The study by Corrado et al.  demonstrated that electroanatomic low-amplitude areas were significantly associated with the histopathologic finding of myocyte loss and fibrofatty replacement at EMB, thus confirming that RV loss of voltage reflects the replacement of action potential-generating myocardial tissue with electrically silent fibrofatty tissue. Moreover, there was a concordance between the presence and location of RV low-voltage areas identified by electroanatomic map and akinetic/dyskinetic regions detected by echocardiography and/or angiography. The low-amplitude electrogram values were distinctively recorded in the RV free wall, predominantly involving the anterolateral, infundibular, and infer-obasal regions, and spared the interventricular septum (Fig. 17.1). Such a special distribution is similar to that observed at autopsy in the hearts of patients with ARVC/D, in whom most severe RV myocardial atrophy and wall aneurysms are found predominantly in the anteroinfundibular free wall and underneath the tricuspid valve [2,4, 5].
The majority of ARVC/D patients with an abnormal electroanatomic voltage mapping reported by Corrado et al.  had a familial form of disease. This find ing is consistent with the genetic background of the disease which has been demonstrated in over 50% of ARVC/D patients, with either autosomal or, less frequently, recessive pattern of inheritance and age-related and variable penetrance . There are similarities between the etiopathogenesis of familial ARVC/D and Duchenne's and Becker's skeletal muscle dystrophies, in which the progressive loss of muscle is the result of a genetically-determined ultrastructural defect . In patients with ARVC/D, the defective genes encode for proteins involved in desmosome and intercellular junctions such as plakoglobin, desmoplakin, plakophilin-2, and desmoglein-2. . It has been suggested that under mechanical stress, abnormal desmo-somes incorporating defective proteins may lead to detachment and death of myocytes at the intercalated disc and as a consequence, there is a progressive loss of muscle and subsequent fibrofatty replacement .
In the above study, 35% of patients who fulfilled the Task Force diagnostic criteria for ARVC/D by noninvasive evaluation, showed evidence neither of electroanatomic low-voltage regions nor of fibrofatty replacement at voltage mapping and EMB. Comparison of mapping results and clinical patient characteristics in the present study suggests that the finding of normal RV voltage values characterizes a distinct subgroup of patients with a peculiar etiopathogenetic, clinical, and prognostic profile. Patients with normal and abnormal electroanatomic voltage mapping did not differ with regard to mean age and mean time interval between symptoms onset and time of electroanatomic evaluation. Moreover, extent of precordial ECG repo-larization changes and severity of morphofunctional abnormalities such as global or segmental right ventricular dilatation/dysfunction, RV wall motion abnormalities, and LV involvement, which were detected by echocardiography/angiography were similar in both subgroups of patients. These findings argue against the possibility that failure to detect electroanatomic RV low-voltage areas reflects early stages or minor variants of ARVC/D. Of note, our results differ from those of other studies in which all patients with suspect ARVC/D had a positive voltage mapping . This discrepancy may be explained by different study populations with different prevalence of inflammatory car-diomyopathy as well as by non comparable study design and diagnostic algorithms, with histopathologic data provided only by our investigation.
Myocarditis Mimicking ARVC/D
All patients with a normal electroanatomic voltage mapping were "sporadic" cases, showing neither a familial history of sudden death nor evidence of familial ARVC/D at clinical screening of nuclear family members. It is noteworthy that, all but one patient showed histopathologic changes consistent with the diagnosis of myocarditis at EMB. In the majority of patients, the association between active inflammatory changes and focal replacement fibrosis suggested either a persistent or recurrent myocardial inflammatory process at different stages of healing [31-33].
There is both experimental and clinical evidence that myocarditis can mimic ARVC/D. Some experimental myocarditis is exclusively limited to the right ventricle. Matsumori and Kawai reported selective RV chronic perimyocarditis in BALB/C mice after Coxsackie virus B3 infection . Chronic myocarditis clinically mimicking ARVC/D has been reported in patients who do not have familial disease [35, 36]. Recently, Frustaci et al.  analyzed the EMB histologic findings in 30 patients (19 males and eleven females, with a mean age of 27±10 years) with nonfamilial ARVC/D and found diagnostic histo-logic features of myocarditis according to Dallas criteria (in the absence of significant fibrofatty myocardial atrophy) in 70% of the patients. No differences between patients with myocarditis and those with ARVC/D with regard to ECG/arrhythmic pattern and structural/functional RV abnormalities were observed, a finding in keeping with results of the present study.
In this subset of patients with normal mapping and no apparent regional scar the finding of wall motion abnormalities observed at echocardiographic and an-giographic studies can be explained by the inflammatory cardiomyopathy in itself. Segmental wall motion abnormalities (hypokinetic, akinetic or diskinetic areas) are not so uncommon features of inflammatory cardiomyopathy and there are several studies in which myocarditis is reported to mimic myocardial infarction with a pattern of asynergic areas (involving either the left or the right ventricle) and require coronary angiography and endomyocardial biopsy for differential diagnosis [37, 38]. This finding of akinetic/diskinetic ventricular regions (contrasting with areas of relatively preserved contraction) in the absence of regional myocardial scar has been explained by the nonhomo-geneous, patchy myocardial involvement of the my-ocardial inflammatory process .
ARVC/D and Dilated Cardiomyopathy
There are similarities between ARVC/D and dilated cardiomyopathy in terms of ventricular dilatation/
dysfunction, progression to congestive heart failure, and risk of sudden arrhythmic death that may suggest a similar spectrum of etiopathogenetic mechanisms. Dilated cardiomyopathy represents a common expression of myocardial damage that may be produced by either genetically-determined or acquired myocardial insults [38, 39]. At least 30% of cases of dilated cardiomyopathy are familial and linked to genetic defects in structural heart proteins, while a significant percentage of the remaining sporadic cases recognize a viral and/or immune myocarditis patho-genesis. Likewise, ARVC/D includes both familial cases, characterized by a distinctive loss of myocardium reflecting a genetically-determined dys-trophic process, and sporadic form that, in part, may be the result of an inflammatory myocardial disease predominantly involving the RV . Electroanatomic voltage mapping combined with EMB may detect these pathobiologic features, thus allowing a differential diagnosis between inherited and inflammatory forms.
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