Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease.

BACKGROUND: There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. OBJECTIVES: The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. METHODS: The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. RESULTS: The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months' extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). CONCLUSIONS: In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555).

Feasibility of Quantitative Flow Ratio in Adult Patients With Anomalous Aortic Origin of the Coronary Artery With 5 Years of Clinical Follow-up.

OBJECTIVES: Anomalous origin of the right coronary artery (ARCA) represents the most common form of abnormal coronary origin and may potentially increase the risk for sudden cardiac death. Morphological and functional evaluation of ARCA in adult patients referred for invasive coronary angiogram (ICA) is challenging. Quantitative flow ratio (QFR) is an available method able to virtually calculate fractional flow reserve using 3-dimensional quantitative coronary angiography (3D-QCA) based on ICA. We aimed to evaluate the feasibility of QFR analysis in patients with ARCA and its clinical impact. METHODS: Using the registry of proximal anomalous connections of coronary arteries (ANOCOR registry), a multicenter observational registry including 472 adult patients with ANOCOR between 2010 and 2013, we retrospectively performed QFR analysis from ICA and evaluated the rate of death, myocardial infarction, and unplanned revascularization at 5 years. RESULTS: Among 128 patients with ARCA, 41 (32%) could have QFR analysis with median clinical follow-up of 8.3 years. The mean QFR value was 0.90 ± 0.10, and 3D-QCA analysis showed preserved lumen area despite the elliptical shape of the proximal part of the ARCA, which in the worst cases appeared on ICA as a significant narrowing. The event rate was 12.2% (n = 5), including 3 deaths (1 due to cancer, 1 due to stroke, and 1 cause unknown) and 2 unplanned revascularizations at 5 years. No myocardial infarctions were reported. CONCLUSIONS: When QFR analysis of ARCA is feasible, non-significant QFR values are associated with good clinical outcome at 5 years.

Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With Diabetes.

Importance: Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned. Objective: To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography. Design, Setting, and Participants: This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018. Main Outcomes and Measures: Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. Results: Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status. Conclusions and Relevance: Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.

Outcome impact of coronary revascularization strategy reclassification with fractional flow reserve at time of diagnostic angiography: insights from a large French multicenter fractional flow reserve registry.

BACKGROUND: There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography. METHODS AND RESULTS: The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P=0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P=0.75). Reclassification safety was preserved in high-risk patients. CONCLUSION: This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.

Coronary vasomotor response to the selective B1-kinin-receptor agonist Des-Arg9-bradykinin in humans.

OBJECTIVES: The aim of the present study was to assess the effects of selective B1-receptor stimulation with des-Arg9-bradykinin on coronary vasomotion in transplanted and non-transplanted patients. BACKGROUND: Bradykinin B1-receptors have been identified on endothelial and smooth muscle cells in human coronary arteries in vitro; however, their physiologic role in the coronary circulation is unknown. METHODS: Twelve heart transplant patients were compared with 10 control subjects at 3.2 +/- 2.2 months after surgery. Coronary flow velocity was measured using guide-wire Doppler. The diameter of 3 epicardial segments of the left coronary artery and coronary blood flow were assessed at baseline, immediately after infusions of increasing doses of des-arginine(Arg9)-bradykinin at estimated coronary blood concentrations of 5.4 x 10(-9), 5.4 x 10(-8), 5.4 x 10(-7) and 1.6 x 10(-6) mol/liter, and of acetylcholine at 10(-8), 10(-7) and 10(-6) mol/liter). RESULTS: Des-Arg9-bradykinin induced a similar decrease in all measured epicardial diameters in both groups and no change in coronary blood flow. Vasoconstriction was significant only at the 2 highest concentrations: -6 +/- 9% (p < 0.01) and -7 +/- 11% (p < 0.01) in control subjects, and -8 +/- 8% (p < 0.001) and -9 +/- 11% (p < 0.001) in heart transplant patients. Acetylcholine induced significant epicardial vasodilation in control subjects and vasoconstriction in transplant patients. The presence of allograft rejection did not modify the responses to des-Arg9-bradykinin with regard to both conductance and resistance vessels. CONCLUSIONS: Kinin B1-receptors exist and can be stimulated in humans. The vasoconstrictive action on epicardial coronary arteries of des-Arg(9)-bradykinin in humans argues for a predominant action of B1-receptor stimulation at the level of smooth muscle cells.

Evaluation of carotid artery and aortic intima-media thickness measurements for exclusion of significant coronary atherosclerosis in patients scheduled for heart valve surgery.

OBJECTIVES: We assessed the value of carotid intima-media thickness (CIMT) and thoracic aorta intima-media thickness (AoIMT) in ruling out significant coronary artery disease (CAD) in patients scheduled for heart valve surgery. BACKGROUND: Evaluation of CAD is needed in most patients undergoing heart valve surgery because of the high surgical morbidity in patients with significant CAD, raising the need for sensitive tests to exclude CAD. Coronary angiography is the reference standard, but this invasive procedure is not cost-effective, because more than two-thirds of these patients do not have significant CAD. METHODS: In a pilot study, CIMT and AoIMT cutoff values separating low- from high-risk groups were determined in 96 patients by using receiver-operating characteristic curves. Then, a prospective study was conducted in 152 patients to determine the statistical power of these cutoff values used alone or in combination. In both studies, carotid artery ultrasonography and transesophageal echocardiography were performed before coronary angiography and valve surgery. RESULTS: In the pilot study, CIMT < 0.55 mm and AoIMT < 3 mm were excellent predictors of the absence of CAD. In the prospective study, CIMT and AoIMT criteria were independent predictors of significant CAD in these patients, as assessed by logistic regression analysis. Carotid IMT criterion had 100% sensitivity and 100% negative predictive value. For the AoIMT criterion, sensitivity was 98%, and negative predictive value 99%. Combining the two criteria did not change sensitivity and negative predictive value but increased specificity to 78%. CONCLUSIONS: Measurements of CIMT and AoIMT may be useful in selecting patients who do not require coronary angiography before heart valve surgery.