Diabetes induces remodeling of the left atrial appendage independently of atrial fibrillation in a rodent model of type-2 diabetes

Abstract

Background Diabetic patients have an increased predisposition to thromboembolic events, in most cases originating from thrombi in the left atrial appendage (LAA). Remodeling of the LAA, which predisposes to thrombi formation, has been previously described in diabetic patients with atrial fibrillation, but whether remodeling of the LAA occurs in diabetics also in the absence of atrial fibrillation is unknown. To investigate the contribution of diabetes, as opposed to atrial fibrillation, to remodeling of the LAA, we went from humans to the animal model. Methods We studied by echocardiography the structure and function of the heart over multiple time points during the evolution of diabetes in the Cohen diabetic sensitive rat (CDs/y) provided diabetogenic diet over a period of 4 months; CDs/y provided regular diet and the Cohen diabetic resistant (CDr/y), which do not develop diabetes, served as controls. All animals were in sinus rhythm throughout the study period. Results Compared to controls, CDs/y developed during the evolution of diabetes a greater heart mass, larger left atrial diameter, wider LAA orifice, increased LAA depth, greater end-diastolic and end-systolic diameter, and lower E/A ratio—all indicative of remodeling of the LAA and left atrium (LA), as well as the development of left ventricular diastolic dysfunction. To investigate the pathophysiology involved, we studied the histology of the hearts at the end of the study. We found in diabetic CDs/y, but not in any of the other groups, abundance of glycogen granules in the atrial appendages , atria and ventricles, which may be of significance as glycogen granules have previously been associated with cell and organ dysfunction in the diabetic heart. Conclusions We conclude that our rodent model of diabetes, which was in sinus rhythm, reproduced structural and functional alterations previously observed in hearts of human diabetics with atrial fibrillation. Remodeling of the LAA and of the LA in our model was unrelated to atrial fibrillation and associated with accumulation of glycogen granules. We suggest that myocardial accumulation of glycogen granules is related to the development of diabetes and may play a pathophysiological role in remodeling of the LAA and LA, which predisposes to atrial fibrillation, thromboembolic events and left ventricular diastolic dysfunction in the diabetic heart.

Dense SEC connection with Left Atrial Appendage Asynchrony and Mechanical Function in patients with Non-Valvular Atrial Fibrillation

“…Development of diabetes may play a pathophysiological role in remodeling of the LAA and LA, which predisposes to atrial brillation, thromboembolic events and left ventricular diastolic dysfunction in the diabetic heart [22]. It is consistent with our research results.…”

Left Atrial Appendage Depth and Tachycardia Bradycardia Syndrome as Important Predictors of Left Atrial Appendage Thrombus in Patients with Nonvalvular Atrial Fibrillation

“…With the development of NVAF, the LAA develops mechanical dysfunction and fibroelastotic changes on the endocardial surface and this results in LAA remodeling and ultimately left atrial appendage thrombus (LAAT) [ 6 – 8 ]. A larger left atrial diameter, wider LAA orifice, and increased LAA depth indicate remodeling of the left atrial and LAA [ 9 ]; we measured the left atrium anteroposterior diameter (LAD), LTD, left atrial lateral diameter (LLD), maximum LAA ostium axis (max-LAAOA), minimum LAA ostium axis (min-LAAOA), and LAAD with CTA to compare the difference between the LAAT group and non-LAAT group.…”

Glycemic control and atrial fibrillation: an intricate relationship, yet under investigation

“…The stiffening of the cardiac muscle promotes diastolic dysfunction of the left ventricle (LV) and left atrium (LA); the ensuing increase in left ventricular filling pressures and LA dilation promotes AF [ 5 ]. Experimentally, excessive myocardial accumulation of glycogen granules seems to be related to larger LA diameter, wider orifice and increased depth of the left atrial appendage, greater end-diastolic and end-systolic diameter, and lower E/A ratio [ 41 ]. Moreover, LV hypertrophy—a well-known risk factor and prognostic modifier of AF [ 42 ]—has been also associated with DM and abnormal glucose tolerance [ 36 , 43 ].…”