Idiopathic right ventricular dilation. Special reference to "arrhythmogenic right ventricular dysplasia" and analogous lesions

Two autopsy cases which showed marked depletion of the right ventricular musculature of the heart accompanied with marked infiltration of the adipose tissue were reported. The first cases was an 18-year-old female who died of right sided congestive heart failure after about 4-years clinical course. The autopsy disclosed marked dilation of the right atrium and ventricle. The entire free wall of the right ventricle was markedly thin. Microscopically, most of the myocardial fibers of the right ventricle were replaced by fat and fibrous tissue. The second case, a 15-year-old boy, whose identical twin was previously diagnosed as arrhythmogenic right ventricular dysplasia designated by Fontaine et al., died suddenly during exercise. He showed no cardiac symptoms but electrocardiogram was abnormal. Autopsy revealed majority of the myocardial fibers of the right ventricular free wall were replaced by fatty tissue. In both cases, fatty infiltration was mainly noticed at the epicardial side and some myocardial fibers remained in the fatty tissue showed hypertrophic and/or degenerative changes. Review of the literature on similar cases showing depletion of the right ventricular musculature including so-called adult's Uhl anomaly, ARVD and dilated right ventricular myocardiopathy was conducted and the relationship of the present cases with these lesions was discussed.     

致心律失常性右室心肌病心力衰竭期的病理特点分析

目的 通过分析致心律失常性右室心肌病(ARVC)心力衰竭期的病理改变,以进一步了解其临床分期与病理表型的关系.方法 从2004-2007 年在阜外心血管病医院接受心脏移植的心力衰竭病例中,收集病理诊断为ARVC的受体心脏8例,测量心脏重量,评价左右心室心腔扩张、心肌细胞肥大、脂肪浸润、纤维化、附壁血栓和伴发心肌炎等指标,注意左心室受累情况,并进行病理分型.结果 8例中的7例为经典型(即右心室改变为主),1例为左优势型(左心室改变为主),未见双室型病例.组织学均为纤维脂肪型,未见单纯脂肪型病例.经典型病例的右心室中、重度扩张,少数有室壁瘤形成,其中6例伴左心室受累,受累左心室轻、中度扩张,心肌广泛间质纤维化,部分病例伴替代性疤痕,而脂肪浸润量小,多局限于心外膜下.左心室心肌细胞肥大普遍.而左优势型的左心室重度扩张,弥漫间质纤维化和局部透壁性脂肪浸润.8例中3例左心室明显肥厚,3例查见双室附壁血栓,1例伴局灶性心肌炎.结论 ARVC心力衰竭期的左心室受累多见而严重,左心室间质纤维化突出,心肌细胞肥大明显,但脂肪替代少见和局限.左、右心室多扩张,可见附壁血栓,应注意与扩张型心肌病等鉴别.     

Pathologic evidence of extensive left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (also known as arrhythmogenic right ventricular dysplasia) is characterized by adipose or fibroadipose tissue replacement of the right ventricular myocardium, whereas the left ventricle is substantively spared. Two cases of the disease with evidence of extensive left ventricular involvement at pathologic examination are described. Hearts from two patients who died suddenly showed full-thickness right ventricular fatty infiltration associated with extensive left ventricular involvement (greater than 50% of myocardial thickness). These findings might explain the reported clinical features of left ventricle dysfunction in a subset of patients with arrhythmogenic right ventricular cardiomyopathy. In view of the biventricular involvement of the disease, it should simply be termed "arrhythmogenic cardiomyopathy."     

An unusual cardiac tumour found at post-mortem

This is a case of a 77-year-old man who was admitted to hospital complaining of palpitations, dizziness and sweating. During his hospital admission he was treated for various arrhythmias. An echocardiogram was performed which detected a possible infiltrative mass within the right ventricle but a subsequent echocardiogram showed right ventricular hypertrophy. Whilst awaiting further investigations, the patient self discharged and unfortunately died suddenly at home. An autopsy was conducted which showed a large tumour mass infiltrating the full wall thickness of the right ventricle with extension towards the right atria. The remaining heart structures were otherwise normal.Histological examination of the cardiac tumour showed a diffuse infiltration of atypical lymphoid cells with marked nuclear pleomorphism and mitotic activity. Immunohistochemistry confirmed that the atypical cells were lymphoid in origin and were strongly positive for CD45 and CD20. The proliferation index, determined using Mib-1 was focally high, and these findings were consistent with a diagnosis of diffuse large B-cell lymphoma.Primary cardiac lymphomas are rare and are associated with a high mortality, although some case reports have highlighted that early diagnosis and management can result in prolonged survival.     

