Showing papers by "Angelo Branzi published in 2002"

Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial.

Abstract: CONTEXT: Percutaneous coronary intervention (PCI) is associated with excellent short-term improvements in ischemic symptoms, yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events (MACE). OBJECTIVE: To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted at 77 referral centers in Europe, Canada, and Brazil. PATIENTS: A total of 1677 patients (aged 18-80 years) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL (3.5-7.0 mmol/L), with fasting triglyceride levels of less than 400 mg/dL (4.5 mmol/L). INTERVENTIONS: Patients were randomly assigned to receive treatment with fluvastatin, 80 mg/d (n = 844), or matching placebo (n = 833) at hospital discharge for 3 to 4 years. MAIN OUTCOME MEASURE: Survival time free of MACE, defined as cardiac death, nonfatal myocardial infarction, or reintervention procedure, compared between the treatment and placebo groups. RESULTS: Median time between PCI and first dose of study medication was 2.0 days, and median follow-up was 3.9 years. MACE-free survival time was significantly longer in the fluvastatin group (P =.01). One hundred eighty-one (21.4%) of 844 patients in the fluvastatin group and 222 (26.7%) of 833 patients in the placebo group had at least 1 MACE (relative risk [RR], 0.78; 95% confidence interval [CI], 0.64-0.95; P =.01). This result was independent of baseline total cholesterol levels (above [RR, 0.76; 95% CI, 0.56-1.04] vs below [RR, 0.77; 95% CI, 0.57-1.02] the median). In subgroup analysis, the risk of MACE was reduced in patients with diabetes (n = 202; RR, 0.53; 95% CI, 0.29-0.97; P =.04) and in those with multivessel disease (n = 614; RR, 0.66; 95% CI, 0.48-0.91; P =.01) who received fluvastatin compared with those who received placebo. There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group. CONCLUSION: Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events.

The new clinical trials on pharmacological treatment in pulmonary arterial hypertension.

Abstract: Past medical therapy for pulmonary arterial hypertension included the use of calcium-channel antagonists in acute vasoreactive subjects and oral anticoagulants and continuous intravenous administration of epoprostenol in the more severe cases. Recently, the thromboxane inhibitor terbogrel, the prostacyclin analogues treprostinil, beraprost and iloprost, and the endothelin receptor antagonist bosentan have been tested in clinical trials in >1,100 patients. Except for terbogrel, all compounds improved the mean exercise capacity by different degrees, as assessed by the 6-min walk test. In the evaluation of the clinical relevance of exercise capacity improvements, additional elements need to be considered, such as baseline functional class and concomitant favourable effects on combined clinical events (including hospitalisations, mortality and rescue therapies), quality of life and haemodynamics. No trials have shown effects on mortality, as the study protocols were not designed for assessing this end-point. Each new compound presents side-effects that are unpredictable in the individual patient and require appropriate attention upon treatment initiation and maintenance. These new therapeutic options will be available in the near future and will allow tailoring of the most appropriate treatment to the single patient, according to an individualised benefit-to-risk ratio.

Accelerated QRS widening as an independent predictor of cardiac death or of the need for heart transplantation in patients with congestive heart failure

Abstract: We analyzed QRS interval for 6 months or more in 82 patients with dilated cardiomyopathy. At 1 year, the incidence of cardiac death/need for heart transplantation was higher among patients with QRS-interval widening of 0.5 msec/month or greater (p = 0.002). At multivariate analysis, QRS widening independently and unfavorably predicted cardiac death/need for heart transplantation (p = 0.029). Randomized prospective studies are necessary to confirm the prognostic value of accelerated QRS widening in patients with dilated cardiomyopathy and to investigate its significance in selecting candidates for electrical resynchronization and heart transplantation.

Combined use of morphology discrimination, sudden onset, and stability as discriminating algorithms in single chamber cardioverter defibrillators.

