EGFR trans-activation by urotensin II receptor is mediated by ß-arrestin recruitment and confers cardioprotection in pressure overload-induced cardiac hypertrophy.

Urotensin II (UTII) and its seven trans-membrane receptor (UTR) are up-regulated in the heart under pathological conditions. Previous in vitro studies have shown that UTII trans-activates the epidermal growth factor receptor (EGFR), however, the role of such novel signalling pathway stimulated by UTII is currently unknown. In this study, we hypothesized that EGFR trans-activation by UTII might exert a protective effect in the overloaded heart. To test this hypothesis, we induced cardiac hypertrophy by transverse aortic constriction (TAC) in wild-type mice, and tested the effects of the UTII antagonist Urantide (UR) on cardiac function, structure, and EGFR trans-activation. After 7 days of pressure overload, UR treatment induced a rapid and significant impairment of cardiac function compared to vehicle. In UR-treated TAC mice, cardiac dysfunction was associated with reduced phosphorylation levels of the EGFR and extracellular-regulated kinase (ERK), increased apoptotic cell death and fibrosis. In vitro UTR stimulation induced membrane translocation of ß-arrestin 1/2, EGFR phosphorylation/internalization, and ERK activation in HEK293 cells. Furthermore, UTII administration lowered apoptotic cell death induced by serum deprivation, as shown by reduced TUNEL/Annexin V staining and caspase 3 activation. Interestingly, UTII-mediated EGFR trans-activation could be prevented by UR treatment or knockdown of ß-arrestin 1/2. Our data show, for the first time in vivo, a new UTR signalling pathway which is mediated by EGFR trans-activation, dependent by ß-arrestin 1/2, promoting cell survival and cardioprotection.

Effects of exercise training on high-mobility group box-1 levels after acute myocardial infarction.

BACKGROUND: High-mobility group box-1 (HMGB1) is a novel predictor of adverse postinfarction clinical outcomes, playing a crucial role in the appropriate postinfarction healing process. METHODS AND RESULTS: Seventy-five postinfarction patients were enrolled in a single-center randomized study (clinicaltrial.gov identifier: NCT00755131). Group T patients (training, n = 37) underwent 6-month exercise-based cardiac rehabilitation (CR) program, whereas group C patients (controls, n = 38) were discharged with generic instructions for maintaining physical activity and a correct lifestyle. After 6 months, HMGB1 levels were significantly reduced in the total population (26.1 ± 23.5 vs. 16.2 ± 12.9 ng/mL; P = .0006). After adjusting for several confounders, linear regression analysis showed that the inclusion in the training group (ß = -10.54, P = .043) was associated with marked reduction of HMGB1 levels. After 6 months, HMGB1 levels were significantly lower in trained patients compared to controls (11.7 ± 7.0 vs. 20.5 ± 15.6 ng/mL, P = .0027, respectively). In trained patients, decreased HMGB1 levels were significantly associated with the improvement in peak oxygen consumption (ß = -3.879, P = .003) and heart rate recovery (ß = -2.492, P = .002), and with reduced left ventricular end-diastolic volume (ß = 1.412, P = .001) and wall motion score index (ß = 1.138, P = .002). CONCLUSIONS: The decrease in HMGB1 levels after anterior myocardial infarction was associated with exercise training and with the improvement of cardiopulmonary and autonomic function, and with favorable cardiac remodeling.

Molecular imaging of atherosclerosis in translational medicine.

Functional characterization of atherosclerosis is a promising application of molecular imaging. Radionuclide-based techniques for molecular imaging in the large arteries (e.g. aorta and carotids), along with ultrasound and magnetic resonance imaging (MRI), have been studied both experimentally and in clinical studies. Technical factors including cardiac and respiratory motion, low spatial resolution and partial volume effects mean that noninvasive molecular imaging of atherosclerosis in the coronary arteries is not ready for prime time. Positron emission tomography imaging with fluorodeoxyglucose can measure vascular inflammation in the large arteries with high reproducibility, and signal change in response to anti-inflammatory therapy has been described. MRI has proven of value for quantifying carotid artery inflammation when iron oxide nanoparticles are used as a contrast agent. Macrophage accumulation of the iron particles allows regression of inflammation to be measured with drug therapy. Similarly, contrast-enhanced ultrasound imaging is also being evaluated for functional characterization of atherosclerotic plaques. For all of these techniques, however, large-scale clinical trials are mandatory to define the prognostic importance of the imaging signals in terms of risk of future vascular events.

