QFR for the Revascularization of Nonculprit Vessels in MI Patients: Insights From the FIRE Trial.

BACKGROUND: The role of quantitative flow ratio (QFR) in the treatment of nonculprit vessels of patients with myocardial infarction (MI) is a topic of ongoing discussion. OBJECTIVES: This study aimed to investigate the predictive capability of QFR for adverse events and its noninferiority compared to wire-based functional assessment in nonculprit vessels of MI patients. METHODS: The FIRE (Functional Assessment in Elderly MI Patients With Multivessel Disease) trial randomized 1,445 older MI patients to culprit-only (n = 725) or physiology-guided complete revascularization (n = 720). In the culprit-only arm, angiographic projections of nonculprit vessels were prospectively collected, centrally reviewed for QFR computation, and associated with endpoints. In the complete revascularization arm, endpoints were compared between nonculprit vessels investigated with QFR or wire-based functional assessment. The primary endpoint was the vessel-oriented composite endpoint (VOCE) at 1 year. RESULTS: QFR was measured on 903 nonculprit vessels from 685 patients in the culprit-only arm. Overall, 366 (40.5%) nonculprit vessels showed a QFR value ≤0.80, with a significantly higher incidence of VOCEs (22.1% vs 7.1%; P < 0.001). QFR ≤0.80 emerged as an independent predictor of VOCEs (HR: 2.79; 95% CI: 1.64-4.75). In the complete arm, QFR was used in 320 (35.2%) nonculprit vessels to guide revascularization. When compared with propensity-matched nonculprit vessels in which treatment was guided by wire-based functional assessment, no significant difference was observed (HR: 0.57; 95% CI: 0.28-1.15) in VOCEs. CONCLUSIONS: This prespecified subanalysis of the FIRE trial provides evidence supporting the safety and efficacy of QFR-guided interventions for the treatment of nonculprit vessels in MI patients. (Functional Assessment in Elderly MI Patients With Multivessel Disease [FIRE]; NCT03772743).

Quantitative flow ratio-based outcomes in patients undergoing transcatheter aortic valve implantation quaestio study.

Background: Coronary artery disease (CAD) is common in patients with aortic valve stenosis (AS) ranging from 60% to 80%. The clinical and prognostic role of coronary artery lesions in patients undergoing Transcatheter Aortic Valve Implantation (TAVI) remains unclear. The aim of the present observational study was to estimate long-term clinical outcomes by Quantitative Flow Ratio (QFR) characterization of CAD in a well-represented cohort of patients affected by severe AS treated by TAVI. Methods: A total of 439 invasive coronary angiographies of patients deemed eligible for TAVI by local Heart Teams with symptomatic severe AS were retrospectively screened for QFR analysis. The primary endpoint of the study was all-cause mortality. The secondary endpoint was a composite of cardiovascular mortality, stroke/transient ischemic attack (TIA), acute myocardial infarction (AMI), and any hospitalization after TAVI. Results: After exclusion of patients with no follow-up data, coronary angiography not feasible for QFR analysis and previous surgical myocardial revascularization (CABG) 48/239 (20.1%) patients had a QFR value lower or equal to 0.80 (QFR + value), while the remaining 191/239 (79.9%) did not present any vessel with a QFR positive value. In the adjusted Cox regression analysis, patients with positive QFR were independently associated with an increased risk of all-casual mortality (Model 1, HR 3.47, 95% CI, 2.35-5.12; Model 2, HR 5.01, 95% CI, 3.17-7.90). In the adjusted covariate analysis, QFR+ involving LAD (37/48, 77,1%) was associated with the higher risk of the composite outcome compared to patients without any positive value of QFR or non-LAD QFR positive value (11/48, 22.9%). Conclusions: Pre-TAVI QFR analysis can be used for a safe, simple, wireless functional assessment of CAD. QFR permits to identify patients at high risk of cardiovascular mortality or MACE, and it could be considered by local Heart Teams.

The role of neopterin in cardiovascular disease.

Inflammation plays a key role in the initiation and progression of atherosclerosis but also in the pathophysiology of atheromatous plaque disruption and the development of acute coronary syndromes. Neopterin is a marker of inflammation and of immune system activation, it is synthesized by macrophages, that, once activated, release this substance. Indeed, in clinical evaluation of patients, measurements of plasma levels of neopterin are usually used to evaluate progression of viral infections, renal transplant rejection, severe systemic inflammatory diseases, nephritic syndrome and several autoimmune diseases. This mediator is able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation. Recent data indicate that serum levels of neopterin are elevated in patients with coronary and peripheral artery disease and seem to be a prognostic marker for major adverse cardiovascular events. In particular, neopterin levels predict future major cardiac and vascular adverse events in patients presenting with chronic coronary artery disease, with acute coronary syndromes, and in those with critical limb ischemia. This renders this molecule a useful marker of atherosclerotic plaque activity, permitting the identification of the subjects at highest risk for major adverse cardiovascular events. In line with the above mentioned evidences, patients with high neopterin levels may require aggressive risk factor modification and intensive medical treatment irrespective of the severity of their coronary artery disease. This data suggest a potential clinical use of neopterin as a marker for disease activity in patients with cardiovascular disease.

HMG-CoA reductase inhibitors reduce nicotine-induced expression of cellular adhesion molecules in cultured human coronary endothelial cells.

BACKGROUND: Smoking predisposes to the development of atherosclerosis and of its complications. The mechanisms responsible for these effects are not completely understood. We have investigated whether nicotine might promote a proatherosclerotic state in human coronary endothelial cells (HCAECs), studying the role of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in preventing these phenomena. METHODS AND RESULTS: Real-time PCR showed that nicotine induced a dose-dependent increase in mRNA levels for vascular cellular adhesion molecule-1 (VCAM-1)/intercellular adhesion molecule-1 (ICAM-1). Fluorescent-activated cell sorting analysis showed that nicotine induced expression of functionally active VCAM-1/ICAM-1, since they increased leukocyte adherence to HCAECs. Oxygen free radicals, Rho A and nuclear factor kappaB (NF-kappaB) play a pivotal role in modulating these effects. Indeed, nicotine caused oxygen free radical production as well as activation of Rho A and NF-kappaB pathways, evaluated by malondialdehyde levels, pulldown assay and by electrophoretic mobility shift assay, respectively. Superoxide dimutase, Rho A (Y-27639) and NF-kappaB inhibitors (pyrrolidine dithiocarbamate ammonium, Bay 11-7082) suppressed nicotine effects on CAM expression. HMG-CoA reductase inhibitors prevented these nicotine-mediated effects by inhibiting free radical generation and by modulating activation of Rho A and NF-kappaB pathways. CONCLUSIONS: Nicotine promotes CAM expression on HCAECs, shifting them toward a proatherosclerotic state. These effects might explain, at least in part, the deleterious cardiovascular consequences of cigarette smoking. HMG-CoA reductase inhibitors play an important role in preventing these phenomena.