Abstract 304: Adaptive Sarcomeric Remodeling of Left Atrial Cardiomyocytes in Non-failing Non-valvular Atrial Fibrillation

Abstract

Contractile remodeling in sustained atrial fibrillation (AF) has been analyzed by limited studies whose results were confounded by either coexisting systolic heart failure or valve disease (valvular AF) or origin of tissue (right chamber instead of left, atrial appendage instead of main wall). We sought to assess the structural changes in contractile apparatus and its physiological implications on single cardiomyocyte mechanics in patients with non-failing non-valvular AF. We utilized left atrial wall tissue from rejected donor hearts from 5 subjects in sinus rhythm (SR) and 3 with AF (age 50, 2♀ vs 60, 1♀), all with no signs of cardiovascular or valvular disease. Isolated single skinned myocytes were mounted to a force transducer and length controller and set to an initial sarcomere length of 2.1 μm. Isometric active and passive forces were recorded using custom software during [Ca2+] solution switching (0.79 - 46.8 μM). Surprisingly, we found that isometric maximal calcium-activated force (Fmax) was almost two times higher in AF compared to SR patients (n: SR = 15 cells, AF = 9 cells, p < 0.0001). This was unexpected, as previous studies found that AF patients had depressed contractile function, although these were confounded by heart failure and valve disease. There were no differences in calcium sensitivity, hill coefficient, or cell cross-sectional area (CSA) between SR and AF. We next performed 1D SDS-PAGE electrophoresis to compare myosin heavy chain (MHC) isoforms. In SR patients, atrial expression of β-MHC was very low (14% of total MHC expression), but this was significantly elevated in AF patients (37%, p = 0.05). The observed rise in contractile force might be a compensatory adaptation to sustain ventricular filling in initial stages of non-valvular non-failing AF patients. Or it may be a maladaptive response to atrial unloading resulting in wasted energy utilization. The contribution of this cellular increase in contractility to whole organ function is unclear. There is strong evidence that fibrotic remodeling and inflammation play an important role in AF, but the clinical challenge is still significant. Conversely, there has been very little work done on the contractile apparatus in AF, and whether it may represent a possible therapeutic target.