Idiopathic hypertrophic subaortic stenosis (IHSS)
also called hypertrophic obstructive cardiomyopathy (HOCM), is a genetic form of hypertrophic cardiomyopathy (HCM)
Characterized by marked hypertrophy of the interventricular septum:
Reduces the diameter of the left ventricular outflow tract, leading to outflow tract obstruction
Overtime it leads to:
LVH and increased diastolic filling pressure
It is the most common (Mendelian) genetic heart disease, occurring at rate of approximately 1 in 500.
Autosomal dominant pattern of inheritance with variable penetrance leading to a high degree of phenotypic heterogeneity, which makes genetic testing implausible
Monogenic disease where in 1 of the 13 genes lead to a single amino acid change in proteins that compose the sarcomere complex
Presents after puberty (Average in mid-20s, but increasingly seen in 40-50s)
Common in young athletes
May present with symptoms or sudden cardiac death (SCD)
Ordinarily, muscle cells line up linearly
In IHSS, mutations lead to myofibrillar disarray (disorganization or haphazard arrangement of the muscle fibers).
Myocardium is unable to contract properly and the heart compensates for this lack of effective contraction by undergoing hypertrophy.
The walls of the heart thicken and the interventricular septum becomes asymmetrically enlarged leading to a narrowing of the left ventricle outflow tract.
Papillary muscles are deformed by the thickened septum and thickening of the mitral valve leaflet commonly occurs, as well.
Ejection of the blood through a narrowed outlet leads to a phenomenon known as the venturi effect:
Venturi forces pull anterior mitral leaflet toward septum during systole causing obstruction = systolic anterior movement of mitral valve (SAM).
Eventually, leads to diastolic heart failure through intermittent outflow obstruction Degree of obstruction is dependent on ionotropy and chronotropy:
During periods of strenuous exercise, HR incr → decr diastolic filling time (relaxation/filling) → decreased preload to the ventricle → narrowing of the outflow tract and incr obstruction
Note: paradoxically, when HR is decr/incr diastolic filling time → outflow tract expands and is less obstructed
History – Most patients have few or no symptoms
Physical Exam –
Extra heart sounds – S4 (non-compliance of left ventricle during diastole)
LVH, LA abnormality, LAD, deep & wide Q waves*, T wave changes
Certain mutations may exhibit WPW
*inferior and lateral precordial leads due to septal hypertrophy
IV Septum: LV wall thickness ratio (> 1.5:1)
Other: Cardiac MRI, Catheterization, Genetic testing, BNP, Cardiac muscle biopsy
Treatments & approach:
Surgical resection of a portion of the interventricular septum, enlarging the outflow tract and improving gradients
First line reduction therapy – superior because it yields a larger outflow tracts on average
If performed successfully, survival rates are similar to those of the general public
Mitral valve surgery (i.e. repair, replacement) may be necessary
Percutaneous alcohol ablation
Injection of absolute alcohol into the first or largest of the septal perforating branch of LAD, creating a transmural infarct of the septum leading to reduced contractility and thickness of the proximal interventricular septum
Alternative therapy – less invasive, but with an increased risk of arrhythmia and 10-20% chance of permanent pacemaker
Suggested in patients with higher risk because they are older, have comorbidities or are averse to surgery
LV assist device
Experimental due to small LV cavity and current generation of LVADs
Peak oxygen consumption and Minute ventilation – carbon dioxide production relationship (VE/VCO2) measured during cardiopulmonary exercise