Pathophysiology of iron overload cardiomyopathy:
Cardiac iron is regulated through transferrin-mediated uptake mechanisms. During iron overload, transferrin is saturated, and non-transferrin-bound iron is released into the circulation and enters cardiac myocytes in the ferrous form through L-type calcium channels.
Iron is then bound to ferritin and transported to lysosomes for degradation and long-term storage in the cardiac myocyte. When the antioxidant capacity of the cell is exceeded, iron is catalyzed by the rapid Fenton reaction producing hydroxyl ions, which is an extremely reactive free radical species that causes cell damage and death.
Pathologic iron deposition begins initially within the epicardium and extends to the myocardium and then the endocardium, which helps explain the preservation of systolic function until very late in the disease. Thus, iron deposition is probably due to reversible storage than infiltration.
Presentation of iron overload cardiomyopathy:
Patients may be asymptomatic or present with exertional shortness of breath.
Severely overloaded patients develop advanced heart failure if left untreated, and average survival is less than a year.
Paroxysmal atrial fibrillation is the most common form of arrhythmia seen and is invariably associated with myocardial damage.