Showing papers by "Angelo Branzi published in 2004"

The endothelin system in pulmonary arterial hypertension

Abstract: Endothelin-1 (ET-1), a peptide produced primarily by vascular endothelial cells, was discovered in 1980 and it was characterized as a powerful vasoconstrictor and mitogen for smooth muscle. ET-1 binds to two types of receptors, ETA and ETB: ETA-receptors are found in smooth muscle cells, whereas ETB-receptors are localized on both endothelial cells and in smooth muscle cells. Activation of ETA- and ETB-receptors on smooth muscle cells mediates the vasoconstrictive and mitogenic effects of ET-1. Stimulation of endothelial ETB-receptors promotes ET-1 clearance and activation of NO and prostacyclin release. Pulmonary arterial hypertension (PAH) is a severe condition characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. An activation of the ET-1 system has been demonstrated in both plasma and lung tissues of PAH patients as well as in animal models of PAH. The most efficient way to antagonize the ET-1 system is the use of ET-1 receptor antagonists that can block either ETA- or ETA- and ETB-receptors. These drugs are effective in animal models of PAH and have been tested in multiple clinical trials in patients with PAH. Bosentan, an orally active, dual ET-1 receptor antagonist has been shown to improve symptoms, exercise capacity, hemodynamics, echocardiographic parameters and the outcome of patients with severe PAH, and it has been approved for clinical use in many countries. The selective ETA-receptor antagonist sitaxentan has improved exercise capacity and hemodynamics of PAH patients in two preliminary studies. The main side effect of ET-1 antagonists is the increase of liver enzymes likely due to an accumulation of bile salts cytotoxic to hepatocytes. Additional trials with these drugs are currently ongoing. In conclusion, the hypothesis that the ET-1 system over-activation can be successfully antagonised in patients with PAH has been clearly demonstrated.

Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular diseases and in successful ageing: genetic background of male centenarians is protective against coronary heart disease

Abstract: Centenarians escape, or at least have a delay in, age associated diseases that normally cause mortality at earlier ages. Considerable evidence supports the involvement of genetic components to longevity. Accordingly, the siblings of centenarians have a markedly increased probability of living to 100 years of age. A recent study showed that the offspring of centenarians had a markedly reduced prevalence of age associated diseases, particularly cardiovascular disease and cardiovascular risk factors. On the other hand, this is not unexpected in view of the fact that cardiovascular diseases account for about 50% of all deaths worldwide.1–3 ### Key points

Hydroxymethyl-Glutaryl Coenzyme A Reductase Inhibition Limits Cytomegalovirus Infection in Human Endothelial Cells

Abstract: Background— Statins exert anti-inflammatory effects independently of cholesterol-lowering properties. Cytomegalovirus (CMV) infection appears to be implicated in the pathophysiology of atherosclerosis by inducing inflammatory modifications in endothelial cells, especially in immunosuppressed patients. We investigated whether the activity of statins can inhibit replication of CMV in human endothelial cells. Methods and Results— Human umbilical vein endothelial cells (HUVECs) were infected with CMV and coincubated with fluvastatin at 0.1 and 0.2 μmol/L. Fluvastatin inhibited (P<0.001) CMV antigen expression, and this effect was dose related (P<0.001). Quantitative polymerase chain reaction showed that CMV DNA concentration was consistently lower in supernatants from fluvastatin-treated cells than in infected controls, and viral particle concentration was up to 30 times lower in 0.2 μmol/L fluvastatin-treated cells than in infected controls (10.5±0.9 versus 0.34±0.03 per 103 pfu/mL, P<0.001). Addition of mev...

Pharmacological cardioversion of atrial fibrillation: current management and treatment options.

Abstract: Atrial fibrillation (AF) is the most common form of arrhythmia, carrying high social costs. It is usually first seen by general practitioners or in emergency departments. Despite the availability of consensus guidelines, considerable variations exist in treatment practice, especially outside specialised cardiological settings. Cardioversion to sinus rhythm aims to: (i) restore the atrial contribution to ventricular filling/output; (ii) regularise ventricular rate; and (iii) interrupt atrial remodelling. Cardioversion always requires careful assessment of potential proarrhythmic and thromboembolic risks, and this translates into the need to personalise treatment decisions. Among the many clinical variables that affect strategy selection, time from onset is crucial.

Evaluation of pulmonary arterial hypertension

Abstract: Purpose of review Pulmonary arterial hypertension (PAH) is defined as a group of diseases characterized by a progressive increase of pulmonary vascular resistance leading to right ventricular failure and premature death. The purpose of this review is to analyze the current knowledge of the evaluation of PAH patients. Recent findings Recently, the diagnostic approach has been more clearly defined according to the new clinical classification and with consensus reached on algorithms of various investigative tests and procedures that exclude other causes and ensure an accurate diagnosis of PAH. The diagnostic procedures include clinical history and physical examination, ECG, chest radiography, transthoracic Doppler echocardiography, pulmonary function tests, arterial blood gases, ventilation and perfusion lung scan, high-resolution CT of the lung, contrast-enhanced spiral CT of the lung and pulmonary angiography, blood tests and immunology, abdominal ultrasound scan, exercise capacity assessment, and hemodynamic evaluation. Summary Invasive and noninvasive markers of disease severity, either biomarkers or physiologic parameters and tests that can be widely applied, have been proposed to reliably diagnose PAH and monitor the clinical course.

