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Diego Ardissino

Publications and source records attributed to Diego Ardissino.

At least 19 recordsLinked to original sources
PubMed2006

The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size.

The N700S polymorphism of thrombospondin-1 (TSP-1) has been identified as a potential genetic risk factor for myocardial infarction (MI). In a large case-control study of 1425 individuals who survived a myocardial infarction prior to age 45, the N700S polymorphism was a significant risk factor for myocardial infarction in both homozygous (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.3, P = .01) and heterozygous carriers of the S700 allele (OR 1.4, 95% CI 1.1-3.3, P = .01). TSP-1 has been shown to reduce von Willebrand factor (VWF) multimer size, and the domain responsible for VWF-reducing activity has been localized to the calcium-binding C-terminal sequence. As the N700S polymorphism was previously shown to alter the function of this domain, we investigated whether the altered VWF-reducing activity of TSP-1 underlies the observed prothrombotic phenotype. The TSP1 N700S polymorphism did not influence VWF multimer size in patients homozygous for either allele nor was there a significant reduction of VWF multimer size following incubation with recombinant N700S fragments or platelet-derived TSP-1.

Alleles↗
PubMed2006

[Multivessel percutaneous coronary interventions. When incomplete revascularization may represent a therapeutic option].

Scientific evidence that prognosis of patients with ischemic heart disease, treated by either surgery or percutaneous revascularization, is similar, has led interventional cardiologists to search for an aggressive approach in percutaneous revascularization of patients with multivessel disease. It is still matter of debate which strategy is preferable between pursuing complete revascularization or performing revascularization of the culprit vessel and later of the other vessels. According to American and European guidelines for percutaneous coronary intervention (PCI) in patients with acute coronary syndromes with ST-segment elevation and multivessel disease, primary angioplasty should only be directed to the infarct-related artery (culprit vessel), with decision about PCI of non-culprit lesions guided by objective evidence of residual ischemia at later follow-up. PCI should not be performed in a non-infarct-related artery at the time of primary angioplasty in patients without hemodynamic impairment. In patients with acute coronary syndromes without persistent ST-segment elevation the decision to perform either culprit vessel or complete revascularization can be made on individual basis; in patients with favorable anatomy, the competent practitioner can perform either single or multivessel PCI with a high likelihood of success and low risk of morbidity and mortality. The endothelial dysfunction induced by coronary angioplasty, the occurrence of post-procedural infarction and contrast-induced nephropathy, the X-ray exposure, the problem of the informed consent, the procedural costs are aspects that strongly support a strategy based on staged revascularization when appropriate.

Angina, Unstable↗
PubMed2005

Effect of sirolimus-eluting stent in diabetic patients with small coronary arteries (a SES-SMART substudy).

Randomized clinical trials have shown that sirolimus-eluting stents (SESs) decrease restenosis rates compared with bare metal stents (BMSs), but their efficacy among patients who have diabetes mellitus remains to be established. This study investigated the effect of SES implantation in a high-risk population (i.e., patients who had diabetes and small coronary vessel disease). For this purpose, we analyzed outcomes of the subset of patients who had diabetes and were enrolled in the SES-SMART, a randomized trial that compared the results of implantation of SESs and BMSs in small coronary arteries. Twenty-nine patients who had diabetes were originally randomized to receive SESs and 45 patients received BMSs. The use of SESs was associated with approximately 60% decreases in the relative incidence of in-segment angiographic restenosis (63% vs 25%, p = 0.003) and in-segment late loss (0.76 vs 0.28 mm, p <0.002). Angiographic patterns of restenosis were more favorable in the SES group. SES implantation was associated with a 15% absolute decrease in adverse clinical events. In patients who had insulin-dependent diabetes mellitus, SESs showed a high in-segment restenosis rate (40%) that was principally due to persistent restenosis. In conclusion, in diabetics with small coronary arteries, SES implantation significantly reduces the incidence of the 8-month angiographic restenosis rate compared with BMSs.

Aged↗
PubMed2005

Mortality at 1 year for the direct comparison of tirofiban and abciximab during percutaneous coronary revascularization: do tirofiban and ReoPro give similar efficacy outcomes at trial 1-year follow-up.

