In trials of patients with left ventricular dysfunction or heart failure, ACE inhibitor use was unexpectedly associated with reduced myocardial infarction (MI). Using the Heart Outcomes Prevention Evaluation (HOPE) trial data, we tested prospectively whether ramipril, an ACE inhibitor, could reduce coronary events and revascularization procedures among patients with normal left ventricular function.

Vascular endothelial dysfunction may predict future atherosclerosis. Hence, an antihypertensive agent that reverses endothelial dysfunction and lowers blood pressure might improve the prognosis of patients with hypertension. We hypothesized that nebivolol, a vasodilating beta-blocker, could improve endothelial dysfunction. We tested this hypothesis by comparing the effects of nebivolol and atenolol on endothelial function.

This study investigated the effect of the phosphodiesterase 5 inhibitor sildenafil on the pulmonary vascular response to hypoxia in humans and mice.

Pharmacodynamics of eptifibatide, a cyclic heptapeptide antagonist of platelet glycoprotein IIb/IIIa, are substantially altered by anticoagulants that chelate calcium, resulting in overestimation ex vivo of the in vivo effects of this agent. We conducted a dose-ranging study to characterize the pharmacodynamics and pharmacokinetics of eptifibatide under physiological conditions.

Platelet deposition and aggregation are central to the pathogenesis of ischemic complications of acute coronary syndromes (ACS). Pharmacodynamic effects of the platelet glycoprotein IIb/IIIa antagonist eptifibatide have been delineated in healthy subjects but not in patients with ACS. We assessed effects of eptifibatide on ex vivo platelet aggregation in patients enrolled in the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy (PURSUIT) trial of ACS.

We studied whether lipid-lowering therapy with atorvastatin (target LDL cholesterol [LDL-C] <100 mg/dL) compared with a moderate treatment regimen that used other lipid-lowering drugs led to a lesser progression of atherosclerosis and to different changes in plaque echogenicity in patients with coronary artery disease.

The aim of this study was to use serial intravascular ultrasound (IVUS) to evaluate the long-term effect of stent-based 7-hexanoyltaxol (QP2, a taxane analogue) delivery on neointimal tissue growth within the stent and on vessel dimensions at the adjacent reference segments.

The short-term effects of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) on endothelial function at doses that do not affect plasma lipid levels are not known.

To assess the reliability of pediatric echocardiographic measurements, we compared local measurements with those made at a central facility.

Patients with abdominal aortic aneurysms (AAAs) exhibit arterial dilation and altered matrix composition throughout the vasculature. Matrix metalloproteinase-2 (MMP-2) is the dominant elastase in small AAAs, and overexpression of MMP-2 in vascular smooth muscle cells (SMCs) may be a primary etiological event in aneurysm genesis. The aim of this study was to investigate MMP-2 production in vascular tissue remote from the abdominal aorta.

Catheter ablation of pulmonary vein ectopic foci is a potentially curative treatment strategy for patients with atrial fibrillation. However, identification of arrhythmogenic pulmonary veins with conventional mapping is difficult, especially in patients with rare focal activity, multiple active foci, or extrapulmonary foci. The present study was designed to investigate use of simultaneous noncontact mapping in this setting.

In patients with left ventricular dysfunction, atrial fibrillation and flutter (AF and AFl, respectively) are common arrhythmias associated with increased morbidity and mortality. The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm, which might reduce mortality and hospitalizations.

We investigated whether serum concentration of carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type I synthesis, can be used to assess the ability of antihypertensive treatment to regress myocardial fibrosis in hypertensive patients.

Candesartan, an AT(1) receptor antagonist, has been reported to have no association with persistent cough in subjects with hypertension, but there has been no study on the safety of its administration to hypertensive patients with symptomatic asthma. The aim of this study was to compare the adverse effects of candesartan and calcium antagonists on cough, pulmonary function, and bronchial hyperresponsiveness in these patients.

Human immunodeficiency virus protease inhibitors (HIV PIs) are associated with hyperlipidemia, hyperglycemia, and obesity; however, it is not known whether they increase risk of atherosclerotic vascular disease. The purposes of this study were to characterize the lipoprotein abnormalities associated with use of HIV PIs in individuals with HIV infection and to determine the pathophysiological significance of these changes by assessing their effect on endothelial dysfunction.

This study was designed to investigate the effects of lipid-lowering by simvastatin on human atherosclerotic lesions.

