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Biomedical subjects

F Crea

Publications and source records attributed to F Crea.

At least 19 recordsLinked to original sources
PubMed2007

Ximelagatran/melagatran against conventional anticoagulation: a meta-analysis based on 22,639 patients.

BACKGROUND: The oral direct thrombin inhibitor ximelagatran, and its active form, melagatran, have been tested in various clinical conditions as a promising alternative to conventional anticoagulant therapy (CAT), despite some concerns over potentially serious liver injury. OBJECTIVES: To assess its risk/benefit profile, a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing xi-/melagatran to CAT was performed. METHODS: Leading medical databases were searched. The rates of major adverse events (MAE: all cause death, nonfatal myocardial infarction, nonfatal thromboembolic stroke, nonfatal pulmonary embolism), major bleeds (MB), and hepatotoxicity were compared. Out of 140 potentially relevant citations, 13 RCTs enrolling 22,639 patients were included. Indications for treatment were: 1) perioperative prophylaxis of deep vein thrombosis (DVT); 2) management of DVT; and 3) stroke prevention in atrial fibrillation. RESULTS: Overall, the risk of MAE (OR 0.98 [0.83-1.17]) and MB (OR 1.01 [0.69-1.47]) did not differ significantly between xi-/melagatran and CAT. There was a clear trend towards an increased risk of hepatotoxicity (OR 1.74 [0.50-6.01]), with an incidence of 5.8% with xi-/melagatran versus 2.3% with CAT (p<0.001); more specifically, the rate of hepatotoxicity was markedly augmented in the management of DVT (OR 5.16 [3.38-7.89]), for treatment durations > or = 3 months (OR 6.73 [5.01-9.05]), and in the prevention of atrial fibrillation-related stroke (OR 8.31 [5.65-12.23]). Two fatal cases of liver injury occurred with xi-/melagatran. CONCLUSIONS: Although comparable to CAT in terms of MAE and MB, xi-/melagatran carries a prohibitive risk of hepatotoxicity that cannot be ignored. Newer long-term alternatives are urgently needed.

Anticoagulants↗
PubMed2006

Outcome after redo coronary artery bypass grafting in patients with ischaemic cardiomyopathy and viable myocardium.

BACKGROUND: Repeat coronary artery bypass grafting (redo-CABG) in patients with ischaemic cardiomyopathy is associated with high perioperative risk and worse long-term outcome compared with patients undergoing their first CABG. OBJECTIVE: To assess whether patients with viable myocardium undergoing redo-CABG have a better outcome. METHODS: 18 patients with ischaemic cardiomyopathy underwent redo-CABG and 34 underwent their first CABG; all had substantial viability (> or =25% of the left ventricle) on dobutamine stress echocardiography (DSE). Left ventricular ejection fraction (LVEF) and heart failure symptoms were assessed before and 9-12 months after revascularisation. Cardiac event rate was assessed during the follow-up period (median 4 years, 25-75th centile 2.8-4.9 years). RESULTS: The extent of viable myocardium on DSE was comparable in the two groups (11.3 (3.9) segments in patients who underwent redo-CABG v 12.8 (3.0) in patients who underwent their first CABG; p = NS). LVEF improved from 32% (9%) to 39% (12%); p = 0.01, in patients who underwent redo-CABG and from 30% (7%) to 36% (7%); p<0.01, in those who underwent their first CABG; New York Heart Association class improved from 2.5 (1.1) to 1.9 (0.8); p = 0.03, and from 2.7 (1.0) to 1.8 (0.70); p<0.01, respectively. In patients who underwent redo-CABG, the perioperative mortality was 0, post-surgery inotropic support was needed in 11% of the patients and mid-term (4-year) survival was 100%, with a total event rate of 28%. All these variables were not statistically different from patients who underwent their first CABG (p = 0.50, 0.90, 0.08 and 0.81, respectively). CONCLUSION: Patients with ischaemic cardiomyopathy and substantial viability undergoing redo-CABG benefit from revascularisation in terms of improvement in LVEF, heart failure symptoms, angina and mid-term prognosis.

Aged↗
PubMed2005

Prognostic value of ventricular arrhythmias and heart rate variability in patients with unstable angina.

