Head-to-head comparison of indices of left ventricular contractile reserve assessed by high-dose dobutamine stress echocardiography in idiopathic dilated cardiomyopathy: five-year follow up.

OBJECTIVE: To compare head to head the indices of left ventricular contractile reserve assessed by high-dose dobutamine in the five-year prognosis of patients with idiopathic dilated cardiomyopathy. DESIGN AND SETTING: Prospective study in a tertiary care centre. PATIENTS: 63 consecutive patients with idiopathic dilated cardiomyopathy. INTERVENTIONS: High-dose dobutamine stress echocardiography was performed in progressive stages lasting 5 min each. Wall motion score index, ejection fraction, cardiac power output and end systolic pressure to volume ratio were evaluated as indices of left ventricular contractility. MAIN OUTCOME MEASURE: Five-year cardiac mortality. RESULTS: During the follow up of 59 patients, 27 (45.8%) died of cardiac causes. According to Kaplan-Meier and receiver operating characteristic analyses all indices of contractile reserve differentiated patients with respect to cardiac death. Wall motion score index achieved the best separation (log rank 21.75, p < 0.0001, area under the curve 0.84), followed by change in ejection fraction (log rank 11.25, p = 0.0008, area under the curve 0.79), end systolic pressure to volume ratio (log rank 14.32, p = 0.0002, area under the curve 0.75) and cardiac power output (log rank 9.84, p = 0.0017, area under the curve 0.71). Cox's regression model identified wall motion score index as the only independent predictor of cardiac death. CONCLUSIONS: These data show that all examined indices of left ventricular contractile reserve are predictive of five-year prognosis, but change in wall motion score index may have the greatest prognostic potential.

Myocardial fibrosis assessment by semiquantitative, point-counting and computer-based methods in patients with heart muscle disease: a comparative study.

AIMS: No study has directly compared different histomorphometric methods of quantification of myocardial fibrosis. Therefore we compared the results of semiquantitative, point-counting and computer-based methods in the assessement of myocardial fibrosis in a consecutive series of endomyocardial biopsy samples from patients with heart muscle disease. METHODS AND RESULTS: Histological samples (at least three per patient) were obtained by endomyocardial biopsy from 11 patients with focal myocarditis and from 24 ambulatory patients with idiopathic dilated cardiomyopathy, or during surgery in 10 patients who underwent partial left ventriculectomy. Samples were cut and stained with Masson-trichrome for better contrast. From each sample, a representative field was digitized, and the amount of fibrosis was assessed by semiquantitative scoring, by point-counting, and by computer-based software. Semiquantitative scoring correlated with both point-counting (Spearman's r = 0.69, P < 0.0001) and computer-based (Spearman's r = 0.83, P < 0.0001) methods. There was also a good correlation between point-counting and computer-based methods (r = 0.71, P < 0.0001). However, when compared with the point-counting method, the computer-based method overestimated percent fibrosis by 3.0 +/- 6.7% (P = 0.004). This overestimation correlated with the mean percent fibrosis (r = 0.38, P = 0.014). CONCLUSIONS: Our data show good correlations between the three methods of myocardial fibrosis assessment. However, systematic differences between them emphasize that this should be taken into consideration when comparing results of the studies using different methods of fibrosis assessment.

Myocardial catecholamines in primary heart muscle disease: fact or fancy?

The pathophysiological role of myocardial catecholamines in cardiomyopathies is still not completely understood. We there-fore assessed myocardial catecholamine concentrations (MCC) in 34 patients with hypertrophic cardiomyopathy (HCM) (76.5% males; mean age 46.7 +/- 11.6 years; left ventricular ejection fraction [LVEF] 75.3 +/- 9.8%) and in 32 patients with dilated cardiomyopathy (DCM) (87.5% males, mean age 43.1 +/- 12.5 years, LVEF 34.9 +/- 8.3%). Initial assessment included clinical work up, cardiac catheterization and endomyocardial biopsy. Myocardial norepinephrine (MNEC), epinephrine (MEC), and dopamine (MDC) concentrations in endomyocardial biopsy samples were measured using the catechol-O- methyl transferase radioenzymatic method. Significantly higher MNEC and MEC were demonstrated in HCM than in DCM patients (MNEC: 781.9 +/- 125.8 ng.g-1 fresh myocardial tissue (ft) HCM vs 262.6 +/- 68.9 ng.g-1 ft DCM, p < 0.01; and MEC: 91.6 +/- 13.9 ng.g-1 ft HCM vs 35.8 +/- 6.2 ng.g-1 ft DCM, P < 0.01). The difference in MDC did not reach statistical significance (76.1 +/- 8.3 ng.g-1 ft HCM vs 70.1 +/- 11.8 ng.g ft DCM; P > 0.05). In addition, we compared the MCC levels in 24 patients, clinically presented as dilated cardiomyopathy categorized according to the various aetiologies: 12/24 with primary DCM (75.0% males, mean age 49.6 +/- 9.5 years; LVEF 25.8 +/- 63%), 7/24 with alcohol-induced heart disease (85.7% males, mean age 46.8 +/- 7.1 years; LVEF 26.4 +/- 4.6%), and 5/24 with hypertensive heart disease (100% males, 45.1 +/- 10.6 years; LVEF 25.6 +/- 9.1%), but no significant difference was found among them (P > 0.05). There was no significant difference in tissue dopamine concentrations.

