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Biomedical subjects

D Ardissino

Publications and source records attributed to D Ardissino.

At least 19 recordsLinked to original sources
PubMed2006

MRI evaluation of myocardial viability.

Cardiac magnetic resonance imaging (MRI) has become an accurate noninvasive imaging procedure for the study of postischaemic residual cardiac function, thanks to the evolution of MRI machines, postprocessing software and, above all, sequences. After infarction, and in chronic myocardial ischaemia, the degree of contractile dysfunction is one of the main determinants of longterm survival. The identification and quantification of viable dysfunctional myocardium and the possibility of improving its contractility after revascularisation improves patient prognosis and quality of life. In current clinical practice, myocardial viability is evaluated with stress echocardiography and nuclear methods. Thanks to its intrinsic characteristics and to the delayed-enhancement technique (DE-MRI), MRI has recently emerged as the only noninvasive modality able to provide a three-dimensional (3D) evaluation of cardiac viability with a multiparametric approach.

Humans↗
PubMed2006

Imaging of post-traumatic cardiac rhabdomyolysis with normal coronary arteries.

Numerous cases of acute myocardial infarction (AMI) have been reported in the literature following closed chest injuries, due to post-traumatic dissection or thrombosis of a coronary artery. In the follow-up of AMI, wall thickness during diastole and systole provides important information on heart viability. Multidetector computed tomography (MDCT) is currently the only noninvasive instrumental investigation which provides an appreciable assessment of the coronary arteries, as well as heart wall thickness measurements. We describe and discuss the clinical and imaging findings, especially of MDCT, in a case of post-traumatic regional myocardial necrosis with normal coronary arteries.

Cardiomyopathies↗
PubMed2005

Direct thrombin inhibitors for the treatment of acute coronary syndromes and during percutaneous coronary interventions.

As acute coronary syndromes are principally sustained by plaque complication and subsequent thrombus formation, anticoagulant therapy plays a central role in avoiding ischemic events; its main targets are thrombin activity and generation. Despite its limitations, such as its scarce ability to activate bound thrombin and its unpredictable pharmacological response, heparin is the most widely used drug for this purpose. Direct thrombin inhibitors are biologically superior to heparin principally because they inhibit clot-bound and circulating thrombin without interacting with other plasma proteins. Their clinical role in acute coronary syndromes and during coronary intervention has been tested in several trials. This article overviews the principal trials involving active-site direct thrombin inhibitors in acute coronary syndrome and during coronary intervention and compares their efficacy and safety with unfractionated heparin. It also describes ongoing trials and analyzes further clinical developments such as their use in addition to the glycoprotein IIb/IIIa inhibitors and the potential advantage possible with new agents orally administered.

Angioplasty, Balloon, Coronary↗
PubMed2003

Risk of intracranial haemorrhage with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction. Dichotomous response as a function of age in the GUSTO V trial.

BACKGROUND: Intracranial haemorrhage is an important limitation to pharmacologic reperfusion therapy for acute myocardial infarction. The combination of a glycoprotein IIb/IIIa inhibitor, half-dose plasminogen activator and reduced-dose heparin has been evaluated as an alternative to standard fibrinolytic therapy in this setting. METHODS AND RESULTS: We evaluated the relation between univariate and multivariate predictors of intracranial haemorrhage and the effect of treatment with either reteplase alone (10 U bolus twice, 30 min apart) with standard-dose heparin (5000 U bolus followed by an infusion of 1000 Uh(-1)for patients > or =80 kg and 800 Uh(-1)for those <80 kg) or combination therapy with abciximab (0.25mg/kg bolus and 0.125 microg/kg/min for 12h) and half-dose reteplase (two boluses of 5U 30 min apart) with reduced-dose heparin (60 Ukg(-1)bolus, maximum 5000 U, followed by an infusion of 7 Ukg(-1)h(-1)) in the 16 588 patients randomized in the GUSTO V trial. Overall, the incidence of intracranial haemorrhage was similar in the two groups (0.6% vs 0.6%; OR 1.05, 95% CI 0.71, 1.56). The median (25th-75th) time from drug administration to intracranial haemorrhage was 5.5 (3.4-11) hours with combination therapy and 9.2 (5.9-22) hours with reteplase (P=0.048). Among the multivariable predictors of intracranial haemorrhage, only age showed a significant interaction with treatment effect (age per treatment interaction chi-square 4.60, P=0.032) with a lower risk of combination therapy for younger patients and a higher risk for the elderly. CONCLUSIONS: Although no additional risk of intracranial haemorrhage has been observed with combination therapy in the whole population, a significant age pertreatment interaction exists, with a lower risk with combination therapy in younger patients, and a higher risk in the elderly.

