[The epidemiology of heart failure: a growing public health problem].
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Adolescent↗
Biomedical subjects
G Sinagra
Publications and source records attributed to G Sinagra.
Linkage of familial dilated cardiomyopathy to chromosome 9. Heart Muscle Disease Study Group.
Idiopathic dilated cardiomyopathy is a heart muscle disease of unknown etiology, characterized by impaired myocardial contractility and ventricular dilatation. The disorder is an important cause of morbidity and mortality and represents the chief indication for heart transplantation. Familial transmission is often recognized (familial dilated cardiomyopathy, or FDC), mostly with autosomal dominant inheritance. In order to understand the molecular genetic basis of the disease, a large six-generation kindred with autosomal dominant FDC was studied for linkage analysis. A genome-wide search was undertaken after a large series of candidate genes were excluded and was then extended to two other families with autosomal dominant pattern of transmission and identical clinical features. Coinheritance of the disease gene was excluded for > 95% of the genome, after 251 polymorphic markers were analyzed. Linkage was found for chromosome 9q13-q22, with a maximum multipoint lod score of 4.2. There was no evidence of heterogeneity. The FDC locus was placed in the interval between loci D9S153 and D9S152. Several candidate genes for causing dilated cardiomyopathy map in this region.
Cardiomyopathy, Dilated↗
[Safety and tolerability of beta-blockers in severe cardiac decompensation from dilated cardiomyopathy].
BACKGROUND: Several reports from controlled and uncontrolled studies, mainly in the setting of heart failure due to dilated cardiomyopathy (DCM), indicate that chronic betablockade may improve hemodynamics and clinical function. There are few reports on the effects of betablockers in patients with severe heart failure. METHODS: Thirty-five patients (27 M; 8 F; mean age 44.3 +/- 16.7 years; range 14-66 years) with DCM, advanced functional (NYHA III-IV) and severe left ventricular dysfunction (LVEF < or = 25%) underwent a test dosage with metoprolol (5 mg b.i.d.). Five patients (14%) did not tolerate the drug; 30 were chronically treated with metoprolol (mean dosage 127 +/- mg/die). No differences in baseline characteristics were observed between tolerant and not tolerant patients, except for the E-deceleration time (103 +/- 42 ms vs 84 +/- 17 ms; p<0.05). Seven alive patients did not reach a minimum follow up of 18 months. Nineteen patients (54.3%) had a follow up of at least 18 months. They were classified as ¿improved¿ (11 pts; and ¿not improved¿ (8 pts; 42%) on the basis of a score, which included left ventricular ejection fraction (> or = 0.10), left ventricular end diastolic diameter (> or = 10%), regression of restrictive filling pattern, NYHA functional class (> or = 1), cardio-thoracic ratio (> or = 10%) and exercise time (> or = 2 min). No differences were observed at baseline between ¿improved¿ and ¿not improved¿ patients, with exception for a history of slight hypertension (p<0.01), congestive heart failure score (p<0.04) and right ventricular function (p<0.05). RESULTS: An overall improvement of all the main clinical-instrumental parameters were observed in the 19 long term treated patients. At the end of follow up 16 long term treated patients were in NYHA class > or = 2 and in 9 LVEF was > or = 40%. During follow up, among the 30 patients who tolerated the drug, 1 pt died suddenly after 12 months of betablocker therapy and 5 pts were transplanted. No major events occurred among ¿improved¿ patients, after 24 +/- 6 months of follow-up. The actuarial survival curve of our study population shows that survival at 1, 2, 3 and 4 years was respectively 87%, 75%, 67% and 66%. These results confirm previous trials evidence that a progressively increasing dose of beta-blockers confers functional benefit in DCM with severe heart failure.
Adolescent↗
[Heart failure: causes and therapy of unstableness].
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Aged↗
Improved exercise hemodynamic status in dilated cardiomyopathy after beta-adrenergic blockade treatment.
