What causes left ventricular hypertrophy (LVH)?

Causes of Left Ventricular Hypertrophy

Left ventricular hypertrophy (LVH) results from either genetic sarcomeric mutations (hypertrophic cardiomyopathy), chronic pressure overload (most commonly systemic hypertension and aortic stenosis), volume overload conditions, infiltrative diseases, or metabolic/storage disorders.

Primary Genetic Causes

Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere genes, inherited in an autosomal dominant pattern, and represents the most common genetic heart disease with prevalence of 1:200 to 1:500 in young adults. 1 The disease-causing variants are typically in sarcomere or sarcomere-related genes, though genetic etiology may remain unresolved in some cases. 1

Pressure Overload Causes

Systemic Hypertension

• Hypertension is the most common cause of LVH in clinical practice, producing concentric hypertrophy through chronic pressure elevation. 1, 2
• The elevated systemic pressure increases afterload, leading to addition of sarcomeres in parallel, widening cardiac myocytes and increasing wall thickness. 1
• This adaptive response to high peripheral resistance results in uniformly increased LV wall thickness with normal cavity size. 1

Aortic Stenosis

• Aortic valve stenosis represents another frequent cause of pressure overload-induced LVH. 1, 3
• The obstruction to left ventricular outflow creates chronic pressure elevation similar to hypertension. 4

Volume Overload Causes

Eccentric hypertrophy develops from volume overload conditions such as significant valvular regurgitation or high cardiac output states. 1 This pattern differs from pressure overload by causing:

• Increased diastolic wall stress leading to sarcomere addition in series (lengthening myocytes). 1
• Increased LV cavity size with normal wall thickness but elevated total LV mass. 1
• Normal systemic pressure without increased peripheral resistance. 1

Infiltrative and Storage Diseases

Multiple systemic disorders produce LVH through distinct pathophysiologic mechanisms that differ from sarcomeric HCM, including: 1

• Fabry disease, cardiac amyloidosis, and sarcoidosis (infiltrative processes). 3
• Glycogen and lysosomal storage diseases (metabolic disorders). 1
• Mitochondrial myopathies and RASopathies (genetic syndromes affecting RAS-MAPK signaling). 1
• Danon cardiomyopathy and hemochromatosis. 1

These conditions should not be labeled as HCM despite similar morphologic appearance, as their natural history and treatment strategies fundamentally differ. 1

Secondary and Physiologic Causes

Critical Illness

Chronic critical illness, particularly in infants with chronic lung disease, directly causes LVH through metabolic stress, increased intrathoracic pressure changes during mechanical ventilation, myocardial scarring, and systemic hypertension. 5 Chronic hypoxemia, hypercarbia, and acidosis increase cardiac output and stimulate the renin-angiotensin system, elevating afterload. 5

Metabolic Factors

• Obesity is associated with increased LV volumes, increased LV mass, and typically increased relative wall thickness. 1
• Insulin resistance, metabolic syndrome, and type 2 diabetes mellitus are similarly associated with increased LV mass, relative wall thickness, and diastolic dysfunction. 1
• Diabetes patients additionally demonstrate decreased systolic function. 1

Athletic Training

• Physiologic LVH from athletic training ("athlete's heart") represents an adaptive response that does not require treatment. 1, 3
• Strength training may produce concentric hypertrophy patterns. 1

Critical Diagnostic Distinctions

When evaluating LVH, clinicians must differentiate between: 1

• Primary HCM (sarcomeric gene variants) versus secondary causes
• Pressure overload (concentric pattern) versus volume overload (eccentric pattern)
• Physiologic adaptation versus pathologic hypertrophy
• Treatable infiltrative diseases versus irreversible conditions

The distinction is essential because treatment strategies, prognosis, and natural history vary dramatically based on etiology. 1, 3 Hypertensive cardiomyopathy, left-sided obstructive lesions, and post-infarction obstruction can create diagnostic challenges requiring careful clinical evaluation. 1