Hypertrophic Cardiomyopathy Is Not a Diagnosis of Exclusion
Hypertrophic cardiomyopathy (HCM) is not a diagnosis of exclusion but rather a specific clinical entity defined by left ventricular hypertrophy (LVH) that is unexplained by secondary causes. According to the 2020 AHA/ACC guidelines, HCM is characterized by LVH in the absence of another cardiac, systemic, or metabolic disease capable of producing the magnitude of hypertrophy evident in a given patient 1.
Diagnostic Criteria for HCM
In Adults:
- LV wall thickness ≥15 mm in one or more myocardial segments measured by echocardiography or CMR
- More limited hypertrophy (13-14 mm) can be diagnostic when present in family members of HCM patients or with a positive genetic test
- Diagnosis requires the absence of another cause that could explain the degree of hypertrophy
In Children:
- Z-score >2.5 may be appropriate for asymptomatic children with no family history
- Z-score >2 may suffice for children with a definitive family history or positive genetic test
Differential Diagnosis
HCM must be differentiated from other conditions that can cause LVH:
Systemic disorders:
- RASopathies (variants in RAS-MAPK signaling genes)
- Mitochondrial myopathies
- Glycogen/lysosomal storage diseases
- Fabry disease, amyloidosis, sarcoidosis, hemochromatosis, Danon cardiomyopathy
Secondary causes of LVH:
- Athletic training ("athlete's heart")
- Long-standing systemic hypertension
- Aortic stenosis or other obstructive lesions
- Infiltrative diseases
- Metabolic and endocrine disorders
Diagnostic Approach
The 2020 AHA/ACC guidelines outline a systematic approach to diagnosing HCM 1:
- Imaging confirmation: Document increased LV wall thickness using echocardiography or CMR
- Exclude secondary causes: Rule out conditions that could explain the degree of hypertrophy
- Family history assessment: Evaluate for familial pattern of disease
- Genetic testing: Identify disease-causing sarcomere variants (found in 30-60% of cases)
Laboratory Testing
The 2014 ESC guidelines recommend specific laboratory tests to exclude phenocopies 1:
- Hemoglobin
- Renal function tests
- Liver transaminases
- Creatine phosphokinase
- Alpha-galactosidase A (for Fabry disease)
- Immunoglobulin free light chain assay (for amyloidosis)
- Fasting glucose
- Brain natriuretic peptide and troponin T
- Thyroid function tests
- Plasma lactate
Key Distinction
It's important to understand that while HCM requires the exclusion of secondary causes of LVH, this doesn't make it a "diagnosis of exclusion" in the traditional sense. A diagnosis of exclusion typically refers to a condition that can only be diagnosed after all other possible causes have been ruled out, with no specific positive diagnostic criteria.
HCM, by contrast, has specific positive diagnostic criteria (degree of LVH, genetic testing) alongside the requirement to exclude secondary causes. The 2020 AHA/ACC guidelines clearly define HCM as "a disease state in which morphologic expression is confined solely to the heart... characterized predominantly by LVH in the absence of another cardiac, systemic, or metabolic disease capable of producing the magnitude of hypertrophy" 1.
Common Pitfalls in Diagnosis
- Failing to consider phenocopies: Some conditions mimic HCM but require different management approaches
- Misdiagnosing athlete's heart: Athletic remodeling can be distinguished by LV cavity dimension, diastolic function, and response to deconditioning
- Overlooking HCM in hypertensive patients: HCM should be considered when LVH is disproportionate to the severity and duration of hypertension
- Misinterpreting focal hypertrophy: HCM can present with limited hypertrophy confined to only 1-2 LV segments
In summary, HCM is a specific clinical entity with defined diagnostic criteria that includes both positive findings (degree of LVH) and the absence of secondary causes, making it distinct from a true diagnosis of exclusion 2.