OBJECTIVES: This study was performed to investigate exercise hemodynamic status in a double-blind, placebo-controlled trial and was a substudy in the Metoprolol in Dilated Cardiomyopathy Trial. BACKGROUND: Previous open studies have shown beneficial effects on exercise hemodynamic status after beta-adrenergic blocking agent therapy in patients with congestive heart failure. METHODS: The study included 41 patients with idiopathic dilated cardiomyopathy with ejection fraction < 0.40 (metoprolol, 20 patients; placebo, 21 patients) whose hemodynamic status was investigated at rest and during supine submaximal exercise, at baseline and after 6 and 12 months of treatment. Myocardial metabolism was evaluated in a subset of 19 patients. RESULTS: Metoprolol-treated patients responded favorably, as expressed by improved exercise cardiac index ([mean +/- SD] placebo 4.8 +/- 1.6 to 4.7 +/- 1.8 liters/min per m2, metoprolol 4.3 +/- 1.1 to 5.4 +/- 1.9 liters/min per m2, p = 0.0001) and stroke work index (placebo 44 +/- 20 to 41 +/- 27 g.m/m2, metoprolol 35 +/- 16 to 58 +/- 28 g.m/m2, p < 0.0001). Exercise systolic arterial pressure increased (placebo 161 +/- 25 to 151 +/- 23 mm Hg, metoprolol 155 +/- 29 to 165 +/- 37 mm Hg, p = 0.0003) as well as exercise oxygen consumption index (placebo 463 +/- 194 to 474 +/- 232 ml/min per m2, metoprolol 406 +/- 272 to 507 +/- 298 ml/min per m2, p = 0.045). There was a significant increase in exercise duration in the metoprolol group (63 +/- 38 s) compared with the placebo group (-24 +/- 42 s) (p = 0.01). Net myocardial lactate extraction increased in the metoprolol group, suggesting less myocardial ischemia (placebo 17 +/- 22 to 9.5 +/- 6.4 mmol/min, metoprolol -32 +/- 100 to 42 +/- 45 mmol/min, p = 0.03). Peripheral levels of norepinephrine tended to decrease at rest and during exercise, whereas myocardial net spillover was unchanged. CONCLUSIONS: Metoprolol improved hemodynamic status in patients with dilated cardiomyopathy at rest and had a more pronounced effect during exercise. These positive effects were achieved along with improved or stable myocardial metabolic data.
Analysis of Variance↗
Changing mortality in dilated cardiomyopathy. The Heart Muscle Disease Study Group.
OBJECTIVE: To analyse the changes in mortality in dilated cardiomyopathy over the past 15 years and to identify the factors that might have influenced survival. DESIGN: Follow up study of 235 patients (aged 16-70) systematically enrolled on a register from 1 January 1978 to 31 December 1992. SETTING: Hospital department of cardiology. PATIENTS: Three groups corresponding to three periods of 5 years: group 1 (diagnosis between 1 January 1978 and 31 December 1982) 26 patients; group 2 (diagnosis between 1 January 1983 and 31 December 1987) 65 patients; and group 3 (diagnosis between 1 January 1988 and 31 December 1992) 144 patients. MAIN OUTCOME MEASURES: Death or heart transplantation. RESULTS: Two and four year survival was 73.8% and 53.8% in group 1, 87.7% and 72.3% in group 2, and 90.3% and 82.9% in group 3 (P = 0.02). During the 15 years of the study period the number of cases increased progressively and the baseline clinical characteristics changed (that is, patients were younger and less severely affected), partly explaining the improvement in survival. None the less, the three mortality curves tended to diverge progressively and the improvement in survival in the different groups was still significant after stratification for the severity of the disease, suggesting that treatment had a sustained effect. A progressively higher proportion of patients were treated with angiotensin converting enzyme (ACE) inhibitors and more recently with beta blockers. In group 2, after stratification for the severity of heart failure, patients who were treated with ACE inhibitors showed a better survival than patients who were not. Furthermore, analysis of group 3 showed that beta blockers had a significant additive effect with conventional therapy both by intention to treat and actual treatment. Four year survival in patients with mild and moderate to severe heart failure treated with beta blockers, and usually digitalis and ACE inhibitors, was respectively 90% and 87.5%. CONCLUSIONS: The improvement in the survival of patients with dilated cardiomyopathy over the past 15 years may be explained by earlier diagnosis, new treatments, and a change in the clinical characteristics of the patients at enrolment.
Adolescent↗
[New knowledge on the subject of therapy in cardiac decompensation in the light of large trials].
Although an underlying disturbance in cardiac function can be identified in most patients with congestive heart failure, manifestations of the disease are greatly influenced by other factors, particularly neurohumoral and peripheral adaptive responses which occur secondary to impaired cardiac function. Until recently diuretic agents and digoxin formed the basis of conventional treatment of this condition. The majority of clinical trials published since 1980, indicate that digoxin lessens symptoms and reduces morbidity associated with congestive heart failure particularly in patients with more advanced symptoms and ventricular dysfunction. The efficacy of digitalis in congestive heart failure may in part result from sympathoinhibitory properties such as the activation of baroreceptorial mechanisms. At present there is no conclusive evidence that cardiac glycosides improve survival. Several trials clearly indicate that angiotensin converting enzyme inhibitors (enalapril, captopril) can reduce both morbidity and mortality in symptomatic congestive heart failure. Asymptomatic patients like those with severe left ventricular dysfunction and those who are at high risk for left ventricular remodeling after anterior wall myocardial infarction may also benefit from ACE-inhibition therapy. Increasing evidence suggests that beta-adrenergic blockade can produce symptomatic and hemodynamic improvement in heart failure of idiopathic and ischemic aetiology. Appropriately powered randomized controlled trials are required to determine the impact on survival of beta-blockers.