Arrhythmogenic right ventricular cardiomyopathy: clinicopathologic correlation based on a revised definition of pathologic patterns.

Different morphologic features of arrhythmogenic right ventricular cardiomyopathy (ARVC) have been described. However, it is still unclear whether they correspond to distinct forms of the same disease. A pathologic study was performed on a series of ARVC (15 from heart transplant and 12 from autopsy) from 2 Italian referral university hospitals. Based on both myocellular features and the nature of myocardial replacement, hearts were divided into 2 groups: infiltrative, with a lacelike pattern of transmural fatty infiltration and strands of normal residual cardiomyocytes (n = 11); and cardiomyopathic, with massive myocardial replacement by fibro fatty tissue and cardiomyopathic changes (such as hypertrophy and myofibril loss) of residual cardiomyocytes (n = 16). Hearts from the infiltrative group were mostly obtained at autopsy of patients who died suddenly. Fatty substitution was limited almost exclusively to the right ventricle. Mitral valve dysplasia (prolapse or cleft) was frequently present. Hearts from the cardiomyopathic group came mainly from heart transplants for congestive heart failure. Fibro fatty replacement was more extensive, usually biventricular. Active myocarditis and features suggestive of myocardial transdifferentiation were also observed. Despite these differences in clinical outcome and morphologic features, patients from the 2 groups showed similar mean age, sex distribution, occurrence of threatening ventricular arrhythmias, and prevalence of family history of sudden death, arrhythmias, or cardiomyopathy. Infiltrative and cardiomyopathic patterns represent different clinical and pathologic subsets of ARVC. Myocellular features are an important clue in the distinction between the two entities. The differentiation between the 2 patterns is feasible on endomyocardial biopsy and could give important prognostic information.     

Primary cardiac fibroma of the right ventricle in an adult: report of one case

Cardiac fibroma is a rare primary benign cardiac tumor, especially in adults. It often occurs in the interventricular septum and free wall of the left ventricle and is solitary and space-occupying with clear boundaries. Here we report a 27-year-old male with a cardiac fibroma in the right ventricle, with extensive infiltrative growth. He was admitted to hospital with the complaint of exertional chest tightness, shortness of breath, hemoptysis, and edema of lower extremities. Ultrasound showed a large right ventricular mass blocking the outflow tract. The patient underwent palliative resection. Pathologic examination and Masson staining showed that collagen tissue proliferated and infiltrated myocardial fibers. The final diagnosis was cardiac fibroma.     

Cardiomyopathy characterized by abnormal accumulation of desmin-type intermediate filaments in cardiac muscle fibers. A case report and review of the literature

A 42-year-old Japanese male, who had been suffering from congestive heart failure and electrocardiographic abnormalities (A-V block, intraventricular conduction disturbance, ventricular tachycardia), died after a clinical course of 2 years and 1 month. Macroscopic investigation revealed dilation of the left ventricle and thickening of the right ventricular wall. The unique finding in this case was a circumferential fibrous scar in the median circular layer and outer oblique layer of the left ventricular wall. Biopsy and autopsy materials revealed diffuse loss of myofibrils in the central zone of cardiac muscle fibers, and replacement with aniline blue-positive homogeneous material (17-35% of the area of one muscle fiber). Electron microscopy revealed abnormal accumulation of fine filamentous material (7.5-25 nm in diameter), which was immunohistochemically proved to be desmin-type intermediate filament. Moreover, sarcoplasmic reticulum-like material was detected in the degenerated area. At autopsy, degeneration was detected all over the heart. The ventricular muscle fibers were more severely affected than the atrial muscle fibers. The conduction system was also affected, in some parts more severely than the surrounding ordinary muscle fibers. The pathogenesis of this disorder remains to be clarified.     

