Transthyretin-related amyloid cardiomyopathy: A single-center experience in southern Poland, an endemic area.

BACKGROUND

Transthyretin amyloid cardiomyopathy (ATTR CA) is a rare, fatal disease characterised by the deposition of amyloid fibrils derived from misfolded transthyretin (TTR) protein. This single-center study investigated the clinical characteristics, genetic profile, and geographic distribution of ATTR CA patients in southern Poland, a suspected endemic area.

MATERIAL AND METHODS

This prospective study was conducted between 2020 and 2025 involving 100 adults, including a cohort of consecutive index patients with confirmed ATTR CA. Furthermore, all consenting first-degree relatives were invited to undergo targeted assessment through a familial cascade screening approach. The study incorporated clinical data, echocardiography, scintigraphy, genetic testing, and prospective follow-up for five years to assess all-cause mortality.

RESULTS

Among 100 participants (27 index patients and 73 relatives), 6 relatives were diagnosed with ATTR CA and 15 were identified as carriers of a pathogenic TTR variant. The most frequently identified TTR variant was Phe53Leu, suggesting a high regional prevalence in southern Poland, alongside Glu109Lys, Glu122Lys, and Glu82Lys. The presence of hereditary ATTR CA was significantly associated with increased risk of all-cause mortality (HR, 7.67; 95% CI, 2.33-25.26; P < 0.001). All 33 patients with ATTR CA were eligible for tafamidis; moreover, two patients in this cohort with polyneuropathy were treated with inotersen, representing the first applications of these therapies in Poland.

CONCLUSION

A comprehensive diagnostic approach is crucial for timely initiation of disease-modifying therapies. Our study suggests that, in this region, there is a high rate of the Phe53Leu TTR variant; however, further research is needed to validate these findings (NCT05814380).