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M Galvani

Publications and source records attributed to M Galvani.

At least 37 records · Page 2Linked to original sources
PubMed2000

In vivo thrombin generation and activity during and after intravenous infusion of heparin or recombinant hirudin in patients with unstable angina pectoris.

In patients with unstable angina, intravenous heparin reduces thrombin activity but does not influence thrombin generation. Recombinant hirudin, a direct thrombin inhibitor, may be more effective in inhibiting both thrombin generation and activity. We measured the plasma levels of prothrombin fragment 1+2 (a marker of thrombin generation) and fibrinopeptide A (a marker of thrombin activity) in 67 patients with unstable angina enrolled in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial who were receiving either recombinant hirudin (31 patients) or heparin (36 patients). Blood samples were obtained at baseline (before any treatment), after 3 to 5 days of study drug infusion (immediately before discontinuation), and 1 month later. In the patients receiving recombinant hirudin, the prothrombin fragment 1+2 levels measured immediately before drug discontinuation were significantly lower than at baseline (P:=0.0014), whereas they had not changed in the patients receiving heparin; at this time point, the difference between patients receiving hirudin and those receiving heparin was statistically significant (P:=0.032). One month later, the prothrombin fragment 1+2 levels in both groups were similarly persistently high and did not differ from baseline. Fibrinopeptide A plasma levels at the end of infusion were significantly lower than at baseline in both treatment groups (P:=0. 0005 for hirudin and P:=0.042 for heparin) and remained lower after 1 month (P:=0.0001 for both hirudin and heparin). The fibrinopeptide A plasma levels were not different between patients treated with hirudin versus heparin at baseline, at the end of infusion, and after 1 month. Thus, in patients with unstable angina, in vivo thrombin generation and activity are reduced during intravenous infusion of recombinant hirudin. However, the inhibition of thrombin generation is not sustained, and after 1 month, the majority of patients have biochemical signs of increased thrombin generation.

Aged↗
PubMed2000

[The role of biochemical markers of myocardial damage in clinical practice: the diagnosis of infarct and risk stratification. The Intersociety Interdisciplinary Study Group of the ANMCO-SIBioC-SIMeL, Markers of Muocardial Lesions. L'Associazione Nazionale Medici Cardiologi Ospedalieri-Società Italiana di Biochimica Clinica-Società Italiana di Medicina di Laboratorio].

For many years creatine kinase (CK) and CK-MB isoenzymes were used together with the ECG to confirm the presence of myocardial infarction. During the last decade newer cardiac markers have been introduced and immunological test systems developed for their quantification. Among these new markers, a prominent role has emerged for cardiac troponins (T or I). These technological advanced assays have shown greater sensitivity compared to "conventional cardiac enzymes;, thereby identifying patients with small--at times, microscopic--infarcts who would not have met defining criteria for myocardial infarction in an earlier era. Another major advantage shown by both cardiac troponins with respect to "conventional cardiac enzymes" is their ability to predict clinical outcome over a short- or long-term follow-up in patients with acute coronary syndromes, and this appears to be particularly relevant in patients with micronecrosis, who constitute a high-risk subgroup of unstable angina patients. Recently, myoglobin has also been widely applied as a marker. Although lacking in myocardial specificity, it is the earliest marker to show an increase after coronary occlusion. Thus, the combined use of myoglobin and a cardiospecific structural protein such as troponin T or I may prove an attractive strategy for biochemical testing in chest pain patients. With the routine use of these novel cardiac markers, fascinating opportunities are now open in the field of diagnostic classification (making the World Health Organization definition of myocardial infarction obsolete) and risk stratification in chest pain patients; opportunities that were unforeseen in the era of cardiac enzymes. However, the use of these markers has also posed some important questions on: a) the best and most cost-effective diagnostic strategy in chest pain patients; b) the remaining role of cardiac enzymes; c) the therapeutic consequences of a positive test result.