AIMS: Compared with placebo, abciximab has been associated with mortality reduction at late follow-up. The TARGET trial was performed to test whether tirofiban and abciximab provide similar efficacy outcomes among patients undergoing non-emergent, stent-based percutaneous coronary intervention. We report here the 1-year mortality of the study population. METHODS AND RESULTS: In 18 countries at 149 hospitals, 4,809 patients undergoing elective or urgent stent implantation were randomly assigned a bolus and infusion of tirofiban or abciximab. Ischaemic events were assessed at 30 days and 6 months and mortality was assessed at 1 year. We previously reported that abciximab was superior to tirofiban considering the composite rate of death or myocardial infarction at 30 days among all patients and at 6 months among those with an acute coronary syndrome (ACS). At 1-year follow-up death occurred in 46 (1.9%) patients who received tirofiban and 42 (1.7%) patients who received abciximab (hazard ratio 1.10, 95% CI 0.72-1.67; P=0.660). Mortality rates for patients with ACS were 2.3% with tirofiban vs. 2.2% with abciximab (hazard ratio 1.03, 95% CI 0.64-1.67; P=0.897) and those without ACS were 1.4 vs. 1.0% (hazard ratio 1.32, 95% CI 0.56-3.13; P=0.530). CONCLUSION: At 1 year, tirofiban provided a similar level of survival benefit compared with abciximab.

Abciximab↗
PubMed2005

Mitral supravalvular ring: a case report.

Supravalvular mitral stenosis is a rare condition characterized by an abnormal ridge, with one or two orifices, covering and obstructing the mitral valve. Preoperative diagnosis is difficult with transtoracic echo (TTE), angiography and magnetic resonance imaging (MRI). In this case, a 36-year-old male, was admitted to our Heart department: He experienced progressive dyspnea on effort and at rest. Diagnosis was made by transesophageal echocardiography which showed, on apical 4-chamber section, an annular structure attached since a membrane to the atrial wall anterior mitral valve leaflet and just proximal to the posterior mitral leaflet. Pre-operative identification of the supravalvular mitral ring is the target for obtaining good surgical results. Cineangiography and MRI both failed in reaching this objective, whereas, transesophageal echocardiography is the best method to identify this congenital heart disease. Using TEE the identification is not only possible but also easier.

Adult↗
PubMed2005

Impact of the elevation of biochemical markers of myocardial damage on long-term mortality after percutaneous coronary intervention: results of the CK-MB and PCI study.

AIMS: Retrospective studies and post hoc analyses have suggested that mild elevations in the creatine kinase-MB (CK-MB) isoenzyme following percutaneous coronary intervention (PCI) may be associated with an increased risk of death in the long term. However, this finding is still controversial, and the prognostic significance of elevations of more sensitive markers of myocardial damage, such as the cardiac troponins, has not been established. In this multicentre prospective cohort study, we evaluated the influence of post-procedural elevations of CK-MB and troponin I (cTnI) on long-term mortality. METHODS AND RESULTS: The CK-MB and PCI study included 3494 consecutive patients undergoing PCI from February 2000 to October 2000 in 16 Italian tertiary centres. Blood samples were collected at baseline, and at 8-12 and 18-24 h after the procedure, and were analysed in a core biochemistry laboratory. CK-MB elevation was detected in 16% of the patients, and was associated with increased 2-year mortality [7.2 vs. 3.8%; odds ratio (OR): 1.9; 95% confidence interval (CI): 1.3-2.8; P<0.001). The degree of CK-MB elevation (peak CK-MB ratio) independently predicted the risk of death (adjusted OR per unit: 1.04; 95% CI: 1.01-1.07; P=0.009). A cTnI elevation was detected in 44.2% of the cases and was not associated with a significant increase in mortality (4.9 vs. 4.0%; OR: 1.2; 95% CI: 0.9-1.7; P=0.2). CONCLUSION: Post-procedural elevations of CK-MB, but not cTnI, influence 2-year mortality.

Aged↗
PubMed2005

Tirofiban in acute coronary syndromes.

Acute coronary syndromes represent a major health problem in terms of incidence and mortality. Intracoronary platelet-rich thrombi may develop in response to plaque rupture, and are involved in the pathogenesis of all acute coronary syndromes. The glycoprotein IIb/IIIa receptor, a platelet surface integrin, plays a key role in platelet aggregation once it has been activated by specific ligands. The development of glycoprotein IIb/IIIa inhibitors has revolutionized the management of acute coronary syndromes. Tirofiban is one of three parenteral glycoprotein IIb/IIIa inhibitors in clinical use, and many trials have demonstrated its clinical efficacy and low rate of adverse effects in patients with non-ST-segment elevation acute coronary syndrome. This article reviews the data concerning its use in the clinical settings of acute coronary syndromes and percutaneous coronary angioplasty, and discusses its benefits in different treatment strategies and in association with other drugs. In particular, the role of early, upstream tirofiban coupled with early aggressive revascularization in the management of high-risk non-ST-segment elevation acute coronary syndromes is emphasized.