OBJECTIVES: To assess the prognostic value of ventricular arrhythmias (VA) and heart rate variability (HRV) in patients with unstable angina. DESIGN: Multicentre prospective study. SETTING: 17 cardiological centres in Italy. PATIENTS: 543 consecutive patients with unstable angina and preserved left ventricular function (ejection fraction >or=40%) enrolled in the SPAI (Stratificazione Prognostica dell'Angina Instabile) study. METHODS: Patients underwent 24 h ECG Holter monitoring within 24 h of hospital admission. Tested variables were frequent ventricular extrasystoles (>or=10/h), complex (that is, frequent or repetitive) VA, and bottom quartile values of time-domain and frequency-domain HRV variables. Primary end points were in-hospital and six-month total and cardiac deaths. RESULTS: Eight patients died in hospital (1.5%) and 32 (5.9%, 29 cardiac) during follow up. Both complex VA and frequent extrasystoles were strongly predictive of death in hospital and at follow up, even after adjustment for clinical (age, sex, cardiac risk factors and history of myocardial infarction) and laboratory (troponin I, C reactive protein and transient myocardial ischaemia on Holter monitoring) variables. At univariate analysis bottom quartile values of three HRV variables (standard deviation of RR intervals index, low-frequency amplitude and low to high frequency ratio) were associated with in-hospital death, and bottom quartile values of most HRV variables predicted six-month fatal events. At multivariate Cox survival analysis reduced low-frequency amplitude was consistently found to be independently associated with fatal end points. CONCLUSION: In patients with unstable angina with preserved myocardial function, both VA and HRV are independent predictors of in-hospital and medium-term mortality, suggesting that these factors should be taken into account in the risk stratification of these patients.

Aged↗
PubMed2005

Impaired coronary and myocardial flow in severe aortic stenosis is associated with increased apoptosis: a transthoracic Doppler and myocardial contrast echocardiography study.

OBJECTIVE: To test the hypothesis that impaired coronary and myocardial blood flow are linked with increased myocyte apoptosis, thus establishing a link between pressure overload and left ventricular (LV) remodelling. METHODS AND RESULTS: Peak diastolic coronary blood flow velocity (CBFV) was evaluated at transthoracic Doppler echocardiography, and signal intensity (SI) and the rate of SI rise (beta) were measured at myocardial contrast echocardiography in 11 patients with severe aortic stenosis and LV hypertrophy. In the same patients, biopsies were obtained from the anterolateral LV free wall during surgery and analysed for cardiomyocyte apoptosis. LV mass corrected CBFV (CBFVI) was significantly lower in patients than in controls (median 0.100 cm.g/s (interquartile range 0.07-0.115) v 0.130 cm.g/s (0.130-0.160), p = 0.002). Similarly, SI*beta was significantly lower in patients than in controls (11 1/s (8-66) v 83 1/s (73-95), p = 0.001). Apoptotic rate was increased in aortic stenosis more than 100-fold versus controls (1.2% (0.8-1.4) v 0.01% (0.01-0.01), p < 0.001) and inversely correlated with lower CBFVI and SI*beta (r = -0.77, p = 0.001 for both). CONCLUSIONS: Patients with severe aortic stenosis and LV hypertrophy have impaired myocardial perfusion, which is associated with enhanced cardiomyocyte apoptosis. Impaired myocardial perfusion and the ensuing oxygen demand-supply imbalance may, at least partially, be responsible for increased apoptosis and possible transition to heart failure, thus establishing a link between pressure overload, LV remodelling, and heart failure.

Aged↗
PubMed2005

Long term prognostic value of myocardial viability and ischaemia during dobutamine stress echocardiography in patients with ischaemic cardiomyopathy undergoing coronary revascularisation.

OBJECTIVE: To evaluate the relative merits of viability and ischaemia for prognosis after revascularisation. METHODS: Low-high dose dobutamine stress echocardiography (DSE) was performed before revascularisation in 128 consecutive patients with ischaemic cardiomyopathy (mean (SD) left ventricular ejection fraction (LVEF) 31 (8)%). Viability (defined as contractile reserve (CR)) and ischaemia were assessed during low and high dose dobutamine infusion, respectively. Cardiac death was evaluated during a five year follow up. Clinical, angiographic, and echocardiographic data were analysed to identify predictors of events. RESULTS: Univariable predictors of cardiac death were the presence of multivessel disease (hazard ratio (HR) 0.21, p < 0.001), baseline LVEF (HR 0.90, p < 0.0001), wall motion score index (WMSI) at rest (HR 4.02, p = 0.0006), low dose DSE (HR 7.01, p < 0.0001), peak dose DSE (HR 4.62, p < 0.0001), the extent of scar (HR 1.39, p < 0.0001), and the presence of CR in > or = 25% of dysfunctional segments (HR 0.34, p = 0.02). The best multivariable model to predict cardiac death included the presence of multivessel disease, WMSI at low dose DSE, and the presence of CR in > or = 25% of the severely dysfunctional segments (HR 9.62, p < 0.0001). Inclusion of ischaemia in the model did not provide additional predictive value. CONCLUSION: The findings of the present study illustrate that in patients with ischaemic cardiomyopathy, the extent of viability (CR) is a strong predictor of long term prognosis after revascularisation. Ischaemia did not add significantly in predicting outcome.

Echocardiography, Stress↗
PubMed2004

G20210A prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta-analysis of 12 034 subjects.

