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Immunosuppressive treatment in autoreactive myocarditis--results from a controlled trial.

It is still a matter of controversy whether immunosuppressive therapy is beneficial in patients with acute myocarditis, although autoimmune mechanisms play an important role in the development of myocarditis and its sequelae, for example, in dilated heart muscle disease, particularly because it is postulated that in man immunosuppression may aggravate the viral cell damage that is proposed to trigger the myocarditis. We report the clinical (NYHA-class), haemodynamic (improvement of left ventricular ejection fraction, left ventricular end-diastolic volume index), histological (infiltrate, fibrosis, myocyte hypertrophy) and immunohistological (immunoglobulin and C3-binding) findings in a controlled study including 17 patients with active myocarditis or acute perimyocarditis who were treated with a combination of prednisone and azathioprine for 3 months. We compared them with 21 patients of comparable clinical and haemodynamic compromise who underwent conventional treatment. Follow-up examinations were performed after 3 months. There was significant improvement of ejection fraction and NYHA-classification under immunosuppressive treatment. Infiltrates were reduced significantly in the immunosuppressed patients group only. Binding of IgG and IgM in the endomyocardial biopsy was diminished slightly but not significantly by both regimens. Fibrosis and myocyte hypertrophy were augmented in both treatment arms. There was no difference with respect to prognosis: four patients died or underwent heart transplantation in the immunosuppressive treatment group compared to five conventionally treated patients.

Acute Disease↗

A case of hypereosinophilic syndrome with asymmetric septal hypertrophy.

A case of idiopathic hypereosinophilic syndrome (HES) with asymmetric septal hypertrophy (ASH) is described: this is a very rare association. The patient was a 56-year-old male with hypereosinophilia lasting for 10 years. The white blood cell count was 11200/mm3, with 22% eosinophils, and eosinophilic hyperplasia (7.2%) was noted in the bone marrow. A peripheral blood smear showed vacuolated eosinophils with a reduced content of granules. An ultrastructure study of the eosinophils revealed reduced numbers of crystalloid granules which appeared to be dissolving with reversal of normal staining. An echocardiogram and a biventriculoglam indicated ASH with the interventricular septal wall thickness of 2.4 cm and the left ventricular posterior wall thickness of 1.5 cm. Right ventricular endomyocardial biopsy revealed no eosinophilic infiltration, but endocardial thickening, subendocardial fibrosis, hypertrophy, myocytolysis, and fragmentation of muscle bundles were observed.

Biopsy↗

Computerized scoring of histopathology for predicting coronary vasculopathy, validated by intravascular ultrasound.

BACKGROUND: Allograft coronary vasculopathy results from a complex interplay between immunologic and non-immunologic factors. We devised a computerized biopsy scoring method based on histopathology to predict the development of coronary vasculopathy. METHODS: One hundred forty heart transplant recipients underwent serial intravascular ultrasound analysis at baseline (within 1 month) and at 1 year after transplantation and were evaluated for development of coronary vasculopathy (change in coronary maximal intimal thickness, CMIT). We evaluated serial endomyocardial biopsy specimens for cellular rejection, vascular rejection, ischemia, and fibrosis. In a mathematical model, we computed a biopsy score in each patient based on the duration and severity of histopathology. RESULTS: We found a significant correlation between biopsy score (RY) and progression of coronary vasculopathy (r = 0.54, p = 0.001). Using a sensitivity analysis method, an RY value of > or =560 predicted development of coronary vasculopathy with a sensitivity of 86%, specificity of 62%, and diagnostic accuracy of 80%. Compared with patients with low-risk biopsy scores (RY < 560, n = 37), patients with high-risk biopsy scores (RY > or = 560, n = 103) had increased progression of coronary vasculopathy (CMIT, 0.59 +/- 0.29 vs 0.19 +/- 0.10 mm, p < 0.001) and worse 7-year event-free survival (60% vs 91%, p = 0.01). CONCLUSION: The biopsy score is an effective method for predicting the development of coronary vasculopathy and for predicting outcome in cardiac transplant recipients.

Adult↗

Left ventricular systolic function in aortic stenosis.

