≤3.0 mm2 and %PB >75%, with accuracy of 60% for MLA, 50% for %PB and 56% for their combination, and AUC of 0.618, 0.511 and 0.533, respectively. MLA BCV ≤3.0 mm2 had higher predictive power than %PB BCV >75% or their combination. Independent predictors of functional significance were male gender (odds ratio 1.76 [95% confidence interval: 1.19-2.62]), left ventricular ejection fraction (LVEF, 0.98 [0.96-0.99]), LAD lesion (2.52 [1.73-3.67]), reference vessel diameter (0.60 [0.41-0.86]), lesion length (1.04 [1.02-1.06]) and MLA (0.79 [0.69-0.92]). False negative lesion incidence was 24.4% in association with race (for Asians, 0.391 [0.219-0.698]), LAD lesion (2.677 [1.709-4.191]) and LVEF (0.977 [0.957-0.997]). False positive lesion incidence was 17.0% in association with non-LAD lesion (2.444 [1.620-3.686]). CONCLUSIONS Combined IVUS parameters did not improve the accuracy of functional significance prediction. Discrepancy between IVUS and FFR, which was not rare, should be taken into account in clinical decision making.

Clinical Relevance of Functionally Insignificant Moderate Coronary Artery Stenosis Assessed by 3‐Vessel Fractional Flow Reserve Measurement

Background Understanding of the risk conferred by functionally insignificant lesions in multiple coronary vessels is limited. We investigated the prognostic implications of coronary artery disease (CAD) based on 3‐vessel fractional flow reserve (FFR). Methods and Results A total of 1,136 patients underwent FFR measurement in the 3 major epicardial arteries. We defined vessels with “Moderate CAD” as vessels with FFR, 0.81 to 0.87. Patients were classified into Group 1: No apparent CAD (FFR>0.87 in all 3‐vessels); Group 2: Single‐vessel moderate CAD; Group 3: Multivessel moderate CAD; and Group 4: Functionally significant CAD (FFR≤0.80) in any vessel. The primary end point was 2‐year major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia‐driven revascularization. Forty‐three percent of patients had moderate CAD (Group 2: 403/1136, 35.5%; Group 3: 84/1136, 7.4%). The 2‐year risk of major adverse cardiac events was not significantly different between patients with single‐vessel moderate CAD and no apparent CAD (2.6 versus 2.6%; HR, 1.1; 95% confidence interval, 0.4%–2.8%; P=0.89). However, patients with multivessel moderate CAD were at significantly higher risk than Group 1 (7.4 versus 2.6%; hazard ratio, 3.3; 95% confidence interval, 1.1%–9.8%; P=0.03). The risk of major adverse cardiac events in patients with multivessel moderate CAD was comparable to that of patients with functionally significant CAD (hazard ratio, 1.2; 95% confidence interval, 0.5%–3.0%; P=0.67). In a multivariable regression model, multivessel moderate CAD was an independent predictor of greater risk of 2‐year major adverse cardiac events. Conclusions Global physiologic assessment with FFR measurement of 3 vessels can identify multivessel moderate CAD. The prognostic implication of multivessel moderate CAD appears comparable to that of functionally significant CAD. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01621438.

Comparison of Fractional FLow Reserve And Intravascular ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients with InteRmediate Stenosis (FLAVOUR): Rationale and design of a randomized clinical trial.

Background: Coronary angiography has limitations in defining the ischemia‐causing stenotic lesion, especially in cases with intermediate coronary stenosis. Fractional flow reserve (FFR) is a current standard method to define the presence of ischemia, and intravascular ultrasound (IVUS) is the most commonly used invasive imaging tool that can provide the lesion geometry and can provide the information on plaque vulnerability. The primary aim of this study is to compare the safety and efficacy of FFR‐guided and IVUS‐guided percutaneous coronary intervention (PCI) strategies in patients with intermediate coronary stenosis. Trial design: Comparison of Fractional FLow Reserve And Intravascular ultrasound‐guided Intervention Strategy for Clinical OUtcomes in Patients with InteRmediate Stenosis (FLAVOUR) trial is an international, multicenter, prospective, randomized clinical trial. A total of 1,700 consecutive patients with intermediate stenosis (40%‐70% by visual estimation) in a major epicardial coronary artery will be randomized 1:1 to receive either FFR‐guided or IVUS‐guided PCI strategy. Patients will be treated with PCI according to the predefined criteria for revascularization; FFR ≤ 0.80 in the FFR‐guided group and Minimal Lumen Area (MLA) ≤3 mm2 (or 3 mm2 < MLA ≤4 mm2 and plaque burden >70%) in the IVUS‐guided group. The primary end point is the patient‐oriented composite outcome, which is a composite of all‐cause death, myocardial infarction, and any repeat revascularization at 24 months after randomization. We will test noninferiority of current standard FFR‐guided PCI strategy compared with IVUS‐guided decision for PCI and stent optimization strategy. Conclusion: The FLAVOUR trial will compare the safety and efficacy of FFR‐ and IVUS‐guided PCI strategies in patients with intermediate coronary stenosis. This study will provide an insight on optimal evaluation and treatment strategy for patients with intermediate coronary stenosis.