What is the cardinal description of Hypertrophic Cardiomyopathy (HCM)?

Cardinal Description of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic heart disease characterized primarily by left ventricular hypertrophy (typically ≥15 mm wall thickness in adults) in the absence of another cardiac, systemic, or metabolic disease capable of producing the magnitude of hypertrophy evident in a given patient. 1

Key Diagnostic Features

Morphological Characteristics

• Left Ventricular Hypertrophy:

  • Wall thickness ≥15 mm anywhere in the left ventricle in adults 1
  • More limited hypertrophy (13-14 mm) can be diagnostic in family members of HCM patients 1
  • Most commonly affects the basal anterior septum in continuity with the anterior free wall 1
  • Can present with virtually any pattern of LV wall thickening (diffuse or segmental) 1

• Distribution of Hypertrophy:

  • Typically asymmetric in distribution 1
  • Can be limited and focal in some patients, confined to only 1 or 2 LV segments 1
  • Various morphologic subtypes exist, including apical hypertrophy and septal hypertrophy with reverse/neutral curvature 1

Functional Characteristics

• Left Ventricular Function:

  • Nondilated and hyperdynamic LV chamber (often with systolic cavity obliteration) 1
  • Preserved or increased ejection fraction 2
  • Diastolic dysfunction is frequently present 2

• Outflow Obstruction:

  • Left ventricular outflow tract obstruction (LVOTO) is present at rest in approximately one-third of patients 2
  • Can be provoked in another third of patients 2
  • Caused by systolic anterior motion (SAM) of mitral valve leaflets making mid-systolic contact with the hypertrophied ventricular septum 3
  • Results in characteristic apical systolic ejection murmur 1

Histopathological Features

• Myocyte disarray 2
• Myocardial hypertrophy 2
• Interstitial fibrosis 2
• Abnormal small intramural arterioles with thickened walls and narrowed lumen 1

Genetic Basis

• Autosomal dominant inheritance pattern 1
• Caused by mutations in genes encoding sarcomere proteins or sarcomere-associated proteins 1
• Eight genes definitively cause HCM: beta myosin heavy chain, myosin binding protein C, troponin T, troponin I, alpha tropomyosin, actin, regulatory light chain, and essential light chain 1
• MYH7 and MYBPC3 are the two most common genes involved, accounting for approximately 50% of HCM families 2
• In approximately 40% of HCM patients, the causal genes remain unidentified 2

Clinical Presentation

• Highly variable clinical manifestations:
  • Many patients remain asymptomatic
  • Common symptoms include dyspnea, chest pain, palpitations, and syncope 1
  • Sudden cardiac death may be the first manifestation, particularly in young adults 1
  • Heart failure symptoms may develop due to diastolic dysfunction, outflow obstruction, or systolic dysfunction in advanced cases 4

Important Distinctions

• HCM should be distinguished from other causes of LV hypertrophy:
  • Secondary causes (hypertension, aortic stenosis)
  • Athlete's heart
  • Infiltrative diseases (amyloidosis, Fabry disease)
  • Storage diseases
  • Syndromic disorders (RASopathies, mitochondrial disorders) 1

Epidemiology

• Prevalence estimated at 1:500 to 1:200 in the general population 1
• Equal distribution by sex, although women are diagnosed less commonly than men 1
• Most common cause of sudden cardiac death in young athletes 1

Disease Pathways

HCM may progress along one or more major disease pathways:

1. Arrhythmic sudden death risk
2. Progressive heart failure due to dynamic LV outflow obstruction
3. Progressive heart failure due to systolic dysfunction in absence of obstruction
4. Atrial fibrillation with risk of stroke 4

This comprehensive description captures the cardinal features of HCM as a genetically determined primary myocardial disorder with distinctive morphological, functional, and histopathological characteristics that distinguish it from other forms of cardiac hypertrophy.