In aortic valve stenosis, concentric hypertrophy develops which is characterized by a reduced end-diastolic radius-to-wall thickness ratio (r/h) with an essentially normal cavity shape. As long as the product of (r/h) and LV systolic pressure remains constant, hypertrophy is appropriate. An increase in the product, which represents an increase in wall stress signals inadequate LV hypertrophy. Although at first glance, massive LV hypertrophy appears favourable for the maintenance of a normal LV ejection fraction in aortic stenosis, data from 23 studies of the literature have shown an inverse relationship between ejection fraction and LV angiographic mass m-2 (r = -0.59). Both a degree of hypertrophy inadequate to keep systolic wall stress within normal limits and a reduction of LV contractility may explain the depression of ejection fraction when LV angiographic mass is sizeably increased. Conversely, a normal ejection fraction in aortic stenosis may not be indicative of normal systolic myocardial function under all circumstances. In the presence of mildly reduced contractility, a normal ejection fraction may be maintained by the use of preload reserve. Assessment of myocardial structure from LV endomyocardial biopsies revealed no differences in muscle fibre diameter, interstitial fibrosis and volume fraction of myofibrils between patients with aortic stenosis having a normal and those with a depressed ejection fraction. Preoperative ejection fraction is a poor predictor of postoperative survival, whereas markedly increased preoperative angiographic mass and end-systolic volume have been reported to predict an unsatisfactory postoperative outcome characterized by either death or poor LV function.

Aortic Valve↗

[Left ventricular aneurysm in a patient with mildly dilated cardiomyopathy].

We describe the case of a patient with mildly dilated idiopathic cardiomyopathy and left ventricular aneurysm, diagnosed in absence of a prior clinical history and anatomo-pathological features of myocardial infarction. To ascertain the diagnosis of idiopathic cardiomyopathy, the patient underwent cardiac catheterization with coronary angiography, that showed the lack of epicardial artery stenosis and a slow run-off of the contrast. An endomyocardial biopsy showed the presence of hypertrophic myocytes and interstitial fibrosis. Moreover, a thoracic high resolution computed tomography showed the features of pulmonary bilateral basal emphysema, interstitial thickening and bronchiectasis. Alfa1-anti-trypsin plasma levels were reduced. The patient, because of worsening of clinical and hemodynamic conditions, underwent at age of 36 a combined heart-lung transplantation. The pathological examination of the native organs confirmed the previous diagnosis. At the moment, this is the second report in the literature concerning the presence of left ventricular aneurysm in a patient with idiopathic cardiomyopathy without an underlying coronary artery disease or prior history of myocardial infarction.

Adult↗

[Arrhythmogenic dysplasia of the right ventricle: a cause of ventricular tachycardia in childhood].

We describe a 9-year old patient with arrhythmogenic right ventricular dysplasia. The patient presented with sustained ventricular tachycardia in an apparently normal heart. The diagnosis was suspected by the electrocardiographic morphology of the tachycardia and definitive diagnosis was made by right ventricular angiogram, echocardiogram and the ventricular endomyocardial biopsy findings (replacement of myocardial by adipose tissue and fibrosis). We believe that this condition may be a common etiology of ventricular tachycardia with left bundle branch block conduction pattern in children with otherwise normal hearts.

Adipose Tissue↗

[Relation between systolic and diastolic elastic muscle properties and the morphology of the hypertrophic pressure-loaded left ventricle].

According to Maxwell's model, left ventricular (LV) systolic elastic properties are characterized by a series-elastic element and LV diastolic properties by a parallel-elastic element. It is not known whether this functional concept is reflected by some morphological counterparts. In 12 patients with aortic stenosis (AS) before and 19 months after aortic valve replacement, and in ten controls, LV biplane volume and simultaneous high-fidelity pressure measurements were performed during diagnostic catheterization. The constant (k) of systolic myocardial stiffness was determined from LV peak wall stress, the maximum rate of systolic stress rise and instantaneous LV midwall circumferential fiber shortening rate at peak stress. The constant (k*; circ-1) of diastolic stiffness was assessed from the diastolic stress-stiffness relationship, using a viscoelastic model. In AS patients pre- and postoperative endomyocardial biopsies were taken to assess muscle fiber diameter, interstitial fibrosis and LV fibrous content. Systolic myocardial stiffness constant was 15 circ-1 in controls, 14 circ-1 in preoperative and 12 circ-1 in postoperative AS patients (P less than 0.01 vs. controls). Diastolic myocardial stiffness constant was 19 circ-1 in controls, 23 circ-1 in preoperative AS patients and increased slightly but not significantly to 33 circ-1 after valve replacement. Parallel to the postoperative decrease in systolic stiffness, muscle fiber diameter decreased significantly from 33 to 27 mu (P less than 0.05). The slight increase in diastolic stiffness was accompanied by a significant increase in interstitial fibrosis from 15% to 26% (P less than 0.05); LV fibrous content remained essentially unchanged after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Stenosis↗

[Factors related to the pathogenesis and clinicopathological findings in dilated cardiomyopathy].