Sudden unexpected death in a 31-year-old man caused by arrhythmogenic right ventricular cardiomyopathy

A 31-year-old white man collapsed suddenly at a graduation ceremony and was pronounced dead after attempted resuscitation. He had no pertinent medical or familial history. Postmortem toxicologic studies showed negative results. A complete autopsy revealed a cardiac cause of death. Grossly, the right ventricular chamber was moderately to markedly dilated, and its free wall showed extensive myocardial adiposity. Microscopically, the right ventricular free wall consisted predominantly of adipose tissue, with only small subendocardial islands of hypertrophied myocytes and interstitial fibrosis. These features are characteristic of arrhythmogenic right ventricular cardiomyopathy. Moreover, Purkinje-like cells were observed among right ventricular myocytes and may have increased the likelihood of developing an arrhythmia. To our knowledge, this finding has not been previously emphasized. Because arrhythmogenic right ventricular cardiomyopathy accounts for 10% of cases of sudden unexpected cardiac death, recognition of this disease by pathologists is important, especially in cases of otherwise unexplained death in young persons.     

A case of overlap syndrome of systemic sclerosis and dermatomyositis with right ventricular dysplasia

We report a 39-year-old woman with overlap syndrome of systemic sclerosis and dermatomyositis who died of congestive heart failure. The pathologic findings of the heart included contraction band necrosis and myocardial fibrosis. Unique was the finding of remarkable replacement of the right ventricle with fatty tissue.     

Anthracycline induced myocardial damage. An analysis of 16 autopsy cases

The hearts of 16 autopsy cases with a past history of administration of anthracycline antitumor drugs (DNR, ADR and ACM) and a sign of cardiac failure were investigated morphologically. In macroscopic observation, both ventricles were more or less dilated with thinning of the ventricular wall. Mural thrombi were recognized in the left ventricle of 2 cases. Histologically, the myocardial lesions could be roughly classified into two groups, a) myocardial changes in cases with rapidly developed cardiac failure (acute form), and b) myocardial changes in cases with relatively slowly developed cardiac failure. In acute form, myocardial cells showed marked swelling with dilatation of central sarcoplasmic core, marked reduction of myofibrils, vacuolization of cytoplasm and enlargement of nucleus accompanied by distinct large nucleolus. Necrotic myocardial cells were scattered among these degenerative cells. These degenerative and necrotic cells were distributed diffusely in both ventricular walls, but were more frequent in the left ventricular wall than in the right one. Inflammatory cell infiltration was also recognized not only in the myocardium, but also in the endocardium and epicardium. In chronic form, on the other hand, atrophy and attenuation of myocardial cells with a hypereosinophilic change of the cytoplasm and an increase in number of brown pigments, and marked reduction of myocardial cells were most common findings. These changes of chronic form, however, could not be identified as the specific changes of anthracycline cardiotoxicity. Fibrosis was hardly seen in the myocardium of both acute and chronic forms.     

Right ventricular cardiomyopathy and sudden death in young people

From 1979 to 1986, we conducted postmortem studies of 60 persons under 35 years of age who had died suddenly in the Veneto Region of northeastern Italy. Unexpectedly, we found that 12 subjects--7 males and 5 females ranging in age from 13 to 30 years--had morphologic features of right ventricular cardiomyopathy. This disorder had not been diagnosed or suspected before the subjects died. In five cases, sudden death was the first sign of disease; the remaining seven subjects had a history of palpitation, syncopal episodes, or both, and in five of those seven, ventricular arrhythmias had previously been recorded on electrocardiographic examination. Ten of the subjects had died during exertion. At autopsy, the subjects' heart weights were normal or moderately increased. Two main histologic patterns were identified--a lipomatous transformation or a fibrolipomatous transformation of the right ventricular free wall (6 cases each); in all cases, the left ventricle was substantially spared. Signs of myocardial degeneration and necrosis, with or without inflammatory infiltrates, were occasionally observed. These findings indicate that right ventricular cardiomyopathy, the cause of which is still unknown, may be more frequent than previously thought. At least in this area of Italy, it may represent an important cause of sudden death among young people.     

Dilated cardiomyopathy in Noonan's syndrome: a first autopsy case

The first autopsy case of dilated cardiomyopathy associated with Noonan's syndrome is described. A 9-month-old girl with Noonan's syndrome died from cardiac failure. Autopsy showed biatrial and biventricular enlargement of the heart. The posterior half of the ventricular septum and right ventricular wall were remarkably thin. Other parts of the wall were nearly normal in thickness, but both ventricular cavities were dilated. Microscopically, the myocardium of both ventricles consisted of mainly abnormally thinned, elongated, and loosely arranged myocardial fibers lacking immunoreactivity to anti-dystrophin antibody. Myocardial disarray was not found except for where it normally existed. The abnormal changes of the myocardial fibers were considered to be primary. Common cardiomyopathy associated with Noonan's syndrome is a hypertrophic type. Various types of cardiovascular abnormality associated with Noonan's syndrome, including dilated cardiomyopathy, might be disclosed by further investigation and precise diagnosis of Noonan's syndrome.     

