Diagnostic Differentiation Between Arrhythmogenic Cardiomyopathy and Athlete’s Heart by Using Imaging

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death (SCD) in youth and athletes. In the last decade, several studies focused on right ventricular (RV) remodeling in athletes and revealed that features of the physiological adaptation of the right heart to training, such as RV dilation, may overlap with those of ARVC. Therefore, a careful multiparametric evaluation is required for differential diagnosis in order to avoid false diagnosis of ARVC or, in contrast, fail to identify the risk of causing SCD. This review summarizes physiological adaptation of the RV to exercise and describes features that could help distinguishing between athlete’s heart and ARVC.     

以猝死首发表现的ARVC 1例

致心律失常性右室心肌病(arrhythmogenic right ventricular cardiomyopathy,ARVC)是一种原因不明的心肌疾病,病变主要累及右室,临床主要表现为室性心律失常或猝死,为一少见病,国内经病理确诊者少见,最近我们遇到1例,现报告如下。     

Multiecho dixon fat and water separation method for detecting fibrofatty infiltration in the myocardium

Conventional approaches for fat and water discrimination based on chemical‐shift fat suppression have reduced ability to characterize fatty infiltration due to poor contrast of microscopic fat. The multiecho Dixon approach to water and fat separation has advantages over chemical‐shift fat suppression: 1) water and fat images can be acquired in a single breathhold, avoiding misregistration; 2) fat has positive contrast; 3) the method is compatible with precontrast and late‐enhancement imaging, 4) less susceptible to partial‐volume effects, and 5) robust in the presence of background field variation; and 6) for the bandwidth implemented, chemical‐shift artifact is decreased. The proposed technique was applied successfully in all 28 patients studied. This included 10 studies with indication of coronary artery disease (CAD), of which four cases with chronic myocardial infarction (MI) exhibited fatty infiltration; 13 studies to rule out arrhythmogenic right ventricular cardiomyopathy (ARVC), of which there were three cases with fibrofatty infiltration and two confirmed with ARVC; and five cases of cardiac masses (two lipomas). The precontrast contrast‐to‐noise ratio (CNR) of intramyocardial fat was greatly improved, by 240% relative to conventional fat suppression. For the parameters implemented, the signal‐to‐noise ratio (SNR) was decreased by 30% relative to conventional late enhancement. The multiecho Dixon method for fat and water separation provides a sensitive means of detecting intramyocardial fat with positive signal contrast. Magn Reson Med 61:215–221, 2009. © 2008 Wiley‐Liss, Inc.     

The p.A897KfsX4 frameshift variation in desmocollin-2 is not a causative mutation in arrhythmogenic right ventricular cardiomyopathy

Mutations in genes encoding desmosomal proteins have been reported to cause arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), an autosomal-dominant disease characterised by progressive myocardial atrophy with fibro-fatty replacement. We screened 112 ARVC/D probands for mutations in desmocollin-2 (DSC2) gene and detected two different amino-acid substitutions (p.E102K, p.I345T) and a frameshift variation (p.A897KfsX4) in 7 (6.2%) patients. DSC2a variant p.A897KfsX4, previously reported as a p.E896fsX900 mutation, was identified in five unrelated probands. Four of them were found to carry one or two mutations in different ARVC/D genes. Unexpectedly, p.A897KfsX4 variation was also found in 6 (1.5%) out of 400 control chromosomes. In vitro functional studies showed that, unlike wild-type DSC2a, this C-terminal mutated protein was localised in the cytoplasm. p.A897KfsX4 variation affects the last five amino acids of the DSC2a isoform but not of DSC2b. In contrast with what we found in other human tissues, in the heart DSC2b is more expressed than DSC2a, suggesting that relative deficiency of DSC2a might be compensated by isoform b. In conclusion, DSC2 gene mutations are not frequently involved in ARVC/D. The p.A897KfsX4 variation, identified in several Italian healthy control subjects, which affects only one of the two DSC2 isoforms, may be considered a rare variant, though possibly affecting phenotypic expression of concomitant ARVC/D mutations.     

Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy

A single report has associated mutations in TMEM43 (LUMA) with a distinctive form of arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed at performing mutational analysis of the gene and characterizing the associated immunohistochemical features. Sixty-five unrelated patients (55 fulfilling Task Force criteria and 10 borderline cases) were screened for mutations in TMEM43. Immunohistochemistry with anti-TMEM43, anti-plakoglobin, anti-plakophilin-2, anti-connexin-43, and anti-emerin antibodies was performed on myocardium from TMEM43-positive patients (n = 3) and healthy controls (n = 3). The genetic screening identified heterozygous variants in two families: one reported mutation (c.1073C> T; in two related patients) and one novel variant (c.705+ 7G> A; in one patient) of unknown significance. All three patients fulfilled Task Force criteria and did not carry mutations in any other ARVC-related gene. Immunostaining with TMEM43 antibody showed intense staining of the sarcolemma. The signal level was reduced in all the three TMEM43-positive patients. Immunostaining with plakoglobin-specific antibody also showed reduced signal levels in the three carriers. All patients displayed a similar immunoreactive signal for plakophilin-2, connexin-43, and emerin. In conclusion, two TMEM43 sequence variants were identified in this Danish ARVC cohort. Evaluation of the expression of TMEM43 showed a unique cardiac localization. The immunoreactive signal for the desmosomal protein plakoglobin was reduced in mutation carriers. The TMEM43 gene underlies a distinctive form of ARVC which may share a final common pathway with desmosome-associated ARVC.