It has been suggested that various factors related to dilated cardiomyopathy (DCM) may concern its onset and/or progression. This study was performed to clarify whether these factors contribute different clinical and morphological characteristics. Subjects were 39 patients with DCM, consisting of 28 men and 11 women whose average age was 46.5 years. The subjects were divided into five groups; namely, the Familial, Myocarditic, Alcoholic, Hypertensive, and Unknown Groups. Clinical parameters including past history, blood pressure, chest radiographs, electrocardiograms, echocardiograms and left ventricular end-diastolic pressures (LVEDP) were evaluated. Morphology of right ventricular endomyocardial biopsy specimens was evaluated in terms of hypertrophy, disarrangement, fibrosis, degeneration, endocardial thickening, interstitial changes, and types of fibrosis. The results were as follows: The Familial Group was characterized by the onset at younger age, highly elevated LVEDP, a lack of myocardial hypertrophy, and proliferation of small vessels. The Myocarditic Group was characterized by the onset at young age, elevated LVEDP, severe fibrosis showing a plexiform pattern in more than half of the patients, cellular disarrangement, and cellular infiltration. The Alcoholic Group showed possible improvement clinically and fatty infiltration in half of the patients. The Hypertensive Group was characterized by high prevalence of a previous alcohol intake, high diastolic blood pressure on admission, clinical improvement, and myocardial hypertrophy with a mild degree of perivascular fibrosis. From these findings, it is thought that each factor related to DCM offers a somewhat different clinical and histological profiles and that these factors may play an important role in the onset and/or progression of DCM. Furthermore, it is highly suggestive that specific therapy against these factors or the removal of these factors is especially necessary for favorable long-term prognosis of DCM.

Adolescent↗

Re-entry circuit in ventricular tachycardia due to focal fatty-fibrosis in a patient with myotonic dystrophy.

A 69-year-old man with a recurrent ventricular tachycardia (VT) was admitted. The patient was diagnosed as myotonic dystrophy type 1 (DM1) and DNA analysis revealed 1,800 CTG-repeat expansion in the myotonic dystrophy protein kinase (DMPK) gene. Ultrasonic cardiogram (UCG), left ventriculogram (LVG) and magnetic resonance imaging (MRI) did not show any abnormal sign including fatty infiltration. But, endomyocardial biopsy obtained from ventricular outflow tract revealed severe fatty infiltration and interstitial fibrosis. Radiofrequency catheter ablation at the biopsy site could eliminate VT, so it was strongly suggested that the re-entry circuit was formed by focal fatty-fibrosis. Careful observation should be continued for a long period.

Adipose Tissue↗

Myopericarditis associated with ECHO virus type 3 infection--A case report.

A case with myopericarditis caused by type 3 ECHO virus was reported. The diagnosis was based on a significantly increased hemagglutination-inhibiting antibody titer (from 4:6 to 4:516) against type 3 ECHO virus in the acute and the convalescent phase. A 29-year-old male was hospitalized for chest pain and fever. The patient had congestive heart failure, pericardial effusion and temporarily appearing abnormal Q waves on his electrocardiogram in the acute phase all of which gradually improved within about 3 weeks. Cardiac catheterization performed on the 21st day of hospitalization disclosed normal coronary arteries, but a partially hypokinetic region was found in the left ventricular free wall. A right ventricular endomyocardial biopsy study revealed histological features of a small number of mononuclear cell infiltrations, myocardial cell necrosis and early fibrosis associated with an increased number of fibroblasts and ultrastructural changes including myocytolysis, vacuolation in sarcoplasm and dissociation of some intercalated discs. The endomyocardial biopsy study, and the electrocardiographic and cineangiographic findings in this case suggest that viral infection may induce clinical signs of myocardial infarction in the heart with normal coronary arteries.

Adult↗

Morphologic criteria of progression and regression of cardiac hypertrophy.