Cardiac tamponade due to rupture of a subepicardial aneurysm following myocardial infarction

A 71-year-old male died of cardiac tamponade due to cardiac rupture 22 days after onset of acute myocardial infarction. Autopsy revealed rupture of an unusual ventricular aneurysm characterized by abrupt interruption of the myocardium, a narrow neck, a thin fibrous outer wall partially showing myocardial fibers, and lack of adhesion between the epicardium and pericardium. A review of the literature revealed that 11 among 32 autopsy cases of false aneurysm showed a similar morphology to the present case, these being classifiable as subepicardial aneurysm.     

Isolated right ventricular myocardial infarction. A case report

Isolated right ventricular infarction is uncommon. A 73-year-old man without previous cardial complaints was admitted pulseless to hospital. An infarct of the left ventricle was suspected. Autopsy showed a fresh thrombus located in a small branch artery of the right coronary artery accompanied by a fresh infarction of the anterior free wall of the right ventricle. Only 8 cases of isolated right ventricular infarction located in the anterior free wall were found in a review of the literature of right ventricular infarction. The diagnosis, treatment and prognosis of right ventricular infarction are discussed.     

Hamartomas of mature cardiac myocytes: report of 7 new cases and review of literature

Only 8 cases of hamartomas of mature cardiac myocytes have been reported. The aim of the study was to describe 7 new cases and provide clinicopathologic correlation. Our anatomical pathology database was searched for all cases of cardiac hamartoma, of which 7 represented mature myocyte type. Medical records were reviewed for clinical information, and microscopic slides were evaluated for extent of characteristics. Five males and 2 females ranged in age from 6 months to 74 years (mean, 23 years). There were 11 ventricular hamartomas (8 left free wall, 2 right free wall, 1 septum). Death in 3 infants was unrelated to incidental hamartomas discovered at autopsy. A 10- and 16-year-old were asymptomatic but had abnormal electrocardiogram (ECG) results, which led to detection of cardiac masses by imaging studies. Two adult males had only mild coronary disease angiographically. The 57-year-old, who died suddenly, had a 7-year history of abnormal ECG results. The 74-year-old, who died after aortic surgery, had a 3-year history of chest discomfort. Their hamartomas were identified at autopsy and contributed to sudden death in 1. Microscopically, all hamartomas were involved by myocyte hypertrophy and disarray, without inflammation or calcification. Myocyte vacuolization and venular dilatation occurred only in the pediatric cases, and interstitial adipose tissue only affected 1 adult. In conclusion, hamartomas of mature cardiac myocytes may be detected at any age. They primarily affect males, arise predominantly in the left ventricle, are asymptomatic, may have nonspecific ECG findings, and rarely may be associated with sudden death. Microscopic findings in infants differ from older patients.     

A patient with ventricular tachycardia showing remarkable fatty infiltration and lymphocytic myocarditis in the right ventricular wall

A 14-year-old boy without overt heart disease underwent encircling ventriculotomy and cryoablation because of ventricular tachycardia resistant to antiarrhythmic therapy. Resection of the right ventricular wall with the origin of the ventricular tachycardia was performed on the basis of information obtained by epicardial mapping at operation, and histological examination showed unique findings of remarkable fatty infiltration and lymphocytic myocarditis.     

