Flow-mediated dilatation (FMD) of the brachial artery assessed by high-resolution ultrasound is widely used to measure endothelial function. However, the technique is not standardized, with different groups using occlusion of either the wrist or the upper arm to induce increased blood flow. The validity of the test as a marker of endothelial function rests on the assumption that the dilatation observed is endothelium-dependent and mediated by nitric oxide (NO). We sought to compare the NO component of brachial artery dilatation observed following wrist or upper arm occlusion. Dilatation was assessed before and during intra-arterial infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) following occlusion of (i) the wrist (distal to ultrasound probe) and (ii) the upper arm (proximal to ultrasound probe) for 5 min in ten healthy males. Dilatation was significantly greater after upper arm occlusion (upper arm, 11.62+/-3.17%; wrist, 7.25+/-2.49%; P=0.003). During L-NMMA infusion, dilatation after wrist occlusion was abolished (from 7.25+/-2.49% to 0.16+/-2.24%; P<0.001), whereas dilatation after upper arm occlusion was only partially attenuated (from 11.62+/-3.17% to 7.51+/-2.34%; P=0.006). The peak flow stimulus was similar after wrist and upper arm occlusion. We conclude that dilatation following upper arm occlusion is greater than that observed after wrist occlusion, despite a similar peak flow stimulus. L-NMMA infusion revealed that FMD following wrist occlusion is mediated exclusively by NO, while dilatation following upper arm occlusion comprises a substantial component not mediated by NO, most probably related to tissue ischaemia around the brachial artery. FMD following wrist occlusion may be a more valid marker of endothelial function than dilatation following upper arm occlusion.

Mechanical circulatory support represents an evolving field of clinical research and practice. Currently, several cardiac assist devices have been developed but, among different institutions and countries, a large variation in indications for use and device selection exists. The Impella platform is an easy to use percutaneous circulatory support device which is increasingly used worldwide. During 2014, we established a working group of European physicians who have collected considerable experience with the Impella device in recent years. By critically comparing the individual experiences and the operative protocols, this working group attempted to establish the best clinical practice with the technology. The present paper reviews the main theoretical principles of Impella and provides an up-to-date summary of the best practical aspects of device use which may help others gain the maximal advantage with Impella technology in a variety of clinical settings.

Background-Homocysteine is a risk factor for coronary artery disease (CAD), although a causal relation remains to be proven. The importance of determining direct causality rests in the fact that plasma homocysteine can be safely and inexpensively reduced by 25% with folic acid. This reduction is maximally achieved by doses of 0.4 mg/d. High-dose folic acid (5 mg/d) improves endothelial function in CAD, although the mechanism is controversial. It has been proposed that improvement occurs through reduction in total (tHcy) or free (non-protein bound) homocysteine (fHcy). We investigated the effects of folic acid on endothelial function before a change in homocysteine in patients with CAD. Methods and Results-A randomized, placebo-controlled study of folic acid (5 mg/d) for 6 weeks was undertaken in 33 patients. Endothelial function, assessed by flow-mediated dilatation (FMD), was measured before, at 2 and 4 hours after the first dose of folic acid, and after 6 weeks of treatment. Plasma folate increased markedly by 1 hour (200 compared with 25.8 nmol/L; PϽ0.001). FMD improved at 2 hours (83 compared with 47 m; PϽ0.001) and was largely complete by 4 hours (101 compared with 51 m; PϽ0.001). tHcy did not significantly differ acutely (4-hour tHcy, 9.56 compared with 9.79 mol/L; PϭNS). fHcy did not differ at 3 hours but was slightly reduced at 4 hours (1.55 compared with 1.78 mol/L; Pϭ0.02). FMD improvement did not correlate with reductions in either fHcy or tHcy at any time. Conclusions-These data suggest that folic acid improves endothelial function in CAD acutely by a mechanism largely independent of homocysteine.

Flow-mediated dilatation (FMD) of the brachial artery assessed by high-resolution ultrasound is widely used to measure endothelial function. However, the technique is not standardized, with different groups using occlusion of either the wrist or the upper arm to induce increased blood flow. The validity of the test as a marker of endothelial function rests on the assumption that the dilatation observed is endothelium-dependent and mediated by nitric oxide (NO). We sought to compare the NO component of brachial artery dilatation observed following wrist or upper arm occlusion. Dilatation was assessed before and during intra-arterial infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) following occlusion of (i) the wrist (distal to ultrasound probe) and (ii) the upper arm (proximal to ultrasound probe) for 5 min in ten healthy males. Dilatation was significantly greater after upper arm occlusion (upper arm, 11.62+/-3.17%; wrist, 7.25+/-2.49%; P=0.003). During L-NMMA infusion, dilatation after wrist occlusion was abolished (from 7.25+/-2.49% to 0.16+/-2.24%; P<0.001), whereas dilatation after upper arm occlusion was only partially attenuated (from 11.62+/-3.17% to 7.51+/-2.34%; P=0.006). The peak flow stimulus was similar after wrist and upper arm occlusion. We conclude that dilatation following upper arm occlusion is greater than that observed after wrist occlusion, despite a similar peak flow stimulus. L-NMMA infusion revealed that FMD following wrist occlusion is mediated exclusively by NO, while dilatation following upper arm occlusion comprises a substantial component not mediated by NO, most probably related to tissue ischaemia around the brachial artery. FMD following wrist occlusion may be a more valid marker of endothelial function than dilatation following upper arm occlusion.

The method may offer potential advantages of practical use and sensitivity over conduit artery diameter responses to measure endothelial dysfunction.

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BackgroundRecent recommendations suggest that in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation and coexistent significant coronary artery disease, the latter should be treated before the index procedure; however, the evidence basis for such an approach remains limited. We performed a systematic review and meta‐analysis to study the clinical outcomes of patients with coronary artery disease who did or did not undergo revascularization prior to transcatheter aortic valve implantation.Methods and ResultsWe conducted a search of Medline and Embase to identify studies evaluating patients who underwent transcatheter aortic valve implantation with or without percutaneous coronary intervention. Random‐effects meta‐analyses with the inverse variance method were used to estimate the rate and risk of adverse outcomes. Nine studies involving 3858 participants were included in the meta‐analysis. Patients who underwent revascularization with percutaneous coronary intervention had a higher rate of major vascular complications (odd ratio [OR]: 1.86; 95% confidence interval [CI], 1.33–2.60; P=0.0003) and higher 30‐day mortality (OR: 1.42; 95% CI, 1.08–1.87; P=0.01). There were no differences in effect estimates for 30‐day cardiovascular mortality (OR: 1.03; 95% CI, 0.35–2.99), myocardial infarction (OR: 0.86; 95% CI, 0.14–5.28), acute kidney injury (OR: 0.89; 95% CI, 0.42–1.88), stroke (OR: 1.07; 95% CI, 0.38–2.97), or 1‐year mortality (OR: 1.05; 95% CI, 0.71–1.56). The timing of percutaneous coronary intervention (same setting versus a priori) did not negatively influence outcomes.ConclusionsOur analysis suggests that revascularization before transcatheter aortic valve implantation confers no clinical advantage with respect to several patient‐important clinical outcomes and may be associated with an increased risk of major vascular complications and 30‐day mortality. In the absence of definitive evidence, careful evaluation of patients on an individual basis is of paramount importance to identify patients who might benefit from elective revascularization.

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