The heart is able to adapt itself to a demanded load by increasing (hypertrophy) or decreasing (regression of hypertrophy) its muscular mass within a wide range. Overstressing of the ability of adaptation is accompanied by degenerative changes of myocytes. Semiquantitative investigations of endomyocardial biopsies (EMCBs) of patients with dilative cardiomyopathy (DCM) and hypertrophic nonobstructive cardiomyopathy (HNCM) show a fibrosis of the interstitial space, as well as almost similar changes of myofibrils and mitochondria. A reduced number of myocytes in hearts with DCM could explain the decreased functional capacity. Quantitative investigations of endomyocardial biopsies and myectomy specimens in patients with hypertrophic obstructive cardiomyopathy have revealed that hypertrophy and, to a certain extent, hyperplasia of muscle fibers cause asymmetrical thickening of the septum. Experimental investigations of the regression of training-induced hypertrophy in rats have shown that nearly all parameters (cardiac weight, thickness of muscle fibers, myofibrillar mass, interstitial space, and capillary width) returned to the values of controls 14 days after termination of a swimming training regimen. A significantly higher density of capillaries after regression of muscle fiber hypertrophy compared to controls points to a temporal dissociation in the regression of myocyte size and capillary network. Decrease in RNA concentration and an increased number of autophagic vacuoles give evidence for decreased anabolism and increased catabolism may occur during regression. In humans, fibrosis of the myocardium and scar formation explain the irreversibility of cardiac hypertrophy, as observed in some patients with valvular heart disease, despite valve replacement.

Adult↗

Biochemical and histologic correlates of ventricular end-diastolic pressure.

The associations of elevated left ventricular (LV) and right ventricular (RV) end-diastolic pressure (EDP) were evaluated in 28 patients with non-ischemic congestive cardiomyopathy. Right-sided endomyocardial biopsies from each patient were evaluated for ATP content, percent fibrosis and myocardial fiber diameter. The resting RVEDP and LVEDP and the post-angiographic LVEDP were correlated with the results from the biopsies. There was a correlation of the LVEDP with the RVEDP (r = 0.67, P less than 0.001) by a linear plot. There was no correlation of any EDP measurement with the percent fibrosis. There was, however, a rough correlation of the myocardial fiber diameter with RVEDP (r = 0.40, P less than 0.05). Myocardial ATP content correlated with the RVEDP (r = -0.53, P less than 0.005), the LVEDP (r = -0.65, P less than 0.001) and the post-angiographic LVEDP (r = -0.72, P less than 0.001). These data demonstrate that an elevated ventricular EDP correlates most closely with depressed levels of myocardial ATP. The myocardial cell diameter correlated less well and there was no correlation of EDP with fibrosis. Metabolic factors may be more important than histologic parameters in the elevated ventricular EDP of non-ischemic congestive cardiomyopathy.

Adenosine Triphosphate↗

Pathology of cardiac transplantation: recipient hearts (chronic heart failure) and donor hearts (acute and chronic rejection).

Pathologic examination of both the recipient and the donor heart is critical to the success of cardiac transplantation. Idiopathic dilated cardiomyopathy and end-stage ischemic heart disease are still the most common diagnoses for which cardiac transplantation is performed in the United States. After transplantation, the donor heart is susceptible to immunologic (acute and chronic rejection), infectious, and ischemic injury. Other long-term changes, such as hypertrophy of the myocytes and interstitial fibrosis, may also affect the function of the transplanted heart. Periodic endomyocardial biopsies are important for monitoring the status of the transplanted heart. In patients treated with cyclosporine, the clinical signs of rejection may be minimal, and routine biopsy is the only means of detecting early rejection.

Acute Disease↗

Aging of the human myocardium: a histologic study based upon endomyocardial biopsy.

This study assesses the effect of aging on human myocardial morphology. Fifteen patients, ranging in age from 28 to 75 with normal cardiac history, physical examination and noninvasive tests of left ventricular function, underwent right ventricular endomyocardial biopsy prior to cancer chemotherapy. Cell diameter, nuclear area and fibrosis were quantified by light microscopy. Semiquantitative methods of electron microscopy were used to grade lipofuscin deposition, tubular dilation, myofibrillar loss, folding of discs and lipid deposition. The results demonstrated that myocardial cell diameter correlated directly with age (r = 0.73, p less than 0.01) and systolic blood pressure (r = 0.51, p less than 0.05). Nuclear area (r = 0.76, p less than 0.01) and folded discs (r = 0.53, p less than 0.05), two signs of increased protein production also correlated with age. Lipid deposition (r = 0.40), tubular dilation (r = 0.31) and lipofuscin deposition (r = 0.20) increased with, but did not correlate significantly with age. Lipid deposition (r = 0.56, p less than 0.05) and tubular dilation (r = 0.43, p less than 0.05) did correlate with cell diameter. Thus, the aging myocardium is characterized by increased cell size and some degenerative changes.

