A case of myxedema with diffuse myocardial fibrosis proven by endomyocardial biopsy

We report a middle-aged woman with myxedema heart who presented both clinical features resembling dilated cardiomyopathy and the diffuse myocardial fibrosis proven by endomyocardial biopsy. Thirty years previously, when she was 36 years old, partial thyroidectomy had been performed after a diagnosis of hyperthyroidism was made. Four years later, she experienced dry skin and peripheral edema, and hypothyroidism was diagnosed. Several months after, replacement therapy for hypothyroidism improved her symptoms. However, the therapy was discontinued because of her ignorance of the disease. Twenty six years later (64 years old), she felt exertional dyspnea, and was admitted to Fukuoka University Hospital for evaluation of her cardiac state. Thyroid function test revealed primary hypothyroidism with low T3, low T4 and high TSH levels. Cardiothoracic ratio on chest X-ray film was 69%. Electrocardiogram showed low voltage in the limb leads and intraventricular conduction disturbance. Echocardiogram demonstrated marked dilatation and severely reduced wall motion of the left ventricle and pericardial effusion. Left ventriculogram showed diffuse hypokinesis with 27% of the ejection fraction. No significant stenosis was observed on coronary arteriogram. Seventeen-month replacement therapy did not improve these cardiac findings significantly. Transvenous right ventricular endomyocardial biopsy demonstrated diffuse myocardial fibrosis without inflammatory infiltrate, which was interpreted as a sequel of interstitial lesions of the myxedema heart such as edema or mucoid infiltration. This pathological finding suggests that long-standing untreated hypothyroidism can cause irreversible myocardial damage.     

A case of myxedema heart showing the improvement of impaired alpha-hANP secretion by administration of ATP and dibutyryl cAMP

A 40-year old female was admitted with complaints of general fatigue and dyspnoea brought on by effort. There were edema on the face, a diffuse and slightly hard goiter on the neck and non-pitting edema in the lower legs. Laboratory findings showed low levels of serum T3 (0.37 ng/ml) and T4 (2.0 micrograms/dl), a very high level of serum TSH (549.8 microU/l), positive thyroid test (x 400) and positive microsome test (x 102,400). The chest roentgenogram showed an enlargement (CTR 62%) of the cardiac silhouette in the shape an ice bag, and the electrocardiogram revealed low QRS voltage with T-wave flattening in all leads. Remarkable pericardial effusion was shown on the two-dimensional echocardiogram. Judging from the indications of hypothyroidism, positive antithyroid antibody and pericardial effusion. This patient was diagnosed as having myxedema heart due to chronic thyroiditis. The levels of plasma alpha-hANP did not elevate so much as the levels in normal controls after right atrial (RA) pacing, although mean right atrial pressure was higher than in normal controls after RA pacing. The levels of plasma alpha-hANP after RA pacing in euthyroid state were higher than those in hypothyroid state. The levels of plasma alpha-hANP after RA pacing became higher after the administration of ATP or db-cAMP both in euthyroid and hypothyroid states. These results indicate that the impaired alpha-hANP secretion in myxedema heart is improved by the administration of thyroxine, ATP or db-cAMP.     

Idiopathic restrictive cardiomyopathy in the young: report of two cases

Two cases of idiopathic restrictive cardiomyopathy in young age are reported. This rare kind of restrictive cardiomyopathy is characterized by the absence of specific histologic features of myocardial abnormalities. In both cases (aged 12 and 9 years at diagnosis), the clinical picture was characterized by severe and slowly progressive congestive heart failure. The electrocardiogram showed biventricular hypertrophy, right bundle branch block and pseudoinfarctional Q waves. Echocardiography revealed moderate pericardial effusion, biatrial enlargement, and normal or nearly normal biventricular dimensions and systolic function. Cardiac catheterization disclosed the typically restrictive filling pattern. Right ventricular endomyocardial biopsy demonstrated moderate interstitial fibrosis and cellular hypertrophy without any evidence of infiltrative or storage myocardial disease or endocardial pathology. One patient underwent cardiac transplantation, whereas in the other, transplantation was contraindicated because of longstanding pulmonary hypertension and liver cirrhosis. The knowledge of this rare entity may correctly orient the diagnostic process in children suspected of having restrictive myocardial disease. Heart, or even heart-lung, transplantation must be considered in cases with congestive heart failure before irreversible damage occurs in many organs.     

