preprints.org > medicine and pharmacology > cardiac and cardiovascular systems > doi: 10.20944/preprints202405.1195.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 16 May 2024 / Approved: 17 May 2024 / Online: 17 May 2024 (15:36:19 CEST)

Nonischemic dilated cardiomyopathy (DCM) is a complex cardiovascular condition often characterized by genetic pathogenesis. Comprehensive genetic testing has become a crucial aspect of DCM diagnosis and management, offering insights into prognosis and the identification of at-risk individuals. This case series and mini literature review examines the diagnostic and therapeutic dimensions of DCM, emphasizing the role of genetic evaluation. We delve into distinct genetic pathways associated with DCM and their pathogenetic mechanisms, emphasizing the evolving significance of genetic markers, particularly in cases where arrhythmia risk is heightened. The historical reliance on cardiac morphology to subtype cardiomyopathies is being complemented by the identification of genetic variants, further refining DCM subtypes, and aiding in clinical management.The giant sarcomere protein, titin, is a pivotal determinant of cardiomyocyte stiffness and plays a crucial role in cardiac strain sensing. Titin's extensive size and complexity make it susceptible to dysregulation, which has far-reaching consequences in cardiac disorders. This case series with a literature review explores the molecular mechanisms governing titin-based forces in both health and disease. It highlights the influence of isoform diversity and post-translational modifications on myocardial stiffness and contractility. In the context of cardiac diseases, we discuss how titin properties are altered, focusing on changes in titin stiffness and protein quality control. Notably, we address the pathomechanisms associated with truncation in the titin gene (TTN) in human cardiomyopathy, shedding light on potential therapeutic approaches for conditions such as HFpEF and TTN-truncation cardiomyopathy.This comprehensive understanding of DCM and Titin’s role in cardiac physiology and pathology provides a solid foundation for addressing cases like that of our patients, who were presented with features of heart failure and arrhythmias. Despite immediate and extensive resuscitative measures, the patient's protracted response to the treatment raised questions about the potential underlying genetic factors contributing to their clinical presentation. These cases underscore the importance of genetic evaluation in unraveling the complexity of cardiomyopathies, ultimately enhancing our ability to manage and treat such challenging cases.

cardiology; dilated cardiomyopathy; titin; ischemic cardiomyopathy

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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