Methods for the prevention or treatment of heart failure

Abstract

The disclosure provides methods of preventing or treating heart failure in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof.

1 . A method of treating heart failure or hypertensive cardiomyopathy in a mammalian subject, comprising administering to the mammalian subject in need thereof a therapeutically effective amount of the peptide D-Arg-2′6′-Dmt-Lys-Phe-NH 2  or Phe-D-Arg-Phe-Lys-NH 2.    
     
     
         2 . The method of  claim 1 , wherein the peptide is D-Arg-2′6′-Dmt-Lys-Phe-NH 2 . 
     
     
         3 . The method of  claim 1 , wherein the peptide is Phe-D-Arg-Phe-Lys-NH 2 . 
     
     
         4 . The method of  claim 1 , wherein the subject is suffering from heart failure. 
     
     
         5 . The method of  claim 4 , wherein the heart failure results from hypertension; ischemic heart disease; exposure to a cardiotoxic compound; myocarditis; thyroid disease; viral infection; gingivitis; drug abuse; alcohol abuse; pericarditis; atherosclerosis; vascular disease; hypertrophic cardiomyopathy; acute myocardial infarction; left ventricular systolic dysfunction; coronary bypass surgery; starvation; an eating disorder; or a genetic defect. 
     
     
         6 . The method of  claim 1 , wherein the subject is suffering hypertensive cardiomyopathy. 
     
     
         7 . The method of  claim 1 , wherein myocardial contractility and cardiac output in the subject administered the peptide are increased compared to a control subject not administered the peptide. 
     
     
         8 . The method of  claim 7 , wherein the myocardial contractility and cardiac output in the subject are increased at least 10% compared to a control subject not administered the peptide. 
     
     
         9 . The method of  claim 1 , wherein the subject is a human. 
     
     
         10 . The method of  claim 1 , wherein the peptide is administered orally, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly. 
     
     
         11 . The method of  claim 1 , further comprising separately, sequentially or simultaneously administering a cardiovascular agent to the subject. 
     
     
         12 . The method of  claim 11 , wherein the cardiovascular agent is selected from the group consisting of: an anti-arrhthymia agent, a vasodilator, an anti-anginal agent, a corticosteroid, a cardioglycoside, a diuretic, a sedative, an angiotensin converting enzyme (ACE) inhibitor, an angiotensin II antagonist, a thrombolytic agent, a calcium channel blocker, a throboxane receptor antagonist, a radical scavenger, an anti-platelet drug, a β-adrenaline receptor blocking drug, α-receptor blocking drug, a sympathetic nerve inhibitor, a digitalis formulation, an inotrope, and an antihyperlipidemic drug. 
     
     
         13 . A method for increasing myocardial contractility and cardiac output in a subject suffering from heart failure or hypertensive cardiomyopathy comprising administering to the subject a therapeutically effective amount of the peptide D-Arg-2′6′-Dmt-Lys-Phe-NH 2  or Phe-D-Arg-Phe-Lys-NH 2 .