Biochemical Phenomena↗
PubMed1999

Prothrombotic genetic risk factors in young survivors of myocardial infarction.

It has long been thought that an individual thrombotic tendency increases the risk of myocardial infarction, especially in young adults. Several "prothrombotic" genetic factors that may influence the individual thrombotic risk have been identified. To investigate the association between the risk of myocardial infarction at a young age and genetic factors thought to be associated with an increased tendency to thrombosis (the polymorphisms 4G/5G of the PAI-1 gene, PIA1/PIA2 of the platelet glycoprotein IIIa, C3550T of the platelet glycoprotein Ib gene, G10976A of the factor VII gene, C677T of the methylenetetrahydrofolate reductase gene, G1691A of the factor V gene, and G20210A of the prothrombin gene), we performed a case-control study evaluating 200 survivors (185 men, 15 women) of myocardial infarction who had experienced the event before the age of 45 years and 200 healthy subjects with a negative exercise test, individually matched for sex, age, and geographic origin with the cases. The presence of the PIA2 polymorphic allele was the only prothrombotic genetic factor associated with the risk of myocardial infarction at a young age. The odds ratio for carriers of the PIA2 allele compared with those of the PIA1 allele was 1.84 (95% confidence intervals (CI) 1.12 to 3.03). There was a significant interaction between the presence of the PIA2 allele and smoking: with their simultaneous presence, 46% (95% confidence intervals 11% to 81%) of premature myocardial infarctions were attributable to the interaction between the two factors. In conclusion, carrying the PIA2 polymorphic allele of platelet glycoprotein IIIa was the only genetic prothrombotic factor associated with the risk of developing myocardial infarction at a young age. The clinical expression of this genetic predisposition seems to be enhanced by smoking.

Adult↗
PubMed1999

Early risk stratification of unstable angina/non-Q myocardial infarction: biochemical markers of coronary thrombosis.

Coronary thrombosis is an important determinant of prognosis in patients with acute coronary syndromes (ACS). However, the identification of patients at high-risk for progression of coronary thrombosis is difficult partly because we currently lack clinically meaningful laboratory methods for its detection. The most promising approaches involve the measurement in plasma of markers of fibrin formation and degradation. Thrombin activity, as reflected by plasma or urine concentrations of fibrinopeptide A, is increased in patients with ACS and is associated with adverse outcome. However, the use of fibrinopeptide A as a marker of fibrin formation is limited by the very short half-life of the compound, by artifact due to sample acquisition, and by extremely long turnaround times. To overcome these limitations, measurement of soluble fibrin has been proposed. We have recently explored the prognostic value of a new fibrin-specific ELISA assay for soluble fibrin in patients with ACS and found that patients with the highest levels had a 2-fold increased risk of early and late cardiac events. Increases in plasma concentrations of cross-linked fibrin degradation products (XL-FDPs), which reflect increased fibrin turn-over, are a marker of risk for complications of myocardial infarction. However, until recently, assays for XL-FDPs lacked specificity, because they did not distinguish between fibrin and fibrinogen degradation products. Recently, fibrin-specific ELISAs have been described and a rapid whole blood assay for D-dimer has been developed. We recently validated the prognostic value of this whole blood agglutination assay in patients with ACS. These results suggest that: (1) The detection of significant activation of the coagulation and/or fibrinolytic system may be important for rapid risk stratification of patients with ACS; (2) patients with biochemical evidence of ongoing coronary thrombosis may particularly benefit from aggressive antithrombotic strategies; (3) sequential measurement of these markers may be useful to guide antithrombotic treatment during the unstable phase of coronary artery disease.

Angina, Unstable↗
PubMed1999

Clinical relevance of prodromal angina before acute myocardial infarction.

