IDIOPATHIC RIGHT VENTRICULAR DILATION

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 F ontaine 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."     

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.     

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.     

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.     

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.     

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.     

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.     

Arrhythmogenic right ventricular cardiomyopathy versus fatty replacement of the right ventricle. An autopsy case report

We report an autopsy case of a cardiomyopathy characterized by fatty replacement of the right ventricular myocardium and compare its clinical and histologic characteristics with those of the arrhythmogenic right ventricular cardiomyopathy. A 39-year old male died suddenly in a hospital room. He had an alcoholic cirrhosis with ascitis, but the clinical examination and the biology showed no abnormalities explaining the death. Histologically, in the right ventricle, large areas of cardiomyocytes were replaced by fat, but there was no fibrosis. In contrast, fibrosis is present in association with fat in arrhythmogenic right ventricular cardiomyopathy. Fatty replacement of the right ventricle is likely to be a distinct entity. Right ventricular failure has been shown to be a possible complication. Sudden death is probably rare and is likely to occur when other arrhythmogenic factors are associated.     

Chronic right ventricular pressure overload results in a hyperplastic rather than a hypertrophic myocardial response

Myocardial hyperplasia is generally considered to occur only during fetal development. However, recent evidence suggests that this type of response may also be triggered by cardiac overload after birth. In congenital heart disease, loading conditions are frequently abnormal, thereby affecting ventricular function. We hypothesized that chronic right ventricular pressure overload imposed on neonatal hearts initiates a hyperplastic response in the right ventricular myocardium. To test this, young lambs (aged 2-3 weeks) underwent adjustable pulmonary artery banding to obtain peak right ventricular pressures equal to left ventricular pressures for 8 weeks. Transmural cardiac tissue samples from the right and left ventricles of five banded and five age-matched control animals were studied. We found that chronic right ventricular pressure overload resulted in a twofold increase in right-to-left ventricle wall thickness ratio. Morphometric right ventricular myocardial tissue analysis revealed no changes in tissue composition between the two groups; nor were right ventricular myocyte dimensions, relative number of binucleated myocytes, or myocardial DNA concentration significantly different from control values. In chronic pressure overloaded right ventricular myocardium, significantly (P < 0.01) more myocyte nuclei were positive for the proliferation marker proliferating cellular nuclear antigen than in control right ventricular myocardium. Chronic right ventricular pressure overload applied in neonatal sheep hearts results in a significant increase in right ventricular free wall thickness which is primarily the result of a hyperplastic myocardial response.     

Cardiac function in open-chest dogs after left to right ventricular shunting and right coronary artery occlusion

Patients with acquired ventricular septal defect (VSD) after myocardial infarction have a particularly bad prognosis if right ventricular function is severely impaired. The significance of an ischaemic right ventricular free wall on cardiac function during interventricular shunting was examined in open-chest dogs. An external interventricular shunt could be opened and closed at will, and by occlusion of the right coronary artery (RCA), a part of the right ventricular free wall was rendered ischaemic. Aortic flow decreased by 8 +/- 2% when the shunt was opened in the presence of a normal right ventricle, and by 16 +/- 2% (difference: P less than 0.05) in the presence of right ventricular ischaemia. Aortic flow fell by 19 +/- 3% when the RCA was occluded. Right ventricular dyskinesia was demonstrated after occlusion of RCA, by recording segment lengths in the right ventricular free wall. The dyskinesia was aggravated when the shunt was opened. The left ventricle exerted a 'negative' work on the ischaemic right ventricular free wall. Retention of blood in the right ventricle, with a subsequent decline in left ventricular filling and an almost unchanged interventricular shunting of blood, explain why aortic flow fell more when the shunt was opened in the presence of right ventricular ischaemia.     

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.     

Uhl's anomaly in the mink. Partial absence of the right atrial and ventricular myocardium

Congenital marked hypoplasia of the right atrial and ventricular myocardium (Uhl's anomaly), without other cardiac anomalies, was observed at autopsy in a mink. The animal died unexpectedly without previous symptoms at the age of 2 years, suggesting that the cause of sudden death was acute congestive heart failure. This cause demonstrates that this malformation can occur in species other than man. Embryologically, this anomaly might be due to myocardial injury to the right cardiogenic fold at a relatively early stage of embryogenesis.     

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.     

Correlation of magnetic resonance imaging with histopathology in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an asymptomatic cardiac disease characterized by fatty infiltration of the right ventricular myocardium and often results in sudden cardiac death. ARVD/C diagnosis includes the assessment of fatty infiltration, which can be achieved noninvasively with cardiovascular magnetic resonance (CMR). The standard CMR protocol places the signal-generating coil directly on the anterior chest wall and produces a nonspecific high intensity signal that obscures the high signal from fatty infiltration. The aim of this study was to determine whether increasing the coil-to-chest distance would improve identification of fatty infiltration. Thoraces from seven embalmed cadavers were imaged on a conventional 1.5 Tesla CMR scanner using the control protocol and an experimental protocol, with a 6 cm coil-to-chest distance. A representative axial MR image and corresponding gross section of the heart were analyzed in each case. Fatty infiltration was graded in a blinded fashion on the MR images with independent histopathologic assessment. In five of the seven cases, the experimental protocol provided a correlation between CMR and histopathology that was as good as or better than the control protocol. The experimental protocol was also better in preventing false positive diagnosis in cases of minimal infiltration. Thus, the experimental protocol showed a stronger correlation with histopathology than did the control protocol. Increasing the distance between the anterior surface coil and chest wall may improve classification of presence or absence of fatty infiltration in the right ventricular myocardium, potentially improving the noninvasive detection of ARVD/C with CMR.     

