Cardiac remodeling and arterial stiffness progression in wild-type vs hereditary transthyretin amyloidosis in Crete.

BACKGROUND

Hereditary transthyretin amyloidosis (hATTR) and wild-type transthyretin amyloidosis (ATTRwt) are two distinct forms of cardiac amyloidosis (CA) differing in genetics, clinical progression, and cardiac remodeling patterns. Understanding these differences is critical for accurate diagnosis and personalized management. This study compared cardiac remodeling progression and arterial stiffness in patients with wild-type and hereditary transthyretin CA in a well-characterized Cretan cohort.

METHODS

We prospectively enrolled 39 CA patients who underwent TTR genotyping and comprehensive clinical, echocardiographic, and vascular assessments, including pulse wave velocity (PWV). Functional capacity and quality of life were evaluated at baseline and six months after tafamidis initiation.

RESULTS

Pathogenic TTR variants were identified in 56 %, mainly pVal114Ala (38.5 %) and pVal50Met (18 %). Mutation carriers were younger (60.8 versus 79.1 years, p < 0.001) and had better functional capacity (6-min walk test, 439 ± 121 m vs. 351 ± 103 m, p = 0.021) and superior myocardial strain (global longitudinal strain) than ATTRwt-CA patients. hATTR-CA showed less left ventricular hypertrophy and atrial dilation. Arterial stiffness (carotid-radial PWV) was higher in hATTR both at baseline and follow-up (p < 0.05), with a trend toward improvement post-treatment. Quality of life favored hATTR after six months. ATTRwt patients showed a trend toward left ventricular hypertrophy regression absent in hATTR.

CONCLUSIONS

TTR genotype influences cardiac remodeling, vascular involvement, and function in CA. hATTR patients with pVal50Met and pVal114Ala variants are younger with better myocardial function but increased arterial stiffness compared to ATTRwt. Our findings indicate the need for genotype-specific assessment and management.