The term preconditioning was applied to the observation made in 1986 by Murry and colleagues that canine myocardium subjected to brief episodes of ischemia and reperfusion would tolerate a more prolonged episode of ischemia better than myocardium not previously exposed to ischemia. Since that seminal observation, protective effect of preconditioning was demonstrated in all animal species tested, resulting in the strongest form of in vivo protection against myocardial injury other than early reperfusion. Angina heralding acute myocardial infarction may represent the clinical correlate of preconditioning phenomenon in humans. Data from small pathophysiological studies demonstrated that prodromal angina (<48 hours prior to index myocardial infarction) causes a reduction of infarct size and consequently a better left ventricular function compared with patients without such clinical feature before myocardial infarction. The protective effect of prodromal angina was also confirmed in larger prospective studies; its presence translates into a significant reduction of a combination of death, cardiogenic shock and pulmonary edema during hospital stay. The exact mechanism of such clinical phenomenon is however not known, but it may include preconditioning. Other mechanisms have been also claimed to play an important role, like a more rapid lysis of the occlusive thrombus within the infarct-related artery, or a rapid opening of intramural collateral not visible at angiography. Whatever the mechanism, it appears that patients with prodromal angina before myocardial infarction exhibit, when rapidly reperfused, a better post-infarction clinical outcome. At the present "optimal preconditioning-mimetic agents" are yet to be found, and "putting preconditioning in a bottle" still remains a pharmacologic challenge.

Angina, Unstable↗
PubMed1999

Direct comparison of early elevations of cardiac troponin T and I in patients with clinical unstable angina.

BACKGROUND: The aim of this study was to compare the prognostic efficacy of cardiac troponin T (cTnT) and I (cTnI) in patients with clinical unstable angina. METHODS: We studied 74 patients with chest pain at rest, electrocardiographic evidence of myocardial ischemia, and normal (<6.7 ng/mL) values of creatine kinase-MB. cTnT was measured with a commercial assay (cutoff level 0.1 ng/mL) and cTnI with a preliminary research application (cutoff level 3.1 ng/mL). All patients had blood drawn at baseline and 8 hours thereafter. The prospectively defined end point was the proportion of patients identified by each assay as having myocardial damage. RESULTS: cTnT and cTnI were elevated in the same percentage of patients (18 of 74; 24%). Overall, 23 patients had elevations of 1 or both markers. In 13 there were elevations of both. Ten patients had elevations of only one (5 for each marker). In 51 patients, no elevations were present. Death or nonfatal myocardial infarction was more frequent in patients with elevated cTnI (27.7% vs 5.3%; P =.02) than those with normal values. The prognostic influence of cTnT was less (17% vs 8.5%; P =.2). However, the difference between the 2 markers when compared directly was not statistically significant (27.7% vs 17%; P = NS). CONCLUSIONS: These data indicate that both markers identify myocardial damage in equal numbers of patients with clinical unstable angina. Patients with elevations had a worse short-term outcome. The significance of the minor differences in prognostic value will require additional studies.

Aged↗
PubMed1998

New markers for early diagnosis of acute myocardial infarction.

The availability of 'new' biochemical markers of myocardial injury such as creatine kinase isoforms and troponins has renewed the interest for rapid confirmation/exclusion of myocardial infarction in patients presented to the hospital for suspected acute myocardial ischemia. Many of these protein markers have the potential to allow the diagnosis of acute myocardial infarction at a time from the onset of symptoms when the activity of creatine kinase MB is still within the reference range. However, the exclusion of classical myocardial infarction as defined by WHO criteria does not allow to conclude that the patient is at low-risk and can be safely sent home since he may have high-risk unstable angina. The sensitivity for the detection of myocardial damage of troponins is such that a substantial proportion of patients with unstable angina develop elevations of troponins in the absence of creatine kinase MB increases. It is now clear that such patients have an increased risk of cardiac events over the short and long-term similar to that of patients with definite myocardial infarction. Such finding may help in developing selective admission policies and deciding which patients deserve aggressive treatment.

Biomarkers↗
PubMed1998

[AI-CARE: a multicentric study on unstable angina. Methodology and preliminary data of a project on the improvement of health care quality in Emilia-Romagna].

