What is the estimated percentage of patients with Hypertrophic Cardiomyopathy (HCM) that will experience sudden cardiac death?

Estimated Percentage of Patients with HCM That Will Experience Sudden Death

The annual rate of sudden cardiac death (SCD) in the general hypertrophic cardiomyopathy (HCM) population is approximately 0.5% to 1% per year, with an estimated 5-year risk of 5.9% in patients without conventional risk factors. 1

Risk of Sudden Death in HCM

The risk of sudden death in HCM varies significantly based on several factors:

General Population Risk

• Contemporary management strategies have reduced HCM-related mortality to approximately 0.5% per year 2
• Only about 25% of HCM patients ultimately die from their disease, with the majority of deaths being unrelated to HCM, especially in older adults 2
• In patients without conventional risk factors but with no or mild symptoms, the sudden death event rate is 0.6% per year 1

Age-Related Risk

• Risk is highest in young patients (under 30 years of age) 2
• Children and adolescents experience sudden death rates near the top of the range (1.5% per year) 3
• SCD risk is inversely related to age, while heart failure and stroke death risk increases with age 1
• Age-specific annual mortality rates:
  • Ages 5-15 years: 1.8% per year
  • Ages 16-65 years: 1.0-1.5% per year
  • Ages 66-75 years: 3.9% per year
  • Ages >75 years: 4.7% per year 3

Risk Stratification

The 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR guideline identifies several major risk factors for SCD in HCM 2:

1. Previous cardiac arrest or sustained ventricular arrhythmias
2. Family history of SCD in first-degree relatives under 50 years
3. Unexplained syncope (especially within 6 months of evaluation)
4. Massive left ventricular hypertrophy (≥30 mm wall thickness)
5. LV systolic dysfunction (EF <50%)
6. LV apical aneurysm
7. Extensive late gadolinium enhancement on CMR (≥15% of LV mass)
8. Non-sustained ventricular tachycardia on ambulatory monitoring

High-Risk Subgroups

Patients with extreme hypertrophy (wall thickness ≥30 mm) have substantially higher risk:

• 20% over 10 years
• 40% over 20 years
• Annual mortality approximately 2% 2

Clinical Implications

1. Risk Assessment: All HCM patients (particularly those under 60 years) should undergo comprehensive annual risk stratification including:

   • Personal and family history
   • Echocardiography
   • 24-48 hour ambulatory ECG monitoring
   • Blood pressure response during exercise 2

2. Risk Calculator: For adults with HCM, calculating the estimated 5-year SCD risk using validated models is recommended to guide ICD decisions 2

3. Negative Predictive Value: Patients with no risk factors have an excellent prognosis and generally can lead a normal life 4

4. Multiple Risk Factors: The relationship between mortality risk and number of risk factors is nonlinear—each additional risk factor is associated with disproportionately greater risk 3

Important Caveats

1. Even patients with wall thickness less than 30 mm can die suddenly—the majority of patients who die suddenly have wall thicknesses less than 30 mm 2

2. A small subset of patients with high-risk genetic mutations (particularly troponin T and I) may experience SCD despite mild or even normal wall thickness 2

3. Only about 3% of HCM patients who die suddenly have none of the currently acknowledged risk markers 2

4. Two-thirds of HCM-related deaths in individuals between 5 and 59 years occur during routine daily activities (43%) or rest/sleep (24%), not during intense physical activity 2

Understanding the risk of sudden death in HCM is essential for appropriate risk stratification and management decisions, particularly regarding ICD implantation for primary prevention.