Contemporary and Future Approaches to Inherited Cardiomyopathies

Dear Colleagues,

Inherited cardiomyopathies are predominantly caused by variants in genes encoding sarcomeric, cytoskeletal, desmosome, nuclear envelope, enzymes or other proteins (such as transthyretin). While next-generation sequencing has vastly improved our ability to detect these variants, translating genetic insights into meaningful clinical outcomes remains challenging due to incomplete penetrance and environmental factors. This issue of Cardiogenetics focuses on the evolving understanding of the genetic, immunologic, and therapeutic dimensions of inherited cardiomyopathies.

Emerging evidence underscores the active role of the innate and acquired immune system in modulating disease onset and progression. Inflammatory pathways, immune cell infiltration, and autoimmune mechanisms may act as critical modifiers, particularly during arrhythmogenic phases. These findings could potentially lead to immune-targeted interventions, either alone or in combination with genetic therapies, especially in cases with active myocardial inflammation or immune dysregulation.

Gene therapy represents one of the most promising frontiers in this field. Approaches based on adenoviral (AAV) vectors for gene therapy are rapidly progressing toward clinical application. However, these strategies are intimately linked to the host immune response, which can impact both efficacy and safety. Immune recognition of viral capsids or transgene products may elicit neutralizing antibodies or cytotoxic responses, necessitating careful patient selection and immunomodulatory strategies. Beyond AAVs, other genome editing tools (e.g., CRISPR, base and prime editors) have emerged, especially for suppressing the abnormal proteins production or to correct the variant genome sequence.

This issue emphasizes the need for an integrated perspective that considers the genetic substrate, the phenotypic spectrum, and immune mechanisms when designing therapeutic strategies. By aligning precision diagnostics with immune-aware, gene-based therapies, the field moves closer to delivering transformative, individualized treatments for inherited cardiomyopathies.

Dr. Michele Ciabatti
Dr. Alessia Argiro
Guest Editors

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