BACKGROUND: Recent Italian legislative directives have focused on lowering health-service costs and improving the quality of health care. The AI-CARE study on unstable angina represents the initial observational step in a survey on health-care quality in the Italian region Emilia-Romagna. AIM OF THE STUDY: This study was performed to identify the processes usually involved in the management of patients with unstable angina admitted to a regional cardiology department. The consumption of health service resources and the clinical events related to angina were evaluated. METHODS: AI-CARE is an observational, descriptive and prospective study. Between 15/3/95 and 15/6/95, the patients admitted consecutively to 25 cardiology units for unstable angina, as diagnosed on a clinical basis, were enrolled in the study. A six-week follow-up was provided. The data regarding demographics, history, entry electrocardiogram, symptoms, examinations, treatment and outcome were recorded on a detailed personal questionnaire. The participating centers have been divided according to complexity of organization: 18 with intensive care unit as level I, five with hemodynamic laboratory as level II and two with cardiosurgery as level III. Mortality, myocardial infarction, revascularization procedures and readmissions for angina were considered clinical events. RESULTS: We recruited 463 patients. At discharge, 411 patients were affected with unstable angina while other 40 developed non-Q wave infarctions. The final study population comprised 451 patients. The mean age was 68 years (range 61-76). There were 316 men (69%, mean age 68) and 135 women (mean age 72). All 451 patients were stratified according to the Braunwald classification: IIIB in 66.9%, IIIC in 9.9%, IB in 9.9%. Mean hospital stay was 10 +/- 6 days, while mean stay in intensive care units was 4.3 +/- 2.9 days. Medical treatment included antiplatelet agents (89%), nitrates i.v. (81%), nitrates per os (86%), heparin (55%) and beta-blockers (47%). The most common non-invasive test performed was echocardiogram (70% of patients), Holter ECG and exercise stress testing (19%). Selective coronary arteriography was performed in 50% of patients (23% during the first 10 days). Additionally, 32% of patients underwent revascularization. During follow-up, ten patients (2.21%) had a myocardial infarction, nine patients (1.99%) died and 49 patients (10.8%) were readmitted for angina. CONCLUSIONS: This study indicates that in spite of the poor use of diagnostic procedures (especially coronary arteriography) and myocardial revascularization, mortality and morbidity were relatively low. Our data are similar to the results of the recent Italian EARISA study but differ greatly from the results of foreign studies. Consequently, further observation of our study population is needed.

Aged↗
PubMed1997

Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina.

BACKGROUND: Elevations of the MB isoform of creatine kinase (CK) and cardiac troponin T seem to confer an adverse prognosis in unstable angina. We examined whether this prognostic influence is also present for cardiac troponin I (cTnI), a new and even more specific marker of myocardial injury. METHODS AND RESULTS: We studied 106 patients with the clinical diagnosis of unstable angina showing chest discomfort at rest within 48 hours of admission, ECG evidence of myocardial ischemia, and normal values of total CK over the initial 16 hours of observation. The primary end point was death or nonfatal myocardial infarction (MI) at 30 days; the secondary end point was the incidence of cardiac events at 1 year. Blood was drawn every 8 hours for 3 days. Thirteen patients were excluded because of increased CK-MB mass concentrations within 16 hours of admission (non-Q-wave MI) and 2 because of inadequate blood sampling. Of the remaining 91 patients, 22 had cTnI elevations on admission (n=7) or after 8 hours (n=15). At 30 days, no deaths (0%) and 4 MIs (5.8%) occurred in the 69 patients with normal cTnI compared with 2 deaths (9.1%) and 4 MIs (18.2%) in the 22 patients with elevated cTnI. The combined incidence of death and nonfatal MI was 5.8% and 27.3%, respectively (P=.02). At 1 year, only 68% of patients with elevated cTnI were free of cardiac events, compared with 90% of those without elevations (P=.01). CONCLUSIONS: These data indicate that cTnI is an important prognostic variable in patients with unstable angina. Elevations of cTnI predict an adverse short- and long-term prognosis.