Adrenergic beta-Antagonists↗
Idiopathic left ventricular aneurysm: a clinical and pathological study of a new entity in the spectrum of cardiomyopathies.
In a prospective study on 340 cases with primary myocardial disease, eight patients (six males, two females, mean age 36 years, range 24-47) with an idiopathic left ventricular aneurysm were observed. All patients had normal coronary arteries, no angina or history of myocardial infarction; all but one had no risk factors for ischaemic heart disease; all had normal right ventricles; one patient had a history of familial dilated cardiomyopathy, two of 'flu-like' syndrome at the time of first symptom and two of alcohol abuse. All patients had ventricular tachycardia (VT), five sustained (of right bundle branch block morphology in three, and of different morphologies in two), three non-sustained. Patients with sustained VT had inducible VT (resembling the clinical one) on electrophysiological study. Electrocardiogram (ECG) showed an infarction pattern in three cases. Aneurysms were of limited size (2.1 +/- 1/11 segments on echocardiography) and were located in the septum, apex or posterior wall. Left ventricular ejection fraction (LVEF) was reduced (< 0.50) in six patients and was not correlated with the aneurysm size. The duration of illness was inversely correlated with LVEF (P < 0.05). Endomyocardial biopsy showed evidence of diffuse pathological changes in all cases (cell hypertrophy, myofibrillar lysis, mitochondriosis). During follow-up (64 +/- 32 months), patients were successfully treated with anti-arrhythmic drugs: no patients required surgical treatment to control ventricular arrhythmia. Considering the clinical and pathological features of idiopathic left ventricular aneurysm, this primary myocardial disease could be classified as a novel peculiar form of cardiomyopathy.
Adult↗
Restrictive left ventricular filling pattern in dilated cardiomyopathy assessed by Doppler echocardiography: clinical, echocardiographic and hemodynamic correlations and prognostic implications. Heart Muscle Disease Study Group.
OBJECTIVES: This study was undertaken to evaluate the frequency of restrictive left ventricular filling pattern in dilated cardiomyopathy, as well as its clinical and hemodynamic correlations and prognostic implications. BACKGROUND: In dilated cardiomyopathy, as in other heart diseases, different left ventricular filling patterns were observed on Doppler echocardiography. Some patients showed a "restrictive filling pattern," similar to that associated with restrictive cardiomyopathy, characterized by predominant E waves and a shortened E deceleration time. METHODS: Pulsed Doppler transmitral curves were analyzed in 79 consecutive patients with dilated cardiomyopathy assigned to two study groups according to E deceleration time: group 1 (n = 36) had a restrictive left ventricular filling pattern (E deceleration time < 115 ms); group 2 (n = 43) had an E deceleration time > or = 115 ms. RESULTS: Patients in group 1 were significantly younger, in a higher New York Heart Association functional class, more frequently had a third heart sound and had a higher left ventricular filling pressure at catheterization. In addition, they showed more severe left and right ventricular dysfunction and dilation, a larger left atrium and more severe mitral regurgitation. A restrictive filling pattern was associated at Doppler study with a higher E wave velocity, lower A wave velocity and higher E/A ratio. During a follow-up interval of 22 +/- 14 months, all 14 patients who subsequently died or required heart transplantation showed a restrictive left ventricular filling pattern. At multivariate analysis, E deceleration time was the most powerful independent prognostic indicator of poor outcome or transplantation. CONCLUSIONS: Restrictive left ventricular filling pattern is frequent in dilated cardiomyopathy, is associated with more severe disease and is a powerful indicator of increased mortality risk and need for heart transplantation.
Adolescent↗
Right ventricular dysplasia: a clinical and pathological study of two families with left ventricular involvement.
BACKGROUND: Right ventricular dysplasia is a heart muscle disease of unknown cause that is often familial and is anatomically characterised by adipose or fibroadipose infiltration of the right ventricular myocardium. It is generally regarded as a selective disorder of the right ventricle. AIM: To investigate the prevalence and characteristics of left ventricular involvement in two families in which at least one member had right ventricular dysplasia confirmed at necropsy. METHODS AND RESULTS: Eight patients were found to be affected by right ventricular dysplasia. In three of them this was confirmed at necropsy. Echocardiography or angiography or both showed left ventricular involvement in seven. This ranged from localised wall motion abnormalities to moderate or severe left ventricular dysfunction. The disease was progressive in four cases. At necropsy the left ventricular myocardium showed predominant fibrosis and degenerative changes of the myocardial cells. There were areas of myocardial thinning with fatty infiltration at the apex in two patients. CONCLUSIONS: Familial right ventricular dysplasia can be a progressive disorder that affects the left ventricle. Advanced disease may be clinically confused with dilated cardiomyopathy.
