(P162) HEREDITARY PATTERNS AND FAMILY SCREENING IN TRANSTHYRETIN CARDIAC AMYLOIDOSIS

Background: The prevalence of hereditary transthyretin amyloidosis (hATTR) among patients with transthyretin amyloid cardiomyopathy (ATTR) remains poorly documented, particularly in Canada. Additionally, the effectiveness of cascade genetic screening following hATTR diagnosis in family members has been poorly studied.

METHODS AND RESULTS: In this retrospective cohort study, the infiltrative cardiomyopathy clinic and the genetics clinic databases were searched for ATTR cases between 2014 and 2024. Diagnostic criteria for ATTR were an uptake of grade 2 or 3 on myocardial pyrophosphate scintigraphy in the absence of monoclonal protein, or a histological confirmation of TTR amyloidosis on cardiac biopsy. Clinical characteristics were compared using chi-square and student t-tests where appropriate.

Among 212 patients with ATTR, 179 (84%) individuals underwent genetic testing, among whom 13% (23/179) tested positive for a (likely) pathogenic TTR variant. Patients with hATTR were younger than wild-type ATTR (ATTRwt) at diagnosis (mean age, 73 ± 11 years vs 81 ± 7 years, respectively, P=0.002). The most common variant was V142I (17/23, 74%).

Analysis of comorbidities showed that 60% of ATTRwt patients had atrial fibrillation compared to 30% in hATTR (P=0.014). Laboratory, imaging, and neurological findings did not reveal significant differences between hATTR and ATTRwt. Five families with hATTR underwent cascade genetic testing of family members, leading to the identification of one (1/13, 8%) new case of hATTR. This individual has been initiated on Tafamidis. Among all family members tested, 46% of individuals (6/13) tested positive for a TTR mutation (mean age 62 ± 11 years and 83% female) but did not display the phenotype of ATTR-cardiomyopathy.

Conclusion: Our findings suggest that the prevalence of hereditary cardiac amyloidosis in an unselected cohort is lower than previously reported. Clinical data alone is insufficient for predicting whether ATTR cardiomyopathy is attributed to hATTR or ATTRwt, underscoring the importance of genetic testing. Furthermore, the efficacy of family testing cascade warrants longer-term evaluation of family members.