Diagnostic Approach to Hypertrophic Cardiomyopathy

Initial Mandatory Testing

The European Society of Cardiology recommends measuring maximum diastolic wall thickness using 2D short-axis views in all LV segments from base to apex 1
The European Society of Cardiology suggests performing imaging at rest and during Valsalva maneuver in sitting and semi-supine positions, then standing if no gradient is provoked 1
The European Society of Cardiology advises assessing for left ventricular outflow tract obstruction, measuring peak instantaneous gradients 1
The European Society of Cardiology recommends evaluating LV diastolic function including pulsed Doppler of mitral valve inflow, tissue Doppler velocities at mitral annulus, pulmonary vein flow velocities, pulmonary artery systolic pressure, and left atrial size/volume 1

The European Society of Cardiology suggests considering TTE with LV cavity opacification using intravenous echocardiographic contrast agents in patients with suboptimal images or suspected LV apical hypertrophy or aneurysm as an alternative to CMR 1
The European Society of Cardiology recommends considering TOE when the mechanism of LVOTO is unclear, when assessing mitral valve apparatus before septal reduction procedures, or when severe mitral regurgitation from intrinsic valve abnormalities is suspected 1

The European Society of Cardiology notes that increased interatrial septum thickness should prompt consideration of amyloidosis 1
The European Society of Cardiology advises that increased AV valve thickness should prompt consideration of amyloidosis or Anderson-Fabry disease 1
The European Society of Cardiology recommends considering alternative diagnoses such as amyloidosis, myocarditis, Anderson-Fabry disease, or Noonan syndrome when increased RV free wall thickness is observed 1
The European Society of Cardiology suggests that mild to moderate pericardial effusion should prompt consideration of amyloidosis or myocarditis 1
The European Society of Cardiology notes that a ground-glass appearance should prompt consideration of amyloidosis 1
The European Society of Cardiology advises that concentric LVH should prompt consideration of glycogen storage disease, Anderson-Fabry disease, or PRKAG2 mutations 1
The European Society of Cardiology recommends considering Danon disease or Pompe disease when extreme concentric LVH (wall thickness ≥30 mm) is observed 1
The European Society of Cardiology suggests that global LV hypokinesia should prompt consideration of mitochondrial disease, TTR-related amyloidosis, PRKAG2 mutations, Danon disease, myocarditis, or advanced sarcomeric HCM 1

The European Society of Cardiology recommends performing exercise TTE in standing, sitting, or semi-supine position to detect provocable LVOTO and exercise-induced mitral regurgitation in symptomatic patients with resting or provoked peak instantaneous LV outflow tract gradient <50 mm Hg 1

The American College of Cardiology recommends obtaining a detailed 3-generation family pedigree to identify relatives with HCM, unexplained sudden death, heart failure, cardiac transplantation, or pacemaker/ICD implants 2, 3
Document symptoms including dyspnea, chest pain, palpitations, syncope, and lightheadedness, particularly in relation to exertion 2
Assess for syndromic features or extracardiac manifestations (ataxia, hearing/visual impairment, cognitive abnormalities, neurodevelopmental issues) that may suggest phenocopy conditions 2
Physical examination must include provocative maneuvers (Valsalva, squat-to-stand, passive leg raising, walking) to elicit left ventricular outflow tract obstruction 2

A 12-lead ECG is mandatory in the initial evaluation of all patients with suspected HCM 4, 5, 6, 7
Transthoracic echocardiography (TTE) is the primary imaging modality recommended for initial evaluation of all patients with suspected HCM 4, 5, 6, 7
Diagnostic criteria include ≥15 mm maximal wall thickness in any left ventricular segment in adults, and ≥13 mm in first-degree relatives of patients with confirmed HCM 3
Exercise TTE should be performed when resting gradients are absent but symptoms suggest dynamic obstruction, to detect and quantify exercise-induced left ventricular outflow tract obstruction 6

Genetic testing is recommended in the index patient to facilitate identification of at-risk first-degree family members 4, 5, 7
Counseling by someone knowledgeable in cardiovascular genetics must accompany testing 4, 3

For first-degree relatives of confirmed HCM patients, clinical screening (physical exam, ECG, TTE) is mandatory unless genotype-negative in families with known definitive mutations 4, 5, 6, 7
Children should be screened every 12-18 months starting at age 12 years, and adults approximately every 5 years if asymptomatic 4, 5, 6, 7, 8

Age-specific considerations are crucial, including inherited metabolic disorders and congenital dysmorphic syndromes in neonates/infants, and wild-type TTR-related amyloidosis in men >65 years 3
Physiologic athletic remodeling must be distinguished from pathologic hypertrophy 9
Long-standing systemic hypertension, renal disease, and infiltrative diseases (amyloidosis) are important mimics 2, 3