Abstract: The present invention relates to treating or ameliorating heart disease associated with poor myocardial performance, e.g., diabetic cardiomyopathy and associated disorders, particularly to treating, preventing or ameliorating such disorders through inhibition of O-GlcNAcylation and/or increased activity of O-GlnNAcase. The invention provides vectors for gene transfer of O-GlnNAcase. In one aspect, the invention provides cells, vectors, formulations comprising them and methods of using them, for the gene transfer of the human O-GlnNAcase gene, e.g., to treat conditions and diseases associated with impaired cardiac contractility, such as that, found associated with diabetic cardiomyopathy. In another aspect, the invention provides non-human transgenic animals and host cells comprising genetically engineered cells having increased activity of O-GlnNAcase.