What are the common causes of Left Ventricular Hypertrophy (LVH) in pediatric patients?

Common Causes of Left Ventricular Hypertrophy in Pediatric Patients

In pediatric patients, the causes of LVH vary significantly by age, with newborns primarily affected by congenital structural heart defects and maternal diabetes, while adolescents are predominantly affected by hypertrophic cardiomyopathy from sarcomeric gene mutations, followed by systemic hypertension and obesity. 1, 2

Age-Specific Etiologies

Newborns and Infants

Structural congenital heart defects represent the most critical causes in this age group:

• Critical aortic stenosis or aortic atresia is the most important structural cause in fetuses and newborns, associated with impaired postnatal pulmonary vascular adaptation 1
• Coarctation of the aorta causes pressure overload leading to compensatory LV hypertrophy, with the hypertrophy initially lowering wall stress to compensate for increased afterload 1
• Hypoplastic left heart syndrome presents with a small, hypertrophied LV, often accompanied by endocardial fibroelastosis and elevated LV end-diastolic pressure 1
• Mitral stenosis variants elevate left atrial pressure through transmitral valve gradients, causing secondary LV hypertrophy 1

Metabolic and maternal factors are particularly important in neonates:

• Infants of diabetic mothers develop transient ventricular hypertrophy even after good diabetic control during pregnancy, representing a metabolic cause that typically resolves over time without specific intervention 2, 1
• Metabolic storage diseases including Pompe disease, Danon disease, Anderson-Fabry disease, and mitochondrial disorders cause LV hypertrophy in newborns 2, 1
• AMP-Kinase disorders (PRKAG2 mutations) cause glycogen accumulation and contribute to LV hypertrophy 2, 1

Genetic syndromes associated with neonatal LVH:

• Malformation syndromes including Noonan syndrome, LEOPARD syndrome, Costello syndrome, and cardiofaciocutaneous syndrome are linked to LV hypertrophy in newborns 2, 1
• These syndromes are caused by mutations in genes coding for proteins of the Ras/MAPK pathway 2

Critical illness-related causes in infants:

• Chronic lung disease develops LV hypertrophy through metabolic stress, increased intrathoracic pressure changes, myocardial scarring, and systemic hypertension 1, 3
• Systemic hypertension develops in up to 43% of infants with chronic lung disease, with mean age of diagnosis at 4.8 months 1
• Corticosteroids used for chronic lung disease management can cause systemic hypertension and contribute to LV hypertrophy 1, 3

Adolescents

The majority of cases in adolescents are caused by mutations in sarcomere protein genes:

• Hypertrophic cardiomyopathy (HCM) from mutations in MYBPC3, MYH7, TNNT2, TNNI3, and TPM1 genes accounts for the majority of unexplained LV hypertrophy in adolescents 2, 1
• HCM accounts for approximately 25-30% of cases with identified genetic causes 2
• Increased LV wall thickness may develop during childhood and adolescence despite previously normal echocardiographic evaluations, necessitating serial evaluations in patients with gene-positive or suspected HCM 2

Systemic hypertension is a major acquired cause:

• Essential hypertension is prevalent in children and adolescents, with 38.5% of hypertensive pediatric patients demonstrating LVH 4
• In children with sustained hypertension, 8-41% have LV mass index above the 95th percentile 5
• The presence of obesity is associated with higher LV mass index than is found in children with hypertension alone 5

Key independent correlates of LV mass in hypertensive adolescents include:

• Male sex, body mass index, dietary sodium intake, age at diagnosis, and systolic blood pressure at maximum exercise are significant direct correlates 4
• These variables account for a substantial portion (56%) of LV mass index variance 4

All Age Groups

Neuromuscular diseases (rare except Friedreich's ataxia):

• Friedreich's ataxia is the most common neuromuscular disease associated with HCM 2
• Some muscular dystrophies and congenital skeletal myopathies (e.g., nemaline myopathy) can present with HCM 2
• Desmin gene mutations typically cause dilated and restrictive cardiomyopathies but can present with HCM and AV block 2

Infiltrative diseases:

• Cardiac amyloidosis results in progressive increase in LV and RV myocardial thickness, though this is extremely rare in pediatrics 2
• Myocardial edema and cellular infiltration in acute myocarditis can mimic HCM, but this is usually transient 2

Endocrine disorders:

• Pheochromocytoma and acromegaly are associated with LVH in adults, but treatment of the underlying endocrine disorder usually results in resolution of hypertrophy 2

Drug-induced causes:

• Chronic use of anabolic steroids, tacrolimus, and hydroxychloroquine can cause LVH, though they rarely result in LV wall thickness ≥1.5 cm 2
• Corticosteroids can cause systemic hypertension and contribute to LV hypertrophy 1

Critical Diagnostic Considerations

Echocardiography is superior to ECG for detecting LVH, as ECG screening alone frequently misses hypertrophy documented by echo or autopsy 1, 3

When LVH is identified, the following screening is necessary:

• Screen for systemic hypertension requiring blood pressure control 1, 3
• Evaluate for left-to-right shunting 1
• Assess medication effects, particularly corticosteroids 1, 3
• Serial echocardiograms are necessary to monitor the degree of hypertrophy and myocardial function 1, 3

CMR is superior to echocardiography in identifying focal and limited LVH, which is present in up to 5% of children with HCM 2

In children with chronic kidney disease, left ventricular hypertrophy develops relatively early and becomes more prevalent as kidney function decreases 5