Implications of cardiac resynchronization therapy and prophylactic defibrillator implantation among patients eligible for heart transplantation.

Abstract: This study analyzed the relations and time-related changes in eligibility for cardiac resynchronization therapy and prophylactic defibrillator implantation in 161 potential candidates for heart transplantation. Although up to 62% of patients who fulfilled the severity criteria for heart transplantation were eligible for either device, this percentage increased as clinical/instrumental parameters of heart failure severity worsened.

Effect of fluvastatin on long-term outcome after coronary revascularization with stent implantation☆

Abstract: We assessed the impact of long-term fluvastatin treatment on adverse atherosclerotic cardiac events (cardiac death, myocardial infarction, and revascularization excluding repeat interventions due to restenosis in the first 6 months) in 847 patients (fluvastatin [n = 417] or placebo [n = 430]) with average cholesterol levels treated with stents in the Lescol Intervention Prevention Study (LIPS). During the 4-year follow-up period, fluvastatin significantly decreased total cholesterol and low-density lipoprotein cholesterol levels and decreased the risk of first adverse atherosclerotic cardiac events by 30% compared with placebo (95% confidence interval -49 to -3.4, p = 0.03).

Clinical relevance of homocysteine levels in patients receiving coronary stenting for unstable angina.

Abstract: BACKGROUND We prospectively investigated whether plasma homocysteine (HCY) concentrations are related to target lesion revascularization (TLR) rates in patients with unstable angina undergoing stenting. METHODS We enrolled 196 consecutive patients with at least one successful coronary stent implantation for unstable angina. RESULTS The mean vessel diameter was 3.1 +/- 0.5 mm. At follow-up (17.8 +/- 7.5 months), patients with higher HCY levels (> 17 micromol/l, 4th quartile) had similar TLR rates to the rest of the sample (11.1 vs 13.2%, p = 0.90). On the other hand, high HCY levels did seem to be associated with higher total (13.3 vs 0.7%, p = 0.001) and cardiac (6.7 vs 0%, p = 0.01) mortality rates. At multivariate analysis, only target vessel diameter independently predicted TLR, while both HCY levels and target vessel size predicted late total mortality. CONCLUSIONS At least in patients with a mean vessel diameter > 3 mm, HCY levels cannot be taken as a prognostic indicator of in-stent restenosis for patients with unstable angina. However, in spite of successful percutaneous revascularization, HCY values do seem to strongly influence late mortality.

Prognostic stratification of patients with right bundle branch block using dobutamine stress echocardiography.

Abstract: The presence of a right bundle branch block (RBBB) is associated with increased mortality. We studied the role of dobutamine stress echocardiography for the prognostic stratification of patients with RBBB. The presence of an abnormal dobutamine stress echocardiography was the strongest predictor of cardiac events and provided incremental prognostic information to clinical and stress test data.

New insights on pulmonary arterial hypertension

Abstract: The 3rd World Symposium on Pulmonary Arterial Hypertension has been a forum for the presentation and discussion of overviews on several aspects of this devastating disease, including pathology and pathobiology, genetics, epidemiology, nomenclature and classification, diagnosis and assessment, medical treatments, interventional and surgical treatments and future directions. This editorial will provide a brief overview of the new findings emerging in this field including new pathologic and pathobiologic concepts, changes in the clinical classification and in the diagnostic definitions. In addition, new treatment strategies and future perspectives will be discussed.

Long‐term clinical and angiographic outcome of patients with occlusive in‐stent restenosis treated with (32P) β‐brachytherapy

Abstract: The objective of this study was to determine the safety and efficacy of 32P β-brachytherapy in totally occlusive in-stent restenosis (ISR). Patients with occlusive ISR were generally excluded from the randomized clinical trials on intracoronary brachytherapy (utilizing either γ- or β-sources) that have shown reductions in restenosis rate and need for revascularization procedures. We analyzed short- and long-term effects of 32P β-brachytherapy (20 Gy) in 27 patients (28 lesions) with occlusive ISR and 84 (99 lesions) patients with nonocclusive high-risk ISR. The primary outcome measure was frequency of in-lesion angiographic binary restenosis at 7 months. Secondary endpoints were rates of major adverse cardiac events (MACE), target vessel revascularization (TVR), clinically driven TVR, and target lesion revascularization (TLR). 32P β-brachytherapy was feasible and safe and provided similar postprocedural angiographic results in the two clinically comparable groups. However, the 7-month binary restenosis rate was higher in the occlusive group, as were the MACE and late total occlusion rates. Multivariate logistic analysis of the overall population indicated occlusive pattern to be the only independent predictor of angiographic restenosis. In both groups, recurrent lesions most often showed a focal pattern with significant reduction of length. Although safe and effective in high-risk ISR, 32P brachytherapy at 20 Gy does not appear to be sufficient to avoid long-term restenosis in patients with occlusive lesions. Further studies should determine the most suitable source and dosage of brachytherapy for patients with occlusive ISR. Catheter Cardiovasc Interv 2004;63:433–438. © 2004 Wiley-Liss, Inc.