OBJECTIVE: To investigate the possible link between the G20210A prothrombin gene variant and different forms of ischaemic heart disease. DESIGN: Phenotype-specific meta-analysis of 19 studies published within March 2002, globally including 4944 patients and 7090 controls. Sample size, inclusion criteria, geographical location, clinical presentation, age, cardiovascular risk factors, and angiographic extent of disease were extracted from each study. Analyses were done according to Mantel-Haenszel. RESULTS: Overall, the odds ratio (OR) for unspecified ischaemic heart disease associated with the 20210A allele was 1.21 (95% confidence interval (CI) 0.99 to 1.59, n = 12 034). Similar findings were seen for acute coronary syndromes (unstable angina and myocardial infarction) and for myocardial infarction without age limits (OR 1.24, 95% CI 0.98 to 1.63, n = 10 240; and OR 1.19, 95% CI 0.93 to 1.58, n = 9765). The effects were similar in male and female subjects. In the 1931 subjects < 55 years of age, the OR for myocardial infarction increased to 1.77 (95% CI 1.16 to 3.42) and in the 1359 subjects < 45 years to 2.30 (95% CI 1.27 to 4.59). No significant association was found between the 20210A allele and the presence of angiographically documented coronary disease (OR 1.08, 95% CI 0.70 to 1.64, n = 3444). However, patients with 0/1 vessel disease at angiography showed a greater prevalence of the A allele than those with multivessel disease (relative risk 2.0, 95% CI 1.2 to 3.1, n = 2376). CONCLUSIONS: G20210A prothrombin gene polymorphism may represent a modest but significant risk factor for myocardial infarction at young ages and favour the expression of ischaemic heart disease among individuals who have a limited extent of coronary atherosclerosis at angiography.

Adult↗
PubMed2004

Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe?

BACKGROUND: Cyclo-oxygenase-2 (COX-2) is induced in cardiomyocytes only in response to stress, such as ischaemia. OBJECTIVE: To assess COX-2 expression at the site of recent myocardial infarction. METHODS: COX-2 expression was evaluated by specific immunostaining in cardiomyocytes from 23 subjects who died 10-60 days after acute myocardial infarction. The relation between COX-2 myocardial expression and apoptotic rate was investigated. Cardiomyocyte apoptotic rate was defined as the number of cells co-expressing in situ end labelling of DNA fragmentation (TUNEL) and immunostaining for activated caspase-3. RESULTS: COX-2 expression was found in cardiomyocytes at the site of infarction in nine of 23 cases (39%). It was associated with fivefold higher apoptotic rates (median 17.9% (interquartile range 11.0-25.4%) v 3.7% (0.6-12.8%); p = 0.016), and apoptotic rate increased progressively from mild to intense COX-2 staining (p for trend 0.009). COX-2 expression co-localised with TUNEL nuclear staining in myocytes, and there was a high concordance between COX-2 and hypoxia induced factor 1-alpha staining (78%, p = 0.021) and between COX-2 and bax (83%, p = 0.014). Subjects showing myocardial COX-2 expression were more likely to have enlarged hearts (p = 0.050), and intense COX-2 staining was strictly associated with symptomatic heart failure (p = 0.035). CONCLUSIONS: COX-2 is expressed in cardiomyocytes in nearly 40% of cases at the site of recent acute myocardial infarction, even late after the index event. Its expression was associated with extremely high apoptotic rates. These findings suggest a potential cause-effect link between COX-2 expression and enhanced myocardial apoptosis in ischaemic cardiomyopathy.

Aged↗
PubMed2004

A comparison of coronary artery stenting with angioplasty for isolated stenosis of the proximal left anterior descending coronary artery: five year clinical follow up.

BACKGROUND: Stent implantation for isolated stenosis of the proximal left anterior descending coronary artery (LAD) with preserved left ventricular function has been found to have a better clinical and angiographic outcome at one year than balloon angioplasty (PTCA). OBJECTIVE: To establish whether those results are maintained at five year follow up. METHODS: Patients were followed at least every six months. For those who died during follow up, data were obtained from medical records. MAIN OUTCOME MEASURES: Freedom from death, non-fatal myocardial infarction, cerebrovascular accident, and repeated target lesion revascularisation. Secondary end points were revascularisation in a remote region and freedom from angina. RESULTS: Follow up was complete in all patients. At five years, the primary end point was reached more often by patients randomised to stent implantation than to PTCA (80% v 53%; odds ratio (OR) 0.29 (95% confidence interval (CI) 0.13 to 0.69); p = 0.0034). In the PTCA group, 35% of patients underwent target lesion revascularisation v 15% in the stent group (OR 0.33, 95% CI 0.13 to 0.80; p = 0.014). There was a trend towards increased mortality in the PTCA group than in the stent group (17% v 7%; OR 0.36, 95% CI 0.10 to 1.21; p = 0.098). No significant differences were found between PTCA and stent groups for non-fatal myocardial infarction (8% v 5%; OR 0.58, 95% CI 0.13 to 2.54; p = 0.46) or cerebrovascular accident (2% v 0%). CONCLUSIONS: In patients with isolated stenosis of the proximal LAD, a five year clinical follow up confirmed a better outcome in those treated with stenting than with PTCA.

Acute Disease↗