Apical Hypertrophic Cardiomyopathy in ATTR Val142Ile Carrier: When Genes and Phenotype Diverge

Pathogenic transthyretin (TTR) variants, such as V142I, demonstrate incomplete, age-dependent penetrance and may be present in patients without clinical transthyretin cardiac amyloidosis cardiomyopathy (ATTR-CM). Distinguishing true ATTR-CM from phenocopies like apical HCM (ApHCM) is critical to guide management.

A 61-year-old African-American male with longstanding ApHCM was found to carry the pathogenic TTR V142I variant. Despite genotype positivity, technetium-99m pyrophosphate scintigraphy (H/CL 1.01, visual grade 0) excluded ATTR-CM, and cardiac magnetic resonance imaging confirmed apical-predominant hypertrophy with patchy late gadolinium enhancement consistent with ApHCM. The patient remained stable on medical therapy with ongoing surveillance.

This case illustrates genotype-phenotype discordance in TTR carriers and highlights the importance of integrating genetic data with multimodality imaging. Recognition of phenocopies in patients with the TTR gene prevents misdiagnosis and unnecessary therapy and emphasizes the need for longitudinal surveillance in at-risk patients.

TTR genotypes can be associated with an HCM phenotype. Clinical and imaging correlation is essential to interpret genetic findings and avoid misdiagnosis.