Adult↗

Unique presentation of hypereosinophilic syndrome: recurrent mitral prosthetic valve thrombosis without endomyocardial disease.

Hypereosinophilic syndrome (HES) is defined as a prolonged, unexplained peripheral eosinophilia in a patient presenting with end-organ damage. The heart is frequently involved, resulting in eosinophilic endomyocardial disease, which is characterized by mural thrombus formation and endocardial fibrosis. Thromboembolic complications in HES are mediated by material released from eosinophilic granules. Herein is reported the case of a patient who presented, 15 years after valve replacement with a mechanical prosthesis, with clinical signs of recurrent prosthetic valve thrombosis that was caused by missed hypereosinophilia. The unique feature of the case was that the mitral prosthetic valve obstruction was the result of an eosinophilic thrombus, though no tissue infiltration or inflammation had been detected by random biopsy of the left ventricular myocardium. After nine years of effective treatment of HES there were no cardiac or extracardiac complications.

Heart Valve Prosthesis↗

[Sudden unexpected nocturnal death: report of a case and review of the literature].

Sudden death usually affects individuals with severe heart disease. A more dramatic phenomenon is the sudden unexpected death of individuals with no evidence of heart disease. It has been described mainly in young healthy males under severe stress. We present a 32 year old man who presented ventricular fibrillation during sleep and was resuscitated by his wife. Recurrent episodes of VF occurred in the following hours. The study, including coronary angiography, revealed a normal heart. Endomyocardial biopsy showed minimal alterations with scarce areas of atrophy and fibrosis. Electrophysiologic evaluation showed an extremely short refractory period of the right ventricle, but the arrhythmia could not be induced by electrical stimulation. An internal cardioverter defibrillator was implanted since the risk of recurrent VF was high. A review of the literature concerning this unusual entity is offered.

Adult↗

[Reversibility of alcoholic myocardiopathy with abstinence: presentation of 2 cases].

The sustained alcohol intake results in the development of a dilated cardiomyopathy; its pathogenesis and prognostic and evolutive factors have not yet been completely defined. It is classically considered that alcoholic cardiomyopathy has a poor prognosis, as two thirds of patients die within three years. However, in recent years some isolated cases of clinical reversibility after short abstinence periods have been reported without identification of the involved factors. Two chronic alcoholic patients are reported with congestive heart failure at admission; a diagnosis of alcoholic cardiomyopathy was made after cardiac catheterization and endomyocardial biopsy. The morphometric study of endomyocardial biopsy showed a preservation of the myofibrillary fraction with mild fibrosis. The clinical outcome was favorable: after three months of alcoholic abstinence, a complete clinical recovery with definite improvement of echocardiographic parameters and left ventricular ejection fraction in the radionuclide ventriculography were observed. Finally, the factors that appear to be involved in the presence or absence of reversibility of this type of cardiomyopathy are discussed.

Adult↗

[A case of cardiac sarcoidosis with various electrocardiographic change].

The patient was a 61 year old woman of Japanese who was in good health until May 1983, when she came to our hospital because of the visual disturbance. The chest X-ray film showed bilateral hilar lymphadenopathy and a transbronchial lung biopsy revealed sarcoid granuloma. She received systemic steroids (10 to 40 mg/2 days of prednisolone) for visual disturbance from August 1983 to May 1986. Then steroid therapy was suspended temporarily. In August 1987, she was readmitted because of syncopal episodes. She was noted to have irregular bradycardia and the electrocardiogram revealed atrioventricular block and paroxysmal polymorphous ventricular tachycardia. Initially cardioversion to sinus rhythm was accomplished with direct current electric shock and temporary pacemaker was inserted and subsequently a permanent transvenous demand pacemaker implanted. The patient then became asymptomatic. Coronary arteriography revealed no significant organic stenosis and left ventriculogram showed a left ventricular aneurysm of the inferior wall of the left ventricle. A transvenous percutaneous right ventricular endomyocardial biopsy revealed non-specific myocardial degeneration with slight interstitial fibrosis. Thallium-201 myocardial perfusion scans revealed the inferior left ventricular defects. We conclude the syncopal episodes and electrocardiographic abnormalities of this case were due to massive myocardial sarcoidosis which caused left ventricular aneurysm.

Cardiomyopathies↗