What are the causes of left ventricular (LV) hypertrophy in a newborn?

Causes of Left Ventricular Hypertrophy in Newborns

In newborns, left ventricular hypertrophy results primarily from congenital structural heart defects (critical aortic stenosis, coarctation of aorta, hypoplastic left heart syndrome), maternal diabetes, genetic cardiomyopathies, and less commonly from chronic lung disease with associated systemic hypertension. 1

Congenital Structural Heart Disease

Critical aortic stenosis or aortic atresia represents the most important structural cause in fetuses and newborns, associated with increased pulmonary vascular muscularization and arterialized pulmonary veins present in utero. 1 These changes impair postnatal pulmonary vascular adaptation and development, with decreased LV size imposing additional diastolic abnormalities not seen in acquired forms. 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 (including Shone syndrome and parachute mitral valve) elevate left atrial pressure through transmitral valve gradients, causing secondary LV hypertrophy. 1

Maternal Diabetes

Transient ventricular hypertrophy occurs in infants of diabetic mothers, even after good diabetic control during pregnancy. 1 This represents a metabolic cause that typically resolves over time without specific intervention. 1

Genetic Cardiomyopathies

The European Society of Cardiology identifies multiple genetic causes relevant to newborns: 1

• Sarcomeric hypertrophic cardiomyopathy from mutations in genes including MYBPC3, MYH7, TNNT2, TNNI3, and TPM1. 1

• Metabolic storage diseases including:

  • Pompe disease (glycogen storage disease type II) 1
  • Danon disease 1
  • Anderson-Fabry disease 1
  • Mitochondrial disorders 1

• Malformation syndromes such as Noonan syndrome, LEOPARD syndrome, Costello syndrome, and cardiofaciocutaneous syndrome. 1

• AMP-Kinase disorders (PRKAG2 mutations) causing glycogen accumulation. 1

Chronic Lung Disease of Infancy

Infants with chronic lung disease develop LV hypertrophy through multiple mechanisms: 1, 2

• Metabolic stress from chronic hypoxemia, hypercarbia, and acidosis increases cardiac output and stimulates the renin-angiotensin system, elevating afterload. 1, 2

• Increased intrathoracic pressure changes during mechanical ventilation create more negative inspiratory pressures that directly increase LV afterload. 1, 2

• Systemic hypertension develops in up to 43% of infants with chronic lung disease, with mean age of diagnosis at 4.8 months (range 2 weeks to 15 months). 1

• Myocardial scarring may result from prolonged metabolic stress. 1, 2

Drug-Induced Causes

Corticosteroids used for chronic lung disease management can cause systemic hypertension and contribute to LV hypertrophy. 1 Decreasing the dose, changing to nebulized administration, or discontinuation should be considered when hypertension develops. 1

Diagnostic Approach

Echocardiography is superior to ECG for detecting LV hypertrophy, as ECG screening alone frequently misses hypertrophy documented by echo or autopsy. 2 Serial echocardiograms are necessary to monitor the degree of hypertrophy and myocardial function. 1, 2

When LV hypertrophy is identified, screen for: 1, 2

• Systemic hypertension requiring blood pressure monitoring and control
• Left-to-right shunting via patent ductus arteriosus or large systemic-to-pulmonary collateral vessels
• Medication effects, particularly corticosteroids

Critical Pitfalls

Endocardial fibroelastosis was the most frequent autopsy finding (92%) in cases of fetal ventricular hypertrabeculation/noncompaction, challenging simple embryonic pathogenetic hypotheses. 3 This highlights that postnatal development and acquired factors may play larger roles than previously recognized. 3

Fetal ventricular hypertrabeculation/noncompaction can present with isolated LV involvement (36% of cases) or with multiple associated cardiac abnormalities (64%), with survival rates of 38% overall. 3 Survivors present less frequently with fetal hydrops (13% vs 62%), complete heart block (27% vs 78%), and more frequently with isolated findings (52% vs 19%). 3