Acute Disease↗
PubMed2005

[Pathogenesis of acute coronary syndromes: the activated plaque].

Atherosclerosis is a chronic disease potentially involving the whole arterial system that causes a spectrum of clinical manifestations ranging from acute myocardial infarction to stable angina or stroke. The continuous accumulation of lipids, and fibrous and inflammatory elements in the arterial wall of the coronary tree leads to progressive lumen narrowing with subsequent ischemia and symptom-limited exercise. Acute coronary syndromes (unstable angina, acute myocardial infarction) have a more complex and dynamic pathogenesis of which coronary plaque rupture and thrombosis represent only the final common pathway that suddenly compromises resting coronary flow. As only some plaques lead to clinical manifestations whereas many others remain asymptomatic, the aim of this review was to analyze the complex mechanisms leading to plaque complication and rupture with respect to systemic and local features.

Acute Disease↗
PubMed2004

Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial.

CONTEXT: Percutaneous coronary revascularization of small vessels is associated with a high restenosis rate. Sirolimus-eluting stents reduce restenosis in simple and previously untreated lesions of large coronary arteries, but their outcomes in small vessels have not been adequately investigated. OBJECTIVE: To determine whether sirolimus-eluting stents are associated with a reduced 8-month rate of angiographic restenosis in comparison with an uncoated stent. DESIGN, SETTING, AND PATIENTS: This was a randomized, multicenter, single-blind, prospective trial performed with 257 patients undergoing percutaneous coronary revascularization for ischemic heart disease, and who had a previously untreated atherosclerotic lesion located in a small segment with a diameter of 2.75 mm or less, in 20 Italian centers between August 2002 and December 2003. INTERVENTION: Patients were randomly assigned to receive a sirolimus-eluting stent (129 patients) or an uncoated stent having an identical architecture and radiographic appearance (128 patients). MAIN OUTCOME MEASURES: The primary end point was the 8-month binary in-segment restenosis rate; secondary end points included procedural success and the 8-month rate of major adverse cardiac and cerebrovascular events. RESULTS: The mean (SD) reference diameter of the treated segment was 2.2 (0.28) mm; the lesion length, 11.84 (6.15) mm. After 8 months, the binary in-segment restenosis rate was 53.1% (60/113) in the patients receiving an uncoated stent and 9.8% (12/123) in those receiving a sirolimus-eluting stent (relative risk [RR], 0.18; 95% confidence interval [CI], 0.10-0.32; P<.001). Fewer patients randomized to sirolimus-eluting stents experienced major adverse cardiac events (12/129 [9.3%] vs 40/128 [31.3%]; RR, 0.30; 95% CI, 0.15-0.55; P<.001) mainly because of a reduction in target lesion revascularization (9/129 [7%] vs 27/128 [21.1%]; RR, 0.33; 95% CI, 0.14-0.70; P = .002) and myocardial infarction (2/129 [1.6%] vs 10/129 [7.8%]; RR, 0.20; 95% CI, 0.01-0.93; P = .04). CONCLUSION: The use of sirolimus-eluting stents to treat atherosclerotic lesions in small coronary arteries reduces restenosis and may also reduce major adverse cardiac events.

Aged↗
PubMed2004

Different quantitative apoptotic traits in coronary atherosclerotic plaques from patients with stable angina pectoris and acute coronary syndromes.

