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L Mestroni

Publications and source records attributed to L Mestroni.

At least 19 recordsLinked to original sources

Beta-adrenergic neuroeffector abnormalities in the failing human heart are produced by local rather than systemic mechanisms.

In order to investigate the general cause of beta-adrenergic receptor neuroeffector abnormalities in the failing human heart, we measured ventricular myocardial adrenergic receptors, adrenergic neurotransmitters, and beta-adrenergic receptor-effector responses in nonfailing and failing hearts taken from nonfailing organ donors, subjects with endstage biventricular failure due to idiopathic dilated cardiomyopathy (IDC), and subjects with primary pulmonary hypertension (PPH) who exhibited isolated right ventricular failure. Relative to nonfailing PPH left ventricles, failing PPH right ventricles exhibited (a) markedly decreased beta 1-adrenergic receptor density, (b) marked depletion of tissue norepinephrine and neuropeptide Y, (c) decreased adenylate cyclase stimulation in response to the beta agonists isoproterenol and zinterol, and (d) decreased adenylate cyclase stimulation in response to Gpp(NH)p and forskolin. These abnormalities were directionally similar to, but generally more pronounced than, corresponding findings in failing IDC right ventricles, whereas values for these parameters in nonfailing left ventricles of PPH subjects were similar to values in the nonfailing left ventricles of organ donors. Additionally, relative to paired nonfailing PPH left ventricles and nonfailing right ventricles from organ donors, failing right ventricles from PPH subjects exhibited decreased adenylate cyclase stimulation by MnCl2. These data indicate that: (a) Adrenergic neuroeffector abnormalities present in the failing human heart are due to local mechanisms; systemic processes do not produce beta-adrenergic neuroeffector abnormalities. (b) Pressure-overloaded failing right ventricles of PPH subjects exhibit decreased activity of the catalytic subunit of adenylate cyclase, an abnormality not previously described in the failing human heart.

Adenylyl Cyclases

[Beta blocking agents in the treatment of dilated cardiomyopathy: review of the literature and clinical experience with 67 patients].

BACKGROUND: Several reports suggest that chronic beta blockade, most often with the beta 1 selective agent metoprolol, may improve hemodynamic and clinical function in patients with idiopathic dilated cardiomyopathy. However, controlled trials are limited and some studies have not shown beneficial effects in short term trials. Mechanisms of effectiveness are still debated and probably concern the capacity to avoid toxic myocardial damage by catecholamines, to induce receptor up-regulation, to contribute to the control of arrhythmias, to improve diastolic relaxation and other mechanisms. METHODS: After a revision of the literature, a preliminary clinical experience with metoprolol in dilated cardiomyopathy diagnosed according to the WHO definition is reported. Sixty-seven patients symptomatic for congestive heart failure or with complex ventricular arrhythmias associated with severe left ventricular dysfunction were submitted to test dose with metoprolol 5 mg bid for 2-7 days. All patients were completely studied, including coronary angiography and endomyocardial biopsy to exclude ischemic heart disease and active myocarditis. Four pts (6%) did not tolerate the first test dosage of metoprolol and twenty-two patients were excluded from analysis because of inadequate follow-up or because they were enrolled in an international trial. Forty-one patients underwent long-term treatment with metoprolol at a final mean dosage of 150 mg a day (range 50-200 mg) and are presently analyzed. The dosage was gradually increased during the first seven weeks. RESULTS: After 6 +/- 2 months and 12 +/- 2 months, 34 patients were stable or ameliorated (Group 1) and experienced an overall significant improvement of functional class (all pts in class I-II NYHA), of left and right ventricular ejection fraction (from 28 +/- 8.8% to 35.8 +/- 13.7% to 33.2 +/- 12.3% and from 38.6 +/- 11.8% to 42.4 +/- 5.8% to 45.2 +/- 12.2% respectively), of clinical signs of congestive heart failure, of cardiothoracic index, of left ventricular diameters and of arrhythmic pattern. Furthermore, the rate of ventricular couplets > 20/24h and of non-sustained ventricular tachycardia changed respectively from 46% and 54% to 4% and 21% at 12 +/- 2 months. None in Group 1 died nor is any waiting for heart transplantation. Eleven patients (Group 2) did not tolerate the drug acutely (4 pts) or deteriorated during the first 6 +/- 2 months (7 pts) of the treatment. In this group a worsening or an insignificant variation of all clinical and instrumental parameters was observed. During follow-up four patients of this group underwent heart transplantation (one died shortly after the operation because of infective complications), one died while waiting, two are currently waiting for heart transplantation, and three are still in heart failure (class III NYHA). No cases of sudden death occurred in any group of patients (15 pts with follow-up > 12 mo). CONCLUSIONS: Our uncontrolled study seems to confirm the beneficial effect of betablockers in a subgroup of patients with idiopathic dilated cardiomyopathy. The characterization of responders to this therapy is still undefined and will constitute the aim of future analyses.