Histological findings of the right and left ventricular myocardium and clinical follow up in idiopathic ventricular tachycardia

In order to evaluate the etiology of so-called idiopathic ventricular tachycardia, endomyocardial biopsies were performed in four patients with electrocardiographically documented recurrent and sustained ventricular tachycardia. During the episodes of ventricular tachycardia, standard ECG showed a QRS pattern of right bundle branch block with left axis deviation in two patients and left bundle branch block in two patients. The episodes were associated with palpitation, dyspnea and hypotension in all cases. No organic heart disease was detected by physical examination, chest X-ray films, echocardiograms, left ventriculograms or coronary cineangiograms. His bundle electrograms showed blocks at various sites in the atrioventricular conduction system. The biopsy specimens revealed nonspecific myocardial degeneration in the right and left ventricles. These findings suggest mild but wide-spread myocardial damage in both the working myocardium and the conduction system. The clinical course of these patients appeared benign according to follow-up data of one to nine years' duration. None developed overt clinical signs of dilated, hypertrophic or restrictive cardiomyopathy.     

Findings on endomyocardial biopsy in infants and children with dilated cardiomyopathy

Fifteen infants and children with dilated cardiomyopathy underwent transvascular endomyocardial biopsy. The light and electron microscopic findings were reviewed to evaluate the presence of lymphocytes as an indicator of active myocarditis. Both ventricles were biopsied in 13 patients, and the right ventricle only was biopsied in 2. None of the endomyocardial specimens obtained by biopsy revealed an inflammatory process. Interstitial fibrosis, myofiber hypertrophy, degeneration and necrosis were found. Ultrastructural abnormalities of the mitochondria, T tubules or Z bands were noted in approximately one-third of patients. Persistent, active myocarditis is an uncommon cause of dilated cardiomyopathy in children. Immunosuppressive therapy, which may be harmful, should be considered only after myocardial inflammation has been documented by endomyocardial biopsy.     

Treatment of acute inflammatory myocarditis assisted by endomyocardial biopsy

Right ventricular endomyocardial biopsy was performed to make a diagnosis of inflammatory myocarditis in 10 patients with congestive heart failure. All 10 patients were treated with immunosuppressive agents (either prednisone alone or prednisone in combination with azathioprine) and were followed up prospectively. Each patient had serial invasive and noninvasive assessments of cardiac performance, and 9 of 10 had one or more follow-up endomyocardial biopsies. The course of four patients who showed dramatic improvement in association with immunosuppressive therapy is described in detail. In addition to these four patients, one other had definite improvement and four subjects had stabilization of previously progressive heart failure; the condition of one patient worsened, and he died despite immunosuppression. In the seven patients who had cell inflammation, six underwent a second biopsy after a period of immunosuppressive therapy, and in each case, the inflammatory infiltrate had been eliminated. In two of these patients, signs and symptoms of myocarditis recurred after discontinuation of therapy, and myocardial biopsy confirmed the recrudescence of cell inflammation. Reinstitution of therapy improved symptoms and histologic findings.It is concluded that endomyocardial biopsy can be used to diagnose inflammatory myocarditis and to monitor the histologic results of therapy. Our findings constitute circumstantial evidence that immunosuppressive therapy is effective in eliminating myocardial cell inflammation and thereby improving myocardial performance.     

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.     

Hypothyroid dilated cardiomyopathy

Most patients with dilated cardiomyopathy have a poor prognosis due to progressive and irreversible myocardial dysfunction. Rarely, is a metabolic etiology responsive to specific therapy identified. Although many studies have confirmed that thyroid hormone deficiency is associated with a reversible decrease in myocardial contractility, it has remained controversial whether hypothyroidism alone can cause a dilated cardiomyopathy and clinical heart failure. In this study, we report the case of a patient with severe hypothyroidism and a dilated cardiomyopathy complicated by heart failure, which has receded after recovery to euthyroidism with L-thyroxin therapy. This case suggests that hypothyroidism should be evoked systematically when a dilated cardiomyopathy is diagnosed.     

Echocardiographic evaluation of pericardial effusion in myxedema. Incidence and biochemical and clinical correlations.

