Shared splicing dysregulation in heart failure associated with dilated and ischemic cardiomyopathy and spatial specificity across cardiac regions

This study presents the first multi-chamber analysis of splicing in human heart failure, revealing a set of splicing events commonly dysregulated in DCM and ICM. These findings support the notion that splicing dysregulation can be a shared molecular response to advanced cardiac remodeling, rather than a driver of etiology-specific pathology. We further uncovered distinct spatial patterns: in DCM, splicing alterations were consistently observed across all cardiac chambers, likely reflecting diffuse myocardial involvement. In contrast, certain splicing changes in ICM were restricted to the left ventricle, consistent with the focal nature of ischemic injury.