Interferon and thymic hormones in the therapy of human myocarditis and idiopathic dilated cardiomyopathy.

It is becoming increasingly apparent that idiopathic dilated cardiomyopathy (IDC) probably results from an acute viral myocarditis. One reasonable hypothesis is that persistent viral infection causes myocardial destruction leading to left ventricular dilatation and heart failure. The aim of this study was to evaluate the efficacy of interferon-alpha (IFN) and thymomodulin in the treatment of idiopathic myocarditis and IDC. Clinical, immunological, haemodynamic and histological evaluation was performed in 40 patients before inclusion in the study. Patients were randomized into three treatment groups: (a) conventional therapy plus IFN, (b) conventional therapy plus thymomodulin and (c) conventional therapy alone. Two-year follow-up included repeated endomyocardial biopsy, echocardiographic evaluation, treadmill exercise test, Holter monitoring study and radionuclide assessment of left ventricular function during exercise. Left ventricular ejection fraction increased during follow-up in most of the IFN-and thymomodulin-treated patients, and only in a few of conventionally treated patients. Left ventricular reserve was significantly higher at 2-year follow-up in patients treated with immunomodulators. No serious adverse effects were noticed during treatment. Our results suggest that treatment of myocarditis and/or IDC with IFN or thymomodulin induces an earlier and significantly superior clinical improvement than conventional therapy alone.

Endomyocardial biopsy: a meta-analysis of diagnostic value.

To clarify the controversy of endomyocardial biopsy (EMB) in terms of its diagnostic value, we performed a meta-analysis of EMB studies published between 1982 and 1993, including our own experience. A total of 255 articles was retrieved using both a computer search of the Medline database and a manual bibliographic search, but only 30 studies with 4,313 patients met the predefined inclusion/exclusion criteria. The diagnostic value of EMB was classified into four categories, according to the effect of EMB findings on the discharge diagnosis: aetiology uncovered, new diagnosis of heart muscle disease (HMD) revealed, clinical diagnosis confirmed, and no useful information obtained. Clarification of aetiology of HMD was reported in 28 out of 30 studies with a total of 4,195 patients and it was achieved by EMB in 17.9% of these patients (95% confidence interval (CI) was 16.8-19.1%). A new unexpected diagnosis of HMD was arrived at in 25 of 30 studies (3,947 patients) and this occurred in 19.3% of patients (95% CI = 18.1-20.6%). Confirmed clinical diagnosis of HMD by EMB was covered by 12 studies (1,231 patients) and was proven in 40.1% of patients (95% CI = 37.3-42.7%). EMB not providing any useful clinical information was mentioned in seven of 30 studies (857 patients); this happened in 5.9% of patients (95% CI = 4.5-7.4%). Therefore, these results confirmed the remarkable diagnostic value of EMB. It was equally helpful in all diagnostic categories and had considerable overall diagnostic utility.

The incidence of myocarditis in endomyocardial biopsy samples from patients with congestive heart failure.

We present the combined experience of three Yugoslavian cardiovascular centers in the application of endomyocardial biopsy for the diagnosis of myocarditis in patients who present clinically with congestive heart failure. The study group comprised 107 patients (mean age, 40.8 years; range, 19 to 61 years). On the basis of patient history and diagnostic tests, the following clinical diagnoses were established: dilated cardiomyopathy (85), myocarditis (16), and alcohol-induced heart disease (6). EMB samples were taken from the left ventricle (95) or both ventricles (12) by use of a King's College bioptome, with a mean of 3.2 samples per patient. Histologic evidence of myocarditis was noted in 10 of 85 patients (12%) with a clinical diagnosis of dilated cardiomyopathy, in 2 of 6 patients (33%) with alcohol-induced heart disease, and in 12 of 16 patients (75%) with a clinical diagnosis of myocarditis. There was confirmation of the clinically suspected diagnosis in 63% of cases, a change of diagnosis based on histology in 15% of cases, and nonspecific findings in 22%. However, useful information was obtained in 78% of the cases, and there was a 22% incidence of histologically proven myocarditis for the entire group. Our results indicate that endomyocardial biopsy is beneficial in determining the true incidence of myocarditis in patients with a clinical presentation of dilated cardiomyopathy.

