Atrial structure and function in patients with amyloidosis: findings from the NEURO-TTRansform study

Abstract Background Amyloidosis is due to misfolded amyloid fibril deposition in multiple tissues resulting in cardiac disease and neuropathy. Amyloid cardiomyopathy, a marker of worse prognosis, is chararacterized by left ventricular hypertrophy, conduction disease, diastolic dysfunction, and possibly left atrial dysfunction. Purpose To assess left atrial (LA) structure and function among patients with amyloid polyneuropathy. Methods Patients enrolled in the NEURO-TTRansform study, an open label study with historical control, randomized to eplontersen vs inotersen, then cross over from inotersen to eplontersen of adult patients with Coutinho Stage 1 OR 2 disease, were studied. Comprehensive echocardiographic analyses were performed in a core laboratory, including detailed LA strain analyses (LA reservoir, LA conduit, LA contractile strain). Patients were grouped based on absence/presence of known cardiac involvement, and on number of abnormalities in LA strain parameters at baseline. Results A total of 204 patients enrolled (mean age 54.9 ± 15.0 years, 141 69.1% male), 79 (39%) had known cardiac involvement. Abnormalities in LA strain were present in 52% of patients in the polyneuropathy group and 75% of those with known mixed phenotype (p 0.01; Panel A). There were 67 (32.8%), 78 (38.2%) and 109 (53.4%) with abnormal reservoir, conduit, or contractile strain, respectively. In comparison, in healthy individuals free of cardiac disease from the Atherosclerosis Risk in Communities (ARIC study) (mean age 75 years), 27.3%, 26% and 12% had abnormalities in LA reservoir, conduit, or contractile strain, respectively. Worse LA reservoir strain was associated with increasing NT-proBNP, worsening Mayo Clinic stage and increased IVS thickness (Panel B). Conclusions In a population of patients with amyloid polyneuropathy, abnormalities of LA strain were highly prevalent, even in patients without known cardiac involvement. This suggests LA strain can be used as a marker of early amyloid cardiac disease and should be looked for in patients with known genetic variants. Figure: A. Number of strain abnormalities by Cardiac Status. B. LA reservoir strain by clinical, genetic, staging, biomarkers, and echocardiographic markers of severity.