This invention relates to methods and compositions for the treatment and diagnosis of cardiac diseases and disorders, such as cardiac hypertrophy, myocardial infarction, stroke, arteriosclerosis and heart failure. The invention also relates to methods and compositions for the treatment of fibrosis-related diseases as well as methods and compositions for reducing apoptosis, increasing ST2L signaling, decreasing NF-κB activation, decreasing IκBα phosphorylation, decreasing P38MAPK phosphorylation, decreasing JNK phosphorylation, decreasing reactive oxygen species generation, decreasing macrophage infiltration and/or decreasing the expression of hypertrophic genes. More specifically, the invention relates to IL-33 and/or soluble ST2 inhibiting agents for use in the methods and compositions provided.