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Biomedical subjects

Luigi Tavazzi

Publications and source records attributed to Luigi Tavazzi.

At least 73 records · Page 4Linked to original sources
PubMed2004

The effect of ITF-1697 on reperfusion in patients undergoing primary angioplasty. Safety and efficacy of a novel tetrapeptide, ITF-1697.

AIM: ITF-1697 is a C-reactive protein-derived tetrapeptide that, based on pre-clinical studies, is thought to reduce reperfusion injury. We performed a dose-finding study to assess safety, preliminary efficacy and clinical outcome of prolonged i.v. infusion of ITF-1697 in patients with an acute myocardial infarction (AMI) who were eligible for percutaneous coronary intervention (PCI). METHODS AND RESULTS: This was a multicentre dose-finding study that was randomised, double blind, and placebo-controlled. Four hundred and two patients were enrolled. Intravenous infusion of four dosages of ITF-1697 (0.1, 0.5, 1.0 or 2.0 microg/kg/min) or placebo was started before PCI and continued for 24 h. After interim analysis of data from 242 patients the study continued with the 0.1 and 1.0 microg/kg/min ITF-1697 regimes. Analysis did not raise any safety concerns. Post-procedure perfusion, assessed by TIMI flow, corrected TIMI frame count, blushgrade and ST-segment resolution, was similar for the placebo, 0.1 and 1.0 microg/kg/min regimes. Furthermore, the results showed no differences between the treatment regimes in enzymatic infarct size or clinical outcome up to 30 days. CONCLUSION: ITF-1697 was well tolerated. However, neither a dose-relation nor improvement of perfusion, clinical outcome or reduction of myocardial damage could be demonstrated with ITF-1697 during and after primary PCI for AMI.

Adult↗
PubMed2004

Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure.

BACKGROUND: The GISSI Heart Failure project is a large-scale, randomized, double-blind study designed to investigate the effects of n-3 polyunsaturated fatty acids and rosuvastatin on mortality and morbidity in patients with symptomatic heart failure. METHODS AND RESULTS: Patients with New York Heart Association classes II to IV heart failure, already receiving optimized recommended therapy, will be recruited in a nation-wide network of more than 300 cardiology and internal medicine services to be randomly allocated to treatment with n-3 polyunsaturated fatty acids (1 g daily) or the corresponding placebo. Patients with no clear indication or contraindication to cholesterol-lowering therapy will be further randomized to receive low-dose rosuvastatin (10 mg daily) or placebo. According to data available in heart failure registries, it is expected that 70% of the patients will be suitable to enter both components of the trial, which assume the same co-primary endpoints: (a) 15% reduction of all-cause mortality and (b) 20% reduction of all-cause mortality or cardiovascular hospitalizations. The trial is event-driven and will continue either until at least 1252 deaths have been recorded or a reduction of all-cause mortality will satisfy the significance boundaries, which have been established to stop the study. The recruitment of the planned sample size of approximately 7000 patients randomized in the n-3 PUFA trial is expected to be completed within 18 months from the trial start. As of February 29, 2004, 4624 heart failure patients have been included in the trial. CONCLUSION: The GISSI-HF project, with its protocol articulated into two independent randomization schemes, has the aim and the power to verify the hypothesis that n-3 polyunsaturated fatty acids and rosuvastatin can favorably modify the prognosis of patients with symptomatic heart failure.

Fatty Acids, Omega-3↗
PubMed2004

Genetic predisposition to heart failure.

This review describes the numerous and complex molecular systems that are either known players or candidates in heart failure(HF). All systems whose genetic background has been investigated to date in HF are listed and discussed. Discussion also includes functional notes and known genetic polymorphisms already investigated in HF or candidates that have not yet been investigated. Despite substantial research on HF, relatively few coordinated studies have been conducted that assign precise risk to specific genetic polymorphisms. Identification of risk associated with genetic variations and subsequent translation of genetic knowledge into clinical practice will likely progress only in cases of large coordinated studies based on identical standards. The potential result will be a more accurate definition of HF identified as an evolving complex of cardiovascular diseases.

Adenosine Monophosphate↗
PubMed2004

Effect of drug therapy for heart failure on quality of life.