Adolescent

[The pathogenesis of dilated cardiomyopathy: current progress].

The pathogenesis of dilated cardiomyopathy (DCM) is still unknown; however, some factors that seem to play an important role in the development of the disease have recently been identified: they are enteroviral infections, immune mechanisms and genetic factors. Enteroviral infection (particularly due to Coxsackie virus B) has long been suspected to be the cause of myocarditis and subsequent DCM. However, only recent techniques of genetic engineering have been able to demonstrate the presence of enteroviral RNA in endomyocardial biopsy of patients with DCM. The role of the viral particles contained in the myocardium is still undetermined. Changes in the immune system concerning cell-mediated and humoral immunity have been recently detected. It has been suggested that an autoimmune process could be the actual cause of DCM in some patients, rather than the consequence. The immune system is strictly related to the major histocompatibility complex. As in some autoimmune diseases, a relationship between DCM and HLA class II phenotype has been found: particularly the DR4 antigen seems to be associated with a high risk of disease. Besides immunogenetic factors, other genetic factors seem to play a role in the pathogenesis of DCM. In 6-8% of cases a familial history of cardiomyopathy has been observed. In clinical studies on familial DCM different phenotypes have been shown, suggesting that different genetic mechanisms are involved in the pathogenesis of the disease. At least two main mechanisms can be hypothesized: the transmission of "predisposing" factors or a defect in proteins essential for the cardiac muscle cell function. Viral agents, autoimmune reactions, immunogenetic and genetic factors seem to cause myocardial damage individually or with complex interactions: the research should be devoted to these topics in the future.

Antibody Formation

Clinical aspects and haemodynamics in the follow-up of dilated cardiomyopathy and myocarditis.

Many studies on the natural history of dilated cardiomyopathy show high probability of death or of cardiac transplantation in a large percentage of patients. These studies have several methodological limitations. Our prospective study, carried out from 1971, and which evaluated 120 patients, showed improved survival in more recent years. Survival 3 years after diagnosis changed from 30% (1971-6/1981) to 88.4% (7/1986-1/1989). Thirty patients were investigated by haemodynamic exercise test to assess their haemodynamic behaviour during exercise, to evaluate the effects of pharmacological treatment and to define parameters of prognostic value. Different haemodynamic behaviours were observed. Haemodynamic investigation during exercise is useful to assess the effect of treatment and may have prognostic value. Myocarditis presents a spectrum of clinical symptoms and echocardiographic abnormalities. In patients with congestive heart failure left ventricular dysfunction is common. Patients with atrioventricular block or chest pain usually have good left ventricular function. During follow-up, improvement is possible but persistent left ventricular dysfunction is associated with a high mortality rate. When left ventricular function is good at presentation and does not deteriorate during follow-up the prognosis is good.

Cardiomyopathy, Dilated

Clinical and pathologic study of familial dilated cardiomyopathy.

To evaluate the occurrence of familial cases of dilated cardiomyopathy (DC), 165 consecutive patients were studied. Diagnosis of myocardial disease was based on clinical, hemodynamic, bioptic, postmortem or a combination of these criteria. Twelve patients (7% of cases) showed evidence of myocardial disease in greater than or equal to 1 relative; 27 patients with myocardial disease were detected in the 12 families, but a suspected history of myocardial involvement was present in a further 16 cases. In 6 families proband and relatives were affected by DC (total 14 cases); in 1 of these families the disease began with an atrioventricular block. In 4 families the relatives showed the presence of myocarditis at the endomyocardial biopsy. In 2 families the relatives presented a right ventricular cardiomyopathy. The mode of inheritance was autosomal dominant in 7 families, recessive in 4; X-linked pattern may be hypothesized in 1. Nine patients died under the age of 45 years: 2 of sudden death, 6 of chronic heart failure and 1 of cerebral embolism. Familial transmission is not rare. Different modes of genetic transmission (autosomal dominant, recessive and X-linked) and different forms of myocardial disease suggest that familial DC may be a multifactorial disease.