Aged↗
PubMed1997

The importance of antibody specificity in measuring cross-linked fibrin degradation products by ELISA.

We and others have previously shown that plasma concentrations of XL-FDPs are accurately characterized with an enzyme-linked immunosorbent assay (ELISA) based on the monoclonal antibody DD-3B6/22, which is specific for D-dimer, and a pan-specific tag antibody (DD-4D2/182) in patients with thrombotic disorders. However, in patients treated with fibrinolytic agents, increases in non-cross-linked fibrin(ogen) degradation products are detected by the pan-specific tag antibody due to formation of complexes between non-cross-linked derivatives and XL-FDPs. Assays based on the use of fibrin degradation product-specific tag antibodies appear to be more specific, but whether they would be clinically more informative is unclear. Accordingly, in the current study we measured concentrations of XL-FDPs with two ELISAs; one based on the pan-specific tag antibody (DD-4D2/182) and another based on a fibrin degradation product-specific tag antibody (DD-1D2/48) in patients treated with three well-characterized thrombolytic regimens: one associated with minimal fibrinogenolysis (100 mg tissue-type plasminogen activator [t-PA]) over 3 h), moderate fibrinogenolysis (100 mg t-PA over 90 min), and one with marked fibrinogenolysis (1.5 MU streptokinase [SK]). In patients treated with t-PA, increases in XL-FDPs were closely correlated with fibrinogenolysis, as characterized by increases in the concentration of the Bbeta1-42 peptide, when measured with the pan-specific tag ELISA (r = 0.7), but not when measured with the fibrin degradation product-specific tag assay (r = 0.2). In patients treated with SK, concentrations of XL-FDPs were significantly higher (> 2000 ng/ml) with the pan-specific tag ELISA compared with the fibrin degradation product-specific tag ELISA (< 1000 ng/ml) 1, 2 and 8 h after start of the infusion (P < 0.01). Concentrations of XL-FDPs were also higher in patients treated with SK compared with t-PA when measured with the pan-specific tag ELISA, but lower with SK with the fibrin-specific ELISA (P < 0.01). The value of measurement of XL-FDPs in patients treated with fibrinolytic agents will need to be reappraised with the use of fibrin degradation product-specific assays, which appear to provide more accurate information on the kinetics of cross-linked fibrin lysis in patients treated with t-PA or SK.

Antibody Specificity↗
PubMed1996

Conjunctive administration of intravenous heparin attenuates cross-linked fibrin degradation in patients treated with streptokinase.

Increases in thrombin activity occur in patients treated with streptokinase, but conjunctive therapy with intravenous heparin does not appear to improve either the rate of early infarct artery patency or survival in patients with acute myocardial infarction. In a recent study we found that concentrations of fibrinopeptide A, a marker of thrombin-mediated fibrin formation, were lower in the first 3 h in patients treated with intravenous heparin (5000 U bolus followed by a fixed-dose 1000 U/h infusion, n = 14) compared with subcutaneous (12,500 U every 12 h, started 4 h after streptokinse, n = 14) administration, but were increased in both groups of patients, consistent with persistent thrombin activity. To determine whether the differential effects of the intensity of heparinization on thrombin formation were reflected in differences in fibrin degradation, we measured cross-linked fibrin degradation products (XL-FDP) before and 1, 2, 3, 8, 12, and 24 h after streptokinase in the same cohort of patients, with a new ELISA with a D-dimer-specific capture antibody (MAb 3B6) and a fibrin-specific tag antibody (MAb 1D2, Agen, Brisbane, Australia). The incidence of early coronary recanalization assessed by creatine-kinase MM isoforms (increase in activity > or = 0.18%/min), was similar in both groups (79 vs 86%). Concentrations of XL-FDP were similar in patients with and without recanalization, but were lower in patients treated with intravenous compared with subcutaneous heparin at 8 h, but the results did not reach statistical significance (627 +/- 151 ng/ml versus 1007 +/- 157 ng/ ml, p = 0.06), and were significantly lower at 12 h (327 +/- 72 versus 781 +/- 162 ng/ml, p = 0.03 at 12 h) (mean +/- SEM). Concentrations of cross-linked fibrin degradation products were also lower in patients in whom the activated partial thromboplastin time was greater than two times the control, compared with those with inadequate anticoagulation (498 +/- 105 versus 1084 +/- 179 ng/ml; p = 0.02) (mean +/- SEM). Thus, more effective inhibition of thrombin with conjunctive intravenous heparin therapy results in less cross-linked fibrin turnover in the first 12 h after thrombolysis with streptokinase. This probably reflects decreased fibrin formation with therapeutic anticoagulation.