The extent of irreversible myocardial damage and the potential for left ventricular repair after primary percutaneous coronary intervention.

Primary percutaneous coronary intervention (PCI) is currently recognized as a highly effective therapy for acute myocardial infarction (AMI) and has been shown to decrease myocardial damage and improve prognosis. Several diagnostic tools have been proposed to evaluate the myocardium at risk, the occurrence of no-reflow, the final scar size, and the presence of residual viable myocardium in patients treated by primary PCI. A large body of literature documents the relevant impact of each of these variables on outcomes in patients treated for AMI. In patients undergoing primary PCI, a number of treatment approaches have been proposed recently to improve efficacy by increasing myocardial salvage. This article describes the principal diagnostic tools (ie, serum biochemical markers, electrocardiography, echocardiography, nuclear imaging techniques, magnetic resonance imaging, and multidetector computed tomography) applicable for evaluation of the size and severity of myocardial damage in patients with AMI undergoing primary PCI. Proposed therapeutic strategies to repair irreversible myocardial damage in patients treated with primary PCI are also considered, with particular focus on the value of stem cell therapy in this specific setting.

Cardiotoxic effects, or lack thereof, of anti-ErbB2 immunoagents.

This study investigated potential cardiotoxicity as exerted by Erbicin-derived-immunoagents (EDIAs), novel human anti-ErbB2 immunoagents engineered by fusion of a human anti-ErbB2 scFv, Erbicin, with either a human RNase or the Fc region of a human IgG1. EDIAs are strongly cytotoxic on ErbB2-positive cells in vitro and in vivo and bind to an epitope different from that of Herceptin, a humanized anti-ErbB2 mAb effective in the therapy of breast carcinoma, but cardiotoxic in a high percentage of cases. Toxicity and apoptosis were tested in vitro by 3-(4,5-dimethyl-2-thizolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), DNA fragmentation, and immunoblotting analyses. Echocardiography was measured in mice after treatment with each immunoagent. Cardiac fibrosis and detection of apoptosis were examined by Sirius red staining of collagen and TUNEL assay, respectively. EDIAs were found in vitro to have no adverse effects on cardiac cells for which Herceptin is severely toxic. In vivo studies on a mouse model showed that the EDIAs did not alter cardiac function, whereas Herceptin and doxorubicin, used as positive controls, significantly reduced the fractional shortening parameter. Cardiac fibrosis and apoptosis were not significantly affected in mice treated with EDIAs. Thus, EDIAs could fulfill the therapeutic need of patients ineligible for Herceptin treatment due to cardiac dysfunction.

Multicentre experience with MGuard net protective stent in ST-elevation myocardial infarction: safety, feasibility, and impact on myocardial reperfusion.

OBJECTIVE: To report, for the first time, angiographic and ECG results as well as in-hospital and 1-month clinical follow-up, after MGuard net protective stent (Inspire-MD, Tel-Aviv, Israel-MGS) implantation in consecutive, not randomized, STEMI patients undergoing primary or rescue PCI. BACKGROUND: Distal embolization may decrease coronary and myocardial reperfusion after percutaneous coronary intervention (PCI), in ST-elevation myocardial infarction (STEMI) setting. METHODS: One-hundred consecutive patients underwent PCI, with MGS deployment for STEMI, in five different high-volume PCI centres. Sixteen patients presented cardiogenic shock at admission. RESULTS: All patients underwent successful procedures: mean TIMI flow grade and mean corrected TIMI frame count-cTFC(n)-improved from baseline values to 2.85 +/- 0.40 and to 17.20 +/- 10.51, respectively, with a mean difference in cTFC(n) between baseline and postprocedure of 46.88 +/- 31.86. High-myocardial blush grade (90% MBG 3; 10% MBG 2) was also achieved in all patients. Sixty minutes post-PCI, a high rate (90%) of complete (>or=70%) ST-segment resolution was achieved. At in-hospital follow-up, seven deaths occurred: noteworthy, 5 of 16 patients with cardiogenic shock at admission died. After hospital discharge, no Major Adverse Cardiac Events have been reported up to 30-day follow-up. CONCLUSIONS: MGS might represent a safe and feasible option for PCI in STEMI patients, providing high perfusional and ECG improvement. Further randomized trials comparing this strategy with the conventional one are needed in the near future to assess the impact on clinical practice of this strategy.