Adult↗
[The classification of cardiomyopathies: is a revision opportune?].
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Cardiomyopathies↗
Left ventricular involvement in right ventricular dysplasia.
Right ventricular dysplasia, a heart muscle disease of unknown cause, anatomically characterized by variable replacement of myocardial muscle with adipose or fibroadipose tissue, is usually considered a selective disorder of the right ventricle. However, concomitant left ventricular involvement has been noted in a few cases. The aim of this study was to evaluate the prevalence and characteristics of left ventricular involvement in right ventricular dysplasia, as well as possible progression of the disease. Thirty-nine patients with right ventricular dysplasia were studied by M-mode and two-dimensional echocardiography; 28 of them also underwent cardiac catheterization, and in 25 endomyocardial biopsy was performed. On first examination the left ventricle was normal in 25 patients, whereas in the remaining 14 right ventricular abnormalities were associated with left ventricular involvement, characterized by asynergic areas (12 patients) or diffuse mild hypokinesis (two patients). During follow-up (27 patients, 84.1 +/- 66.1 months) 10 patients showed worsening of right ventricular function; in nine the appearance or worsening of left ventricular abnormalities was observed. Five patients died (four in congestive heart failure and one suddenly). Results of postmortem examination (available in two patients) showed atrophy of myocells and a massive fatty and fibrous infiltration of the right ventricular wall, associated with degenerative changes and fibrosis of the left ventricle. In conclusion, right ventricular dysplasia may be associated with left ventricular involvement and the disorder appears to be progressive in some instances.
Adult↗
[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↗
Left ventricular involvement in right ventricular cardiomyopathy.
Right ventricular cardiomyopathy is generally considered a disease with isolated right ventricular involvement, although there are some case reports of concomitant abnormalities of the left ventricle. In order to evaluate the prevalence, characteristics and natural history of left ventricular involvement in this disease, 39 patients with right ventricular cardiomyopathy were studied by 2-dimensional echocardiography. At first evaluation 25 patients (group 1) showed right ventricular abnormalities and a normal left ventricle. In the remaining 14 patients (group 2) the right ventricular abnormalities were associated with left ventricular involvement (asynergic areas and/or mild diffuse hypokinesia). During the follow-up, left ventricular involvement appeared in 6 patients of group 1 and worsened in 4 patients of group 2. Five patients died. Pathological examination (available in 4 cases) showed, at the level of the right ventricle, marked atrophy of myocytes and fibro-fatty replacement, and predominant fibrosis at left ventricular level. Left ventricular involvement is thus frequent in right ventricular cardiomyopathy. At least in some cases the disease appears to be progressive.
Cardiomyopathies↗
[Coronary angioplasty in the aged: short and long term efficacy in patients with unstable angina].
Coronary revascularization procedures in elderly patients are associated with an increase of perioperative complications and death in comparison with younger patients. To assess if a conservative coronary angioplasty approach is useful, 54 consecutive patients (pts) with severe unstable angina were retrospectively evaluated. Mean age was 73 years (range 70-82 years). Multivessel coronary disease was present in 26 pts (48%), angina at rest within the last 2 days in 26 (48%) and an episode of myocardial infarction within 2 weeks in 21 (38%). In 51 cases, regardless of the extension of the coronary disease, only the stenosis considered "culprit" of the symptoms, as assessed by angiography and by noninvasive studies, was dilated. The angiographic success rate was 98% (53 of 54 pts). Two pts had procedure--related myocardial infarction. One patient died after emergency bypass surgery for an abrupt left anterior descending artery occlusion. The mean hospital stay was 8 days (range 2-40 days) and in 75% cases was less than 6 days. Follow-up (achieved in 51 pts) ranged from 1 to 40 months (mean 20 months). In 3 pts a second vessel was treated with a new angioplasty 15-30 days after the first procedure due to the persistence of symptoms. During follow-up three pts died (1 death was cardiac). Of the survivors, 35 were asymptomatic in moderate medical regimen, 1 required bypass surgery and 3 were managed with repeat angioplasty. Survival was 95% at 6 months and 90% at 2 years. At six months 86% of pts were event free (80% and 70% at one and two years, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Endomyocardial biopsy in dilated cardiomyopathy and myocarditis: which role?
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Biopsy↗
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↗
[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↗