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

BACKGROUND: The cardiac manifestations of late-onset hereditary transthyretin amyloidosis with p.A97S variant have not been extensively studied, and the prognostic factors remain unclear. METHODS: 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. RESULTS: 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). CONCLUSION: 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.