The Thickness That Deceives: The Role of Imaging, Biopsy, and Genetics in the Evaluation of Ventricular Hypertrophy

Increased ventricular wall thickness is a common finding in cardiovascular practice and is frequently attributed either to secondary myocardial hypertrophy or to sarcomeric hypertrophic cardiomyopathy (HCM). However, this phenotype may conceal a broad spectrum of genetic, infiltrative, and storage diseases, each associated with distinct prognostic implications and therapeutic strategies. Accurate differentiation between true myocardial hypertrophy and HCM phenocopies—or genocopies—remains a major diagnostic challenge and requires a multimodality approach integrating advanced cardiac imaging, endomyocardial biopsy (EMB), and genetic testing.^–

Cardiac imaging has evolved beyond morphological assessment. Cardiac magnetic resonance (CMR) with tissue characterization has become a cornerstone of noninvasive evaluation in patients with increased myocardial thickness. Parametric mapping techniques, including T1 and T2 mapping and extracellular volume (ECV) quantification, allow the detection of myocardial compositional changes such as edema, fibrosis, and infiltration, providing important diagnostic clues for conditions such as cardiac amyloidosis, Fabry disease, and glycogen storage cardiomyopathies (e.g., PRKAG2-related disease).^– In addition, specific late gadolinium enhancement patterns may further support the suspicion of non-sarcomeric etiologies.^,

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