What are the methods for diagnosing idiopathic hypertrophic cardiomyopathy (iHCP)?

Diagnosis of Hypertrophic Cardiomyopathy (HCM)

The diagnosis of HCM requires demonstrating left ventricular wall thickness ≥15 mm (or ≥13 mm in first-degree relatives of confirmed HCM patients) in one or more myocardial segments on cardiac imaging that is not explained solely by loading conditions, combined with comprehensive clinical evaluation including detailed 3-generation family history, physical examination with provocative maneuvers, 12-lead ECG, and transthoracic echocardiography. 1

Initial Clinical Assessment

History and Physical Examination

• Obtain a detailed 3-generation family pedigree to identify relatives with HCM, unexplained sudden death, heart failure, cardiac transplantation, or pacemaker/ICD implants 1
• Document symptoms including dyspnea, chest pain, palpitations, syncope, and lightheadedness, particularly in relation to exertion 1
• Assess for syndromic features or extracardiac manifestations (ataxia, hearing/visual impairment, cognitive abnormalities, neurodevelopmental issues) that may suggest phenocopy conditions 1
• In neonates, inquire about maternal gestational diabetes; in infants <1 year, exclude systemic diseases 1

Physical examination must include provocative maneuvers (Valsalva, squat-to-stand, passive leg raising, walking) to elicit left ventricular outflow tract obstruction 1:

• Classic findings include harsh crescendo-decrescendo systolic murmur at lower left sternal border (from systolic anterior motion of mitral valve)
• Prominent apical point of maximal impulse
• Abnormal carotid pulse
• Fourth heart sound (S4) 1

Diagnostic Testing Algorithm

Electrocardiography

A 12-lead ECG is mandatory in the initial evaluation of all patients with suspected HCM 1:

• The ECG is useful for raising suspicion in family members without left ventricular hypertrophy 1
• Identifies patterns such as Wolff-Parkinson-White syndrome 1
• ECG abnormalities can precede the onset of hypertrophy in genotype-positive individuals 1

Cardiac Imaging

Transthoracic echocardiography (TTE) is the primary imaging modality recommended for initial evaluation of all patients with suspected HCM 1:

Diagnostic criteria:

• ≥15 mm maximal wall thickness in any left ventricular segment in adults (using any imaging technique: echo, CMR, or CT) 1
• ≥13 mm in first-degree relatives of patients with confirmed HCM 1
• In children: wall thickness >2 standard deviations above predicted mean (z-score >2) 1

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 1, 2

Cardiac MRI is indicated when:

• Echocardiography is inconclusive for clinical decision-making 2
• Additional information about magnitude and distribution of hypertrophy may impact management 2
• Apical HCM is suspected (TTE with contrast agent is reasonable alternative) 1

Ambulatory Monitoring

24-hour Holter monitoring is required in the initial evaluation to detect ventricular tachycardia and identify candidates for ICD therapy 1:

• Event recording is recommended if patients develop palpitations or lightheadedness 1
• Repeat Holter every 1-2 years is reasonable to assess for asymptomatic paroxysmal atrial fibrillation/flutter and identify ICD candidates 1, 2

Genetic Testing

Genetic testing is recommended in the index patient to facilitate identification of at-risk first-degree family members 1:

• Counseling by someone knowledgeable in cardiovascular genetics must accompany testing 1
• Testing is particularly important when clinical presentation is atypical or another genetic condition is suspected 1

Critical caveat: Genetic testing is NOT indicated in relatives when the index patient lacks a definitive pathogenic mutation 1

Differential Diagnosis Considerations

Age-specific considerations are crucial 1:

• Inherited metabolic disorders and congenital dysmorphic syndromes are more common in neonates/infants
• Wild-type TTR-related amyloidosis predominantly affects men >65 years
• Physiologic athletic remodeling must be distinguished from pathologic hypertrophy
• Long-standing systemic hypertension, renal disease, and infiltrative diseases (amyloidosis) are important mimics 1

In relatives with lesser degrees of wall thickening (13-14 mm), diagnosis requires evaluation of additional features including family history, non-cardiac symptoms, ECG abnormalities, and multi-modality imaging 1

Family Screening Protocol

For first-degree relatives of confirmed HCM patients 1:

• Clinical screening (physical exam, ECG, TTE) is mandatory unless genotype-negative in families with known definitive mutations
• Children: screening every 12-18 months starting at age 12 years (or earlier if growth spurt, puberty, competitive sports participation, or family history of sudden cardiac death) 1
• Adults: screening approximately every 5 years if asymptomatic 1

For genotype-positive/phenotype-negative individuals, serial ECG, TTE, and clinical assessment every 12-18 months (children/adolescents) or every 5 years (adults) is required 1, 2

Genotype-negative relatives in families with known mutations do not require ongoing clinical screening 1

Common Diagnostic Pitfalls

• Late-onset disease: HCM can develop well into adulthood, so normal echocardiography in adolescence does not definitively exclude disease 3
• Incomplete penetrance: 20-30% of adults carrying disease-causing mutations may not express the phenotype 4
• Isolated basal septal hypertrophy in elderly may represent age-related changes rather than true HCM 1
• Multiple non-diagnostic morphological abnormalities in relatives (incomplete SAM, elongated mitral leaflets, abnormal papillary muscles) combined with ECG changes increase probability of early/mild disease expression 1