Symptomatic heart failure interferes with a patient's quality of life (QOL) by limiting his or her ability to perform physical tasks and daily activities and by lowering his or her sense of psychological well-being. Therefore, in addition to decreasing mortality and morbidity, improving QOL should be an important goal when selecting pharmacotherapy. QOL questionnaires, both generic and disease specific, are used widely, but in randomized controlled trials of heart failure treatments, QOL has not been a routine study end point. Beta blockers and angiotensin-converting enzyme inhibitors, medications widely used in the management of heart failure and hypertension--one of the most common causes of heart failure--have been associated with negative, neutral, and modestly positive QOL effects. Angiotensin receptor blockers, combined with other therapy, including angiotensin-converting enzyme inhibitors (usually with a diuretic) and/or b blockers in heart failure, have produced improvements in QOL. Patients with hypertension whose blood pressure has been lowered have also experienced an improvement in QOL scores. With current heart failure regimens prolonging life, improving QOL becomes an even more essential end point in assessing the effectiveness of new medications, whether used alone or in combination with standard therapy.

Antihypertensive Agents↗
PubMed2004

Angiotensin-converting enzyme insertion/deletion polymorphism and risk of restenosis after directional coronary atherectomy followed by stent implantation.

The D allele of the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is associated with higher plasma and tissue ACE levels, which enhance the stimulus for neo-intimal hyperplasia. Plaque debulking before stenting reduces the plaque-related determinants of in-stent restenosis and provides an ideal clinical model for studying neointimal hyperplasia. We prospectively studied 113 consecutive patients undergoing elective DCA followed by stent implantation. The presence of I/D in ACE genome DNA was analysed by means of polymerase chain reaction. Follow-up coronary angiography was performed 6-12 months after DCA, and all of the angiograms were quantitatively analysed. The baseline clinical and angiographic characteristics of the patients with a D/D (33%), I/D (52%) and I/I (15%) genotype were well balanced. There were no significant differences in minimal lumen diameter before and after the procedure or at follow-up, and no significant differences in acute gain, late loss or the loss index. Our results indicate that ACE I/D polymorphism does not influence the risk of developing angiographic restenosis in patients undergoing DCA followed by stent implantation.

Atherectomy, Coronary↗
PubMed2004

Epoprostenol in chronic thromboembolic pulmonary hypertension with distal lesions.

BACKGROUND: Although patients with primary pulmonary hypertension and patients with chronic thromboembolic pulmonary hypertension with distal lesions may share similar pathophysiological characteristics, scarce information is available on the usefulness of epoprostenol in this form of secondary pulmonary hypertension. The aim of this study was to evaluate the feasibility, safety and efficacy of epoprostenol therapy in surgically untreatable patients with chronic thromboembolic pulmonary hypertension. METHODS: Continuous infusive therapy with epoprostenol was undertaken in 16 patients with primary pulmonary hypertension and in 11 surgically untreatable thromboembolic pulmonary hypertension patients. The median follow-up was 12.4 months (range 6-23 months). Patients underwent clinical, echocardiographic and hemodynamic evaluation at baseline and a 6-min walk test every 3 months after beginning epoprostenol; ultrasound evaluations were repeated in a subgroup of patients. RESULTS: Epoprostenol therapy improved the clinical status, exercise tolerance and NYHA functional class. A greater left ventricular end-diastolic volume was recorded at echocardiography in both groups. CONCLUSIONS: Epoprostenol therapy may be feasible, safe and clinically effective in patients with surgically untreatable chronic thromboembolic pulmonary hypertension.

Antihypertensive Agents↗
PubMed2003

Enoximone echocardiography: a novel test to evaluate left ventricular contractile reserve in patients with heart failure on chronic beta-blocker therapy.

