What are the common causes of septal hypertrophy?

Causes of Septal Hypertrophy

Systemic hypertension is the most common cause of septal hypertrophy, accounting for the majority of cases, particularly in elderly patients, and should be your primary consideration when evaluating this finding. 1

Primary Etiologies

Systemic Hypertension

• Hypertension causes over 30% of hypertensive patients to develop left ventricular hypertrophy (LVH) on echocardiography, with the majority having maximal interventricular septal thickness <15mm. 1
• Between 32-39% of hypertensive patients demonstrate a septal/posterior wall thickness ratio ≥1.3, which can mimic other pathologic conditions. 2, 3
• The mechanism involves increased systolic stress on the septum due to its flatter, more eccentric contour compared to the free wall, leading to compensatory hypertrophy. 4
• Regression of LVH with tight blood pressure control (<130 mmHg systolic) over 6-12 months strongly confirms hypertensive etiology and argues against hypertrophic cardiomyopathy. 1

Age-Related (Sigmoid Septum)

• Elderly individuals commonly develop mild basal septal hypertrophy (sigmoid septum or septal bulge) associated with increased angulation between the aorta and LV cavity. 1
• This represents adverse ventricular-arterial coupling related to age and blood pressure, often accompanied by mitral annular calcification. 1
• These patients are less likely to have familial disease or sarcomeric protein gene mutations and have no increased cardiovascular mortality after adjusting for risk factors. 1

Hypertrophic Cardiomyopathy (HCM)

• HCM can present with mild septal hypertrophy (13-15mm range), though approximately one-third of HCM patients have largely segmental wall thickening involving only a small portion of the left ventricle. 1
• In first-degree relatives of HCM patients, wall thickness ≥13mm in one or more LV segments is diagnostic when otherwise unexplained. 1
• Critical distinguishing features favoring HCM include: family history of HCM, right ventricular hypertrophy, marked ECG repolarization abnormalities or Q-waves, severe diastolic dysfunction, and late gadolinium enhancement at RV insertion points. 1
• The obstruction mechanism in HCM requires active septal contraction to contribute to dynamic obstruction, not hypokinesia. 5

Aortic Valve Disease

• Between 20-30% of patients with aortic stenosis have an asymmetric pattern of wall thickening, though severity is usually relatively mild (wall thickness ≤15mm). 1
• The pattern and severity of LV remodeling in aortic stenosis correlates modestly with the severity of valve narrowing. 1
• Approximately 78% of patients with aortic stenosis may have septal/posterior wall ratios ≥1.3 at left ventricular midcavity level. 2

Athletic Heart

• Athletic conditioning produces ventricular septal thickening as a physiologic adaptation. 1
• Distinction from pathologic hypertrophy is resolved by: enlarged LV cavity dimension (favoring athlete's heart), normal diastolic function, and decrease in wall thickness after short deconditioning periods. 1

Congenital Heart Disease

• Tetralogy of Fallot causes RV hypertrophy due to antero-cephalad deviation of the conal septum, resulting in malalignment VSD and RVOT obstruction. 6
• Disproportionate ventricular septal thickening occurs in association with parachute deformity of the mitral valve, complete interruption of the aortic arch, and ventricular septal defects. 7

Infiltrative and Storage Diseases

Key Echocardiographic Clues

• Concentric hypertrophy with sparkling or granular myocardial texture, small pericardial effusion, thickening of the interatrial septum, and nodular thickening of the aortic valve suggest amyloidosis. 6, 8
• Increased RV free wall thickness suggests amyloidosis, myocarditis, Anderson-Fabry disease, or Noonan syndrome. 6
• Extreme concentric LVH (wall thickness ≥30mm) suggests Danon disease or Pompe disease. 6
• Global LV hypokinesia with or without LV dilatation suggests mitochondrial disease, TTR-related amyloidosis, PRKAG2 mutations, Danon disease, myocarditis, advanced sarcomeric HCM, Anderson-Fabry disease, or Noonan syndrome. 6, 5

Diagnostic Algorithm

Initial Assessment

• Normal 12-lead ECG or isolated increased voltage without repolarization abnormality favors hypertension. 1
• Maximum LV wall thickness ≥15mm (Caucasian) or ≥20mm (Black) favors HCM. 1
• Marked repolarization abnormalities, conduction disease, or Q-waves on ECG favor HCM. 1

Advanced Testing

• Obtain cardiac MRI with late gadolinium enhancement to distinguish HCM (enhancement at RV insertion points or localized to segments of maximum LV thickening) from hypertensive heart disease. 1
• Assess for regression of LVH with 6-12 months of tight systolic blood pressure control to confirm hypertensive etiology. 1
• Severe diastolic dysfunction favors HCM over hypertensive heart disease. 1

Common Pitfall

• A septal/posterior wall thickness ratio ≥1.3 is common in patients with concentric left ventricular hypertrophy and may occur in 12% of normal subjects; a ratio ≥1.5 may be more specific for genetically determined asymmetric septal hypertrophy. 2