Cardiac manifestations and prognostic implications of hereditary transthyretin amyloidosis associated with transthyretin Ala97Ser

Abstract

The cardiac manifestations of late-onset hereditary transthyretin amyloidosis with p.A97S variant have not been extensively studied, and the prognostic factors remain unclear. The clinical profile, echocardiography, and ECG of patients diagnosed with ATTR p.A97S polyneuropathy between 2000 and 2016 were retrospectively collected. 67 patients with ATTR p.A97S were collected. A total of 82% of patients met the criteria for left ventricular (LV) hypertrophy. Reduced global longitudinal strain (GLS) was noted in 42.1% of patients, and 14% of patients had a relative apical sparing pattern. A low voltage pattern in the ECG was observed in 31.3% of patients, while 64.2% presented with a pseudoinfarction pattern. End-systolic LV inner dimension (HR: 2.25 (95% CI: 1.01-5.01), p=0.048), reduced GLS (HR: 5.26 (1.08-25.0), p=0.039), relative apical longitudinal strain (RALS>1, HR: 8.57 (1.69-43.3), p=0.009), increased E/A ratio (HR: 6.51 (1.17-36.4), p=0.033), and increased QRS duration (HR: 1.02 (1.00-1.04), p=0.05) were correlated with reduced survival in univariate analysis. Multivariate analysis revealed reduced RALS was significantly correlated with reduced survival (HR: 13.00 (1.81-93.45), p=0.011). Our findings reveal that ATTR p.A97S is a cardiomyopathy as well as a polyneuropathic syndrome. Routine use of more contemporary echocardiographic techniques are recommended to identify cardiac amyloidosis and provide prognostic information.