TAC1 and heart failure: It should be noted, however, that except for the short-term beneficial effects in the ischemic myocardium, substance P may play a damaging long-term role in adverse myocardial remodeling and heart failure as prolonged increase in substance P can induce detrimental responses in the form of inflammation, apoptosis, matrix metalloproteinase (MMP) activation, and changes to the extracellular matrix as observed in myocarditis, volume overload, and magnesium deficiency (Dehlin and Levick, 2014).