Coronary embolism by metastatic choriocarcinoma of the uterus: an unusual cause of ischemic heart disease.

Although gestational choriocarcinoma is a rapidly invasive malignancy, metastatic invasion of this tumor to the heart is rare. We report an unusual case of coronary embolism, which was caused by malignant trophoblasts from choriocarcinoma in a 26-year-old woman. The woman presented with classic symptoms of ischemic heart disease after having successfully undergone chemotherapeutic treatment for choriocarcinoma several months earlier. Thus, she was thought to have coronary heart disease or to have developed cardiotoxicity from antineoplastic drugs. This is the first report of this type of metastatic localization and tumor involvement in the heart and underscores the need for suspecting isolated metastases in uncommon sites in patients with choriocarcinoma.

[Pathologic morphology and clinical significance of the anomalous origin of the left circumflex coronary artery from the right coronary artery. General review and autopsy analysis of 30 cases]. / Patoloska morfologija i klinicki znacaj anomalnog izlaska leve cirkumfleksne koronarne arterije is decne koronarne arterije. Opsti pregled i obdukcijska analiza 30 slucajeva.

After an extensive analysis of the world literature (121 references), beginning from the first reported case by Antopol and Kugel, 1933, the general review of the problem stressed especially the following morphologic characteristics and clinical significance of the anomalous origin of the left circumflex coronary artery (LCxA) from the right coronary artery (RCA): The place of the anomalous origin of LCxA from RCA among all other variations and anomalies of LCxA. The anatomical and topographical characteristics of LCxA originating from RCA in normal heart as well as in congenital heart diseases--CHD (especially complete transposition of great arteries--TGA). The formal genesis of LCxA from RCA according to original new Ogden's theory, taking into account the dual origin of the coronary arteries and the peritruncal angioblastic ring that surrounds the developing aorta and pulmonary artery. The frequencies of the origin of LCxA from RCA in autopsy and coronarography series. The importance of LCxA (by its origin and/or caliber) in determination of the right, left or codominance of the coronary arteries including the peculiarities in cases of isolated aortic stenosis and bicuspid aortic valve. The importance of recognizing LCxA from the RCA during implantation of artificial aortic, mitral and tricuspid heart valves, during mitral valve anuloplasty, closure of ostium primum defect as well as during aorto-coronary venous bypass. The LCxA from RCA, especially its proximal segment, shows more frequent and an earlier, faster and heavier obstructive atherosclerosis, causing different manifestations of coronary heart disease and sudden death. Also, mitral insufficiency can be caused by ischemia of the papillary muscles of the left ventricle. The awareness of the possibility that LCxA may arise from the RCA can prevent many complications during cannulations of the coronary arteries for diagnostic coronarography and myocardial perfusion during heart operations. The authors presented their 30 autopsied cases of LCxA from RCA, analysing morphological and topographic data as well as their clinical significance and association with other CHD. There were 6 isolated cases and 24 cases associated with other CHD (20 with TGA and 4 with other CHD). Our first autopsied case of LCxA from RCA was diagnosed as associated with tetralogy of Fallot in 1964. During the period 1964-1985 we had 1015 cases of CHD (including 132 cases of TGA).(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnostic endomyocardial biopsy findings in 160 consecutive patients: the Yugoslavian experience.

Percutaneous endomyocardial biopsy was performed for the diagnosis of various heart disorders in 160 consecutive patients in Belgrade, Yugoslavia. Tissue specimens were taken from the left ventricle in 150 patients and from the right ventricule in 10. To determine the clinical merit of endomyocardial biopsy, patients were divided into six groups based upon the existing clinical findings, including cardiomyopathy, myocarditis, specific heart muscle disease, alcohol-induced heart disease, major dysrhythmias, and other diagnoses. The clinical value of endomyocardial biopsy was gauged by the number of diagnoses that were histologically confirmed by the procedure. We combined the percentages of histologically suspected clinical diagnoses with those of completely changed clinical diagnoses and found that endomyocardial biopsy provided useful information in 70.6% of cases. Nonspecific histological findings were found in 25.6% of cases. The biopsy proved to be of no clinical value in only 3.8% of the cases. Although some investigators still object to the overall clinical usefulness of diagnostic endomyocardial biopsy, our findings help to underscore the value of this procedure for making an accurate diagnosis.