Pericardial effusion is a recognized consequences of myxedema. Its incidence is unknown, primarily because of past difficulties in establishing the diagnosis. We studied 33 hypothyroid patients by echocardiography. Ten of the 33 patients (30%) had positive echoes for pericardial effusion. Seven of these ten patients had enlarged hearts on chest X-ray. Five patients had cardiac enlargement but no echo evidence of pericardial effusion. Serum concentrations of thyroxine, 1.8+/-0.3 vs 1.5+/-0.1 mcg/dl and of thyroid stimulating hormone, 34+/-4 vs 38+/-5 muU/ml did not differ in the groups with and without pericardial effusion, respectively. However, the pericardial effusion group had significantly slower heart rates on ECG than those without pericardial effusion: 53+/-8 vs 68+/-2 beats/min, P less than 0.05. Low voltage was present in five of the ten patients with pericardial effusion and five of the 23 nonpericardial effusion patients. None of the patients with pericardial effusion developed tamponade. Seven patients with pericardial effusion were restudied after periods of thyroxine replacement therapy ranging from six months to two years. All were euthyroid and had negative echoes on follow-up, but two still showed cardiomegaly on chest X-ray (both had associated coronary artery disease). We conclude that pericardial effusion occurs frequently in patients with myxedema. Tamponade is uncommon and the effusions disappear with thyroid replacement therapy. Cardiomegaly on chest X-ray and low voltage on ECG are not reliable indicators of pericardial effusion.     

Recognizing and treating myocarditis in recent-onset systemic sclerosis heart disease: Potential utility of immunosuppressive therapy in cardiac damage progression

Objectives

Scleroderma heart disease is a major risk of death in systemic sclerosis (SSc). Mechanisms underlying myocardial damage are still unclear. We performed an extensive study of SSc patients with recent-onset symptoms for heart disease and examined the efficacy of immunosuppressive therapy.

Methods

A cohort of 181 SSc patients was enrolled. Of these, 7 patients newly developed clinical symptoms of heart disease (heart failure, chest pain, and palpitation); all of them showed mild but persistent increase in cardiac enzymes. These patients underwent Holter ECG, 2D-echocardiography, perfusional scintigraphy, delayed-enhancement-cardiac magnetic resonance (DE-CMR), coronary angiography, and endomyocardial biopsy. Patients were treated for at least 12 months and followed-up for 5 years.

Results

Ventricular ectopic beats (VEBs) were found in 4 patients, wall motion abnormalities in 3, pericardial effusion in 6, and DE in CMR in 6 with T2-hyperintensity in 2. In all patients, histology showed upregulation of endothelium adhesion molecules and infiltration of activated T lymphocytes, with (acute/active myocarditis in 6) or without (chronic/borderline myocarditis in 1) myocyte necrosis. Parvovirus B19 genome was detected in 3. None showed occlusion of coronary arteries or microvessels. Compared with SSc controls, these patients more often had early disease, skeletal myositis, c-ANCA/anti-PR3 positivity, VEBs, pericardial effusion, and systolic and/or diastolic dysfunction. Immunosuppressive therapy improved symptoms and led to cardiac enzyme negativization; however, 2 patients died of sudden death during follow-up.

Conclusions

Myocarditis is a common finding in SSc patients with recent-onset cardiac involvement. Its early detection allowed to timely start an immunosuppressive treatment, preventing cardiac damage progression in most cases.     

Electrophysiologic and histopathologic investigations in children with idiopathic ventricular arrhythmias

Between April 1984 and December 1987, electrophysiological studies and endomyocardial biopsy were performed in 14 pediatric patients, aged from 7 to 15 years, with idiopathic ventricular arrhythmias in whom diagnostic evaluation had revealed no structural heart disease. They were 8 boys and 6 girls. Cardiac catheterization revealed regional wall motion abnormalities of the left ventricle in 3 patients, one of whom showed decreased ejection fraction (EF). Electrophysiologic examination showed sinus node dysfunction in 21%. AV nodal dysfunction in 14% and dual AV nodal pathway in 21%. Histopathologic examination by endomyocardial biopsy showed myocellular hypertrophy, degeneration of myocytes, interstitial fibrosis and endomyocardial thickness in 86%, 36%, 35% and 14%, respectively. Since idiopathic ventricular arrhythmias in pediatric age group included relatively high electrophysiologic and histopathologic abnormalities, which were suggestive of occult myocardial disease and might be the early stage of cardiomyopathy, careful follow-up should be required.     

