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Background: Next generation sequencing technology, coupled with population genetic databases, have made broad genetic evaluation relatively inexpensive and widely available. Our objective was to assess the prevalence of potentially damaging cancer and cardiac gene variants in advanced non-ischemic cardiomyopathy patients.

Methods: Explanted human heart tissue procured at LVAD placement was obtained from the University of Nebraska Medical Center Heart Tissue Bank. Genomic DNA was isolated from tissues and amplified by PCR using targeted ampliseq primer pools from an inherited disease panel. Individual libraries were amplified by emulsion PCR on Ion Sphere particles and sequencing was performed on a PGM sequencer (Ion torrent) using the Ion 316 chip. The Ion Torrent browser suite was used to map the reads and call the variants. The identified single nucleotide polymorphisms, insertions, and deletions were then annotated and characterized with ANNOVAR. Non-synonymous mutations with a population frequency of less than or equal to 1% were identified and analyzed utilizing an open source integrative genomics viewer. Amino acid substitution effects on protein function were determined by a bioinformatics algorithm. Myocardial recovery was defined as an improvement in EF to greater than 45% at three months post implant.

Results: Our sample population included 12 males and 2 females with an average age of 49 and an average EF at presentation of 17%. Damaging cardiac gene variants were present in 11/14 patients. Only 1 of the 11 patients with damaging cardiac gene variants improved their ejection fraction to greater than 45% post LVAD. Two of the 2 patients without mutations improved their ejection fraction to greater than 45%, p-value=.04. Nine of the 14 patients in this population had damaging oncogene mutations.

Conclusions: Damaging variants in cancer and cardiac genes are common in end-stage non-ischemic cardiomyopathy patients undergoing LVAD placement. Genetic variation likely contributes to disease progression and cancer risk.



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