Myocardial fibrosis and diastolic dysfunction in patients on chronic haemodialysis.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is linked to myocardial collagen content in many cardiac diseases. There are no data regarding such relationship in patients with end-stage renal disease (ESRD) undergoing haemodialysis. METHODS: Twenty-five patients with ESRD undergoing haemodialysis were studied by echocardiography. LV diastolic function was investigated by Doppler echocardiography, by analysing LV filling velocities at rest and during loading manoeuvres, which represent an estimate of LV filling pressure. According to the Doppler pattern, LV filling pressure in a given patient was judged to be normal or slightly increased or to be moderately or severely increased. The presence of myocardial fibrosis was estimated by ultrasound tissue characterization with integrated backscatter, which in diastole correlates with the collagen content of the myocardium. RESULTS: Integrated backscatter was higher in patients with moderate or severely increased than in patients with normal or slightly increased LV filling pressure (integrated backscatter: 51.0 +/- 9.8 vs 41.6 +/- 5.6%; P = 0.008). Integrated backscatter was a strong and independent determinant of diastolic dysfunction (odds ratio = 1.212; P = 0.040). CONCLUSION: Our data support the hypothesis that, in a selected population of patients with ESRD undergoing haemodialysis, myocardial fibrosis is associated with LV diastolic myocardial properties.

Prognostic role of myocardial single photon emission computed tomography in the elderly.

The increase in average life expectancy will move the burden of coronary artery disease (CAD) to older patients. Myocardial perfusion imaging by single photon emission computed tomography (SPECT) has been extensively validated for diagnosis and prognostic evaluation in large population series. Yet, its use is usually limited in elderly patients in whom, despite increased absolute cardiovascular risk, diagnostic and therapeutic work-up is often underperformed. American College of Cardiology/American Heart Association guidelines recommend exercise ECG testing as the initial noninvasive method for assessment of CAD in patients with a normal or near-normal resting ECG, regardless of age. However, a considerable proportion of elderly patients is unable to reach an adequate workload during the exercise test and the majority of those undergoing for standard exercise treadmill score are classified as intermediate risk. In elderly patients, SPECT imaging may provide valuable diagnostic and prognostic information for clinical management. In particular, normal or near normal SPECT identifies elderly patients at low risk of major adverse cardiac events at the short-term follow-up.

The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events.

BACKGROUND: The clinical impact of PlA2 polymorphism has been investigated in several diseases, but the definition of its specific role on thrombotic cardiovascular complications has been challenging. We aimed to explore the effect of PlA2 polymorphism on outcome in patients with atherosclerosis. METHODS: We studied 400 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention. A replication study was conducted in 74 hypertensive patients with cerebrovascular events while a group of 100 healthy subjects was included as control population. PlA genotype was determined by PCR-RFLP on genomic DNA from peripheral blood cells. Major adverse cardiac events (MACE), were considered as end points, and recorded at a mean follow up of 24 ± 4.3 months. RESULTS: The frequencies of PlA2 polymorphism was similar between groups and genotype distribution was in Hardy-Weinberg equilibrium. In patients with CAD, the presence of PlA2 allele was associated with higher incidence of cardiac death (13.1% vs. 1.5%, p = 0.0001), myocardial infarction (10.7% vs. 2.6%, p = 0.004) and needs of new revascularization (34.8% vs. 17.7%, p = 0.010). Accordingly, the Kaplan-Meier analysis for event free survival in patients harboring the PlA2 allele showed worse long-term outcome for these patients (p = 0.015). Cox regression analysis identified the presence of PlA2 as an independent predictor of cardiac death (OR: 9.594, 95% CI: 2.6 to 35.3, p = 0.002) and overall MACE (OR: 1.829, 95% CI: 1.054 to 3.176, p = 0.032). In the replication study, the PlA2 polymorphism increased the risk of stroke (OR: 4.1, 95% CI: 1.63-12.4, p = 0.02) over TIA and was identified as an independent risk factor for stroke (B:-1.39; Wald: 7.15; p = 0.001). CONCLUSIONS: Our study demonstrates that in patients with severe atherosclerosis the presence of PlA2 allele is associated with thrombotic cardiovascular complications.

