Author's reply

Abstract

We read with great interest the letter written by Antonio Recupero et al. and we are thankful for their comments regarding our manuscript. The main findings of our study [1] indicate that left atrial (LA) function parameters are significantly altered among patients with systemic light chain amyloidosis (AL) compared to a group of control patients, especially in those with moderate or severe cardiac involvement. Additionally, LA functional parameters are associated with worse diastolic dysfunction and overall mortality irrespective of the New York Heart Association functional class, Mayo Clinic staging, and LA volumes. In our study, LA dysfunction appears to have an incremental prognostic value over the classic prognostic parameters. Its prognostic value was not related only to Mayo Clinic staging as stated in the letter by Recuperon et al. but was also associated with outcome by multivariate analysis independently of the Mayo clinic staging and LA volumes as shown in Table 4 of our paper. Still we acknowledged in the limitations and conclusion in our manuscript that larger studies from other centers are required in order to confirm our findings and to investigate whether LA dysfunction may turn out to be an earlier diagnostic marker of cardiac involvement in AL patients. Moreover, we did not demonstrate only "a continuum in LA dysfunction" from early to mild to moderate then severe Mayo Clinic staging, but it also suggested an early impairment in function when control subjects were compared to stage I AL patients with minimal cardiac involvement (Table 2). This phenomenon was evident even before any significant changes in LA volumes. Our findings suggest that LA dysfunction occurs before the LA begins to dilate in AL patients. The authors of the letter also stated that "the LA chamber might be the primary target" of amyloid deposits in patients with transthyretin amyloidosis because late gadolinium enhancement (LGE) was seen early within the LA wall and before left ventricular (LV) involvement. However, this statement is an assumption since there was no correlation done between LGE and fibril location on myocardial biopsy. Therefore, one cannot state that the LA is infiltrated by amyloid fibrils before the LV unless this statement is supported by histological data in a longitudinal chronological manner. Our current understanding of the disease process in AL amyloidosis is that the amyloid deposits are likely to be first detected at the basal segments of the LV walls (as demonstrated using strain, magnetic resonance imaging and histological correlation by Ternacle et al. in 2016 [2]) and gradually progress toward the LV apex showing a basal-to-apical gradient of amyloid fibrils deposition. Additional histological studies are still required to better understand the course and the natural history of AL amyloidosis.Finally, the association between LA function and outcome that was suggested by our study is beginning to emerge as a concept in other disease states [3]. The recent interest in studying LA functional param...

Current Perspectives on Atrial Amyloidosis: A Narrative Review

“…Heart valves are frequently thickened by amyloid deposits: 42% of patients with light chain amyloidosis had a thickening of 3 mm of the mitral valve at echocardiographic diagnosis. In a study, these patients were often elderly with an advanced NYHA class [ 37 , 38 , 39 , 40 , 41 ]. These alterations can be found also in the other forms of the disease, such as the transthyretin type [ 42 ] and have a negative prognostic significance [ 40 , 43 ].…”