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Biomedical subjects

Angelo Branzi

Publications and source records attributed to Angelo Branzi.

At least 55 records · Page 3Linked to original sources

Emergency balloon aortic valvuloplasty in patients with critical aortic stenosis presenting with cardiogenic shock.

This report describes 2 cases of aortic valvuloplasty performed as emergency treatment in patients with critical aortic stenosis presenting with cardiogenic shock. This procedure can be life-saving, and allows the patients to undergo further evaluation for aortic valve replacement, or other definitive treatments such as the recently developed percutaneous heart valve implantation for patients with unacceptably high surgical risk.

Aged↗

Pulmonary arterial hypertension: therapeutic algorithm.

The numerous controlled clinical trials performed recently in pulmonary arterial hypertension (PAH) can allow us to abandon a clinical-based treatment strategy and adopt an evidence-based therapy. The treatment algorithm is restricted to patients in NYHA class III or IV. The different treatments have been evaluated mainly in sporadic, idiopathic PAH and in PAH associated with scleroderma or to anorexigen use. Extrapolation of these recommendations to other PAH subgroups should be done with caution. High doses of calcium channel blockers are indicated only in the minority of patients who are responders to acute vasoreactivity testing. Patients in NYHA class III should be considered candidates for treatment with either an endothelin receptor antagonist, a prostanoid or a type 5 phosphodiesterase inhibitor. Continuous intravenous administration of epoprostenol is proposed as rescue treatment in NYHA class IV patients. Combination therapy can be attempted in selected cases. Balloon atrial septostomy and/or lung transplantation are indicated for refractory patients or when medical treatments are unavailable.

Algorithms↗

Relationship between psychiatric disorders and physical status during the course of a heart transplantation program: a prospective, longitudinal study.

BACKGROUND: Evidence of a lack of relationship between psychiatric disorders and physical status during a heart transplantation (HT) program would configure mental well-being as an independent endpoint deserving specific interventions. METHODS: We report a prospective, longitudinal study on patients (n=127) undergoing HT in order to investigate the relationship between psychiatric disorders and physical status. RESULTS: At pre-HT evaluation, at least one psychiatric disorder according to the DSM-IV diagnoses was present in 27 patients (21%); the prevalence of psychiatric disorders was not related (p > or = 0.150) to physical status (assessed by clinical, electrocardiographic, echocardiographic, and hemodynamic parameters). At post-HT evaluation 1 year after HT, all clinical-instrumental parameters significantly improved (p < or = 0.016), but not the prevalence of psychiatric disorders, which were diagnosed in 34 patients (p = 0.016 vs pre-HT). CONCLUSIONS: During the HT program, no significant relationship exists between physical status and prevalence of psychiatric disorders, which increases after the operation. This finding indicates the need for the mandatory provision of adequate psychological support during all of the phases of the HT experience.

Echocardiography↗

Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells.

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and by obstructive changes of the pulmonary vasculature including smooth muscle cell proliferation which leads to medial hypertrophy and subsequent luminal narrowing. Sildenafil, an orally active inhibitor of cGMP phosphodiesterase-type-5, exerts pulmonary vasodilator activity in PAH patients. We evaluated the effects of sildenafil on growth of cultured human pulmonary artery smooth muscle cells (PASMC). The results indicate that sildenafil reduced DNA synthesis stimulated by PDGF and dose dependently inhibited PASMC proliferation. These effects were paralleled by a progressive increase in cGMP content, followed by an accumulation of cAMP. The treatment with 8-bromo-cGMP or dibutyryl-cAMP mimicked all the effects of sildenafil. On the other hand, treatment of PASMC with inhibitors of cGMP-dependent protein kinase (PKG) or cAMP-dependent protein kinase (PKA) reversed the antiproliferative effect of sildenafil. In addition, sildenafil inhibited the phosphorylation of ERK, a converging point for several pathways leading to cell proliferation. This effect was partially reduced by PKG inhibition and completely abolished by PKA inhibition.We conclude that sildenafil exerts an antiproliferative effect on human PASMC that is mediated by an interaction between the cGMP-PKG and the cAMP-PKA activated pathways, leading to inhibition of PDGF-mediated activation of the ERK.

