What causes cardiomegaly?

Causes of Cardiomegaly

Cardiomegaly is primarily caused by conditions that lead to increased cardiac workload, myocardial damage, or structural abnormalities, including hypertension, coronary artery disease, cardiomyopathies, valvular heart disease, congenital heart defects, and various systemic disorders. 1

Primary Cardiac Causes

Cardiomyopathies

• Hypertrophic Cardiomyopathy (HCM): Characterized by left ventricular wall thickness ≥15 mm in adults that cannot be explained solely by loading conditions 2

  • Most commonly caused by mutations in sarcomere protein genes, particularly MYH7 and MYBPC3 2
  • Can present with various patterns of left ventricular hypertrophy, most commonly affecting the basal anterior septum 2

• Dilated Cardiomyopathy (DCM): Characterized by ventricular dilatation, systolic dysfunction, and either normal or reduced wall thickness 2

  • Associated with increased diastolic and systolic wall stress, neurohormonal activation, and biventricular enlargement 2
  • Can be primary (genetic) or secondary to various conditions 2

• Restrictive Cardiomyopathy: Characterized by normal or reduced ventricular chamber size with biatrial enlargement 2

  • Causes include amyloidosis, sarcoidosis, hemochromatosis, and familial restrictive cardiomyopathies 2

Coronary Artery Disease

• Myocardial ischemia and infarction can lead to cardiac remodeling and subsequent cardiomegaly 2
• Atherosclerosis accelerated by conditions like diabetes mellitus through vascular smooth muscle cell proliferation and inflammation 2

Valvular Heart Disease

• Chronic valve disorders cause pressure or volume overload leading to cardiac chamber enlargement 2

Systemic Disorders

Endocrine Disorders

• Diabetes Mellitus: Can cause diabetic cardiomyopathy with left ventricular hypertrophy, even in the absence of coronary artery disease 2

  • Characterized by diastolic dysfunction in 40-75% of patients with diabetes 2
  • Mechanisms include insulin resistance, hyperinsulinemia, formation of advanced glycation end products, and activation of the renin-angiotensin-aldosterone system 2

• Acromegaly: Excess growth hormone and IGF-1 cause specific cardiomyopathy 3, 4

  • Concentric hypertrophy is found in more than two-thirds of patients at diagnosis 3
  • Duration of growth hormone excess correlates with biventricular enlargement and diastolic dysfunction 4
  • Treatment of the underlying endocrine disorder can result in resolution of hypertrophy 2, 3

• Pheochromocytoma: Associated with left ventricular hypertrophy that may resolve with treatment of the underlying condition 2

Other Causes

• Pregnancy: Can cause physiological cardiomegaly that typically resolves postpartum 1

• Drug-induced: Chronic use of certain medications can cause left ventricular hypertrophy, including:

  • Anabolic steroids 2
  • Tacrolimus 2
  • Hydroxychloroquine 2

• Genetic disorders:

  • Glycogen storage diseases 2
  • Mitochondrial diseases 2
  • Lysosomal storage diseases (e.g., Anderson-Fabry disease) 2
  • Amyloidosis 2

• Congenital conditions:

  • Infants of diabetic mothers may develop transient ventricular hypertrophy 2
  • Various malformation syndromes (Noonan, LEOPARD, Costello) 2

Pathophysiological Mechanisms

• Pressure Overload: Conditions like hypertension cause concentric hypertrophy as the heart works against increased resistance 2

• Volume Overload: Leads to eccentric hypertrophy with increased myocyte length and chamber dilation 2

• Metabolic Dysfunction: Energy starvation of cardiomyocytes due to impaired glucose utilization and increased reliance on fatty acid metabolism 2

• Fibrosis: Increased collagen deposition and cross-linking leading to myocardial stiffness and impaired cardiac relaxation 2

• Neurohormonal Activation: Activation of the renin-angiotensin-aldosterone system contributes to cardiac hypertrophy and fibrosis 2

Clinical Approach to Diagnosis

• Imaging is essential for diagnosis, with cardiomegaly defined as structural enlargement of the heart detected by:

  • Chest X-ray
  • Echocardiography
  • Cardiac MRI
  • CT scan 1

• When cardiomegaly is detected, a systematic search for the underlying cause should be conducted, including:

  • Evaluation of family history
  • Assessment of non-cardiac symptoms and signs
  • ECG abnormalities
  • Laboratory tests
  • Multi-modality cardiac imaging 2

• In adults with unexplained left ventricular wall thickness ≥15 mm, consider HCM and evaluate for genetic and non-genetic causes 2

• In patients with diabetes, be alert for signs of diabetic cardiomyopathy, especially diastolic dysfunction 2