THE  MORPHOLOGICAL STUDY OF A CASE OF CARDIAC SUDDEN DEATH  (Abstract): We report a case of cardiac sudden death to a 40 years old man without personal and familial cardiac history. The study was made on a necropsic biopsy specimen from the medico-legal laboratory. The diagnosis was made using routine histological techniques. The gross examination revealed a fibro-fatty free left ventricular wall myocardial replacement and a focal white thickening of the left ventricular endocardium. Histologically, we evidentiated a fibro-fatty myocardial replacement of the left ventricular suggesting an arrhythmogenic ventricular dysplasia of cardiomyopathic type without right ventricular involvement and an endomyocardial fibrosis supported by the presence of a subendocardial fibrosis, affecting internal one third of the myocardium. There were no evidence of coronarian and valvular lesions and hipertensive cardiac changes as well. The study revealed the morphological features defining a fibro-fatty myocardial replacement and an endomyocardial fibrosis evidentiating the case particular features as well. 
Key words: RESTRICTIVE CARDIOMYOPATHY, ARRHYTHMOGENIC VENTRICULAR CARDIOMYOPATHY, ENDOMYOCARDIAL FIBROSIS  

INTRODUCTION 
     Previously the cardiomyopathies (CMPs) were defined as “heart muscle disease of unknown cause” and were differentiated from specific heart muscle disease, of known cause (9). 
The CMPs are now classified by the dominant pathophysiology or, if possible, by etiopathogenetic factors and are defined as diseases of the myocardium associated with cardiac dysfunction. They are classified as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and arrhythmogenic cardiomyopathy. 
Dilated cardiomyopathy is characterized by dilatation and impaired contraction of the left ventricular (LV) or both ventricles, with no specific histology, presenting with heart failure, arrhythmias, throembolism, and sudden death.
    Hypertrophic cardiomyopathy is characterized by left and, or right ventricular hypertrophy, which is usually asymmetric and involves the interventricular septum, with normal or reduced left ventricular  volume, presenting with arrhythmias and premature sudden death. 
Restrictive cardiomyopathy (RCM) is characterized by restrictive filling and reduced diastolic volume of either or both ventricles with normal or near normal systolic function and wall thickness.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive fatty or fibro-fatty replacement of right ventricular myocardium, initially with typical regional and later global right and some LV involvement, with relative sparing of the septum, presenting with arrhythmias and sudden death, particularly in the young. 
We take in discussion the last two forms due to evidentiation in our case of morphological changes corresponding with the two-cardiomyopathy types. 
 

MATERIAL AND METHODS 
    The study was made on a necropsing biopsy specimen from a 40 years old male patient, who died suddenly to a high exertion, having no personal and familial cardiac history. On gross examination, we recorded the following features: heart weight, localization of the fibro-fatty myocardial replacement and endomyocardial thickening, and status of valves and coronary arteries. 
    The cardiac sections taken from different sites (aortic infundibulum, anterior, lateral and posterior wall of both ventricles at the middistance from base to apex and ventricular septum) were fixed in buffered 10 % formalin for 12 hours and were coloured with haematoxylin-eosin (HE) and elastic Van Gieson (EVG) stainings. 
 
 

RESULTS 
     The heart was obtained at autopsy of a man of 40 years old who died suddenly, having no proves of occurrence of threating ventricular arrhythmias (AR), or prevalence of family history of sudden death (SD), or cardiomyopathy (CMP). The cardiac size and weight was slight bigger due to left side morphological changes. 
On gross LV examination, the cardiac free wall appearance remembers of myocardial dysplasia, based on the external fibro-fatty wall replacement, appreciated on the LV cut section. The internal LV gross examination revealed a focal postero-basal LV endocardial thickening, involving the papillary muscles as well. The patchy fibrosis may be visible on the cut section involving the subendocardial area, the fibrous plaque extending into the underlying myocardium. 
    On histological examination we revealed a massive outer myocardial fibro-fatty replacement, extending from the epicardium toward the mid myocardium (fig.1). The residual myocytes often arranged in nests, encircled by fibrous tissue, show hypertrophy and degenerative changes, such as perinuclear vacuolization and myofibril loss (fig. 2). 
    The histological examination of the inner LV wall shows a stratified endomyocardial appearance, consisting from a superficial dense fibrin network containing focally blood cells (fig. 3), a middle layer of hyaline collagen, and an outer area composed by a dense fibrous tissue, nests of persisted capillaries and myocardial cells (fig. 4), without inflammatory cells. The rest of myocardial cells between collagen fibres may show degenerative changes (fig. 5). We appreciated this appearance as an evolutive organising process revealed by the presence of neovascularisation and myocytes entrapped in an extensive fibrous tissue. There is no valvular and vascular involvement, intramural and epicardial vessels having a relatively normal structure  (Fig. 6).

