Hypertrophic Cardiomyopathy Is Not a Diagnosis of Exclusion
Hypertrophic cardiomyopathy (HCM) is a specific clinical entity with defined diagnostic criteria and is not a diagnosis of exclusion. According to the 2024 AHA/ACC guidelines, HCM is characterized by left ventricular hypertrophy 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
Adults
- Maximal end-diastolic wall thickness ≥15 mm anywhere in the left ventricle on imaging (echocardiography or CMR)
- More limited hypertrophy (13-14 mm) can be diagnostic when present in:
- Family members of a patient with HCM
- Patients with a positive genetic test identifying a pathogenic variant
Children
- Z-score >2.5 for asymptomatic children with no family history
- Z-score >2 for children with a definitive family history or positive genetic test
Differential Diagnosis
HCM must be differentiated from other conditions that can cause LV hypertrophy, including:
Secondary causes of LVH:
- Systemic hypertension
- Aortic stenosis
- Athletic training ("athlete's heart")
Systemic disorders:
- RASopathies
- Mitochondrial myopathies
- Glycogen and lysosomal storage diseases
- Fabry disease
- Amyloidosis
- Sarcoidosis
- Danon cardiomyopathy
The 2024 AHA/ACC guidelines explicitly state that HCM is "characterized predominantly 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. This definition clearly establishes HCM as a specific entity with defined criteria, not a diagnosis reached after excluding all other possibilities.
Common Diagnostic Pitfalls
- Misdiagnosing athlete's heart as HCM
- Overlooking HCM in patients with hypertension
- Failing to consider phenocopies that mimic HCM
- Misinterpreting focal hypertrophy
Diagnostic Approach
- Imaging confirmation of increased LV wall thickness
- Exclusion of secondary causes through clinical evaluation and appropriate testing
- Family history assessment to identify inherited patterns
- Genetic testing to identify pathogenic variants and enable cascade screening of relatives
Key Distinction
While the diagnosis of HCM requires ruling out other causes of LVH, this does not make it a "diagnosis of exclusion" in the traditional sense. Rather, HCM is a specific entity with positive diagnostic criteria (defined wall thickness thresholds, genetic markers) that is distinguished from other conditions that may present similarly.
The 2023 research evidence incorrectly states that "HCM is a diagnosis of exclusion" 2, but this contradicts the more authoritative and recent 2024 AHA/ACC guidelines that define specific diagnostic criteria for HCM 1.