Adolescent

[The prognostic assessment of dilated cardiomyopathy: a follow-up of 138 patients].

A total of 138 patients with idiopathic dilated cardiomyopathy were assessed and followed-up between July 1973 and October 1985 in order to evaluate prognostic risk indicators. Of these 102 were male and 36 were female with a mean age of 49.1 years. Each patient underwent physical examination, electrocardiography, echocardiography, cardiac catheterization and coronary angiography. The mortality rate was low for the first 3 years (respectively 8, 12.5 and 20%) while it was 57.5 at the end of the 5-year follow-up period. Univariate analysis at the time of the diagnosis revealed that five factors were predictive of the clinical course at the end of the fifth year: the NYHA functional class IV (p less than 0.0001); LV ejection fraction less than 0.30 (p less than 0.01); left ventricular failure, bi-ventricular failure and left ventricular end-diastolic pressure greater than 20 mmHg (p less than 0.05). Multivariate analysis was used to determine which combination of factors could most accurately predict survival. The most important prognostic factor was again the IV NYHA functional class (p less than 0.01) and, to a lesser degree, left ventricular end-diastolic pressure (p less than 0.05). The present study underlines that the survival rate of patients with dilated cardiomyopathy depends upon the selection of patients. This can explain the low 3-year mortality found in our patients. The NYHA functional class may be a useful practical guide for cardiac transplantation.

Adolescent

Correlation between histomorphometric findings on endomyocardial biopsy and clinical findings in idiopathic dilated cardiomyopathy.

Multivariate analysis was used to analyze the morphometric data of endomyocardial biopsies (area, perimeter and minor diameter) of myocardial cells obtained at light microscopy by a computerized approach with 16 clinical parameters and prognosis in 52 patients with idiopathic dilated cardiomyopathy. The best morphometric parameter was "area" (R2 = 0.47). A positive correlation was found with age (p less than 0.02), interval between first symptoms and diagnosis (p less than 0.02), left ventricular end-diastolic volume (p less than 0.02), cardiac index (p less than 0.05) and echocardiographic end-diastolic diameter (p less than 0.1). A negative correlation was found with prognosis (p less than 0.02), ejection fraction (p less than 0.02), shortening fraction (p less than 0.05), echocardiographic end-systolic diameter (p less than 0.06) and mitral regurgitation presence (p less than 0.1). The parameters that provided no correlation were New York Heart Association class, left ventricular end-diastolic pressure, right atrial pressure, cardiothoracic ratio, presence or absence of heart failure, fever or alcohol intake. These findings suggest that endomyocardial biopsy may provide prognostic information and confirm clinical diagnosis.

Adult

Ventricular arrhythmias in dilated cardiomyopathy: efficacy of amiodarone.

Sixty-five patients with dilated cardiomyopathy were studied by means of 24-hour ECG monitoring. Ventricular arrhythmias were present in 62 (95.4%), of whom 52 (80%) showed a complex form (multiform ventricular extrasystoles, pairs, and ventricular tachycardia). Forty-one patients, presenting with complex ventricular arrhythmias, received antiarrhythmic treatment with amiodarone (600 mg/day in the first week, 400 mg/day in the second week, and 200 to 400 mg/day chronically), and were then controlled with periodic 24-hour ambulatory monitoring. A significant reduction in the number of ventricular extrasystoles was seen in over 70% of patients during a 3-year period. There was also a significant decrease in the incidence of complex ventricular arrhythmias (particularly of ventricular tachycardia). Adverse effects were noted in 23 patients, but only four had to stop treatment. During the follow-up period, 19 patients died: 14 of heart failure, four of sudden death, and one of a noncardiac cause; all patients who died suddenly were not treated with amiodarone (p = 0.022). Complex ventricular arrhythmias are frequent in dilated cardiomyopathy and it is suggested that amiodarone is effective in short- and long-term control of these arrhythmias.