Cell Proliferation↗

Monocyte-derived tissue factor contributes to stent thrombosis in an in vitro system.

OBJECTIVES: This study evaluated the role of circulating tissue factor (TF) in mediating thrombus formation on stents in an in vitro model of stent perfusion. BACKGROUND: The traditional view of coagulation has recently been challenged by the demonstration that TF is present in circulating blood. The potential contribution of this intravascular pool of TF to thrombus formation on stents is not known. METHODS: Coronary stents were placed in parallel silicone tubes connected to a roller pump that was set to pump blood at a flow rate of 10 ml/min. Stents were then exposed to heparinized blood from healthy volunteers for 120 min. RESULTS: The presence of the stent in the circuit caused a significant increase in monocyte TF expression, but only monocytes with attached platelets stained positive for TF. Thrombi formed on stents and the thrombi stained positive for TF. Pretreatment of blood with a monoclonal antibody against TF (cH36) caused a 56% reduction in (125)I-fibrin(ogen) deposition on stents compared with controls (p = 0.002). Monocyte depletion of blood reduced (125)I-fibrin(ogen) deposition by 45% (p = 0.01) and TF staining in the thrombus by 83% (p = 0.01). Pretreatment of blood with a monoclonal antibody against P-selectin reduced (125)I-fibrin(ogen) deposition by 24% (p = 0.04). Perfusion of stents with leukocyte-reduced platelet-rich plasma (PRP) produced small thrombi and treatment of PRP with cH36 reduced (125)I-fibrin(ogen) deposition by 43% (p = 0.01). CONCLUSIONS: Circulating TF plays a pivotal role in thrombus formation on stents. Monocytes appear to be the main, but not only, source of TF depositing in the thrombus.

Adult↗

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

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.

Aged↗

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

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.

Adult↗

The endothelin system in pulmonary arterial hypertension.

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.

Animals↗

Hydroxymethyl-glutaryl coenzyme a reductase inhibition limits cytomegalovirus infection in human endothelial cells.

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 micromol/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 micromol/L fluvastatin-treated cells than in infected controls (10.5+/-0.9 versus 0.34+/-0.03 per 10(3) pfu/mL, P<0.001). Addition of mevalonate to treated cultures almost completely abolished fluvastatin inhibition of viral growth. Electrophoretic mobility shift assay showed that fluvastatin reduced nuclear factor-kappaB binding activity in CMV-infected cells. CONCLUSIONS: HMG-CoA inhibition by fluvastatin restrains CMV replication in HUVECs by inhibiting viral antigen expression, DNA synthesis, and viral particle production, conceivably by involving a reduction of nuclear factor-kappaB binding activity.

Antigens, Viral↗

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

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).

Adolescent↗

Long-term clinical and angiographic outcome of patients with occlusive in-stent restenosis treated with (32P) beta-brachytherapy.

The objective of this study was to determine the safety and efficacy of (32)P beta-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 gamma- or beta-sources) that have shown reductions in restenosis rate and need for revascularization procedures. We analyzed short- and long-term effects of (32)P beta-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). (32)P beta-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, (32)P 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.

Aged↗

Efficacy of internal cardioversion for chronic atrial fibrillation in patients with and without left ventricular dysfunction.