Abstract: Morphology Discrimination (MD) is a rhythm discriminator based on QRS morphology analysis that can be combined with other discriminators like Stability, with or without Sinus Interval History (SIH) and Sudden Onset. Thirty-five patients implanted with a St. Jude Medical single chamber ICD were evaluated during exercise testing, during induced AF, and during follow-up for 14 +/- 5 months. At exercise testing (60 episodes detected) MD had a specificity (SP) of 96.7% and Sudden Onset a SP of 91.7%; during induced AF (25 episodes) both MD and Stability had a SP of 96.0%. The diagnostic performance on spontaneous arrhythmias was as follows: for ventricular tachycardia (126 episodes) a sensitivity (SE) of 94.4% for MD, 92.1% for Sudden Onset, 89.7% for Stability without SIH and 79.4% for Stability + SIH; for sinus tachycardia (44 episodes) a SP of 86.4% for MD, 97.7% for Sudden Onset, 2.3% for Stability and of 95.5% for Stability + SIH. For AF (165 cases) a SP of 67.9% for MD, 69.1% for Stability and 90.3% for Stability + SIH, 44.8% for Sudden Onset. Use of MD alone provided a SE of 94.4% and a SP of 71.4% for spontaneous arrhythmias and combined use of the discriminators in a "2 of 3" diagnostic logic implied a SP of 90.9% with maintenance of 96.0% of SE. In single chamber ICDs a wide range of SE/SP ratios may be obtained by use of multiple discriminators, but use of the algorithm in a 2 of 3 diagnostic logic may achieve a SP of 90.9% and a SE of 96.0%.

Oral loading with propafenone for conversion of recent-onset atrial fibrillation: a review on in-hospital treatment.

Abstract: Atrial fibrillation (AF) is a very common arrhythmia. In order to treat acute AF rapidly, effective drug regimens are required. Propafenone is a class IC anti-arrhythmic agent that is suitable for oral loading as it reaches peak plasma concentrations within 2 to 4 hours of administration. The use of propafenone loading in patients with AF must be based on appropriate patient selection in view of the negative inotropic effect and the potential proarrhythmic effects of the drug. A series of controlled trials in patients with recent-onset AF without heart failure who were hospitalised with enforced bed rest has shown that orally loaded propafenone (450 to 600mg as single dose) exerts a relatively quick effect (within 3 to 4 hours) and a high rate of efficacy (72 to 78% within 8 hours). A potentially harmful effect of class IC agents is the risk of transforming AF into atrial flutter (3.5 to 5% of patients). However, atrial flutter with 1 : 1 atrio-ventricular response was observed in only two of 709 patients receiving propafenone (0.3% incidence). Nevertheless, the potential negative inotropic effect of propafenone demands careful patient selection, with systematic exclusion of patients with left ventricular dysfunction or congestive heart failure. Oral loading with propafenone can be considered as an episodic treatment in patients with AF recurrences, as has been proposed for other drugs in the past. However, the safety of oral loading with propafenone as an outpatient treatment in appropriately selected patients has to be assessed by appropriately designed prospective studies.

Hospitalization for congestive heart failure: is it still a cardiology business?

Abstract: Background: Hospital management of CHF and predictors of hospital mortality remain unclear. Methods: To address these issues, we analyzed the hospital admissions for CHF during 1996 in a large university hospital. Patients discharged with the principal diagnosis of CHF were considered eligible for the study. Results: Among the 1511 patients (3% of all discharges) who satisfied the inclusion criteria, 75% were treated in general medicine departments (GMD) and 22% in cardiology units (CU). Patients admitted to GMD were older than those treated in CU (79±10 vs. 68±15 years, P<0.001), included a higher proportion of females (56% vs. 37%, P<0.001), and presented a higher rate of hospital mortality (13% vs. 4%, P<0.001). The overall mean length of stay was 11±9 days. At multivariate analysis, length of stay was not associated with the department (i.e. GMD/CU) (P-0.273). Conclusions: CHF is a common lethal condition often requiring treatment in GMD. Length of stay appears to depend more on patients' characteristics than on differences in practice between GMD and CU. Patients admitted to GMD present higher rates of comorbidity and hospital mortality. Strategies are urgently needed to improve hospital management of CHF.

Current clinical perspectives on implantable devices for atrial defibrillation.