Abciximab↗
PubMed2003

Identification of differentially expressed genes in coronary atherosclerotic plaques from patients with stable or unstable angina by cDNA array analysis.

The composition of atherosclerotic plaques is a crucial factor in determining rupture, thrombosis and clinical events. In this study, we analyzed gene expression in coronary plaques from patients with stable or unstable angina using gene arrays. Total RNA was extracted from eight plaques collected by therapeutic directional coronary atherectomy. cDNA probes, generated by amplification, were hybridized to nylon arrays containing 482 genes. Here we report the results for the inflammation, adhesion and hemostasis subsets. Many genes not previously associated with atherosclerosis, such as the lymphocyte adhesion molecule MadCAM, were expressed in the plaques. anova analysis showed higher tissue factor (TF) expression in unstable angina samples. Five genes were expressed at lower levels in unstable angina samples: anticoagulant protein S, cyclooxygenase (COX)-1, interleukin (IL)-7 and chemokines monocyte chemotactic protein (MCP)-1 and -2. Gene arrays provide a new approach to study plaque composition and identify candidate markers of plaque instability.

Angina Pectoris↗
PubMed2002

Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes; the GUSTO-IIb haemostasis substudy.

AIMS: We compared the effects of hirudin and heparin on thrombin generation and activity among 350 patients with acute coronary syndromes enrolled in the GUSTO-IIb trial. METHODS AND RESULTS: We obtained blood at baseline; at 4, 8, and 24h into infusion; at drug termination; and 6 and 24h after termination. We assayed for thrombin activity (fibrinopeptide A, activated protein C, thrombin-antithrombin complex), thrombin generation (prothrombin fragment 1.2), and platelet activation (platelet factor 4). Median baseline fibrinopeptide A and platelet factor 4 levels were elevated. Thrombin formation tended to increase with hirudin and decrease with heparin; by 8h into infusion, thrombin formation was significantly less for heparin (P<0.01). Most patients showed reduced thrombin activity and platelet activation during infusion of either agent. Hirudin-assigned patients had significantly lower fibrinopeptide A levels during infusion. Six h post-termination, both groups had increased thrombin activity. Thrombin formation was increased in heparin patients (P<0.0001), significantly more than with hirudin (P=0.005). Higher values of haemostasis markers tended to be associated with poorer 30-day outcomes. CONCLUSION: Although hirudin did not prevent generation of new thrombin, it appeared to inhibit thrombin activity more than did heparin and produced slower increases in thrombin formation after discontinuation. The reelevation of thrombotic markers after stopping intravenous antithrombin therapy and the tendency toward increased thrombotic events with post-treatment increases in marker levels suggest an ongoing, clinically significant prothrombotic state. These results raise the possibility of improving on current antithrombotics by preventing thrombin generation and thrombin activity and by sustained suppression of the prothrombotic state.

Acute Disease↗
PubMed2001

Thrombogenic potential of human coronary atherosclerotic plaques.

