Hypertrophic Cardiomyopathy

Description

• Hypertrophic cardiomyopathy (HCM) is a form of primary myocardial hypertrophy, with or without presence of left ventricular outflow tract (LVOT) obstruction; it is characterized by four cardinal features:
  • Idiopathic LV hypertrophy (LVH) in absence of other cardiac or systemic disease causing hypertrophy of such magnitude
  • Cardiac myocyte and myofibrillar disarray
  • Familial occurrence
  • Associated sudden cardiac death (SCD)
• System(s) affected: cardiovascular
• Synonym(s): hypertrophic obstructive cardiomyopathy (HOCM); muscular subaortic stenosis (MSS); idiopathic hypertrophic subaortic stenosis (IHSS)

Epidemiology

• The disorder may present at any age.
• It is seen in equal frequency in both sexes, although it is often underrecognized in females and African Americans.
• Apical HCM is a variant seen more often in China and Japan (Yamaguchi apical variant).

Incidence
~1% of patients with HCM die annually, but this is no different from the overall population.

Prevalence
Prevalence of HCM (positive phenotype or gene carrier) in the adult general population is 1:200 (1).

Etiology and Pathophysiology

• LVH
  • ≥1 region of LV wall are thickened: classically at the basal anterior septum but may involve posterior septum or LV free wall and apex
  • Hypertrophy develops usually in adolescence, with an average 100% increase in LV mass.
• Systolic anterior motion (SAM) of the mitral valve
  • Mitral valve abnormalities are primary manifestations of HCM: One or both leaflets may be elongated.
  • SAM is the abrupt motion of the mitral valve leaflet toward the septum, which creates dynamic LVOT obstruction in contact with the septum.
  • Caused by drag effect of the high-velocity jet caused by ejection through a narrowed LVOT and/or a Venturi phenomenon
• Disorganized myocardial architecture
  • Myocytes and myofilaments are laid down in disorganized pattern, with increased matrix components causing myocyte disarray.
  • Microvascular disease leads to ischemia and replacement fibrosis.
• Diastolic dysfunction
  • Result of reduced ventricular compliance; contributes predominantly to the symptoms of heart failure, such as dyspnea

Genetics

• Inherited as a mendelian autosomal dominant trait with >50% penetrance and variable expressivity
• 11 sarcomeric gene mutations are known, including, among others, β-myosin heavy chain, myosin-binding protein C, and troponins I and T.

Risk Factors

Risk factors for SCD in patients with IHSS include the following (2):

• A prior history of cardiac arrest or spontaneous sustained ventricular tachycardia (VT)
• Family history of premature SCD (especially in first-degree relative[s])
• Unexplained syncope
• Extreme LVH measuring >30 mm
• Hypotensive response to exercise: inability to increase by at least 20 mm Hg or a drop of at least 20 mm Hg
• Nonsustained VT during Holter monitoring
• Other factors that may indicate increased risk are LVOT obstruction (resting gradient >30 mm Hg), LV apical aneurysm, high-risk mutation, delayed enhancement on cardiac MRI.
• A predicted risk ≥6% using a novel risk prediction model is classified as high risk by European Society of Cardiology (3).

General Prevention

• Avoid strenuous exercise (particularly involving burst exertion) and heavy lifting (induces Valsalva maneuver).
• Maintain hydration to avoid volume depletion.
• Avoid alcohol.
• Certain drugs, such as nitrates, digoxin, β-agonists, vasodilators, and diuretics, are best avoided, particularly in the presence of increased LVOT gradient.
• Implantable cardioverter-defibrillator (ICD) is recommended for patients at high risk for SCD (3)[B],(4)[C].