Hemodynamic and Transcriptomic Studies Suggest Early Left Ventricular Dysfunction in a Preclinical Model of Severe Mitral Regurgitation

Abstract Objective Primary mitral regurgitation is a valvular lesion in which the left ventricular ejection fraction remains preserved for long periods, delaying a clinical trigger for mitral valve intervention. In this study, we sought to investigate if adverse left ventricular remodeling occurs prior to a statistically significant fall in ejection fraction and characterize these changes. Methods Sixty-five rats were induced with severe mitral regurgitation by puncturing the mitral valve leaflet with a 23G needle using ultrasound guidance. Rats underwent longitudinal cardiac echocardiography at biweekly intervals, and were terminated at 2wks (n=15), 10wks (n=15), 20wks (n=15), and 40wks (n=15). Sixty age and weight matched healthy rats were used as controls. Unbiased RNA-sequencing was performed at each terminal point. Results Regurgitant fraction was 40.99±9.40%, with pulmonary flow reversal in the experimental group, and none in the control group. Significant fall in ejection fraction occurred at 14wks after MR induction. However, prior to 14wks, end diastolic volume increased by 93.69±52.38% (p Conclusion In this rodent model of mitral regurgitation, left ventricular ejection fraction is preserved for long duration, yet rapid and severe left ventricular dilatation, and biological remodeling occurred prior to a clinically significant fall in ejection fraction.