Successful use of the Cardiva Boomerang™ vascular closure device to close a brachial artery puncture site after emergency PTCA.

Brachial artery access is a good alternative for performing percutaneous transluminal angioplasty when femoral access is contraindicated or not feasible. Although several closure devices are available for femoral access, haemostasis for brachial artery access is still achieved by manual compression with several potential complications, such as bleeding, pseudo-aneurysm formation, especially in patients in which heparin is administered, or thrombotic vessel occlusion. This first-in-human report describes the off-label brachial use of the Cardiva Boomerang™, a novel vascular closure device, which provides haemostasis using a temporary intravascular tampon, thus permitting the easier physiological closure of the puncture site without any important complications.

Aortic valve sclerosis in patients with peripheral and/or coronary arterial disease.

BACKGROUND: Aortic valve sclerosis (AVS) is a marker of cardiovascular risk; its prevalence increases in elderly and in patients with hypertension and/or coronary arterial disease (CAD). There are no data available in patients with peripheral arterial disease (PAD) and with both CAD and PAD. METHODS: To investigate the presence of AVS, 57 patients with stable CAD, 38 with PAD, and 62 with CAD + PAD where studied by echocardiography. RESULTS: The prevalence of AVS progressively increased within groups (P = 0.005). The prevalence of AVS in PAD doubled that in CAD group (42.1% vs. 22.8%, P < 0.05). PAD patients had a 4.634 (95% CI: 1.02-17.88; P = 0.026) fold increased risk of AVS compared to CAD. Also CAD + PAD group had a higher prevalence of aortic sclerosis when compared to CAD group (50.8% vs. 22.8%, P = 0.001). CAD + PAD showed a 3.799 (95% CI: 1.26-11.45; P < 0 .01) fold greater risk of aortic sclerosis than CAD group. There were no differences in AVS prevalence between CAD + PAD and PAD group (50.8% vs. 42.1%; P = 0.36). Age was related to AVS in both analysis (PAD vs. CAD and CAD + PAD vs. CAD: OR = 1.09, 95% CI: 1.02-1.16, P = 0.011 and OR = 1.13, 95% CI: 1.07-1.21; P < 0.001) but no classical cardiovascular risk factors. CONCLUSIONS: PAD patients have an elevated prevalence of AVS greater than CAD patients. In patients with both disease, the prevalence of AVS is similar to that of patients with PAD alone.

Effects of perindopril on cardiac remodelling and prognostic value of pre-discharge quantitative echocardiographic parameters in elderly patients after acute myocardial infarction: the PREAMI echo sub-study.

AIMS: To determine (i) the effect of perindopril on several geometric and functional parameters of the left and right ventricles assessed by echocardiography in the unique Perindopril and Remodelling in Elderly with Acute Myocardial Infarction (PREAMI) population of post-acute myocardial infarction (AMI) elderly patients with preserved left ventricular (LV) function; and (ii) the prognostic predictors at pre-discharge derived from echo-Doppler measurements in the same population. METHODS AND RESULTS: PREAMI included 1252 post-AMI patients (age 73 +/- 6 years, LV ejection fraction 59.1 +/- 7.7%) receiving optimal therapy after AMI, randomized to perindopril 8 mg/day (n = 631) or placebo (n = 621); n = 896 had complete echo-Doppler data. Outcome measures were clinical [death, heart failure (HF)] and standard echo-Doppler parameters. Pre-discharge LV end-diastolic volume (LVEDV) was similar: 81.1 +/- 23.1 (perindopril) and 79.6 +/- 22.7 mL (placebo). At 6 months and 1 year, LVEDV remained unchanged with perindopril (81.2 +/- 24.4 and 81.8 +/- 26.8 mL, respectively), but increased with placebo (83.0 +/- 25.3 and 83.6 +/- 25.7 mL, respectively, both P < 0.001 vs. baseline). Perindopril reduced cardiac sphericity vs. placebo (P = 0.015 at 6 months; P = 0.020 at 1 year). Classification regression tree analysis showed treatment as the most important predictor of remodelling. Multiple pre-discharge echocardiographic variables predicted the death/HF endpoint, independently of treatment (P < or = 0.05). CONCLUSION: Remodelling occurs in post-AMI in elderly patients with normal LV function. Echo-Doppler variables at baseline have prognostic implications. Treatment with perindopril reduces progressive LV remodelling that can occur even in the case of small infarct size.