     
DISCUSSIONS AND CONCLUSIONS
     The present study has two main points of interest: it describes a RCM and ARVC particular case and it try to explain the unexpected sudden death in these circumstances. 
    The first morphological observation corresponds of an apparently LV myocardial dysplasia, also known as ARVC. The pathological diagnosis of ARVC is usually based on both gross and histological findings of fatty or fibro-fatty transmural myocardial replacement. This is defined as a substitution of myocardium from the epicardium to the endocardium, sparing the trabecular myocardium (10).
    This entity is characterized by d’Amati (3) as a progressive fibro-fatty replacement of the right ventricular myocardium, mainly the free wall, followed by rhythm disturbances as major clinical problem, initially with regional changes, which later become global, resulting right and some LV involvement, and with relative sparing of the septum. Di Gioia (2) appreciated that, although the familial form of ARVC disease has been documented and a gene defect was recently localised on chromosome 14q23-q24, the etiopathogenesis of the disease is still obscure. 
    We also noted the presentation with sudden death and possible with arrhythmia, particularly to a young man. The term arrythmogenic used by Richardson (10) emphasizes its electrical disorder, and the term ARVC, emphasizes partial and complete congenital absence of ventricular myocardium resulting from an erroneous process of embryonic development (dysplasia), but in our case contrary to literature dates, we registered a localized dysplastic form involving only the free LV wall. 
As well as Peliccia (3), we appreciated that the findings of adipose tissue in the heart may be an indication of pathologic process, secondary of an inflammatory lesion. So, Peliccia noted, that some clinical and morphological findings demonstrated acquired, progressive, frequent inflammatory character of disease, supporting the notion of chronic, continuous process of injury and repair. Receiving the pathogenesis of ARVC, in this case, we suppose an idiopathic (?viral) myocarditis as the most probable cause. 
    In agreement with Kavantzas (5) we appreciate apoptosis, as another possible cause of ARVC, leading to postnatal morphogenesis to “dysplasia” and paroxysmal arrhythmia. 
    Indeed, we can take in consideration 2 facts: firstly, a myocarditis (MC) with myocyte death leading to the appreciation of the disease as chronic MC, with some immune factors involved, and secondary, a genetic predisposition, including determinated spontaneous cell death (apoptosis). Both theories are in relation with the frequent familial occurrence, which suggest that underlying genetic factor may favor the onset and prognosis of the all involved phenomenon. 
    The inner appearance of endomyocardial fibrosis (EMF) suggests a RCM, characterized by the absence of cardiac hypertrophy or ventricular dilatation, in contrast to other major forms of CMPs. 
Ackerman (1) noted that the most common causes of RCM worldwide are amyloidosis, endocardial or endomyocardial fibrosis (Davies’s disease) and endomyocardial disease with eosinophilia (Löeffler’s disease). 
    The eosinophilic endomyocardial disease, also known as eosinophilic endomyocarditis (Loeffler’s disease) is a result of the toxic effects of hypereosinophilia of different causes. Virmani  (12) noted that the mechanism of the endomyocardial damage secondary to toxic products within eosinophil granules is poorly understood but may involve tissue damage by major basic and cationic proteins, while Liapis (7) considered that there are likely unknown factors other than hypereosinophilia that are responsible for the toxic endomyocardial damage, because some patients with hypereosinophilia do not develop cardiac tissue damage. 
    However, Edward (4) appreciated that endomyocardial fibrosis may represent an end stage of eosinophilic disease or, the result of chronic low levels of hypereosinophilia related to parasitic infection, but we can not demonstrate it, because there are no clinical and laboratory dates for supporting it, although this hypothesis is the most probable involved cause.
Grossly, Olsen (8) appreciated in EMF the variable distribution of the thickened endocardium involving LV, RV, or both ventricles, while we described only a mild increased heart weight and localized endomyocardial fibrous plaque present in only one ventricle, at the level of postero-basal wall. Contrary to Olsen dates, in our case, the involved LV was relatively normal in size, and no constricted or associated with dilated atria. Similarly with Kushwaha cases (6), the endocardium was of several mm thickness, presenting an organising thrombus superimposed on it.
    Olsen (8) noted that the disease passes through three stages: the first, acute necrotic phase with inflammatory reaction and variable number of eosinophils, the second stage, presenting a thrombus formation, which represents the complication of eosinophilic endomiocarditis and the third, fibrotic stage, representing the last phase with fibrosis and fibrous septa extending into the underlying myocardium. Olsen has suggested that acquired eosinophilia leads to Loeffler’s endocarditis and endomyocardial fibrosis. These two entities belong to the same disease process, because the degranulation of eosinophils is producing myocarditis (MC) with non-specific fibrosis at the end of the process.  
    Histologically, in agreement with Roberts (9), who described 3 stages in the evolution of eosinophilic endomyocardial disease, we also observed the phasic disease evolution, but corresponding to the passing from the second stage to the third stage, the predominant finding being fibrosis without inflammatory cells. The myocardial fibres between the fibrous septa may show degenerative changes, as in other CMPs. We didn’t observe a coexistent valvular involvement, described by Roberts in his papers, and no morphological evidence of coronarian lesions as well.
    Whatever the initial event should be, the progressive pathogenic process lead to the development of two cardiac morphological changes corresponding at two CMP types, this kind of association being no recorded until now in the literature.
 

REFFERENCES 
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