Forearm endothelial dysfunction, characterized by an impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors, including essential hypertension. Although the prognostic value of coronary endothelial dysfunction has been demonstrated, that of forearm endothelial dysfunction is still unknown. Methods and Results-- Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients (age, 35 to 54 years) by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) from basal: group 1, from 30% to 184%; group 2, from 185% to 333%; and group 3, from 339% to 760% increase from basal. During a mean follow-up of 31.5 of months (range, 4 to 84 months), there were 29 major adverse events at the cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level. Events included myocardial infarction, angina, coronary revascularization procedures, stroke, transient cerebral ischemic attack, and aortoiliac occlusive disease. Event rate per 100 patient-years was 8.17, 4.34, and 2.02 in the first, second, and third tertiles of peak percent increase in FBF during ACh infusion. The excess risk associated with an FBF increase in the first tertile was significant (relative risk, 2.084; 95% CI, 1.25 to 3.48; P=0.0049) after controlling for individual risk markers, including 24-hour ambulatory blood pressure.

Platelet activation is pivotal in the pathogenesis of complications after percutaneous coronary interventions (PCI). We previously reported substantial interindividual variability in activation of glycoprotein (GP) IIb/IIIa in response to a low concentration of ADP. We assessed GP IIb/IIIa activation prospectively to determine whether this could differentiate patients at low risk from those at high risk for complications early and late after PCI. Methods and Results-- A total of 112 patients undergoing PCI were studied. Platelet reactivity was determined with the use of flow cytometry. Patients were classified into high and low platelet reactivity groups on the basis of extent of activation of GP IIb/IIIa in response to 0.2 micromol/L ADP. The median value was used for differentiation. The incidence during 90-day follow-up interval of a composite end point (myocardial infarction, urgent revascularization, or repeat revascularization) was determined in each group. Follow up was completed in all 112 patients. The 2 groups were similar with respect to diverse clinical characteristics. Nevertheless, the incidence of the composite end point occurred in 26.8% of the high and 7.1% in the low platelet reactivity group (P=0.01). The difference in the composite end point was most striking during the 30- to 90-day interval after PCI (16.7% versus 1.9%; P=0.02). Repeat revascularization was more frequent in those with increased platelet reactivity (17.9% versus with 3.6%, P=0.029).

We sought to investigate the arrhythmogenic role, incidence, treatment, and prognosis of inflammatory left ventricular (LV) microaneurysms in patients with apparently idiopathic ventricular tachyarrhythmias. Methods and Results-- We studied 156 consecutive patients (71 men, 85 women; mean age, 44.1+/-11.8 years) with severe ventricular arrhythmias and normal 2D echo cardiac parameters by coronary and ventricular angiography, biventricular endomyocardial biopsy, and electrophysiological study. Polymerase chain reaction was used to detect genomic sequences of enterovirus, adenovirus, Epstein Barr virus, cytomegalovirus, herpes simplex viruses, influenza A and B viruses, and hepatitis C virus in frozen endomyocardial samples. Of these patients, 15 (9.6%) showed angiographic evidence of single or multiple LV microaneurysms. All 15 patients had recurrent episodes of ventricular tachycardia with right bundle-branch block morphology, and the arrhythmias originated within or close to the aneurysms in those patients (n=6) undergoing ventricular mapping. A lymphocytic myocarditis was observed in LV biopsies of all patients and in the right ventricles of 3 patients. Polymerase chain reaction analysis was performed in 12 and viral genomes were found in 5 (42%): hepatitis C virus in 2, enterovirus in 2, and influenza virus A in 1. The patients were treated with antiarrhythmics, and cardiac function was preserved for the next 47+/-39.5 months of follow-up. No major clinical event was registered, and arrhythmias were successfully treated by antiarrhythmics.

Previous investigators have shown that systemic markers of inflammation may be increased in patients with acute ischemic syndromes or after percutaneous coronary revascularization and that persistent elevation in these markers is predictive of excess risk of subsequent adverse cardiac events. By virtue of its cross-reactivity with the glycoprotein IIb/IIIa, avbeta3, and alphaMbeta2 receptors, abciximab may reduce inflammatory processes. Methods and Results-- Assays for the inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-alpha were performed on serum samples obtained from 160 patients in a placebo-controlled, randomized trial of abciximab during angioplasty. Eighty patients each had received a placebo or abciximab bolus plus a 12-hour infusion. Serum samples were drawn at baseline (before revascularization), 24 to 48 hours after study drug administration, and 4 weeks after study drug administration. Between baseline and 24 to 48 hours, the increase in C-reactive protein was 32% less in patients receiving abciximab than placebo (P=0.025); the rise in interleukin-6 levels was 76% less in the abciximab group (P<0.001); and the rise in tumor necrosis factor-alpha levels was 100% less with abciximab therapy (P=0.112). By 4 weeks, most marker levels had returned to baseline, with no significant differences between placebo and abciximab groups.