Internal cardioversion can restore sinus rhythm with energies below 6-10 J, often without anaesthesia/sedation. We investigated its safety and short-/medium-term efficacy in patients with persistent atrial fibrillation (AF) with left ventricular dysfunction (defined as ejection fraction < or = 40%). Among 34 patients with persistent AF who agreed to receive internal cardioversion, 16 had left ventricular dysfunction and 18 did not (the groups were similar as regards age, duration of AF and pretreatment with amiodarone). Internal CV was performed delivering 3.0/3.0-ms biphasic shocks between coil catheters using a step-up protocol. Sinus rhythm was always restored. General anaesthesia (administered only when discomfort was not tolerated) was required only in 2 of the 16 (12.5%) patients with left ventricular dysfunction. The defibrillation threshold was similar in patients with and without left ventricular dysfunction (10.2+/-6.9 vs. 8.4+/-4.9 J; p=0.37). Short-term (within 72 h) AF recurrence rates in the presence and absence of left ventricular dysfunction were 19% (3/16) and 6% (1/18), respectively (p=0.51). After cardioversion, all patients received antiarrhythmic drugs (mostly amiodarone in patients with left ventricular dysfunction and class IC agents in the remainder). With mean follow-up periods of about 220 days, AF recurrence rates among patients with and without left ventricular dysfunction were 50% (8/16) and 28% (5/18), respectively (p=0.328). We conclude that even in patients with left ventricular dysfunction, internal CV is safe and effective, minimizing risks from anaesthesia. Although these patients may have a higher risk of short- or medium-term AF recurrence, 6-month maintenance of sinus rhythm is possible in about 50% of cases.

Aged↗

Cardiac resynchronization by pacing: an electrical treatment of heart failure.

Various modalities of cardiac pacing have been proposed in the past to improve hemodynamics, either directly or indirectly. Some of these are conventional ways of cardiac stimulation, others such as biventricular or left ventricular pacing, represent dedicated pacing techniques. Left ventricular and biventricular pacing are successfully applied in those patients with congestive heart failure who have conduction disturbances (i.e. left bundle branch block) as they correct the ensuing intra- and interventricular dyssynchrony. This is the reason why these pacing modalities are described as cardiac resynchronization therapy. According to the results of a series of studies, the cardiac resynchronization therapy seems to have a favourable clinical impact in terms of quality of life, morbidity and hospitalization rate. On-going and future studies should assess the impact of resynchronization therapy on overall mortality and its cost-effectiveness profile in specific subgroups of patients. Other open issues regard (i) the convenience of using biventricular pacing as a pacing-alone therapy or in combination with ventricular defibrillation capability, especially for potential candidates to heart transplantation, and (ii) the ways to identify properly the responders to resynchronization therapy.

Arrhythmias, Cardiac↗

Increase in QT/QTc dispersion after low energy cardioversion of chronic persistent atrial fibrillation.

BACKGROUND: The effects of atrial internal cardioversion on QT interval and QT dispersion (parameters associated with increased risk of ventricular tachyarrhythmias) are unknown. We investigated changes in QT interval, QTc and QT dispersion immediately after shock delivery for internal cardioversion in patients with chronic persistent atrial fibrillation. METHOD: Twenty-two patients with chronic persistent atrial fibrillation (mean duration, 17+/-23 months) underwent transvenous low-energy internal atrial cardioversion with a step-up protocol of shocks delivered between catheters in the right atrium and coronary sinus. (successful shock, 7.2+/-4.2 J). RR interval, QT interval, QTc interval, QT dispersion, and QTc dispersion were all measured on three consecutive beats (at 75 mm/s on at least 9 of 12 leads) and then averaged both before and after (1) the last unsuccessful shock, and (2) sinus rhythm restoration. RESULTS: All parameters remained similar in the minute before and after the last unsuccessful shock. At 1 min after the successful shock, abrupt increases in QT dispersion (+43.8% vs. pre-shock; P<0.001 at least significant difference analysis) and QTc dispersion (+30.0%; P<0.05) were observed, followed by a gradual return to pre-shock values at 15 min. CONCLUSIONS: These findings strongly suggest the likely existence of a brief period of increased electrical vulnerability immediately after restoration of sinus rhythm by internal cardioversion. Particular caution should therefore be applied whenever class III antiarrhythmic drugs are administered immediately after successful internal atrial cardioversion.

Adult↗

Transesophageal echocardiography-guided algorithm for stent-graft implantation in aortic dissection.

