BACKGROUNDCoronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR.
METHODSWe randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk.
RESULTSAt 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, −0.2 percentage points; 95% confidence interval [CI], −2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P = 0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P = 0.001).
CONCLUSIONSCoronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. ( Use of Instantaneous Wave-free R atio in PCI F or the past 20 years, physiological measurements obtained during invasive procedures have been used to guide coronary revascularization. Pioneering work supported the use of flow measurements to make safe decisions about revascularization, 1,2 but this approach was soon superseded by the use of fractional flow reserve (FFR), which measures pressure as a surrogate of flow to estimate the severity of stenosis. 3-5 FFR was successful largely because of its technical simplicity and because clinical trials showed that it was associated with improved clinical outcomes after percutaneous coronary intervention (PCI). 6,7 Consequently, FFR is now included in the appropriate-use criteria for coronary angiography and in the American College of Cardiology-American Heart Association-European Society of Cardiology guidelines; despite these recommendations, its adoption remains limited. [8][9][10] FFR must be measured during maximal hyperemia, which is typically induced with the administration of a potent intravenous or intracoronary vasodilator, such as adenosine. 11 Several studies have...
Human sulfite oxidase (hSO) was immobilised on SAM-coated silver electrodes under preservation of the native heme pocket structure of the cytochrome b5 (Cyt b5) domain and the functionality of the enzyme. The redox properties and catalytic activity of the entire enzyme were studied by surface enhanced resonance Raman (SERR) spectroscopy and cyclic voltammetry (CV) and compared to the isolated heme domain when possible. It is shown that heterogeneous electron transfer and catalytic activity of hSO sensitively depend on the local environment of the enzyme. Increasing the ionic strength of the buffer solution leads to an increase of the heterogeneous electron transfer rate from 17 s(-1) to 440 s(-1) for hSO as determined by SERR spectroscopy. CV measurements demonstrate an increase of the apparent turnover rate for the immobilised hSO from 0.85 s(-1) in 100 mM buffer to 5.26 s(-1) in 750 mM buffer. We suggest that both effects originate from the increased mobility of the surface-bound enzyme with increasing ionic strength. In agreement with surface potential calculations we propose that at high ionic strength the enzyme is immobilised via the dimerisation domain to the SAM surface. The flexible loop region connecting the Moco and the Cyt b5 domain allows alternating contact with the Moco interaction site and the SAM surface, thereby promoting the sequential intramolecular and heterogeneous electron transfer from Moco via Cyt b5 to the electrode. At lower ionic strength, the contact time of the Cyt b5 domain with the SAM surface is longer, corresponding to a slower overall electron transfer process.
This study showed that endothelial functions were impaired in patients with chronic periodontitis and that they improve following initial periodontal therapy.
In our pilot trial, the administration of low-dose intracoronary streptokinase immediately after primary PCI improved myocardial reperfusion but not long-term left ventricular size or function. These findings require clarification in a larger trial. (ClinicalTrials.gov number, NCT00302419.)
These results suggest that with advancing stage of lung cancer, the levels of oxidative stress increase, while levels of antioxidant molecules decrease. Patients with squamous cell carcinoma have higher oxidative stress as reflected by higher levels of malondialdehyde and nitrite.
Direct electronic coupling of peroxidases with bio-compatible interfaces allows for investigation of enzyme's electro-catalytic properties that are essential in the design of bio-electronic devices. Here, a novel dye decolourising-type peroxidase from Pseudomonas putida MET94 (PpDyP) is immobilised on Ag electrodes coated with an alkanethiol self-assembled monolayer. Structural features of the active site, heterogeneous electron transfer and electro-catalytic properties of immobilised PpDyP are addressed by combination of surface enhanced spectroscopic and electrochemical approaches. They reveal that the structural integrity of the heme pocket of PpDyP is preserved upon immobilisation, the enzyme is electronically coupled to the electrode, and it exhibits efficient catalytic activity. Importantly, no significant modulation of the midpoint redox potential (E m ) of the immobilised protein (E m À300 mV) is observed with respect to that in solution (E m,sol À260 mV). This study provides important structural and mechanistic insights into immobilised DyP-type peroxidase, capable of efficient decolourisation of numerous dyes, revealing PpDyP as a promising candidate for biotechnological applications.
A nanostructured gold-silver-hybrid electrode for SER spectroelectrochemistry was developed which advantageously combines the electrochemical properties and chemical stability of Au and the strong surface enhancement of (resonance) Raman scattering by Ag. The layered device consists of a massive nanoscopically rough Ag electrode, a thin (2 nm) organic layer, and a ca. 20 nm thick Au film that may be coated by self-assembled monolayers for protein adsorption. The SERR-spectroscopic and electrochemical performance of this device is demonstrated using the heme protein cytochrome c as a benchmark model system, thereby extending, for the first time, SE(R)R studies of molecules on Au surfaces to excitation in the violet spectral range. The enhancement factor is only slightly lower than for Ag electrodes which can be rationalized in terms of an efficient transfer of plasmon resonance excitation from the Ag to the Au coating. This mechanism, which requires a thin dielectric layer between the two metals, is supported by theoretical calculations.
Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year.
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