Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment.
BACKGROUND
The prevalence of primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis) is reaching epidemic levels worldwide. Iron-overload leads to excessive iron deposition in a wide variety of tissues, including the heart and endocrine tissues.


RESULTS
Iron-overload cardiomyopathy is the primary determinant of survival in patients with secondary iron overload, while also being a leading cause of morbidity and mortality in patients with primary hemochromatosis. Iron-induced cardiovascular injury also occurs in acute iron toxicosis (iron poisoning), myocardial ischemia-reperfusion injury, cardiomyopathy associated with Friedreich ataxia, and vascular dysfunction. The mainstay therapies for iron overload associated with primary hemochromatosis and secondary iron overload is phlebotomy and iron chelation therapy, respectively. L-type Ca(2+) channels provide a high-capacity pathway for ferrous (Fe(2+)) uptake into cardiomyocytes in iron-overload conditions; calcium channel blockers may represent a new therapeutic tool to reduce the toxic effects of excess iron.


CONCLUSIONS
Iron-overload cardiomyopathy is a an important and potentially reversible cause of heart failure at an international scale and involves diastolic dysfunction, increased susceptibility to arrhythmias and a late-stage dilated cardiomyopathy. The early diagnosis of iron-overload cardiomyopathy is critical since the cardiac dysfunction is reversible if effective therapy is introduced before the onset of overt heart failure.
Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Colm J
CJ
Murphy
Gavin Y
GY
Oudit
D000740:Anemia / Q000503:physiopathology; D000975:Antioxidants / Q000627:therapeutic use; D001706:Biopsy; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology*; D015913:Chelation Therapy; D004452:Echocardiography; D004699:Endocardium / Q000473:pathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005293:Ferritins / Q000097:blood; D005820:Genetic Testing; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D019190:Iron Overload / Q000503:physiopathology* / Q000628:therapy*; D019028:Magnetic Resonance Imaging, Cine; D020097:Natriuretic Peptide, Brain / Q000097:blood; D018962:Phlebotomy; D014168:Transferrin / Q000032:analysis; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology
D000975:Antioxidants; D002121:Calcium Channel Blockers; D014168:Transferrin; D020097:Natriuretic Peptide, Brain; D005293:Ferritins