OBJECTIVE: Endovascular stent-graft placement is replacing traditional surgery in type B aortic dissection. Usually stent-graft implantation is performed under fluoroscopic and angiographic guidance, but this relatively new procedure is still burdened with some complications. We investigated the value of a developed algorithm based on transesophageal echocardiography (TEE) for guiding stent-graft implantation in type B aortic dissection. METHODS: Forty-two patients with type B aortic dissection (chronic in 28 patients with aneurysmal dilatation of the false lumen, and acute complicated in 14 patients) underwent endovascular stent-graft reconstruction of the descending thoracic aorta. TEE was always performed after angiography. TEE-induced variations of the procedure, based on the algorithm, were compared with initial angiography-based decisions. RESULTS: TEE was decisive for guidewire repositioning (not possible with fluoroscopy) from the false to the true lumen in 3 patients and for correct guidewire entrance in an elephant trunk prosthesis in another patient. After stent-graft implantation color Doppler TEE enabled detection of proximal peri-stent leaks in 13 patients, whereas only 6 (46%) of the 13 leaks were detectable at angiography (P = .008). Most leaks were subsequently eliminated with balloon dilation or further stent grafting. Pulsed Doppler TEE was also useful for differentiating true leaks (13 patients) from Dacron porosity (7 patients). A pulsed-Doppler velocity cutoff value of 50 cm/s enabled differentiation of Dacron porosity (characterized by slow blood flow) from true peri-stent leak (fast flow). After stent-graft implantation TEE demonstrated new intimal tears in the thoracic aorta in 7 patients, whereas only 2 of the 7 new tears were detectable at angiography (P = .024); in 6 of 7 patients the new distal tears were subsequently resolved with placement of additional stents, whereas in a patient with Marfan syndrome new proximal tears determined a type I endoleak, which could not be resolved. Overall, TEE furnished decisive information additional to angiography in determining successful procedural changes in 16 of 42 patients (38%). There were no in-hospital deaths, and pre-discharge spiral computed tomograms showed a good outcome of stent-graft implantation in 37 of 42 patients (88%), with 5 residual type I endoleaks, all previously detected with TEE but impossible to eliminate with either balloon molding or further stent implantation. All but 2 patients (95%) are currently alive at mean follow-up of 30 +/- 18 months. CONCLUSIONS: TEE algorithm is an easy and useful tool in the operating room to guide correct stent-graft positioning in type B aortic dissection.

Adult↗

The concomitant presence of polymorphic alleles of interleukin-1beta, interleukin-6 and apolipoprotein E is associated with an increased risk of myocardial infarction in elderly men. Results from a pilot study.

Genetic background of inflammatory or anti-inflammatory molecules may be helpful in identifying subjects with increased or decrease risk of developing cardiovascular disease. Bi-allele polymorphism (C > T) in the promoter region (-511) of the interleukin-1beta (IL-1beta) gene and the bi-allele polymorphism (G > C) in the promoter region (-174) of interleukin-6 (IL-6) gene were determined in elderly men patients with myocardial infarction (MI) and healthy controls. Each subject was also genotyped for the triallelic polymorphism of the apolipoprotein E epsilon gene. The IL-6C and APOE epsilon4 alleles were independently associated with a mild or moderate increased risk of MI, whilst the allele C of the IL-1beta was not independently linked to MI risk. However, the simultaneous presence of the allele C of IL-1beta, the allele C of IL-6 and epsilon4 allele of APOE was strongly associated with the disease. Data from this cross-sectional study suggest that the functional interaction of these three genes affects pathogenetic mechanisms of MI and an impaired regulation of immune responses plays a pivotal role in the disease. Furthermore, genetic background of inflammatory genes may influence longevity of human species by affecting inflammatory responses associated to cardiovascular diseases. The administration of anti-inflammatory compounds to middle age healthy subjects with increased genetic susceptibility of developing MI might decrease the incidence and prevalence of cardiovascular events in aging.

Aged↗