An autopsy case of infantile-onset vanishing white matter disease related to an EIF2B2 mutation (V85E) in a hemizygous region

We report a rare autopsy case of early infantile-onset vanishing white matter disease, with a submicroscopic deletion of 14q24.3, which included EIF2B2 and a missense mutation of EIF2B2 (V85E) of the remaining allele. The patient was a 4-year-old boy, who was found to have suddenly died during sleep. Physical and mental development began to deteriorate after convulsions at 10 month of age, and did not recover to baseline measurements. At autopsy, the brain showed a marked decrease in volume of white matter, with no typical cystic rarefaction. Histopathologically, the affected white matter showed diffuse loss of myelin fibers, meager astrogliosis with dysmorphic astrocytes, and loss of oligodendrocytes. Proliferative and apoptotic markers were negative for oligodendrocytes in the severely affected area. These findings may be related to the severity of the disease, and might be a feature of the EIF2B2 mutation pattern of the patient. Additionally, unusual fatty infiltration of both ventricles of the heart was found. These findings were suspected as early pathology of arrhythmogenic right ventricular cardiomyopathy due to characteristic gene mutation in the present case. In the present case, the defect EIF2B2 caused by hemizygosity may be related to early onset of the disease and the unusual pathological changes with vulnerability of oligodendrocytes and astrocytes, as well as cardiac abnormalities and sudden unexpected death.     

Multiple organ involvement in eosinophilic polymyositis: an autopsy report

This report describes autopsy findings of eosinophilic polymyositis in a 29-year-old woman. She complained of muscle pain and tenderness. A serum examination disclosed elevated creatine kinase, and echocardiography showed lowered cardiac function. Electromyography demonstrated myopathic potentials, and the skeletal muscle biopsy revealed degeneration of muscle fibers accompanying marked eosinophilic infiltration. Peripheral eosinophilia was not prominent. A systemic examination excluded possible etiologic factors, such as hypereosinophilic syndrome, collagen vascular diseases, or parasites. The patient died of heart failure after a 4-month clinical course. The autopsy disclosed a set of histological changes indicating tissue injuries, that is, loss of muscle fibers, interstitial fibrosis, and/or infiltrates of lymphocytes not only in the skeletal muscles and heart but also in various visceral organs. Eosinophils were sparsely scattered. These results indicate that the overrun of eosinophils underlying eosinophilic polymyositis, regardless of the presence of hypereosinophilic syndrome or other systemic disorders, could involve wide-ranging visceral organs.     

Fat in the right ventricle of the normal heart

AIMS: Fibrofatty replacement of the right ventricle wall, often with associated inflammation, is the hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), a rare but established cause of sudden cardiac death in young adults. Fatty infiltration of the right ventricle alone without fibrosis may also occur but its relation to sudden death is not well established. In this study we assessed the amount of epicardial and intramyocardial fat in the right ventricle of 'normal' hearts from subjects who had died of non-cardiac causes. METHODS AND RESULTS: Hearts (n = 148) were examined from 81 males and 67 females, with an age range of 6 months to 68 years, who had died of non-cardiac causes. The extent and distribution of right ventricular epicardial and intramyocardial fat was assessed macro- and microscopically, respectively. The majority of hearts (85%) contained at least some intramyocardial fat with significantly more fat replacement noted in the right ventricles of older subjects and in females than in males. There was no significant fibrosis or inflammation in any of the 148 cases. CONCLUSION: Variable amounts of intramyocardial fat may be seen in the right ventricle of subjects dying of non-cardiac related causes. Care should be taken not to confuse this relatively common simple fatty infiltration with ARVC.     

Cardiomyopathy Characterized by Abnormal Accumulation of Desmin-type Intermediate Filaments in Cardiac Muscle Fibers: A Case Report and Review of the Literature

A 42 year old Japanese male, who had been suffering from congestive heart failure and electrocardiographic abnormalities (A V block, intraventricular conduction disturbance, ventricular tachycardia), died after a clinical course of 2 years and 1 month. Macroscopic investigation revealed dilation of the left ventricle and thickening of the right ventricular wall. The unique finding in this case was a circumferential fibrous scar in the median circular layer and outer oblique layer of the left ventricular wall. Biopsy and autopsy materials revealed diffuse loss of myofibrils in the central zone of cardiac muscle fibers, and replacement with aniline blue positive homogeneous material (17–35% of the area of one muscle fiber). Electron microscopy revealed abnormal accumulation of fine filamentous material (7.5–25 nm in diameter), which was immunohisto-chemically proved to be desmin type intermediate filament. Moreover, sarcoplasmic reticulum like material was detected in the degenerated area. At autopsy, degeneration was detected all over the heart. The ventricular muscle fibers were more severely affected than the atrial muscle fibers. The conduction system was also affected, in some parts more severely than the surrounding ordinary muscle fibers. The pathogenesis of this disorder remains to be clarified. Acta Pathol Jpn 39: 266–273, 1989.