What are the causes of left ventricular hypertrophy (LVH) and how is it diagnosed and treated?

Causes of Left Ventricular Hypertrophy

Left ventricular hypertrophy results from diverse etiologies that must be systematically evaluated, with the most common causes being systemic hypertension and aortic valve stenosis, followed by hypertrophic cardiomyopathy, infiltrative diseases, and drug-induced causes. 1, 2

Primary Cardiac Causes

Hypertrophic Cardiomyopathy (HCM)

• HCM is defined by LV wall thickness ≥15 mm in adults that cannot be explained by loading conditions alone. 3
• The majority of cases in adolescents and adults are caused by mutations in sarcomere protein genes, particularly MYH7 and MYBPC3. 3, 4
• In first-degree relatives of HCM patients or those with positive genetic testing, wall thickness of 13-14 mm may be diagnostic. 3
• For children, diagnosis requires LV wall thickness >2 standard deviations above the predicted mean (z-score >2). 3

Valvular Heart Disease

• Aortic stenosis causes pressure overload leading to concentric LVH. 4, 1
• Chronic valve disorders create pressure or volume overload resulting in cardiac chamber enlargement. 4

Ischemic Heart Disease

• Myocardial infarction and chronic ischemia lead to cardiac remodeling and subsequent LVH. 4

Secondary Causes

Systemic Hypertension

• Hypertension is the most common cause of LVH and creates pressure overload leading to concentric hypertrophy. 1, 2
• Long-standing hypertension can produce morphologic changes that overlap phenotypically with HCM, creating diagnostic challenges. 3

Drug-Induced LVH

• Chronic use of anabolic steroids, tacrolimus, and hydroxychloroquine can cause LVH, though they rarely result in wall thickness ≥15 mm. 3, 4

Infiltrative and Storage Diseases

• Amyloidosis (AL amyloidosis and transthyretin-type ATTR) causes restrictive cardiomyopathy with LVH. 3, 4
• Fabry disease, sarcoidosis, and hemochromatosis are infiltrative processes that produce LVH. 4, 1
• Glycogen storage diseases, mitochondrial myopathies, and lysosomal storage diseases can cause LVH, particularly in children. 3, 4

Metabolic and Systemic Disorders

• Diabetes mellitus causes diabetic cardiomyopathy with LVH even without coronary disease, characterized by diastolic dysfunction in 40-75% of diabetic patients through mechanisms including insulin resistance, hyperinsulinemia, and advanced glycation end products. 4
• Pheochromocytoma is associated with LVH that may resolve with treatment. 4

Genetic Syndromes

• RASopathies (Noonan, LEOPARD, Costello syndromes) involve variants in RAS-MAPK signaling genes and can present with LVH. 3, 4
• Infants of diabetic mothers may develop transient ventricular hypertrophy. 4

Physiologic LVH

• Athletic training produces physiologic LVH that does not require treatment but must be distinguished from pathologic causes. 3, 1

Diagnostic Approach

Initial Imaging

• Echocardiography is the first-line imaging modality for detecting and quantifying LVH. 3, 2
• 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, 2, 5

Systematic Evaluation

When LVH is detected, conduct a systematic search for the underlying cause including: 3, 4

• Family history assessment (particularly for HCM, early cardiac death, or genetic syndromes)
• Non-cardiac symptoms and signs (suggesting systemic or infiltrative disease)
• 12-lead ECG abnormalities
• Specialized laboratory testing (for metabolic, storage, or infiltrative diseases)
• Multi-modality cardiac imaging to assess distribution of hypertrophy, fibrosis patterns, and functional abnormalities

Key Diagnostic Distinctions

• Distinguish between concentric hypertrophy (pressure overload from hypertension/aortic stenosis) versus asymmetric septal hypertrophy (typical of HCM). 3, 4
• Evaluate for late gadolinium enhancement on CMR, which helps differentiate HCM (patchy midwall enhancement) from infiltrative diseases (diffuse subendocardial or transmural patterns). 3, 5
• Consider genetic testing in patients fulfilling HCM criteria to enable cascade screening of relatives. 3

Common Diagnostic Pitfalls

• Isolated basal septal hypertrophy in elderly patients can mimic HCM. 3
• Hypertensive heart disease with significant LVH may be difficult to distinguish from HCM, particularly when both conditions coexist. 3
• Late-stage HCM can present with dilated, hypokinetic ventricles and wall thinning, obscuring the diagnosis. 3

Treatment Principles

Etiology-Based Management

• Treatment must target the underlying cause: antihypertensive therapy for hypertension, valve replacement for aortic stenosis, enzyme replacement for Fabry disease, and specific therapies for cardiac amyloidosis. 1, 6
• For hypertension-induced LVH, ACE inhibitors produce the most pronounced regression of LV mass, followed by calcium channel blockers, beta-blockers, and alpha-blockers. 6
• Diuretics and arterial vasodilators cause LVH regression when used long-term for blood pressure control. 6
• Regression of LVH substantially reduces cardiovascular and all-cause mortality risk. 7

HCM-Specific Considerations

• Management focuses on symptom relief, prevention of sudden cardiac death, and treatment of complications rather than reversing hypertrophy. 3
• Genetic counseling and cascade screening of first-degree relatives is essential. 3