Advanced Echocardiographic Assessment in Transthyretin Amyloidosis: Early Phenotype Markers in Mutation Carriers

Background Transthyretin cardiac amyloidosis (ATTR-CA) is a life-threatening heart condition due to mutations in the transthyretin (TTR) gene. This study aimed to investigate ventricular global longitudinal strain (GLS) and global circumferential strain (GCS) alongside traditional echocardiographic measures in TTR carries with preserved ejection fraction (EF). Methods Individuals with a family history of ATTR-CA, positive genetic testing for TTR, no clinical cardiac involvement and preserved EF were matched with healthy controls. Results Sixty-five patients were included: 31 TTR+ and 34 controls. No significant differences in chamber dimensions or EF were observed between groups. However, septal velocities were markedly lower in TTR+ than controls (9 [7;12] cm/s vs. 12 [10;13] cm/s, p=0.003). Additionally, both GCS and GLS were significantly reduced in the TTR+ group compared to controls (-21 ±4% vs. -28 ±4%, p<0.001 and -19 ±3% vs. -25 ±2%, p<0.001, respectively). Furthermore, right ventricular strain showed a similar trend, being lower in the TTR+ group compared to controls (-18 ±4% vs. -25 ±5%, p<0.005). Logistic regression analysis identified GLS (OR = 2.46; 95% CI 1.30-4.62) and E/e’ mean ratio (OR = 2.04; 95% CI 1.09-3.91) as independent predictors of positive genetic testing for TTR. Conclusion Asymptomatic individuals with a family history of ATTR-CA and positive genetic testing for TTR, despite preserved EF, exhibit lower GLS and GCS compared to controls. GLS and the E/e’ ratio were identified as independent predictors of positive genetic testing for TTR.