BACKGROUND: Apoptosis in human atherosclerotic coronary plaques possibly causes plaque destabilization by contributing to the weakening and breaking down of the fibrous cap. We tested the hypothesis that apoptosis is quantitatively increased in unstable atherosclerotic plaques. METHODS AND RESULTS: We analyzed the expression of apoptotic genes such as BAX, CASP1, FAS, FAS L, FOS, MDM2, NFkB2, P53, PCNA, TERT, and XRCC1 in coronary plaques collected with directional coronary atherectomy from 15 patients with stable angina and 15 with acute coronary syndromes without ST elevation (ACS). Total RNA was extracted and cDNA was amplified with a specific set of primers and TaqMan probes. Apoptosis was also revealed by DNA laddering. To clarify the source of mRNAs, we performed in situ reverse transcriptase-polymerase chain reaction coupled with immunocytochemistry and found a substantial overlap between the mRNAs of the above genes and vascular smooth muscle cells. Gene expression analysis showed that the proapoptotic genes (ie, BAX, CASP1, FAS, FAS L, FOS, NFkB2, P53, PCNA) were significantly more expressed (P<0.001) in ACS plaques, whereas the antiapoptotic genes (ie, MDM2, TERT, XRCC1) were more transcribed (P<0.001) in stable angina plaques. Total gDNA gel electrophoresis identified a laddering pattern in the ACS plaques as evidence of end-point apoptosis. Western blotting substantially confirmed the above data. CONCLUSIONS: Our findings support the idea that ACS plaques are committed to apoptosis through an established meshwork of gene activation and inactivation, whereas stable angina plaques retain active cell homeostasis and repair mechanisms.

Acute Disease↗
PubMed2004

Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial.

CONTEXT: Enoxaparin or the combination of glycoprotein IIb/IIIa inhibitor tirofiban with unfractionated heparin independently have shown superior efficacy over unfractionated heparin alone in patients with non-ST-elevation acute coronary syndromes (ACS). It is not clear if combining enoxaparin with glycoprotein IIb/IIIa inhibitors is as safe or as effective as the current standard combination of unfractionated heparin with glycoprotein IIb/IIIa inhibitors. OBJECTIVE: To assess efficacy and safety of the combination of enoxaparin and tirofiban compared with unfractionated heparin and tirofiban in patients with non-ST-elevation ACS. DESIGN, SETTING, AND PARTICIPANTS: A prospective, international, open-label, randomized, noninferiority trial of 1 mg/kg of enoxaparin every 12 hours (n = 2026) compared with weight-adjusted intravenous unfractionated heparin (n = 1961) in patients with non-ST-elevation ACS receiving tirofiban and aspirin. Phase A of the A to Z trial was conducted between December 1999 and May 2002. MAIN OUTCOME MEASURES: Death, recurrent myocardial infarction, or refractory ischemia at 7 days in the intent-to-treat population with boundaries set for superiority and noninferiority. Safety based on measures of bleeding using the Thrombolysis in Myocardial Infarction (TIMI) classification system. RESULTS: A total of 169 (8.4%) of 2018 patients randomized to enoxaparin experienced death, myocardial infarction, or refractory ischemia at 7 days compared with 184 (9.4%) of 1952 patients randomized to unfractionated heparin (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.71-1.08). This met the prespecified criterion for noninferiority. All components of the composite primary and secondary end points favored enoxaparin except death, which occurred in only 1% of patients (23 for enoxaparin and 17 for unfractionated heparin). Rates for any TIMI grade bleeding were low (3.0% for enoxaparin and 2.2% for unfractionated heparin; P =.13). Using a worst-case approach that combined 2 independent bleeding evaluations, use of enoxaparin was associated with 1 additional TIMI major bleeding episode for each 200 patients treated. CONCLUSIONS: In patients receiving tirofiban and aspirin, enoxaparin is a suitable alternative to unfractionated heparin for treatment of non-ST-elevation ACS. The 12% relative and 1% absolute reductions in the primary end point in favor of enoxaparin met criterion for noninferiority and are consistent with prior trials performed without the use of glycoprotein IIb/IIIa inhibitors.

Aged↗
PubMed2004

N-terminal pro-brain natriuretic peptide on admission has prognostic value across the whole spectrum of acute coronary syndromes.

BACKGROUND: The prognostic value of natriuretic peptide elevations in patients with acute coronary syndromes (ACS) is still incompletely defined. We measured N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission in patients with ACS and ECG evidence of myocardial ischemia. METHODS AND RESULTS: The NT-proBNP was measured at a median time of 3 hours after symptom onset in 1756 patients. The outcome measure was death at 30 days, which occurred in 113 patients (6.4%). The median NT-proBNP level was 353 ng/L (107 to 1357 ng/L). Compared with the lowest quartile, patients in the second, third, and fourth quartiles had a relative risk of subsequent death of 2.94 (95% CI, 1.15 to 7.52), 5.32 (95% CI, 2.19 to 12.91), and 11.5 (95% CI, 4.90 to 26.87), respectively. The NT-proBNP was independently associated with death in a logistic regression model, which included clinical variables, ECG, and troponin T in patients either with (OR of highest versus lowest quartile, 7.0; 95% CI, 1.9 to 25.6) or without (OR of highest versus lowest quartile, 4.1; 95% CI, 1.1 to 14.6) persistent ST-segment elevation. NT-proBNP was also an independent predictor of severe heart failure. CONCLUSIONS: The measurement of NT-proBNP on admission improves the early risk stratification of patients with ACS, suggesting the need for the development of targeted therapeutic strategies.