BACKGROUND: It has been suggested that an extensive contractile reserve identified recognised by means of dobutamine stress echocardiography may predict a better prognosis in patients with severe left ventricular dysfunction at rest. However, the clinical use of dobutamine stress echocardiography may be limited in patients with chronic heart failure by the substantial proportion of such patients treated with beta-blockers, since the inotropic response to adrenergic stimulation is known to be attenuated in patients receiving beta-adrenoceptor blockers. Enoximone is a positive inotropic agent that inhibits cyclic adenosine monophosphate-specific phosphosdiesterase. We therefore tested the hypothesis that enoximone may be an alternative to dobutamine in evaluating left ventricular contractile reserve in patients with systolic dysfunction on chronic beta-blocker therapy. METHODS: We studied 26 patients (21 males and five females) with a mean age of 58 PlusMinus; 10 years: 11 were not receiving beta-blockers (noBB group); 15 were receiving carvedilol at a mean dose of 34 mg/day (BB group). Dobutamine was infused at doses of 5 and 10 micrograms/kg/min, and enoximone at a dose of 1.5 mg/kg. RESULTS: The ejection fraction in the noBB group increased by 9% with dobutamine and 8.73% with enoximone (p = 0.86); in the BB group, it increased by 6% with dobutamine and 8.94% with enoximone (p = 0.03). Regional peak systolic velocities were evaluated by means of tissue Doppler imaging in four basal and four medium level segments. In the noBB group, they increased more with dobutamine than with enoximone in three of the eight segments; no significant differences were found in the BB group. Dobutamine induced non-sustained ventricular tachycardia in three patients and supraventricular tachycardia in one, whereas enoximone did not induce any repetitive arrhythmias. CONCLUSIONS: Enoximone might be preferable to low-dose dobutamine for evaluating left ventricular contractile reserve in chronically beta-blocked heart failure patients as it is slightly more potent and has a better safety profile.

Adrenergic beta-Antagonists↗
PubMed2003

Loss of lamin A/C expression revealed by immuno-electron microscopy in dilated cardiomyopathy with atrioventricular block caused by LMNA gene defects.

Mutations of the LMNA gene encoding the lamin A and C nuclear envelope proteins cause an autosomal dominant form of dilated cardiomyopathy (DCM) with atrioventricular block (AVB). The aim of this study was to investigate ultrastructural nuclear membrane changes by conventional electron microscopy and protein expression by immuno-electron microscopy in the heart of patients with DCM and AVB due to LMNA gene mutations. Four immunohistochemical techniques were used: pre-embedding and post-embedding in Epon-Araldite resin and London Resin White (LRW), with and without silver enhancement. Parallel light microscopy immunohistochemistry studies were performed. Conventional electron microscopy showed a loss of integrity of the myocyte nuclei with blebs of the nuclear membrane, herniations and delamination of the nuclear lamina and nuclear pore clustering. Post-embedding LRW was the most informative technique for morphology and immuno-labelling. Immuno-labelling was almost absent in the nuclear envelope of patients with LMNA gene mutations, but intensely present in controls. The loss of labelling selectively affected myocyte nuclei; the endothelial cell nuclei were immunostained in patients and controls. Light immunohistochemistry confirmed the results. These findings confirm the hypothesis that LMNA gene defects are associated with a loss of protein expression in the selective compartment of non-cycling myocyte nuclei.

Adult↗
PubMed2003

Antiremodeling effect of long-term exercise training in patients with stable chronic heart failure: results of the Exercise in Left Ventricular Dysfunction and Chronic Heart Failure (ELVD-CHF) Trial.

BACKGROUND: The effects of exercise training (ET) on left ventricular (LV) remodeling in chronic heart failure are not definitively established, and the safety of ET in these patients is still debated. METHODS AND RESULTS: This multicenter study investigated the long-term effect of moderate ET on LV remodeling, work capacity, and quality of life (QoL) in 90 patients with stable chronic heart failure caused by LV systolic dysfunction, randomized to a 6-month ET program (T, n=45) or a control group (C, n=45). All patients underwent resting echocardiography, a cardiopulmonary exercise test, 6-minute walking test, and QoL assessment at entry and after 6 months. At entry, end-diastolic (EDV) and end-systolic (ESV) volume, ejection fraction, work capacity, peak o2, and walking distance were similar in the 2 groups. After 6 months, LV volumes diminished in T (EDV, from 142+/-26 to 135+/-26 mL/m2, P<0.006; ESV, from 107+/-24 to 97+/-24 mL/m2, P<0.05) but increased in C (EDV, from 147+/-41 to 156+/-42 mL/m2, P<0.01; ESV, from 110+/-34 to 118+/-34 mL/m2, P<0.01). Ejection fraction improved in T (P<0.001) but was unchanged in C (P=NS). Significant improvement in work capacity (P<0.001), peak VO2 (P<0.006), walking distance (P<0.001), and QoL (P<0.01) was observed in T but not in C (P=NS). T showed a trend toward fewer (P=0.05) hospital readmissions for worsening dyspnea in the absence of other adverse cardiac events. CONCLUSIONS: In stable chronic heart failure, long-term moderate ET has no detrimental effect on LV volumes and function; rather, it attenuates abnormal remodeling. Furthermore, ET is safe and effective in improving exercise tolerance and QoL.

