Clinical and echocardiographic signs associated with increased interventricular thickness (IVST) due to TTR related amyloidosis

Background: In patients with cardiac symptoms, echocardiography is the first examination to be performed where interventricular septal thickness (IVST) is measured. Transthyretin amyloidosis (TTR) is one of the causes leading to increase in IVST due to amyloid cardiac infiltration. Two different forms of TTR are known: hereditary transthyretin amyloids (TTR-FAP) and wild type (TTR-WT). Cardiologists are under informed of clinical and echocardiographic signs associated with TTR amyloidosis. Aim: Define the clinical and echocardiographic characteristics associated with increased IVST due to TTR amyloidosis to raise cardiologist's awareness of TTR related amyloidosis. Methods: We analyzed the baseline characteristics of 363 patients with echocardiographic-IVST measurement included in the global multicenter observational Transthyretin Amyloidosis Outcomes Survey (THAOS), representing 24% of the 1488 patients included. Patients were divided in four classes (normal, mild, moderated and severe) of IVST according to the American Society of Echocardiography adapted to gender. Results: Increase in IVST was frequent (≥moderate in 57%), correlated to age (R=0.35) and was more frequent in male. IVST was normal in 71 patients, of whom most had TTR-FAP Val30Met mutation (77%). Their median[IQR] age was 37yrs[33,53]. 86 had mild abnormal IVST (11mm [10,12]) with a median[IQR] age of 47yrs[38,63] of whom 1% were TTR-WT. Moderate increase in IVST (15mm[14,16]) was observed in 64 patients, their median age was 67yrs[57,76] and 73% were male and 38% were TTR-WT. 31% had symptomatic motor neuropathy,64% sensory neuropathy and 53% autonomic neuropathy. Systolic blood pressure, ejection fraction and cardiac out-put were normal as well as the E/A ratio. Of the 142 patients with severely abnormal IVST (20mm[18,22]), the median age was 70yrs[61,75], 85% were male, 30% were TTR-WT. 44% of these patients had symptomatic motor neuropathy, 54% a sensory neuropathy and 56% autonomic neuropathy. Systolic blood pressure was normal: 112mmHg[100,130]. Ejection fraction and cardiac out-put were 44%[35-60] and 4.1L/min[3.8,5.4]. Increased in Right ventricle free wall thickness and prevalence of aortic and mitral thickening were more important in moderated and severe IVST class than in mild and normal (each with overall p