Acute Disease↗
PubMed2004

Thrombocytopenia caused by abciximab or tirofiban and its association with clinical outcome in patients undergoing coronary stenting.

BACKGROUND: Thrombocytopenia is a possible complication of treatment with glycoprotein (GP) IIb/IIIa antagonists during percutaneous coronary interventions, but it is not clear whether different GP IIb/IIIa inhibitors carry a different risk of thrombocytopenia, and its relation to clinical outcome is unknown. METHODS AND RESULTS: We analyzed data from the Do Tirofiban and Reopro Give Similar Efficacy Outcomes (TARGET) study, which compared the safety and efficacy of abciximab and tirofiban in patients undergoing coronary stenting. Platelets were measured at baseline and 6 and 24 hours after the beginning of treatment. Thrombocytopenia (nadir platelet count <100x10(9) cells/L) developed in 2.4% of patients treated with abciximab and 0.5% of those treated with tirofiban (P<0.001). The variables independently associated with thrombocytopenia were treatment with abciximab within the previous 6 months (OR, 4.4; 95% CI, 1.7 to 11.2), baseline creatinine levels of > or =0.8 mg/dL (OR, 3.8; 95% CI, 1.7 to 8.8), previous transient ischemic attack (OR, 3.2; 95% CI, 1.4 to 7.6), female gender (OR, 1.9; 95% CI, 1.2 to 3.1), and history of peripheral vascular disease (OR, 1.78; 95% CI, 1.0 to 3.1). Severe bleeding occurred more frequently in patients with thrombocytopenia (5.1% versus 0.7%, P=0.001), who also more frequently received blood transfusions (6.1% versus 1.4%, P=0.001). At the 30-day follow-up, 2.0% of patients with thrombocytopenia and 0.4% of those without (P=0.022) had died; myocardial infarction occurred in 9.13% versus 6.11% (P=NS); and target vessel revascularization occurred in 6.07% versus 0.60% (P<0.001). CONCLUSIONS: During coronary stenting, abciximab and other risk factors are independently associated with thrombocytopenia. Regardless of the cause, thrombocytopenia is associated with more ischemic events, bleedings, and transfusions.

Abciximab↗
PubMed2004

Activation of the contact system and inflammation after thrombolytic therapy in patients with acute myocardial infarction.

Thrombolytic therapy activates the contact system, and factor XII activation may activate the coagulation cascade and inflammation. It is not known whether an early inflammatory response is induced by thrombolytic therapy in patients with acute myocardial infarction (AMI). We prospectively measured the plasma levels of activated factor XII, cleaved kininogen, prothrombin fragment 1 + 2 (as indexes of the contact phase and coagulation activation), and interleukin-6 and C-reactive protein (CRP) (as indexes of inflammation) in 39 patients hospitalized for AMI within 12 hours of symptom onset: 26 receiving thrombolytic therapy and 13 heparin alone. Blood samples were collected at baseline and after 90 minutes and 24 hours. Patients undergoing thrombolysis had a significant early increase in activated factor XII (from 2.2 ng/ml at baseline to 4.7 ng/ml after 90 minutes; p = 0.0001), cleaved kininogen (from 26% to 37%; p = 0.001), and fragment 1 + 2 (from 1.4 to 2.1 nmol/L; p = 0.0001), whereas the 24-hour levels were similar to baseline levels. The levels of interleukin-6 significantly increased during the first 90 minutes (from 3.9 to 6.3 microg/ml; p = 0.001), and were even higher after 24 hours (11.9 ng/ml, p = 0.0001). CRP levels increased only after 24 hours (p = 0.0001). There were no changes in these parameters in patients receiving heparin alone, except for a 24-hour increase in interleukin-6 and CRP levels. Thus, in patients with AMI receiving thrombolytic therapy, early activation of inflammation parallels the activation of the contact system and the coagulation cascade, which might contribute to microvascular obstruction and reperfusion injury.

C-Reactive Protein↗