Nuevas aportaciones en hipertensión arterial pulmonar

Abstract: El Tercer Simposio Mundial sobre Hipertension Arterial Pulmonar ha sido un foro para la presentacion y discusion de diversos aspectos genericos de esta grave enfermedad, como su anatomia patologica y su patobiologia, sus caracteristicas geneticas, su epidemiologia, su nomenclatura y clasificacion, su diagnostico y evaluacion, sus tratamientos medicos, sus tratamientos quirurgicos y de intervencion, asi como las lineas futuras de investigacion. Este editorial recoge de manera breve los nuevos avances que estan teniendo lugar en este campo, como son los nuevos conceptos anatomopatologicos y patobiologicos, las modificaciones en la clasificacion clinica y los cambios en las definiciones diagnosticas. Ademas, se exponen las nuevas estrategias terapeuticas y las perspectivas futuras.

Which Is the Ideal Drug for Chronic Prophylaxis of Atrial Fibrillation

Abstract: A series of antiarrhythmic agents have been demonstrated to be highly effective in terminating recent-onset atrial fibrillation, class IC agents being the most effective [1, 2]. In contrast with the high efficacy shown in treating recent-onset atrial fibrillation, results obtained in preventing recurrences of atrial fibrillation are scanty [3–6]. Table 1 summarizes reported data from the literature. As shown, the percentage of patients who maintain sinus rhythm without arrhythmia recurrence under placebo treatment is around 30% after 3–6 months and around 20%–25% after 12 months. Antiarrhythmic agents may increase the percentage of patients who maintain sinus rhythm, but the overall efficacy is limited and, except for amiodarone, no more than 50% of the treated patients are free from arrhythmia recurrences after 6–12 months. For amiodarone, efficacy rates of 75%–78.5% at 6 months and of 50%–73% at 12 months have been reported.

The Real Economic Impact of the MADIT-II Study on the European Medical Community

Abstract: One of the most relevant problems in current cardiological practice is the possibility of implementing, in patients who have a specific indication, a series of treatments of proven efficacy but of high cost. This problem involves percutaneous transluminal coronary angioplasty (PTCA) and cardioverter-defibrillators (CDs) [1]. Table 1 shows the number of procedures performed in the year 2000 in the European Union (15 countries) and in the whole of Europe (33 countries). As the table shows, the increase in population obtained by adding 18 countries to those within the European Union is not followed by a parallel increase in the number of high-cost procedures, suggesting marked difficulties due to economic reasons in using these treatments in routine daily practice.

Cardiac Resynchronization Therapy: The Low Voltage Road or the High Voltage Road?

Abstract: Cardiac resynchronization therapy is an additional therapeutic option for heart failure patients that has became available in recent years and aroused great interest among both electrophysiologists and clinical cardiologists managing heart failure patients. The prevalence of conduction disturbances (QRS interval ≥120 ms) among patients with left ventricular dysfunction or overt heart failure has been found to range between 27% and 53% [1–3]. Upon analyzing subjects with varying degrees of functional impairment according to New York Heart Association (NYHA) functional class, wider mean QRS intervals were found in subjects with a higher degree of functional impairment [4]. In subjects with dilated cardiomyopathy the QRS interval was widened in elec- trograms recorded shortly before death as compared to recordings made a mean of 35 months before the terminal event [5]. In unselected patients, left bundle branch block was associated with increased risk of both total mortality and sudden death at 1 year [2]. In another study [6] a QRS duration >110 ms was associated with increased mortality independently of left ventricular ejection fraction. It is a matter for investigation to assess whether left bundle branch block with left QRS axis deviation is most closely related to left ventricular enlargement and left ventricular dysfunction or whether it carries additional prognostic implications [7]. In a recent paper [8], a widening of the QRS interval in patients with heart failure who were followed by a heart failure clinic was a definite and independent predictor of mortality. According to these data, analysis of the QRS interval may provide additional information as a basis for selecting candidates for nonpharmacological treatments.

Cost-Effectiveness of ICD Implantation in Clinical Settings Different From Ischemic Heart Disease: What Do We Know?

Abstract: Sudden cardiac death is responsible for around 50% of all deaths due to cardiovascular causes [1, 2]. The implantable cardioverter defibrillator (ICD) was initially conceived by Mirowski for preventing sudden death in patients who have already experienced a life-threatening ventricular arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation. These patients are at high risk of recurrences of these malignant tachyarrhythmias, with recurrence rates around 30%–50% in a 2-year follow-up period [3]. Prospective controlled studies have demonstrated that ICDs prevent sudden death in these patients, with an improvement in overall survival in a 3- to 5-year follow- up[4–6]. The majority of patients enrolled in these trials had coronary artery disease as predominant etiology, and a wide range of ventricular function compromise was present, as well as a wide range of associated clinical conditions