Cardiac Volume↗
PubMed2003

Current presentation and management of heart failure in cardiology and internal medicine hospital units: a tale of two worlds--the TEMISTOCLE study.

BACKGROUND: The purpose pf the current article is to describe the clinical profile, use of resources, management and outcome in a population of real-world inpatients with heart failure. METHODS AND RESULTS: With a prospective, cross-sectional survey on acute hospital admissions, we evaluated the overall and provider-related differences in patient characteristics, diagnostic work-up, treatment and inhospital outcome of 2127 patients with heart failure admitted to 167 cardiology departments and 250 internal medicine departments between February 14 and 25, 2000. Patients admitted to cardiology units were younger (56.3% >70 years vs 76.2%, P <.0001), had more severe symptoms (NYHA IV 35% vs 29%, P =.00014), and more often underwent evaluation of ventricular function (89.3% vs 54.8%, P <.0001) and coronary angiography (7.5% vs 0.9%, P <.0001) than those admitted to medical units. Moreover, they were more often prescribed beta-blockers (17.8% vs 8.7%, P <.0001). However, prescription of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (78.7% vs 81.5%, P = not significant [NS]) and inhospital mortality (5.2% vs 5.9%, P = NS) were similar. A 6-month follow-up visit was performed in 56.4% of cases (68.2% of cardiology vs 49.4% of medicine patients, P <.0001); 6-month readmission (43.7% vs 45.4%, P = NS) and mortality (13.9% vs 16.7%, P = NS) rates were similar. CONCLUSIONS: Patients with heart failure admitted to cardiology and internal medicine units represent 2 clearly different populations. In both groups, diagnostic procedures and evidence-based treatments, such as beta-blockers, appeared to be underused, and there was a lack of structured follow-up, as well as a poor 6-month prognosis.

Adrenergic beta-Antagonists↗
PubMed2003

Celiac disease in patients with sporadic and inherited cardiomyopathies and in their relatives.

AIMS: To investigate celiac disease (CD) and related co-morbidity in patients with familial and sporadic cardiomyopathy and in their relatives. METHODS AND RESULTS: We screened anti-human-tissue-transglutaminase (IgA and IgG anti-h-tTG) and anti-endomysial antibodies (AEAs) in 238 consecutive adult patients with inherited or sporadic dilated cardiomyopathy (DCM), 418 relatives, and 2000 healthy blood donors. HLADQ2-DQ8 was tested in tTG-positive subjects. The IgA-tTG-positive patients with cardiomyopathy underwent duodenal biopsy. Twenty-six subjects were tTG-positive: five DCM patients (2.1%), two of 28 (7.1%) and three of 390 (0.7%) relatives with and without echocardiographic abnormalities respectively, and 16 controls (0.8%). Twenty-two of 26 subjects were AEA-positive, and 25 HLA-positive. Of the five patients with cardiomyopathy and biopsy-proven CD, four suffered iron-deficiency anaemia. Two CD-positive DCM patients and two tTG-positive relatives were from families with inherited disease in which CD did not co-segregate with DCM. CONCLUSIONS; The higher prevalence of CD in patients with sporadic or inherited DCM, and of tTG-positive serology in relatives with echocardiographic abnormalities, suggests that immune-mediated mechanisms are active in subsets of patients/families. However, gluten intolerance cannot be considered causative since CD seems to be associated but not co-segregated with DCM in familial cases.

Adolescent↗
PubMed2003

Prescription patterns of diuretics in chronic heart failure: a contemporary background as a clue to their role in treatment.