Abstract: The role of devices that deliver shock therapy for atrial fibrillation is still debated. Following technical improvements in catheter-based atrial defibrillation, implantable devices have become available either in the form of stand-alone atrial defibrillators or in the form of dual defibrillators. Although preliminary results do not support their use as a single, unique treatment for atrial fibrillation patients, in combination with drugs, pacing or other treatments such as ablation, atrial defibrillators should help appropriately selected groups of patients.

Atrial signal analysis and defibrillation threshold assessment in chronic persistent and reinduced atrial fibrillation.

Abstract: De. brillation Threshold in Chronic and Reinduced AF.Introduction: Induced versus spontaneous atrial fibrillation (AF) is of interest for assessing atrial defibrillation threshold reproducibility. Methods and Results: Twenty-one patients with chronic AF underwent internal cardioversion with assessment of atrial defibrillation threshold at baseline and at reinduced AF. High right atrial (HRA) and coronary sinus (CS) bipolar recordings were analyzed to measure the mean local atrial period, its coefficient of variation, the 5th (P5) and 95th (P95) percentiles of atrial intervals, and the percentage of points lying at the baseline (number of occurrences), and to quantify AF organization. Atrial defibrillation threshold was comparable in baseline and reinduced AF in terms of leading-edge voltage and delivered energy. Baseline and reinduced AF were comparable with regard to overall signal parameters (both in HRA and CS) and the presence of an organized arrhythmia pattern. As for individual variables, P5 increased while P95 and coefficient of variation decreased in reinduced AF compared with spontaneous AF (statistical significance was achieved for all these parameters in HRA, but only for coefficient of variation and P95 in CS). Conclusion: Sustained AF reinduced after cardioversion of chronic AF is comparable with baseline AF in terms of atrial defibrillation threshold, atrial cycle length, and pattern of organization. Therefore, a clinical model based on reinduction of sustained AF after cardioversion is suitable for studying the effects of a series of interventions on atrial defibrillation threshold. However, because this model does not yield a form of AF with comparable indices of local refractoriness (e.g., P5), it is not recommended when analyzing local electrophysiologic properties.

Frank starling mechanism on alternating pump ventricular models

Abstract: An alternating pump system simulating the left ventricle in a mechanical cardio-vascular model, has been modified to show Frank Starling regulating mechanism. An inextensible thin plastic wall chamber has been put around the syringe's core and connected to the internal syringe's chamber by two lateral holes. During the filling and the expulsion phases the external chamber changes his volume and the net output depends on the filling pressure. The regulating mechanism shows a beat to beat response and the dependence of systolic aortic pressure, systolic ventricular work, stroke output with respect ventricular filling pressure show a "physiological" behavior. This solution will be introduced in the mechanical whole model to study the changes of aorto-ventricular interaction by changing aortic compliance.

A randomised cross-over study on the haemodynamic effects of oral dofetilide compared with oral sotalol in patients with ischaemic heart disease and sustained ventricular tachycardia

Abstract: Objective. To assess the haemodynamic effects of short-term treatment with dofetilide in comparison with sotalol in patients with ischaemic heart disease.

Clinical use of novel antithrombotic agents in the management of acute coronary syndromes.

Abstract: Among patients with ST elevation-acute coronary syndrome (ACS) novel thrombolytic agents can be given as a bolus (reteplase, tenecteplase) and their delivery is easier and may shorten the time to treatment, providing the ideal tool in the pre-hospital setting. Reinfarction after thrombolysis occurs in the 3-5% range in all major trials. Reinfarction after thrombolysis rate may be reduced by abciximab and enoxaparin. However major hemorrhage is doubled by abciximab (but not by enoxaparin). When primary angioplasty is preferred to thrombolysis, adjunctive abciximab decreases the need for urgent target vessel revascularization. A whole body of literature tells that aspirin is not enough in patients without ST elevation ACS. Most patients benefit from concomitant clopidogrel. High-risk patients are candidate to the use GP IIb-IIIA blockers, particularly if they need coronary angioplasty. All patients with glomerular filtration rate ≥ 30 ml / min

[Implantable defibrillators and prevention of sudden death: clinical and economic implications in the light of the MADIT II study].