Higher levels of tissue factor (the initiator of blood coagulation) have been found in coronary atherosclerotic plaques of patients with unstable coronary artery disease, but it is not established whether they are associated with a different thrombotic response to in vivo plaque rupture. In 40 patients undergoing directional coronary atherectomy, prothrombin fragment 1 + 2, a marker of thrombin generation, was measured in intracoronary blood samples obtained proximally and distally to the coronary atherosclerotic plaque before and after the procedure. Before the procedure, plasma prothrombin fragment 1 + 2 levels were significantly increased across the lesion in patients with unstable, but not in those with stable, coronary disease (unstable, median increase, 0.37 nM; range, -0.35-1.16 nM) (stable, median increase, -0.065 nM; range, -0.58-1.06 nM) (P =.0021). After plaque removal, an increase in prothrombin fragment 1 + 2 across the lesion was observed only in patients with unstable coronary disease (unstable, median increase, 0.25 nM; range, -1.04-4.9 nM) (stable, 0.01 nM; range, -0.48-3.59 nM) (P =.036)]. There was a correlation between the tissue factor content of the plaque and the increase in thrombin generation across the lesion (rho = 0.33; P =.038). The higher tissue factor content found in plaques obtained from patients with unstable coronary disease was associated with a local increase in thrombin generation, thus suggesting a link with the in vivo thrombogenicity of the plaque.

Aged↗
PubMed2001

Percutaneous coronary revascularisation in women.

Numerous studies of sex differences in morbidity and mortality after an episode of acute coronary disease shown unclear results. In particular is not clear if women undergoing coronary revascularization procedures have adverse in-hospital and long-term outcomes compared with men. Recent clinical trial have provided new insights into this problem. The influence on gender differences for the decision to undertake coronary angiography and percutaneous transluminal coronary angioplasty will be discussed.

Angioplasty, Balloon, Coronary↗
PubMed2001

Reactivation of ischemic events in acute coronary syndromes: results from GUSTO-IIb. Gobal Use of Strategies To Open occluded arteries in acute coronary syndromes.

OBJECTIVES: We sought to determine the incidence of and risk factors for thrombotic events early after discontinuing antithrombin therapy in patients with acute coronary syndromes. BACKGROUND: Discontinuation of treatment with heparin and other thrombin inhibitors in patients with unstable coronary syndromes has related to clinical and biochemical evidence of early reactivation of thrombosis. METHODS: We studied 8,943 of the 12,142 patients with acute coronary syndromes enrolled in the Global Use of Strategies To Open occluded arteries in acute coronary syndromes trial of hirudin versus heparin. We excluded patients who received no study drug, lacked timing data, died or had myocardial (re)infarction [(re)MI] during study-drug infusion, or began heparin treatment within 2 h after treatment with the study drug was stopped. We assessed the incidence and timing of (re)MI by type and timing of antithrombin treatment. RESULTS: In all, 215 patients (2.4%) suffered (re)MI, 49 within 12 h of antithrombin therapy discontinuation and 166 between hour 12 and hospital discharge. The duration of infusion did not differ between the hirudin and heparin groups. The rate of early re(MI) after drug therapy discontinuation was significantly higher in patients given heparin versus hirudin (0.8% vs. 0.3%, p = 0.002). Patients with (re)MI had higher mortality at 30 days (23.6% vs. 2.4%, p = 0.001) and 1 year (35.2% vs. 6.7%, p = 0.001) compared with patients without (re)MI. CONCLUSIONS: The incidence of (re)MI was clustered within 12 h of heparin therapy discontinuation, with the greatest risk within 4 h. There was no evidence of early reactivation of thrombotic events after hirudin. Patients who had (re)infarction had worse outcomes. Better understanding of the mechanism and possible prevention of recurrent thrombosis is needed.

Aged↗
PubMed2001

Clinical, electrocardiographic, and biochemical data for immediate risk stratification in acute coronary syndromes.

