Description

• Genetic disorder affecting the sarcomere
• Clinical diagnostic criteria: Hypertrophied (regionally or globally), nondilated left in the absence of another cause of degree of hypertrophy observed, such as hypertension or aortic stenosis
• Hypertrophic cardiomyopathy (HCM) unifies over 75 different names historically used
• 2 general types:
  • Obstructive – ≥30 mm Hg left ventricular outflow tract gradient:
    • 67% of patients
    • More severe – estimated 2% annual mortality
  • Nonobstructive – <30 mm Hg gradient:
    • 33% of patients
    • Estimated around 1% annual mortality
• Global disease – >50 countries, all race/ethnic groups
• Manifests at all ages, from neonate to elderly:
  • Most manifest in childhood and adolescence – pubertal growth spurt
  • Usually more severe when diagnosed at younger age
  • Small percent progress to reduced LV function
• Average age of diagnosis in fifth decade:
  • CHF may initially be misdiagnosed as asthma, COPD, deconditioning, or sleep apnea
• Lethal arrhythmias more common in younger patients:
  • Most common cause of atraumatic death in young (<35 yo) persons, not just athletes
  • Most common cause of sudden death in athletes
• Supraventricular arrhythmia incidence increases with age:
  • Atrial fibrillation both common and poorly tolerated
  • Stroke is a high-risk complication
• Prevalence at least 1 in 500 adults:
  • Based on echocardiographic population studies
  • Much smaller number present for care, suggesting many undiagnosed with possible minimal to no adverse effect from phenotypic variety
• Structural pathology:
  • Irregular, marked ventricular wall thickening with disarray of myofibrils in the thickened regions and fibrin deposition:
    • Affects higher-pressure LV more than right and, in obstructive form, if obstruction removed, hypertrophy decreases
    • Some phenotypes have progressive wall thinning with age – usually associated with thicker wall early
  • Thickening usually asymmetric involving the septum to a greater extent than the free ventricular wall ‎ outflow obstruction
  • Atrial dilatation secondary to diastolic filling stiffness ‎ increased risk for atrial fibrillation
  • Impaired microvascular dilation associated with intimal thickening and perivascular collagen deposition ‎ increased risk for angina
• Outpatient long-term management:
  • Avoidance of volume depletion and elevated cardiac demand – depending on degree and location of hypertrophy
  • Pharmacologic
    • β-Blockers or verapamil to slow and control rate, thus prolonging diastole
  • Implantable cardiac defibrillator:
    • In patients with history of syncope, cardiac arrest, family member with sudden death, asymptomatic nonsustained ventricular tachycardia (VT), abnormal BP response to exercise, massive hypertrophy
  • Alcohol ablation of hypertrophic outflow-obstructing septal tissue
  • Surgical septal myectomy – improving statistics with more centers performing

Risk Factors

• First cardiac disorder for which genetic basis identified (1989)
• Autosomal-dominant inheritance:
  • >10 associated genes found:
    • Encode proteins of cardiac sarcomere
    • >1,500 distinct mutations recognized
  • High penetrance
• Highly variable phenotypic expression
• Some genotypes significantly more lethal:
  • Routine screening impractical at present:
    • Mutations do not predict individual clinical course
  • Screening routine for patient family members
    • Mutation negative – no need for further evaluation or follow-up
    • Mutation positive w/no LV hypertrophy – very likely to develop phenotypic manifestation in adulthood – close follow-up recommended, possible intervention
• Increasing complexity with more understanding of interplay between primary sarcomere abnormalities and other genetic and nongenetic factors
• Some mutations affect cell wall pumps; thus, association with dysrhythmias

Etiology

See Genetics