How to diagnose Hypertrophic Cardiomyopathy (HCM)?

Diagnostic Approach for Hypertrophic Cardiomyopathy (HCM)

Transthoracic echocardiography (TTE) is the cornerstone diagnostic test for HCM and should be performed in the initial evaluation of all patients with suspected HCM. 1

Initial Diagnostic Testing Algorithm

Step 1: Imaging Studies

• Transthoracic Echocardiography (TTE) - Class I recommendation

  • Diagnostic criteria: LV wall thickness ≥15 mm in one or more myocardial segments in adults 1
  • For children: LV wall thickness >2 standard deviations above predicted mean (z-score >2) 1, 2
  • First-degree relatives: LV wall thickness ≥13 mm may be diagnostic 1, 2
  • Look for:
    • Pattern and distribution of hypertrophy
    • Left ventricular outflow tract obstruction (LVOTO)
    • Systolic anterior motion (SAM) of mitral valve
    • Mitral regurgitation
    • Diastolic function assessment

• Exercise TTE - Class IIa recommendation

  • Useful for detecting and quantifying dynamic LVOT obstruction not present at rest 1
  • Particularly valuable in patients with exertional symptoms but no resting gradient

• Cardiac MRI - When echocardiography is inconclusive

  • Superior for detecting apical or anterolateral hypertrophy
  • Useful for tissue characterization (fibrosis, infiltration)
  • Essential when apical HCM is suspected 3

Step 2: Electrocardiography

• 12-lead ECG - Class I recommendation 1

  • Abnormal in 94-97% of HCM cases 4, 5
  • Key findings:
    • Left ventricular hypertrophy
    • Pathological Q-waves
    • Deep S-waves in V1-V3
    • High R-waves in V4-V6
    • T-wave inversion (particularly in lateral/inferior leads)
    • Giant negative T-waves (characteristic of apical HCM) 4, 6

• 24-hour Holter monitoring - Class I recommendation 1

  • Essential for:
    • Detecting ventricular arrhythmias
    • Identifying candidates for ICD therapy
    • Detecting paroxysmal atrial fibrillation
  • Should be performed in the initial evaluation of all HCM patients 1

Step 3: Laboratory Testing

• Standard laboratory panel 2

  • Complete blood count
  • Metabolic panel
  • Liver function tests
  • Cardiac biomarkers (troponin, BNP)
  • Thyroid function tests

• Specialized testing (when phenocopies are suspected) 2

  • Alpha-galactosidase A (Fabry disease)
  • Immunoglobulin free light chain assay (amyloidosis)
  • Creatine phosphokinase (muscle disease)

Step 4: Genetic Testing

• Genetic testing - Class IIa recommendation 1, 2
  • Reasonable in index patients to facilitate cascade screening of relatives
  • Focuses primarily on sarcomeric protein genes (MYBPC3, MYH7 most common)
  • Essential genetic counseling before and after testing
  • Not indicated in relatives when index patient has no definitive pathogenic mutation

Family Screening Protocol

1. First-degree relatives - Class I recommendation for screening 1

   • 12-lead ECG
   • Transthoracic echocardiography
   • Clinical assessment

2. Screening intervals 1

   • Children and adolescents: Every 12-18 months
   • Adults: Every 3-5 years
   • More frequent if symptoms develop or clinical status changes

3. For genotype-positive/phenotype-negative individuals 1

   • Serial ECG, TTE, and clinical assessment at periodic intervals
   • Children/adolescents: Every 12-18 months
   • Adults: Every 5 years

Common Diagnostic Pitfalls

1. Misdiagnosing athlete's heart

   • Differentiate by LV cavity dimension, diastolic function, pattern of LVH
   • Consider deconditioning to distinguish 2

2. Overlooking HCM in hypertensive patients

   • HCM more likely when LV thickness ≥25 mm or when LVOT obstruction with SAM is present 2

3. Missing apical HCM

   • Often requires contrast echocardiography or CMR for diagnosis 3
   • Look for giant negative T-waves on ECG 4, 6

4. Failing to consider phenocopies

   • Conditions mimicking HCM include amyloidosis, Fabry disease, glycogen storage diseases
   • ECG patterns may help differentiate 4, 6

5. Relying solely on imaging

   • ECG may be abnormal before hypertrophy is evident on imaging
   • In family screening, ECG has shown higher sensitivity than echocardiography 5

By following this systematic approach to diagnosis, clinicians can accurately identify HCM, distinguish it from phenocopies, and implement appropriate monitoring and management strategies to reduce morbidity and mortality in affected individuals.