AngioJet rheolytic thrombectomy for acute superficial femoral artery stent or femoropopliteal by-pass thrombosis.

Thrombosis of superficial femoral artery (SFA) nitinol stents or polytetrafluoroethylene (PTFE) femoropopliteal bypass grafts after discontinuation of antiplatelet therapy is an emergent clinical challenge of acute limb ischemia (ALI), requiring immediate percutaneous intervention. Currently, there is no evidence-based approach for the management of such complications. We describe the cases of two patients presenting with ALI due to nitinol stent thrombosis after discontinuation of antiplatelet therapy and the case of a patient presenting with ALI due to PTFE femoropopliteal graft thrombosis in which limb salvage was obtained by AngioJet rheolytic thrombectomy and re-stenting. In both cases, the thrombus was successfully removed using the Possis AngioJet mechanical thrombectomy catheter and percutaneous transluminal angioplasty (PTA) was performed to recanalize two femoropopliteal nitinol stents and a femoropopliteal PTFE graft. In both cases, optimal angiographic result was obtained. To the best of our knowledge, these are the first three cases reporting the use of the AngioJet rheolytic thrombectomy in ALI due to stent or graft thrombosis. Taken together, these cases suggest that AngioJet rheolytic thrombectomy might represent a novel effective strategy in the percutaneous treatment of stent or graft thrombosis determining ALI.

Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention.

BACKGROUND: Despite its limitations, unfractionated heparin has been the standard anticoagulant used during percutaneous coronary intervention (PCI). Several small studies have suggested that intravenous enoxaparin may be a safe and effective alternative. Our primary aim was to assess the safety of enoxaparin as compared with that of unfractionated heparin in elective PCI. METHODS: In this prospective, open-label, multicenter, randomized trial, we randomly assigned 3528 patients with PCI to receive enoxaparin (0.5 or 0.75 mg per kilogram of body weight) or unfractionated heparin adjusted for activated clotting time, stratified according to the use or nonuse of glycoprotein IIb/IIIa inhibitors. The primary end point was the incidence of major or minor bleeding that was not related to coronary-artery bypass grafting. The main secondary end point was the percentage of patients in whom the target anticoagulation levels were reached. RESULTS: Enoxaparin at a dose of 0.5 mg per kilogram was associated with a significant reduction in the rate of non-CABG-related bleeding in the first 48 hours, as compared with unfractionated heparin (5.9% vs. 8.5%; absolute difference, -2.6; 95% confidence interval [CI], -4.7 to -0.6; P=0.01), but the higher enoxaparin dose was not (6.5% vs. 8.5%; absolute difference, -2.0; 95% CI, -4.0 to 0.0; P=0.051). The incidence of major bleeding was significantly reduced in both enoxaparin groups, as compared with the unfractionated heparin group. Target anticoagulation levels were reached in significantly more patients who received enoxaparin (0.5-mg-per-kilogram dose, 79%; 0.75-mg-per-kilogram dose, 92%) than who received unfractionated heparin (20%, P<0.001). CONCLUSIONS: In elective PCI, a single intravenous bolus of 0.5 mg of enoxaparin per kilogram is associated with reduced rates of bleeding, and a dose of 0.75 mg per kilogram yields rates similar to those for unfractionated heparin, with more predictable anticoagulation levels. The trial was not large enough to provide a definitive comparison of efficacy in the prevention of ischemic events. (ClinicalTrials.gov number, NCT00077844 [ClinicalTrials.gov].).

Increased high mobility group box-1 protein levels are associated with impaired cardiopulmonary and echocardiographic findings after acute myocardial infarction.