Abstract: The cardioverter-defibrillator is the most effective strategy to prevent sudden death in patients with previous episodes of ventricular tachyarrhythmia (secondary prevention of sudden death). In recent years the possibility of primary prevention of sudden death in selected groups of high risk patients has raised great interest. The MADIT II study highlighted the possibility of preventing sudden death in patients with coronary artery disease. According to this trial, identification of such patients can be performed by means of few clinical data and without expensive screenings (i.e. electrophysiological study). Indeed, patients with a previous myocardial infarction and low left ventricular ejection fraction (< 30%) may benefit from the implant of a cardioverter-defibrillator, with a reduction of the mortality risk by about 31% in the following two years. In the light of these data, implant of a cardioverter-defibrillator should be proposed in such patients, even if the problem of limited economic resources to meet the cost of the devices has to be considered even in the richest country of the world. Despite the positive scientific result, MADIT II has raised the problem of the effective possibility of adopting this therapeutic strategy in clinical practice and this question is still open. Strategies to reduce the theoretically high costs implicated by the MADIT II study include a reduction in the cost of defibrillators through dynamic market forces, the identification of subgroups at higher risk of sudden death, and the use of cheap defibrillators with limited diagnostic and therapeutic options. A long-term evaluation of the cost-effectiveness for western countries of these strategies is necessary to identify in which patient subgroups implant of a cardioverter-defibrillator is acceptable, i.e. cost-effective, in terms of primary prevention.

Atrial Fibrillation Complicated by Heart Failure: First the Chicken or First the Egg?

Abstract: The hemodynamic consequences of atrial fibrillation (AF) are related to loss of atrial contribution to cardiac output, increase in heart rate, with shortening in the duration of diastole, and irregularity in diastolic intervals. The loss of atrial contribution to ventricular filling may be well tolerated in a healthy heart but may have adverse consequences in the presence of left ventricular dysfunction. Loss of atrial transport is particularly significant if there is impairment in left ventricular filling due to reduced diastolic compliance or mitral stenosis. Moreover, in patients of this kind, a high or irregular heart rate with frequent short diastolic intervals will be poorly tolerated. In the long term, sustained, uncontrolled tachycardia with a heart rate higher than 120 beats/min leads to impairment of left ventricular function with various degrees of ventricular dysfunction, which may result in significant worsening of the patient’s clinical condition unless the heart rate can be controlled or sinus rhythm restored. This clinical condition has been called “tachycardiomyopathy” or “tachycardia-induced cardiomyopathy” [1–6].

Is Exercise Testing Useful in Identifying Congenital Long QT Syndrome

Abstract: CK elevation and in the risk of myopathy. In the Expanded Clinical Evaluation of Lovastatin (EXCEL) study with lovastatin treatment for 48 weeks, CK elevation to 10 times the ULN occurred in the range of 0.2% of the population at 20 mg/day to 0.5% at 40 mg twice daily. 8 In the placebo group in the EXCEL study, the frequency was 0.4%. In an 8-week study with cerivastatin, CK elevation to 10 times the ULN occurred in 1.0% of patients at the 0.4-mg/day dose (n 145) and 1.3% at the 0.8-mg/day dose (n 776). 9 In that study, the CK elevations to 10 times the ULN occurred in 5 of 90 women (5.6%) aged 65 years. From the pooled data, it appears that the frequency of signi ficant CK elevations with fluvastatin is low regardless of gender, age, and duration of exposure. It is postulated that fluvastatin’ s high degree of protein binding may limit its potential to cause myopathy, and may explain fluvastatin’ s very low incidence of myopathy. In conclusion, using a pooled analysis of a large population of hypercholesterolemic patients treated with fluvastatin 20 mg, 40 mg, and fluvastatin extended-release 80 mg, the frequency of significant CK elevations is low and not different from those with placebo. This applies to men and women 65 years of age. There were no increases in the frequency of CK elevation with higher doses of fluvastatin.