Cohort Studies↗
PubMed1995

Prodromal angina limits infarct size. A role for ischemic preconditioning.

BACKGROUND: In the experimental setting, it has been demonstrated that preconditioning myocardium before prolonged occlusion with brief ischemic episodes affords substantial protection to the cells by delaying lethal injury, thereby limiting infarct size. Whether the same occurs in humans remains unknown. METHODS AND RESULTS: This study was undertaken to determine whether new-onset prodromal angina, defined as chest pain episodes limited to the 24 hours before myocardial infarction, is the clinical correlate of the ischemic preconditioning phenomenon. Twenty-five patients with their first anterior myocardial infarction treated with thrombolysis (recombinant tissue plasminogen activator [r-TPA], 100 mg/3 hours) were retrospectively included in the study because they met the following criteria: (1) < 120 minutes from onset of symptoms to reperfusion therapy, (2) < 90 minutes from the beginning of thrombolytic therapy to reperfusion (defined as rapid ST elevation reduction > 50%), (3) a patient infarct-related coronary artery with TIMI 3 flow and complete absence of collateral circulation to the infarct related artery (assessed at 24 +/- 5 days), and (4) the presence of new-onset prodromal angina, ie, typical chest pain episodes occurring at rest within 24 hours or, alternatively, a complete absence of symptoms before onset of infarction. Therefore, on the basis of their clinical status before infarction, the patients were divided into two groups: group 1, 13 patients without prodromal angina, and group 2, 12 patients with prodromal angina. Despite no difference in time to treatment (81 +/- 19 versus 75 +/- 21 minutes in group 1 and group 2, respectively; P = NS) and time to reperfusion (58 +/- 34 versus 46 +/- 24 minutes; P = NS), the peak of CKMB release was markedly lower in group 2 (86.3 +/- 66 versus 192.3 +/- 108.3 IU/L; P < .01). In addition, although both groups were comparable in terms of area at risk (amount of myocardium beyond the infarct-related stenosis; 15.1 +/- 4.6 versus 13.7 +/- 4.6 hypokinetic segments in group 1 and group 2, respectively, P = NS), the final infarct size (11 +/- 7.5 versus 5.6 +/- 4 hypokinetic segments, P < .04) was smaller in group 2. Thus, the limitation of the infarct size was significantly greater in group 2 (69% versus 36%; P < .05), and this represents an additional 33% reduction (95% confidence intervals, 7.1% to 58.9%; P = .01) in the group of patients with prodromal angina. Also, the third index, that is, the ECG, showed a favorable trend toward a lesser number of Q waves and a higher sigma R waves, although the values did not reach statistical significance. CONCLUSIONS: Despite a similar area at risk, patients with new-onset prodromal angina showed a significantly smaller infarct size compared with patients without prodromal symptoms. Since the two groups had similar times to reperfusion and no evidence of collateral circulation to the infarct related artery, the protection afforded by angina in group 2 patients might be explained by the occurrence of ischemic preconditioning.

Aged↗