Adolescent

[Cardiac amyloidosis. Invasive and noninvasive diagnosis].

Aim of this study is the analysis of clinical, morphologic and haemodynamic features of cardiac amyloidosis. Cardiac amyloidosis was demonstrated histologically in 7 of our patients: in 6 by endomyocardial biopsy during cardiac catheterization, in one at autopsy. The clinical picture was characterized in every patient by signs and symptoms of congestive heart failure. The electrocardiogram showed several non specific signs: low voltage of the QRS complexes, both in peripheral (4/7) and precordial leads (7/7 cases); marked leftward and upward deviation of the QRS axis (6/7 cases); first degree A-V block (5/7); abnormal Q waves (7/7). M-mode and two-dimensional echocardiography invariably demonstrated a typical pattern: a non dilated left ventricle with thickened and hyper-refractile walls, and usually a slight-moderate diffuse hypokinesia. Other common features were a thickening of right ventricular walls, interatrial septum, and atrioventricular and semilunar valves. Computerized analysis of the M-mode tracings disclosed a marked impairment of the indexes of both systolic and diastolic ventricular function in all patients. By correlating electrocardiographic and echocardiographic data, we found in every case a striking disproportion between the low QRS voltage and the high muscle cross-sectional area (an echocardiographic index of left ventricular mass): this pattern appears to be highly suggestive of infiltrative heart disease. Cardiac catheterization (performed in 6 cases) showed an increase of left ventricular (6/6) and right ventricular (5/6) end-diastolic pressure, with a dip plateau pattern in some cases (4/6 of the left, 2/6 in the right ventricle). The cardiac index was decreased in 3/6 cases. Left ventricular angiography confirmed the echocardiographic data of normal volumes and a slight-moderate decrease of the ejection fraction. We conclude that cardiac amyloidosis usually mimics a restrictive cardiomyopathy (severe congestive heart failure with increased ventricular filling pressures, in the absence of severe systolic ventricular dysfunction). This disease can be suspected clinically by the correlation of the clinical, electrocardiographic and echocardiographic data. The final diagnosis requires an endomyocardial biopsy.

Adult

[Ambulatory ECG in cardiomyopathies].

DILATED CARDIOMYOPATHY - Conduction and rhythm disturbances are frequent findings in dilated cardiomyopathy. 65 patients with dilated cardiomyopathy underwent 24-hour electrocardiographic monitoring: 95.4% showed ventricular arrhythmias, 80% complex ventricular arrhythmias and 44% runs of non-sustained ventricular tachycardia. Over 1000 ventricular extrasystoles in 24 hours were present in 44% of cases. Ventricular tachycardia and multiform and paired ventricular extrasystoles correlated significantly with the severity of cardiac dysfunction and with a worse prognosis. Patients undergoing antiarrhythmic therapy (amiodarone) showed a significant reduction in the number of ventricular extrasystoles and in the incidence of complex ventricular arrhythmias. HYPERTROPHIC CARDIOMYOPATHY - The high incidence of arrhythmias, particularly ventricular arrhythmias (approx. 70% of cases) in hypertrophic cardiomyopathy is well recognized: episodes of ventricular tachycardia are present in 20% of cases and are related to an elevated risk of sudden death. Antiarrhythmic treatment with amiodarone significantly reduces the number of ventricular extrasystoles and the episodes of ventricular tachycardia, may prevent sudden death and improve survival. RESTRICTIVE CARDIOMYOPATHY - Very little information is present in literature concerning this extremely rare form, in which every type of rhythm and conduction disturbance has been observed. CONCLUSIONS - Electrocardiographic monitoring is nowadays a very important tool in the management of cardiomyopathy patients, to identify possible patients at risk and to monitor the antiarrhythmic treatment.

Amiodarone

Arrhythmias in dilated cardiomyopathy.