Clinical, histochemical, and ultrastructural correlation in septal endomyocardial biopsies from chronic chagasic patients: detection of early myocardial damage

In order to recognize early signs of myocardial damage, histologic, histochemical, and ultrastructural studies were performed on septal endomyocardial biopsy tissue obtained from 79 chronic chagasic patients and from 18 patients with atypical chest pain (control group). Abnormal biopsy findings were recognized in 9 of 16 (60%) chagasic patients with no clinical evidence of myocardial damage. In cases of segmental asynergy only, biopsies were abnormal in 18 of 19 patients. When signs of advanced myocardial damage were evidenced by clinical examination or ECGs, all biopsies were abnormal. Mitochondrial, nuclear, and cell membrane irregularities were consistent findings. A peculiar dilatation and filling of the T tubule system with a glycoprotein-like substance and a remarkable increase in monoamine oxidase activity were observed early in the disease and progressed in magnitude and frequency as myocardial damage became more evident by other diagnostic methods. Septal endomyocardial biopsy is a sensitive method for detection of early myocardial damage in chronic chagasic patients. Based on these findings, a modification of the currently used classification is proposed.     

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.     

An elderly case of triple-vessel coronary artery disease with alternating bundle branch blocks in serial electrocardiograms

An 82-year-old woman was admitted with severe chest pain and orthopnea on January 17, 1997. Physical examination revealed bilateral leg edema and cyanosis at the periphery of the extremities. The serum CK level was 488 IU/l on admission and increased to a maximum value of 4,866 IU/l 8 hours after admission. An echocardiogram demonstrated diffuse severe hypokinesis in the left ventricle. Serial electrocardiograms showed transient right bundle branch block, left bundle branch block, and normal sinus rhythm. The patient was diagnosed as having congestive heart failure. Artificial ventilation was performed, and furosemide, isosorbide dinitrate and dopamine were administered. A right ventricular endomyocardial biopsy performed on the 13th hospital day demonstrated moderate hypertrophy and disparity of cardiac myocytes and fibrosis around the myocytes, and few inflammatory cells in the specimens. This biopsy finding was not compatible with acute myocarditis but with the chronic stage of myocarditis. The patient was discharged on the 45th hospital day, but returned because of a recurrence of congestive heart failure. After an improvement of the heart failure, a coronary angiography was performed on the 20th hospital day. The coronary angiography revealed significant stenosis in three vessels. This elderly patient had congestive heart failure and triple-vessel coronary artery disease with transient alternating bundle branch blocks on serial electrocardiograms. Alternating bundle branch blocks and diffuse left ventricular dysfunction was considered to be induced by the aging process, postmyocarditic change of myocytes, and triple-vessel coronary artery disease in this case.     

Hypothyroidism and mild myxedema from thiocyanate intoxication

The patient whose case is reported herein developed hypothyroidism with mild myxedema in the course of prolonged administration of thiocyanate for essential hypertension. Classical cardiac manifestations of myxedema occurred and could be compared with control records made one year previously. Spontaneous, subjective and objective improvement occurred after cessation of thiocyanate therapy. The temporarily enlarged heart receded to dimensions approximating those previously present.     

Acute viral myopericarditis presenting as a transient effusive-constrictive pericarditis caused by coinfection with coxsackieviruses A4 and B3

Acute myopericarditis is usually caused by viral infections, and the most common cause of viral myopericarditis is coxsackieviruses. Diagnosis of myopericarditis is made based on clinical manifestations of myocardial (such as myocardial dysfunction and elevated serum cardiac enzyme levels) and pericardial (such as inflammatory pericardial effusion) involvement. Although endomyocardial biopsy is the gold standard for the confirmation of viral infection, serologic tests can be helpful. Conservative management is the mainstay of treatment in acute myopericarditis. We report here a case of a 24-year-old man with acute myopericarditis who presented with transient effusive-constrictive pericarditis. Echocardiography showed transient pericardial effusion with constrictive physiology and global regional wall motion abnormalities of the left ventricle. The patient also had an elevated serum troponin I level. A computed tomogram of the chest showed pericardial and pleural effusion, which resolved after 2 weeks of supportive treatment. Serologic testing revealed coxsackievirus A4 and B3 coinfection. The patient received conservative medical treatment, including nonsteroidal anti-inflammatory drugs, and he recovered completely with no complications.     

