While splicing alterations in CAMK2D and PDLIM3 were detected across the LV, RV, and IVS in both DCM and ICM, other transcripts (MYL6, ESRRG, EYA4, and SORBS1) differed between DCM and ICM, with DCM showing broader chamber-wide splicing alterations.<h4>Conclusion</h4>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. Here, PDLIM3 is linked to familial dilated cardiomyopathy.