In the latter case, the disease creates blockages in the hearts blood supply, leading to tissue death which causes other areas of the heart to work harder, causing the heart to expand in size.Other possible causes include:

Heart valve disease
Cardiomyopathy (disease of the heart muscle)
Pulmonary hypertension
Pericardial effusion (fluid around the heart)
Thyroid Disorders
Hemochromatosis (excessive iron in the blood)
Amyloidosis
Chagas disease, an important cause of cardiomegaly in Latin America
Viral infection of the heart
Pregnancy, with enlarged heart developing around the time of delivery (peripartum cardiomyopathy)
Kidney disease requiring dialysis
Alcohol or cocaine abuse
HIV infection
Diabetes

Mechanism
Cardiomegaly is a condition affecting the cardiovascular system, specifically the heart. This condition is strongly associated with congestive heart failure. Within the heart, the working fibers of the myocardial tissue increase in size. As the heart works harder the actin and myosin filaments experience less overlap which increases the size of the myocardial fibers. If there is less overlap of the protein filaments within the sarcomeres of the muscle fibers, they will not be able to effectively pull on one another. If the heart tissue gets too big and stretches too far, then those filaments cannot effectively pull on one another to shorten the muscle fibers, impacting the hearts sliding filament mechanism. If fibers cannot shorten properly and the heart cannot contract properly, then blood cannot be effectively pumped to the lungs to be re-oxygenated or to the body to deliver oxygen to the working tissues of the body.A person with an enlarged heart is more susceptible to forming blood clots in the lining of their heart.
"Current Strategies in Diagnosis of Inherited Storage Pool Defects". Transfusion Medicine and Hemotherapy. 37 (5): 248–258. doi:10.1159/000320279. ISSN 1660-3796. PMC 2980509. PMID 21113247. Gresele, Paolo; Fuster, Valentin; Lopez, Jose A.; Page, Clive P.; Vermylen, Jos (2007). Platelets in Hematologic and Cardiovascular Disorders: A Clinical Handbook. Cambridge University Press. ISBN 9781139468763. Retrieved 26 November 2017. External links
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