BACKGROUND: Diuretics are the cornerstone of treatment for the congestive symptoms of heart failure (HF). Despite their widespread use, diuretic prescription data in clinical practice are scarce. In this study we evaluated the prescription pattern of diuretics in a large population of HF outpatients, enrolled by a national network of hospital-based cardiologists. METHODS AND RESULTS: Among 11070 HF outpatients (mean age 64 +/- 12 years, 72.9% men, 29.8% New York Heart Association [NYHA] class III-IV, mean left ventricular ejection fraction [LVEF] 35+/-12%), 9247 took a diuretic, the most frequently prescribed therapeutic agent (83.5%). Loop diuretics were prescribed alone (65.5%) or combined with other diuretics in 91.6% of patients. By multivariate analysis, the strongest independent predictors of diuretic use were a previous hospital admission for HF (odds ratio [OR] 2.55, 95% confidence interval [CI] 2.28-2.86), NYHA class III-IV (OR 2.52, 95% CI 2.14-2.96), LVEF < 30% (OR 1.87, 95% CI 1.57-2.24). Aldosterone antagonists were prescribed to 2142 patients (23.1%); independent predictors of their use overlapped with those of diuretics and moreover included treatment with loop diuretics (OR 3.52, 95% CI 2.66-4.66) and digoxin (OR 1.45, 95% CI 1.29-1.64). CONCLUSIONS: In this wide series of stable HF outpatients, cardiologists prescribed diuretics in accordance with published guidelines. Evolving prescription patterns of aldosterone-receptor blockers need to be further evaluated.

Diuretics↗
PubMed2003

Survival and hospitalization in heart failure patients with or without diabetes treated with beta-blockers.

BACKGROUND: Physicians are still concerned about prescribing beta-blockers in diabetic patients with heart failure. METHODS: In the outcome research study (the Beta-Blockers in Patients With Congestive Heart Failure: Guided Use in Clinical Practice [BRING-UP] study), the responsible clinicians could decide whether to start beta-blocker treatment and which agent to use. A total of 3091 patients were enrolled by 202 cardiologic centers: 25% of the recruited patients were already on beta-blockers, 28% started treatment at the enrollment visit, and 47% were not started on beta-blockers. RESULTS: The 1-year mortality, hospitalization rate, and the combined end point of mortality or hospitalization were higher in diabetic patients (15.8% versus 10.9%; relative risk [RR] = 1.44; 95% confidence intervals [CI] 1.16-1.78, P =.001) (31.0% versus 24.0%; RR = 1.28; 95% CI 1.11-1.49; P =.0009) (40.5% versus 30.1%; RR = 1.35; 95% CI 1.19-1.51; P =.0001). The event-free analysis of the 4 groups (diabetic patients not treated with beta-blockers, diabetic patients treated with beta-blockers, nondiabetic patients not treated with beta-blockers, nondiabetic patients treated with beta-blockers) showed that patients treated with beta-blockers had a higher event-free probability than patients not treated with beta-blockers regardless the presence of diabetes (P <.0001). CONCLUSIONS: On the basis of post hoc analysis, diabetic patients with chronic heart failure benefit from beta-blockers even if at a lower degree. Thus, there are no justifications to avoid beta-blockers in heart failure patients in the presence of diabetes.

Adrenergic beta-Antagonists↗
PubMed2003

Response of the right ventricle to acute pulmonary vasodilation predicts the outcome in patients with advanced heart failure and pulmonary hypertension.

OBJECTIVES: This study was designed to assess whether testing of potential reversibility of pulmonary hypertension (PHT) may be a useful means of defining the short-term prognosis of patients with advanced heart failure and elevated pulmonary artery pressure. In such patients, the reversibility of PHT after acute vasodilator administration is associated with a low early mortality rate after heart transplantation. However, its short-term prognostic value has not yet been determined. METHODS AND RESULTS: Between 1994 and 1998, 76 patients with advanced heart failure and PHT underwent right heart cathetherization. The hemodynamic measurements, including thermodilution-derived right ventricular ejection fraction, were repeated after an intravenous bolus of nitroglycerin (NTG). During a median follow-up period of 8.2 months (25% and 75% centiles, 3.3 and 18.9 months), 47 patients had a cardiac event (death or urgent heart transplantation). With Cox survival analysis, a multivariate model that included the New York Heart Association class and the hemodynamic variables obtained after NTG administration allowed a better assessement of the short-term prognosis of the patients than a model including the baseline variables. The evaluation of right ventricular function during the acute NTG-induced pulmonary vasodilation was of critical importance in obtaining such a refinement in the prognostic stratification. CONCLUSIONS: The prognostic evaluation of patients with advanced heart failure and PHT should include the assessment of the changes of right ventricular ejection fraction after acute afterload reduction.

Aged↗