Radionuclide imaging for assessment of myocarditis and postmyocarditic state in infant and children. Thallium-201 myocardial imaging and technetium-99m-HSA gated equilibrium ventriculography

T1-201 myocardial imaging and Tc-99m-HSA gated equilibrium ventriculography were performed in 1 infant and 11 children between 2 months old and 12 years old with myocarditis. The time of first evaluation was between 1 week and 13 months after the onset. Their clinical manifestations were congestive heart failure in 2 patients, pericardial effusion in 2 patients, syncope in 1 patient, convulsions in 1 patient and palpitations in 7 patients. Significant elevation of virus antibody titer was demonstrated in 6 patients. A perfusion defect was observed with T1-201 imaging in 9 of 12 patients with myocarditis. A right ventricular image was observed in 5 patients. A reduced LVEF was present in 4 patients and a reduced RVEF was found in 2 patients. Cardiac catheterization was performed in 8 patients and an endomyocardial biopsy was done in 7. The myocardial specimens revealed postmyocarditic pathological changes upon microscopic evaluation. No coronary artery obstructive or stenotic lesions were observed in these patients. T1-201 myocardial imaging is a useful non-invasive technique for evaluating the cardiac performance and myocardial damage in acute myocarditis and the postmyocarditic state. We conclude that T1-201 uptake of myocardium is dependent upon both regional coronary perfusion and the activity of myocardial cells in patients with myocarditis and in the postmyocarditic state.     

A case of Wegener's granulomatosis complicated by hypopituitarism]

A 71-year-old male complaining of chest pain was admitted to our hospital. A single cavitary mass shadow was observed on chest X-ray films. Urinalysis revealed microscopic hematuria. CT examination demonstrated a tumorous shadow in the maxillary sinus. The diagnosis of Wegener's granulomatosis was histologically established by biopsy specimens from the nasal mucosa which showed necrotizing vasculitis and granuloma with fibrinoid degeneration. He was treated with combination therapy of prednisolone and cyclophosphamide. The abnormal shadows on chest X-ray and in the maxillary sinus on CT improved rapidly, but the patient developed progressive weight loss and complained of cold intolerance, weakness and dysphagia. Serum T3, T4 and TSH were found to be reduced. Anterior pituitary function tests showed reduction of TSH, GH and ACTH responses, which was probably due to irreversible vasculitis.     

A case of hypereosinophilic syndrome associated with pulmonary infarction and hepatic vein obstruction (Budd-Chiari syndrome)

A 21-year-old man was admitted in March 1987 with low grade fever and chest pain. Eosinophilia had been pointed out and PIE syndrome was diagnosed in another hospital a month before admission. Steroid therapy had been started. On the first admission, the chest roentgenogram showed bilateral pleural effusion and a nodular shadow in the left lower lung field. Open lung biopsy was performed and a diagnosis of pulmonary infarction was made. Eosinophilia, low grade fever and chest pain were improved by steroid therapy. He was discharged in April 1987. He was readmitted in September 1987 because of fever, back pain and abdominal distension. On the second admission, eosinophilia (4,510/mm3) was pointed out. The case was diagnosed as hepatic vein obstruction by hepatic vein angiography, liver biopsy and ultrasonic examination. He had transient remission on corticosteroid and anti-coagulant therapy. This case was considered as a rare case of hypereosinophilic syndrome associated with pulmonary infarction and Budd-Chiari syndrome.     

A case of brain stem encephalitis complicated with bifascicular block caused by rubella virus]

We reported a case of a 29-year-old man who had been in good health until contracting brain stem encephalitis due to a rubella virus 5 years previously, at which time the ECG revealed complete right bundle branch block and right axis deviation. An ECG obtained 6 months earlier had been within normal limits. Since yearly health checkups continued to show the same abnormalities, the patient was admitted for closer examination. At the time of admission, physical findings and blood tests revealed no abnormalities. No cardiomegaly nor pulmonary congestion was observed on chest X-rays either at the time of the original illness or at this time. An endomyocardial biopsy specimen obtained from the right ventricle revealed size variation of cardiac myocytes, moderate disarrangement, and mild myocardial interstitial fibrosis, indicative of post-myocarditic changes. The above findings suggest that bifascicular block (right bundle branch and posterior fascicle) appeared at the time of the rubella virus infection, in the pathogenesis of which the involvement of myocarditis was strongly suspected. Some patients developing myocarditis do not manifest cardiac symptoms such as heart failure. In these cases, conduction disturbances are the sole sequelae. To differentiate pathogenesis in such cases, endomyocardial biopsy was thought to be of value.