BACKGROUND: Several markers of systemic inflammation seem to play an active role in the pathophysiology of acute coronary syndrome and its evolution. High mobility group box-1 (HMGB-1), a ubiquitous nuclear protein constitutively expressed in quiescent cells, was recently recognized as a newer critical mediator of inflammatory diseases. The present study aimed to evaluate the possible association between HMGB-1 levels and structural and functional indices of cardiovascular performance such as cardiopulmonary and Doppler-echocardiography indices in patients after acute myocardial infarction (MI). METHODS AND RESULTS: Fifty-four consecutive patients (mean age 58.3 years, 83% males) recovering from acute MI were included in the study protocol. All patients underwent Doppler-echocardiography, cardiopulmonary exercise, and HMGB-1 assay. HMGB-1 levels in acute MI patients were significantly higher compared with age- and body mass index-matched controls (14.8 +/- 6.8 vs. 2.3 +/- 1.0 ng/mL, P < .0001, respectively). Postinfarction patients showed oxygen consumption at peak exercise (VO(2 peak)) = 14.4 +/- 4.2 mL x kg x min and a slope of increase in ventilation over carbon dioxide output (VE/VCO(2 slope)) = 32.1 +/- 6.2, whereas Doppler-echocardiography values were: left ventricular end-diastolic volume (LVEDV) = 53.4 +/- 8.2 mL/m(2); left ventricular ejection fraction (LVEF) = 41.7 +/- 7.0%. Multiple linear regression analysis (stepwise method) showed that VO(2 peak) (beta = -0.276, P = .012), VE/VCO(2 slope) (beta = 0.244, P = .005), LVEDV (beta = 0.267, P = .018), peak creatine kinase-MB (beta = 0.339, P = .004), peak Troponin I (beta = 0.244, P = .002), and LVEF (beta = -0.312, P = .021) were significantly associated with HMGB-1 levels. CONCLUSIONS: The present study demonstrated that in postinfarction patients, HMGB-1 levels were significantly higher compared with controls, and significantly correlated with cardiopulmonary and Doppler-echocardiography parameters.

Leptin stimulated C-reactive protein production by human coronary artery endothelial cells.

BACKGROUND: Obesity and cardiovascular disease are closely related. Leptin, an adipocyte-produced hormone, is associated with increased cardiovascular risk. Increased plasma levels of leptin are measurable in the plasma of obese individuals. However, the possible links between obesity and cardiovascular disease are not completely understood. C-reactive protein (CRP) is a predictor of future cardiovascular events and plays a role in atherothrombotic disease. Thus, we evaluated whether leptin might play a role in cardiovascular disease, investigating its effects on CRP production by human coronary artery endothelial cells in culture. METHODS AND RESULTS: Leptin induced CRP mRNA transcription as demonstrated by semiquantitative and real-time polymerase chain reaction as well as the release of CRP in the culture medium in a concentration-dependent fashion. Leptin-induced production of CRP was mediated through the RhoA activation of protein kinase Cbeta since both protein kinase C and RhoA pathway inhibitors prevented these leptin effects. Lovastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, by modulating the RhoA activation, significantly reduced leptin-induced CRP production. CONCLUSIONS: This study describes the close relationship between leptin and CRP, providing support to the view that this adipokine, besides being involved in the pathophysiology of obesity, might play a relevant role as an active partaker in obesity, inflammation and atherothrombosis.

Echolucent femoral plaques entail higher risk of echolucent carotid plaques and a more severe inflammatory profile in peripheral arterial disease.

OBJECTIVE: Plaque instability is recognized as a multivessel phenomenon related to inflammation. This study examined if the morphology of femoral plaques was related to that of carotid plaques. METHODS: The echogenicity of femoral and carotid plaques of 102 patients with peripheral artery disease (PAD) was studied and classified as echolucent or echorich according to the gray-scale median (GSM) value, which was 53.6 for femoral plaques and 55.2 for carotid plaques. Serum C-reactive protein (CRP) levels and neutrophil count were also measured. RESULTS: Echolucent carotid plaques were more frequent in patients with echolucent than in those with echorich femoral plaques (55.8% vs 32.0%; P < .01). At multivariate analysis, femoral GSM lower than the median was the only significant predictor of echolucent carotid plaques (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.53-9.83). Patients with echolucent femoral plaques had higher serum CRP levels (P < .01) and a higher neutrophil count (P = .029) than patients with echorich femoral plaques. However, univariate analysis showed that neutrophil count (OR, 3.48; 95% CI, 1.23-9.85) but not hs-CRP was associated with echolucent carotid plaques. At multivariate analysis, neutrophil count exceeding the median remained associated with echolucent carotid plaques (OR, 5.71; 95% CI, 1.37-23.85), whereas the association between femoral and carotid echolucency was attenuated (OR, 3.75; 95% CI, 0.98-4.43). CONCLUSIONS: In PAD, the presence of echolucent femoral plaques is associated with a greater prevalence of echolucent carotid plaques, probably as a consequence of a more pronounced inflammatory profile. This confirms and extends the finding that plaque echolucency is a multivessel phenomenon. Prospective studies are needed to assess whether carotid screening in PAD patients might contribute to improving clinical decision-making.

