Impaired Cardiomyocyte Maturation Leading to DCM: A Case Report and Literature Review.

Background: The maturation of cardiomyocytes is a rapidly evolving area of research within the field of cardiovascular medicine. Understanding the molecular mechanisms underlying cardiomyocyte maturation is essential to advancing our knowledge of the underlying causes of cardiovascular disease. Impaired maturation can lead to the development of cardiomyopathy, particularly dilated cardiomyopathy (DCM). Recent studies have confirmed the involvement of the ACTN2 and RYR2 genes in the maturation process, facilitating the functional maturation of the sarcomere and calcium handling. Defective sarcomere and electrophysiological maturation have been linked to severe forms of cardiomyopathy. This report presents a rare case of DCM with myocardial non-compaction, probably resulting from allelic collapse of both the ACTN2 and RYR2 genes. Case Presentation: The proband in this case was a four-year-old male child who presented with a recurrent and aggressive reduction in activity tolerance, decreased ingestion volume, and profuse sweating. Electrocardiography revealed significant ST-T segment depression (II, III, aVF V3-V6 ST segment depression >0.05 mV with inverted T-waves). Echocardiography showed an enlarged left ventricle and marked myocardial non-compaction. Cardiac magnetic resonance imaging revealed increased left ventricular trabeculae, an enlarged left ventricle, and a reduced ejection fraction. Whole exome sequencing revealed a restricted genomic depletion in the 1q43 region (chr1:236,686,454-237,833,988/Hg38), encompassing the coding genes ACTN2, MTR, and RYR2. The identified variant resulted in heterozygous variations in these three genes, with the ACTN2 g.236,686,454-236,764,631_del and RYR2 g.237,402,134-237,833,988_del variants being the dominant contributors to the induction of cardiomyopathy. The patient was finally diagnosed with DCM and left ventricular myocardial non-compaction. Conclusions: This study reports a rare case of DCM with myocardial non-compaction caused by the allelic collapse of the ACTN2 and RYR2 genes. This case provides the first human validation of the critical role of cardiomyocyte maturation in maintaining cardiac function and stability and confirms the key findings of previous experimental research conducted by our group. This report emphasizes the connection between genes involved in regulating the maturation of cardiomyocytes and the development of cardiomyopathy.

MRI characteristics of primary dilated cardiomyopathy and isolated left ventricular non-compaction / 中国医学影像技术

Objective To explore the MRI characterisitics of primary dilated cardiomyopathy and isolated left ventricular non-compaction.Methods The patients who were diagnosed as primary dilated cardiomyopathy (n=18) and isolated left ventricular non-compaction (n=10) were enrolled,and the MRI was performed.The thickness of non-compaction myocardium (NC),compaction myocardium (C) in end-diastole,the feature of movement of myocardium,the number of non-compaction segment,the fraction shortening of non-compaction and the distribution were compared.Results Totally 823 segments were analyzed in primary dilated cardiomyopathy,in which 124 segments were non-compaction myocardium;397 segments were analyzed in isolated left ventricular non-compaction,in which 115 segments were non-compaction myocardium.The NC,NC/C,NC/(NC+C),and the fraction shortening of the isolated left ventricular non-compaction patients were higher than those of primary dilated cardiomyopathy patients (all P＜0.05).The features of distribution showed that the apical segment was mostly involved,and the basal segment was less involved or hardly involved.The anterior and lateral segments were more involved in the free wall,the septal was less involved.Conclusion The MRI characteristics of primary dilated cardiomyopathy and isolated left ventricular non-compaction are different,especially in the distribution,non compacted segments,NC and NC/C,which is important for diagnosis and differential diagnosis of the two diseases.