Prospective, multi-center evaluation of a silicon carbide coated cobalt chromium bare metal stent for percutaneous coronary interventions: two-year results of the ENERGY Registry.

Background: Novel bare metal stents with improved stent design may become a viable alternative to drug-eluting stents in certain patient groups, particularly, when long-term dual antiplatelet therapy should be avoided.

Purpose: The ENERGY registry aimed to assess the safety and benefits of a cobalt-chromium thin strut bare metal stent with a passive coating in a large series of patients under real-world conditions.

Methods And Materials: This prospective registry recruited 1016 patients with 1074 lesions in 48 centers from April to November 2010.

Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism.

Background: In patients with acute pulmonary embolism, systemic thrombolysis improves right ventricular (RV) dilatation, is associated with major bleeding, and is withheld in many patients at risk. This multicenter randomized, controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis (USAT) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients.

Methods And Results: Fifty-nine patients (63±14 years) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension (RV/LV) ratio ≥1.

Impact of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on the long-term outcome after pulmonary vein isolation for paroxysmal atrial fibrillation.

Objectives: The effect of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) on the long-term outcome after pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) is unknown.

Methods: This matched-pair study included 102 patients with PAF treated with ACE-I or ARBs (group 1) and 102 control subjects (group 2) after standardized PVI. Tele-ECG recorders were used to detect the end point of the first PAF recurrence after a 3-month blanking period.

Introduction of an expert system for the discrimination of local pulmonary vein and atrial far field signals.

Background: Discrimination of local and far field potentials during sinus rhythm and atrial fibrillation (AF) is essential for successful pulmonary vein (PV) isolation. We sought to introduce an expert system for the classification of electrophysiologic PV signals.

Methods: For the expert system database, we analyzed ablation procedures of 50 patients with paroxysmal and persistent AF.

Liberation of vessel adherent myeloperoxidase by enoxaparin improves endothelial function.

Background: Myeloperoxidase (MPO), a leukocyte-derived heme enzyme binds to the endothelium and depletes vascular nitric oxide (NO) bioavailability in animal models. Unfractionated heparins release vessel-bound MPO and increase endothelial NO bioavailability. Whether low molecular weight heparins also affect circulating MPO levels and NO dependent vasoreactivity however remains elusive.

Comparison of quantitative coronary angiography and first-pass perfusion magnetic resonance imaging for the detection of an impaired coronary perfusion in nonsevere coronary stenosis.

Purpose: To compare quantitative coronary angiography (QCA) and first-pass perfusion magnetic resonance imaging (FPP-MRI) in symptomatic patients with nonsevere coronary stenosis to detect a reduced coronary flow velocity reserve (CFVR).

Materials And Methods: In 35 patients, FPP-MRI and CFVR measurements were performed in 40 coronary arteries with a diameter stenosis (DS) <70% by QCA. From FPP-MRI a myocardial perfusion reserve index (MPRI) was calculated.

Impaired capacity for acute endogenous fibrinolysis in smokers is restored by ascorbic acid.

Elevated levels of fibrinogen, C-reactive protein, and increased platelet aggregation are known to be increased by cigarette smoking, but the underlying mechanisms of the prothrombotic state in smokers are not completely understood. Since cigarette smoke contains several oxidants, we investigated the effect of the antioxidant ascorbic acid on stimulated fibrinolytic activity in smokers. Long-term heavy smokers and nonsmokers were studied by measurement of forearm blood flow; coinfusion of ascorbic acid was used to reduce oxidative stress.

Activation of polymorphonuclear neutrophils in patients with impaired left ventricular function.

Activation of leukocytes and in particular polymorphonuclear neutrophils (PMN) has emerged as a critical confounder in the pathophysiology of cardiovascular disease: Myeloperoxidase (MPO), one of the principal proteins hosted in and secreted by activated PMN, has been mechanistically linked to endothelial and left ventricular (LV) dysfunction in rodent models of sepsis and ischemic cardiomyopathy. Whether PMN activation is also overt in patients with LV dysfunction of ischemic and nonischemic origin, however, remains elusive. Prospectively, 447 consecutive, stable outpatients were included in this single-center study.

