What causes mild septal hypertrophy?

Causes of Mild Septal Hypertrophy

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

Primary Etiologies

Hypertensive Heart Disease (Most Common)

• Hypertension accounts for the majority of mild septal hypertrophy cases, with over 30% of hypertensive patients developing left ventricular hypertrophy (LVH) on echocardiography 1
• The majority of patients with hypertensive LVH have maximal interventricular septal thickness <15mm 1
• Asymmetric septal hypertrophy can occur in approximately one-third of patients with severe arterial hypertension, appearing dependent on the duration and severity of hypertension 2
• Key distinguishing feature: Regression of LVH with tight blood pressure control (<130 mmHg systolic) over 6-12 months strongly argues against hypertrophic cardiomyopathy and confirms hypertensive etiology 1

Age-Related Isolated Basal Septal Hypertrophy (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
• Many have a history of hypertension and some have calcification of the mitral valve annulus 1
• These individuals are less likely to have familial disease or sarcomeric protein gene mutations 1
• This represents a manifestation of adverse ventricular-arterial coupling related to age and blood pressure, and is unrelated to cardiovascular disease or mortality after adjusting for risk factors 1

Hypertrophic Cardiomyopathy (HCM)

• HCM can present with mild septal hypertrophy (13-15mm range), though this represents a diagnostic challenge 1
• In first-degree relatives of HCM patients, wall thickness ≥13mm in one or more LV segments is diagnostic when otherwise unexplained 1
• Approximately one-third of HCM patients have largely segmental wall thickening involving only a small portion of the left ventricle 1
• Critical distinguishing features favoring HCM over hypertension 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

Athletic Heart (Physiologic Hypertrophy)

• Athletic conditioning can produce 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

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

Drug-Induced Causes

• Chronic use of anabolic steroids, tacrolimus, and hydroxychloroquine can cause LVH, though they rarely result in wall thickness ≥15mm 1

Infiltrative/Storage Diseases (Phenocopies)

• Metabolic or infiltrative disorders can mimic HCM, including Fabry disease, mitochondrial disease, and amyloidosis 1, 3
• These require disease-specific therapies and should be considered when clinical features suggest systemic involvement 3

Diagnostic Approach

Clinical Features Favoring Hypertension

• Normal 12-lead ECG or isolated increased voltage without repolarization abnormality 1
• Regression of LVH with 6-12 months of tight systolic blood pressure control 1
• Maximal septal thickness typically <15mm in Caucasians (though can be 15-20mm in Black patients, particularly with chronic kidney disease) 1

Clinical Features Favoring HCM

• Family history of HCM or pathogenic sarcomere mutation 1
• Maximum LV wall thickness ≥15mm (Caucasian) or ≥20mm (Black) 1
• Marked repolarization abnormalities, conduction disease, or Q-waves on ECG 1
• Severe diastolic dysfunction 1
• Late gadolinium enhancement at RV insertion points or localized to segments of maximum LV thickening on CMR 1

Common Pitfalls

• Do not diagnose HCM based solely on localized septal hypertrophy, as this is often an incidental echocardiographic finding in patients with other cardiac conditions or no significant disease 4
• A septal/posterior wall thickness ratio ≥1.3 is common in concentric LVH from any cause and occurs in 12% of normal subjects; a ratio ≥1.5 may be more specific for genetically determined asymmetric septal hypertrophy 5
• In older patients with LVH and hypertension, definitive diagnosis of HCM is difficult when wall thickness is <20mm and systolic anterior motion is absent, unless genetic testing identifies a sarcomere mutation 1
• Provocable left ventricular outflow tract obstruction can occur in hypertension and does not constitute a diagnostic criterion for HCM 1