Hypoxic right ventricular cardiomyopathy. A morphological and pathogenetic study on the myocardial atrophy and fatty infiltration

The autopsy report of an asymptomatic, non familial cardiomyopathy with widespread fatty infiltration of the right ventricular wall in two alcoholic subjects, who were also heavy smokers and suffering from a serious laryngeal obstruction, led the Authors to investigate, on the basis of a thorough review of the literature, the possibility that hypoxia, alcoholism and smoke could have caused the development of the cardiac lesion. The presence of myocardial fatty infiltration is explained, under conditions of high-flow hypoxia, by the reduced fatty acid oxidation. The higher tissue levels of fatty acyl-CoA, fatty acyl-carnitine and alpha-glycerophosphate thereby lead to the increased conversion of the FFA into tissue lipids. Under hypoxic conditions there is also an increased polyols synthesis. The reduced conversion of dyacylglycerol into phosphatidic acid causes its tissutal increase and the interaction with fatty acyl-CoA to produce triacylglycerol and CoASH. In alcoholic patients reduced oxidation and increased FFA synthesis is sustained by the altered mitochondrial respiratory control and excess of acetate, with the consequent increase in acetyl-CoA, fatty acyl-CoA and alpha-glycerophosphate concentration. In addition, fatty acid ethyl esters normally absent in the myocardium are formed. The fact that, in hypoxic or alcoholic subjects with cardiomyopathy, an impaired myocardial contractility has been noted as the most relevant haemodynamic factor may be explained by both the reduced energy production following the decrease in aerobic glycolysis and FFA oxidation, and specific genetic changes that lead to both the production of a myosin with lower Ca2 + ATPase activity and a reduced protein (and therefore myofibrillar) synthesis. This fact can result in a severe atrophy of the cardiac myocytes. The lower their contractile activity, the more evident the process of atrophy. The lesion principally affects the right ventricle for both metabolic and anatomical reasons. It has been shown how, under normal conditions, the RV metabolism is suited to a relatively reduced O2 supply situation, with a high lactate dehydrogenase and alpha-hydroxybutiratedehydrogenase activity. It is more likely to be affected therefore whenever there is a chronic state of high-flow hypoxia. While alpha-HBDH allows the RV extensive utilization of ketone bodies as an energy source, its notable increase under hypoxic conditions further increases the synthesis of fatty acids and therefore fatty infiltration of the myocardium. The relatively lower capacity for oxygen extraction and lower tissue perfusion of the RV compared with the left ventricle make an adequate oxygen supply in the case of increased O2 demand even more difficult.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Double-outlet right ventricle without ventricular septal defect. A challenge to the embryologist? microscopic investigation

Summary A male infant died at the age of four weeks with the following clinical diagnosis: ventricular septal defect, patent ductus arteriosus, total heart block. Postmortem X-ray investigation of the heart-lung-specimen (in which the aorta and the pulmonary trunk had a normal interrelationship, with an approximately normal caliber) and succeeding dissection of the heart chambers, revealed that both great arteries took their origin from the right ventricle; there was no ventricular septal defect and consequently the non-functioning left ventricle was rudimentary; ductus arteriosus and foramen ovale were patent.The lack of a ventricular septal defect, from embryologic viewpoint an almost obligatory part of the well-known entity of double-outlet right ventricle, compelled an extensive microscopic serial investigation of the central part of the heart septum (with the adjacent parts of tricuspid and mitral valves) and the outflow tract of the right ventricle, including the arterial orifices and a paraseptal flap of the ventral right ventricular wall.In the ventricular septum, underneath the lower left aortic semilunar cusp, at the usual site of the pars membranacea, a large mass of chondroïd tissue was found, coherent with a vast area filled with inflammatory cells, calcification, necrosis and another, smaller-sized piece of chondroid tissue in the left ventricular septal wall. Furthermore, there was pronounced endocardial fibro-elastosis of the left ventricle, demarcated by a ring of numerous thick-walled arteries with narrowed or even occluded lumina, and with several conspicuous communicating channels toward the left ventricular cavity (arterio-luminal vessels).Most likely this malformation was the result of an embryonic inflammatory process, started before the 16 mm stage and involving the region of the foramen interventriculare so violently as to occlude it before the aorta had reached its left ventricle.The endocardial fibro-elastosis, the large arterio-ventricular communications and the coronary arterial lesions are attributed to the exceeding pressure in the blind left ventricular cavity and the associated ischemia in the left ventricular wall. The ischemia might also have contributed to the aberrant cartilage formation.The significance of the findings for the functional, embryological and anatomical distinction from the usual type of double-outlet ventricle is emphasized.