Contrast-enhanced cardiac MR imaging in the detection of reduced coronary flow velocity reserve.

Purpose: To prospectively evaluate the accuracy of contrast material-enhanced cardiac magnetic resonance (MR) imaging for determining impaired coronary flow velocity reserve (CFR) by using Doppler flow measurement as the reference standard.

Materials And Methods: The study was approved by the institutional ethics committee, and all patients gave written informed consent. Eligible patients underwent contrast-enhanced cardiac MR imaging and invasive measurement of CFR.

Coronary plaque injury triggers neutrophil activation in patients with coronary artery disease.

Activation of leukocytes, in particular polymorphonuclear neutrophils (PMN), is considered an early event in unstable coronary disease. Upon activation PMN liberate myeloperoxidase (MPO), an enzyme which binds to the vessel wall and depletes vascular NO bioavailability. Using coronary balloon angioplasty as a trigger to provoke coronary plaque injury, we assessed the time course of neutrophil activation, local and peripheral levels of myeloperoxidase, and systemic vascular NO bioavailability in patients with stable coronary artery disease.

Inhibition of xanthine oxidase improves myocardial contractility in patients with ischemic cardiomyopathy.

Reactive oxygen species, in particular superoxide, have been closely linked to the underlying pathophysiology of ischemic cardiomyopathy: superoxide not only mediates mechanoenergetic uncoupling of the myocyte but also adversely impacts on myocardial perfusion by depleting endothelial-derived nitric oxide bioavailability. Xanthine oxidase generates superoxide upon oxidation of hypoxanthine and xanthine and has been detected in cardiac myocytes and coronary endothelial cells of patients with ischemic heart disease. Here we investigated the effects of oxypurinol, a xanthine oxidase inhibitor, on myocardial contractility in patients with ischemic cardiomyopathy.

AT1-receptor blockade with irbesartan improves peripheral but not coronary endothelial dysfunction in patients with stable coronary artery disease.

Activation of the renin-angiotensin-aldosterone system plays an important role in the pathogenesis of endothelial dysfunction and atherosclerosis. Studies evaluating the effect of AT1-receptor blockers on endothelial dysfunction in patients with coronary artery disease (CAD) revealed mixed results. Studies addressing the effects of AT1-receptor blockers on the coronary and peripheral function in the same study population, are still lacking.

Implantation of paclitaxel-eluting stents in saphenous vein grafts: clinical and angiographic follow-up results from a multicentre study.

Objective: To define the clinical and angiographic follow-up results after implantation of paclitaxel-eluting stents (PESs) in stenotic saphenous vein grafts (SVGs).

Design: Prospective multicentre study. Comparison with a control group.

Clopidogrel improves systemic endothelial nitric oxide bioavailability in patients with coronary artery disease: evidence for antioxidant and antiinflammatory effects.

Background: Platelet stimulation and activation are known not only as prerequisite of clot formation but are increasingly recognized as important contributors to inflammation and vascular injury. The present study in patients with symptomatic coronary disease investigated whether platelet adenosine diphosphate receptor blockade by clopidogrel exerts beneficial effects on endothelial nitric oxide bioavailability, oxidative stress, and/or inflammatory status.

Methods And Results: One hundred three consecutive patients with symptomatic coronary disease and long-term aspirin therapy were studied.

Heparins increase endothelial nitric oxide bioavailability by liberating vessel-immobilized myeloperoxidase.

Background: Neutrophils and monocytes are centrally linked to vascular inflammatory disease, and leukocyte-derived myeloperoxidase (MPO) has emerged as an important mechanistic participant in impaired vasomotor function. MPO binds to and transcytoses endothelial cells in a glycosaminoglycan-dependent manner, and MPO binding to the vessel wall is a prerequisite for MPO-dependent oxidation of endothelium-derived nitric oxide (NO) and impairment of endothelial function in animal models. In the present study, we investigated whether heparin mobilizes MPO from vascular compartments in humans and defined whether this translates into increased vascular NO bioavailability and function.

Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease.

Coronary endothelial dysfunction is a powerful prognostic marker in patients with coronary artery disease (CAD) that is centrally related to oxidative inhibition of nitric oxide (NO)-dependent vascular cell signaling. Xanthine oxidase (XO), which both binds to and is expressed by endothelial cells, generates superoxide and hydrogen peroxide upon oxidation of purines. Whether inhibition of xanthine oxidase activity results in improved coronary vasomotor function in patients with CAD, however, remains unknown.

Systemic endothelial dysfunction as an early predictor of adverse outcome in heart failure.

Objective: Endothelial dysfunction is an early event in the natural progression of heart failure. Increased oxidative stress has been linked to impaired endothelial function and both may play a prognostic role.

Methods And Results: Endothelium-dependent and endothelium-independent vasodilatation were determined in 289 patients with mild left ventricular dysfunction by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography.

Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins.

Recruitment and activation of polymorphonuclear neutrophils (PMNs) reflects a primary immunological response to invading pathogens and has also emerged as a hallmark of vascular inflammation. One of the principal enzymes released upon PMN activation is myeloperoxidase (MPO), a heme protein that not only generates cytotoxic oxidants but also impacts deleteriously on nitric oxide-dependent signaling cascades within the vasculature. Because MPO also associates with the membrane of PMN, we evaluated whether MPO could also function as an autocrine modulator of PMN activation.

Effect of tirofiban on percutaneous coronary intervention-induced endothelial dysfunction in patients with stable coronary artery disease.

Recent studies demonstrated that glycoprotein (GP) IIb/IIIa receptor antagonists improve endothelial dysfunction of forearm resistance vessels in patients with stable coronary artery disease. However, it remains unclear whether these findings can be extended to the conductance vessel level. In this study, we aimed to evaluate the acute effect of tirofiban on endothelial function of arterial conductance vessels in patients undergoing percutaneous coronary intervention (PCI).

Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion.

Impaired microvascular function during myocardial ischemia and reperfusion is associated with recruitment of polymorphonuclear neutrophils (PMN) and has been attributed to decreased bioavailability of nitric oxide (NO). Whereas myeloperoxidase (MPO), a highly abundant, PMN-derived heme protein facilitates oxidative NO consumption and impairs vascular function in animal models of acute inflammation, its capacity to function in this regard during human myocardial ischemia and reperfusion remains unknown. Plasma samples from 30 consecutive patients (61 +/- 14 years, 80% male) presenting with acute myocardial infarction were collected 9 +/- 4 h after vessel recanalization and compared to plasma from healthy control subjects (n = 12).

Platelet glycoprotein IIb/IIIa receptor blockade improves vascular nitric oxide bioavailability in patients with coronary artery disease.

Background: Platelet glycoprotein IIb/IIIa receptor blockade not only enhances epicardial flow but also improves microvascular perfusion. Inhibition of abnormal platelet-endothelial interactions may contribute to this beneficial effect. The present study was designed to determine whether glycoprotein IIb/IIIa receptor blockade influences endothelial vasomotor function and NO bioactivity in patients with coronary artery disease.

Adverse effects of nitroglycerin treatment on endothelial function, vascular nitrotyrosine levels and cGMP-dependent protein kinase activity in hyperlipidemic Watanabe rabbits.

Objective: With the present studies we sought to determine how treatment with nitroglycerin (NTG) affects endothelial function, oxidative stress and nitric oxide (NO)-downstream signaling in Watanabe heritable hyperlipidemic rabbits (WHHL).

Background: In vitro experiments have demonstrated potent antiatherosclerotic effects of NO suggesting that treatment with NO-donors such as NTG could compensate for the diminished availability of endothelial NO. Nitric oxide may, however, not only be scavenged by reaction with endothelium-derived superoxide but also form the potent oxidant and inhibitor of vascular function, peroxynitrite (ONOO(-)).