Common Causes of Cardiomegaly
Cardiomegaly results from primary cardiac diseases (cardiomyopathies and valve disorders), systemic conditions causing pressure or volume overload (hypertension, diabetes), infiltrative diseases (amyloidosis, hemochromatosis), and endocrine disorders (acromegaly, pheochromocytoma). 1
Primary Cardiac Causes
Cardiomyopathies
Hypertrophic Cardiomyopathy (HCM) is defined by left ventricular wall thickness ≥15 mm in adults that cannot be explained by loading conditions alone, and represents the most common genetic heart disease with prevalence of 1:200 to 1:500 in young adults. 1, 2 The majority of cases are caused by mutations in sarcomere protein genes, particularly MYH7 and MYBPC3, inherited in an autosomal dominant pattern. 3, 2 The most common pattern is asymmetric septal hypertrophy affecting the basal anterior septum. 1
Dilated Cardiomyopathy (DCM) presents with ventricular dilatation, systolic dysfunction, and either normal or reduced wall thickness, associated with increased diastolic and systolic wall stress, neurohormonal activation, and biventricular enlargement. 1
Restrictive Cardiomyopathy is characterized by normal or reduced ventricular chamber size with biatrial enlargement—massive biatrial enlargement combined with normal or reduced ventricular chamber size is a classic morphological pattern. 4, 1 Causes include amyloidosis (AL and transthyretin-type ATTR), sarcoidosis, hemochromatosis, eosinophilic cardiomyopathy, endomyocardial fibrosis, scleroderma, radiation-induced fibrosis, and familial restrictive cardiomyopathies. 4, 1, 3
Valvular Heart Disease
Chronic valve disorders cause pressure or volume overload leading to cardiac chamber enlargement. 1 Mitral regurgitation in HCM can occur secondarily from systolic anterior motion (SAM) or primarily from leaflet abnormalities including excessive leaflet length, anomalous papillary muscle insertion, and anteriorly displaced papillary muscles. 4
Systemic Conditions
Hypertension
Long-standing hypertension is the most common cause of left ventricular hypertrophy in clinical practice, producing concentric hypertrophy through chronic pressure elevation. 2 Elevated systemic pressure increases afterload, leading to addition of sarcomeres in parallel, widening cardiac myocytes and increasing wall thickness uniformly with normal cavity size. 2
Diabetes Mellitus
Diabetes causes diabetic cardiomyopathy with left ventricular hypertrophy even in the absence of coronary artery disease, characterized by diastolic dysfunction in 40-75% of patients. 1 Mechanisms include insulin resistance, hyperinsulinemia, formation of advanced glycation end products, and activation of the renin-angiotensin-aldosterone system. 1 Obesity, insulin resistance, metabolic syndrome, and type 2 diabetes are associated with increased left ventricular mass, relative wall thickness, and diastolic dysfunction. 2
Coronary Artery Disease
Myocardial ischemia and infarction lead to cardiac remodeling and subsequent cardiomegaly, with atherosclerosis accelerated by conditions like diabetes through vascular smooth muscle cell proliferation and inflammation. 1
Endocrine Disorders
Acromegaly
Growth hormone and IGF-I excess induces a specific cardiomyopathy with concentric biventricular hypertrophy found in more than two-thirds of patients at diagnosis. 5, 6 The early phase is characterized by a hyperkinetic syndrome with increased heart rate and systolic output. 5, 6 If untreated, this progresses to diastolic dysfunction and eventually impaired systolic function ending in heart failure. 5, 7 Disease duration plays a pivotal role—longer duration is more closely associated with biventricular enlargement, diastolic dysfunction, heart failure, and valvular disease than the degree of hormone elevation. 8
Pheochromocytoma
Pheochromocytoma is associated with left ventricular hypertrophy that may resolve with treatment of the underlying condition. 1
Infiltrative and Storage Diseases
Genetic disorders causing cardiomegaly include glycogen storage diseases (Danon cardiomyopathy), mitochondrial diseases, lysosomal storage diseases, and amyloidosis. 1, 2 Hemochromatosis causes iron deposition within the myocardium. 4, 2
Medication-Induced Causes
Anabolic steroids, tacrolimus, and hydroxychloroquine can cause left ventricular hypertrophy, though they rarely result in wall thickness ≥15 mm. 1, 3
Pathophysiological Mechanisms
Pressure overload causes concentric hypertrophy as the heart works against increased resistance. 1
Volume overload leads to eccentric hypertrophy with increased myocyte length and chamber dilation. 1
Metabolic dysfunction is characterized by energy starvation of cardiomyocytes due to impaired glucose utilization and increased reliance on fatty acid metabolism. 1
Fibrosis involves increased collagen deposition and cross-linking leading to myocardial stiffness and impaired cardiac relaxation. 1
Neurohormonal activation contributes to cardiac hypertrophy and fibrosis through the renin-angiotensin-aldosterone system. 1
Diagnostic Approach
When cardiomegaly is detected, conduct a systematic search including: family history assessment (particularly for HCM and familial restrictive cardiomyopathies), non-cardiac symptoms and signs (suggesting systemic diseases like amyloidosis or sarcoidosis), ECG abnormalities, specialized laboratory testing (BNP, troponin, metabolic panels, iron studies, serum protein electrophoresis), and multi-modality cardiac imaging. 1, 3
Echocardiography is the first-line imaging modality for detecting and quantifying cardiomegaly and left ventricular hypertrophy. 3
Cardiac MRI is indicated when echocardiography is inconclusive or when there is suspicion of infiltrative/storage disease, and is the gold standard for diagnosis and assessment. 3 Late gadolinium enhancement patterns help differentiate HCM (patchy midwall enhancement) from infiltrative diseases (diffuse subendocardial or transmural patterns). 3
Distinguish between concentric hypertrophy (pressure overload from hypertension/aortic stenosis) versus asymmetric septal hypertrophy (typical of HCM). 3