Abstract 16684: Divergent Left Ventricular Remodeling Pathways in Chronic Primary and Secondary Mitral Regurgitation
Introduction: Left ventricular (LV) dilatation and its transition to decompensatory heart failure (HF) differs in patients with primary and secondary mitral regurgitation (MR). Mapping the temporal changes in LV function, structure and biology in these two MR pathologies, can aid in optimal timing of medical and surgical therapy.
Hypothesis: LV dilatation and its transition to HF is more rapid in secondary MR compared to primary MR.
Methods: One hundred and one rats were randomized to four groups: (1)MR only; (2)MR with a myocardial infarction(MI); (3) MI only; and (4)sham. Moderate-to-severe MR was introduced by perforating the anterior mitral leaflet with a needle via the LV apex (Fig A1-3) and an MI via left coronary artery ligation (Fig A4). All the rats underwent bi-weekly cardiac echo for 20 weeks. At sacrifice, invasive hemodynamics were measured and pathway specific gene expression was quantified.
Results: Moderate-to-severe MR was reproducible and infarct sizes were comparable. EDV was largest in MR+MI at 20 weeks (152% vs.sham, p<0.05), followed by MR only (132% vs.sham, p<0.05), and then MI (121% vs.sham, p<0.05) (Fig B1). Similarly, ESV was highest in MR+MI (245% vs. sham, p<0.05), followed by MI only (179% vs. sham, p<0.05), and then MR (161% vs. sham, p<0.05)(Fig B2). EF was reduced in MI+MR and MI, but preserved in MR (Fig B3). Rightward shift of P-V loops indicative of cardiac dysfunction were observed in MI+MR, MI & MR. Extracellular matrix gene arrays reported significant upregulation of collagen type1,alpha 1 (16.47 fold) & connective tissue growth factor (1.93 fold) in MR+MI vs. sham; and up-regulation of collagen type VIII, alpha 1 (2.03 fold) in MI vs. sham; and no differences in the MR group.
Conclusions: MR induced LV dilatation but preserved LV contraction. MI disturbed systolic function, and MR+MI caused systolic dysfunction and dilatation. This data suggests early intervention to rescue HF progression in secondary MR.
Author Disclosures: D. Onohara: None. W. Shi: None. R. Hernandez-Merlo: None. V.H. Thourani: Research Grant; Modest; Abbott Medical, Medtronic, Edwards Lifesciences, Boston Scientific. Consultant/Advisory Board; Modest; St Jude Medical, Edwards Lifesciences. E.L. Sarin: Consultant/Advisory Board; Modest; W L Gore. R.A. Guyton: None. M. Padala: Research Grant; Modest; American Heart Association, Coulter Foundation, Georgia Research Alliance, Carlyle Fraser Heart Center.
- © 2016 by American Heart Association, Inc.