Concomitant coronary and peripheral arterial disease: relationship between the inflammatory status of the affected limb and the severity of coronary artery disease.

OBJECTIVE: In coronary artery disease (CAD), concomitant peripheral arterial disease (PAD) entails increased systemic inflammatory profile and more severe coronary atherosclerosis. We investigated the relationship between the inflammatory status in the affected limb and CAD severity. METHODS: In 46 CAD+PAD and 31 CAD-alone patients, the inflammatory status of the leg circulation was measured by the transfemoral gradients of neutrophil myeloperoxidase (MPOx) content and interleukin-6 (IL-6). CAD severity was defined by evaluating coronary artery endothelial function, number of significant coronary stenoses, and prevalence of three-vessel CAD and myocardial infarction (MI). RESULTS: In the affected limb of CAD+PAD patients, the transfemoral gradients of neutrophil MPOx content and IL-6 were higher (P < .01, for both) than in the healthy leg of CAD-only patients. At multivariate analysis, CAD+PAD patients with transfemoral gradients of MPOx and IL-6 > median had a more compromised coronary artery endothelial function (P < .05, for both). Furthermore, CAD+PAD patients with transfemoral gradients of neutrophil MPOx content > median showed an independent association with a greater number of significant coronary stenoses, and a greater prevalence of three-vessel CAD and previous MI (P < .01, for all). A more severe coronary atherosclerosis was observed also in CAD+PAD patients with transfemoral gradients of IL-6 > median vs those with IL-6 < median, although differences were not statistically significant. CONCLUSION: In CAD patients, the coexistence of PAD does not necessarily entail a more severe coronary atherosclerosis. Only those with an inflammatory status of the affected limb presents more severe CAD. Future studies will clarify whether the presence of peripheral inflammation plays a mechanistic role in CAD evolution.

Clinical impact of sirolimus-eluting stent in ST-segment elevation myocardial infarction: a meta-analysis of randomized clinical trials.

OBJECTIVES: To evaluate outcome of patients undergoing sirolimus-eluting stent (SES) as compared to bare-metal stent (BMS) implantation during primary angioplasty for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The role of SES in primary percutaneous coronary intervention setting is still debated. METHODS: We searched Medline, EMBASE, CENTRAL, scientific session abstracts, and relevant Websites for studies in any language, from the inception of each database until October 2008. Only randomized clinical trials with a mean follow-up period >6 months and sample size >100 patients were included. Primary endpoint for efficacy was target-vessel revascularization (TVR) and primary endpoint for safety was stent thrombosis. Secondary endpoints were cardiac death and recurrent myocardial infarction (MI). RESULTS: Six trials were included in the meta-analysis, including 2,381 patients (1,192 randomized to SES and 1,189 to BMS). Up to 12-month follow-up, TVR was significantly lower in patients treated with SES as compared to patients treated with BMS (4.53% vs. 12.53%, respectively; odds ratio [OR] 0.33; 95% confidence interval [CI] 0.24-0.46; P < 0.00001). There were no significant differences in the incidence of stent thrombosis (3.02% vs. 3.70%, OR = 0.81 [95% CI, 0.52-1.27], P = 0.81), cardiac death (2.77% vs. 3.28%, OR = 0.84 [95% CI, 0.52-1.35], P = 0.47), and recurrent MI (2.94% vs. 4.04%, OR = 0.71 [95% CI, 0.45-1.11], P = 0.13) between the two groups. CONCLUSION: SES significantly reduces TVR rates as compared to BMS in STEMI patients up to 1 year follow-up. Further studies with larger population and longer follow-up time are needed to confirm our findings.

Thrombosis of mechanical valve prosthesis in patient with recent Caesarean delivery.

We present a case of a mechanical mitral valve thrombosis in a 37-year-old woman occurred 2 days after a Caesarean delivery. The patient stopped warfarin and initiated low-molecular-weight heparin 1 week before the programmed delivery. Subsequently the diagnosis of thrombosis, heparin infusion was started however unsuccessfully and eventually patient was referred for cardiac surgery.