Sixty-five patients with dilated cardiomyopathy underwent 24 hour electrocardiographic monitoring: 62 (95.4%) showed ventricular arrhythmias and 52 (80%) complex ventricular arrhythmias (multiform ventricular extrasystoles, paired ventricular extrasystoles and ventricular tachycardia). Complex ventricular arrhythmias correlated significantly with some haemodynamic indices of ventricular dysfunction: patients with multiform and paired ventricular extrasystoles and with ventricular tachycardia had lower values of ejection fraction (31.9 +/- 11.8%, P = 0.002) and of cardiac index (2.9 +/- 0.7 litres/min/m2, P = 0.029) than the others (41.1 11.1% and 3.5 +/- 0.9 litres/min/m2 respectively). Patients were followed for a period of 30 +/- 18 months (20 days to 64 months). During follow-up 19 died and mortality was higher among patients with multiform and paired ventricular extrasystoles and/or ventricular tachycardia. Complex ventricular arrhythmias are frequent in dilated cardiomyopathy: ventricular tachycardia and multiform and paired ventricular extrasystoles seem to be related to a more depressed ventricular function and to a poor prognosis. The importance of antiarrhythmic treatment in these patients has still to be evaluated.

Adolescent

[The electrocardiogram in dilated cardiomyopathy].

The electrocardiogram (ECG) of 80 patients with dilated cardiomyopathy was studied. An abnormal ECG was present in 100% of our patients, and in 25% it was the first sign of the disease. Thirty-eight cases (47.5%) showed left atrial enlargement, 22 (27.5%) prolonged PR interval, 33 (41.2%) left bundle branch block, 15 (18.7%) abnormal Q waves, 9 (11.2%) primary S-T and T changes. There were significant differences in ejection fraction and in left ventricular end-diastolic volume between patients with right bundle branch block (p less than 0.05 and p = 0.05 respectively). Patients were followed for a period of 29.5 +/- 28.8 months (min. 2 days, max. 10 years): during the observation period the ECG showed in 28 cases an increasing left ventricular conduction delay and a leftward shifting of mean QRS axis. Patients with left ventricular conduction delays showed a worse prognosis. ECG in dilated cardiomyopathy is a nonspecific but sensitive tool, which may be related to different degrees of myocardial impairment and may be useful in the definition of a prognostic profile.

Adolescent

[Retrospective study of coxsackie B virus infections and congestive cardiomyopathy].

Thirty patients with congestive cardiomyopathy (C.C.) have been studied for the prevalence of neutralizing antibodies to coxsackie B viruses in comparison with age and sex matched controls. Seropositivity toward each antigen was similar in cases and controls: an exception was coxsackie B5 virus, where a significantly seropositivity was found in the control group. As a whole, high antibody titers to any antigen were observed more frequently on sera of cardiopathic patients; however the difference between cases and controls of g.m.t. to each antigen tested was not statistically significant, with the exception of coxsackie B1 virus. The absence of a clear relationship between C.C. and viral infections might be explained through biological as well as epidemiological considerations; of particular relevance, the long duration of cardiac disease (average length 71 months, median 54). Final considerations are offered regarding the methodologic approach for a better understanding of the etiology of this elusive disease.

Adolescent

Vasodilators in left ventricular failure.

Vasodilator drugs are generally classified according to their prevalent site of action: arteriolar vasodilators (e.g. phentolamine, hydralazine, nifedipine) which reduce peripheral resistance and, therefore, increase stroke volume and cardiac output; venodilators (e.g. nitrates), which decrease filling pressure, redistributing intravascular blood volume from the central to the peripheral reservoirs and therefore relieve signs and symptoms of congestion; "balanced" vasodilators (e.g. nitroprusside, prazosin, captopril) which present both effects. Vasodilator therapy is indicated in heart failure caused by impaired contractility (congestive cardiomyopathy, ischemic heart disease) and volume overload (mitral and aortic regurgitation, ventricular septal defect). Hemodynamic studies of acute pharmacological effects are necessary for a correct drug choice, even if they are not always predictive of the long-term efficacy. Non-invasive studies (in particular echocardiography) don't seem actually adequate for vasodilator therapy evaluation. Finally it is not known if vasodilator treatment influence prognosis of chronic heart failure (especially survival), but there is evidence that it can lessen symptoms and increase effort tolerance.

Blood Pressure