The recent evolution in therapeutic options for acute coronary syndromes (ACS) mandates early risk stratification in order to select the appropriate treatment strategy for individual patients. Simple clinical data derived from the patient's medical history and physical examination, a standard twelve-lead electrocardiogram (ECG), and determinations of biochemical markers of myocardial damage can be obtained in the emergency room and serve as a guide for deciding appropriate medical management and optimal use of available resources. Even the most important classification of the ACS is based upon a simple and dichotomous description of the ECG, where the presence of ST-segment elevation mandates an immediate attempt to restore coronary perfusion (either pharmacologically or mechanically), whereas its absence suggests pharmacological stabilization before further evaluation. Across the whole spectrum of ACS, clinical history data (such as older age, previous coronary events, and diabetes) and clinical variables (such as higher heart rate, lower blood pressure, and higher Killip class) are the most powerful prognostic determinants at multivariate analyses derived from large databases. The ECG adds significant and independent prognostic information using the analysis of qualitative (direction of ST-segment shift, associated T-wave inversion, and presence of conduction disturbances) and quantitative (number of leads involved, amount of ST- segment shifts, duration of QRS) characteristics. Biochemical markers of myocardial damage have also been identified as independent predictors of events. In addition, retrospective analyses of clinical trials have suggested that biochemical markers might serve as a guide to select pharmacological therapy. However, how to best combine electrocardiographic and biochemical data for immediate risk stratification remains to be further elucidated.

Aged↗
PubMed2001

Laboratory markers of hypercoagulability.

Investigations carried out over the last 40 years have demonstrated that coronary artery thrombosis is the critical event underlying myocardial infarction and unstable angina. The existence of a prolonged hypercoagulable state preceding the thrombotic event has been postulated for some time and significant associations have been established between the plasma concentrations of a number of hemostatic variables and the frequency of myocardial infarction. High plasma fibrinogen, factor VII/VIIa, tissue-type plasminogen activator and plasminogen activator inhibitor levels have been associated with at least as great a risk of developing myocardial (re)infarction or sudden death as high cholesterol levels, especially in the young. In the last year more sensitive assays have been developed, and they should allow a precise biochemical definition of hypercoagulable states. The significance of these new assays and their role in defining a hypercoagulable state in different conditions are analyzed.

Angina, Unstable↗
PubMed2001

Prothrombotic genetic markers.

The last decade has been characterized by an explosion of research studies on genetic epidemiology. In particular, as far as ischemic heart disease is concerned, a lot of research was focused on prothrombotic genetic risk factors. Unfortunately, the success of this approach in the field of venous thrombosis has not been replicated in the field of myocardial infarction. In the present editorial, a comment on the studies already available is provided and the possible limitations of the present approach are analyzed.

Coronary Thrombosis↗
PubMed2001

[New strategies in the treatment of acute myocardial infarction].

A number of experimental and clinical studies have recently underlined the importance, in acute myocardial infarction, of platelet adhesion and aggregation after plaque rupture. During clot resolution, platelet-rich thrombi are relatively resistant to fibrinolytic agents, mainly due to the release of plasminogen inhibitor-1 by platelets which are activated as a result of the increase in thrombin generation induced by plasminogen activator therapy despite heparin administration. Platelet glycoprotein (GP) IIb/IIIa integrin receptor blockers prevent platelet aggregation by blocking the final pathway of platelet activation. Thus, they also prevent the formation of an intraluminal white thrombus without affecting adhesion. Animal and human studies have shown that the potent inhibition of platelet GP IIb/IIIa receptors can lead to modest reperfusion rates even without exogenous fibrinolytic therapy. This suggests that combining the "dethrombotic" effects of a GP IIb/IIIa antagonist with lower fibrynolytic doses may result in a synergistic effect. Preclinical studies including patients with myocardial infarction have shown that such combined treatment increases the incidence, speed and durability of reperfusion. It has also been proved to be useful in improving the microcirculatory coronary flow and in facilitating subsequent percutaneous coronary interventions. In the phase III GUSTO V trial, abciximab combined with 5 + 5 U of reteplase and low-dose weight-adjusted heparin led to a 30-day mortality rate that was similar to that obtained with full-dose reteplase (10 + 10 U) and standard heparin therapy, without causing a significant increase in the incidence of intracranial hemorrhage. The results of this trial offer a rationale for alternative reperfusion therapy, although further analyses, including a 1-year follow-up, are needed to define the patient groups that are most likely to benefit from such a new regimen.

Angioplasty↗