Functional and Structural Differences in Left Ventricular Remodeling in Primary and Secondary Mitral Regurgitation
Daisuke Onohara, Daniella Espiritu, Weiwei Shi, Roberto Hernandez-Merlo, Vinod H. Thourani, Eric L. Sarin, Robert A. Guyton, Muralidhar Padala.
Emory University, Atlanta, GA, USA.
OBJECTIVE: Left ventricular (LV) dilatation and its transition to decompensated heart failure (HF) differ in patients with primary and secondary mitral regurgitation (MR). We sought to map the temporal changes in LV function, structure and biology in these two MR pathologies, to understand the course of cardiac remodeling to failure.
METHODS: Ninety eight rats (n=98) were randomized to four groups: (G1, n=24)MR only; (G2, n=24)MR with a myocardial infarction(MI); (G3, n=28)MI only; and (G4, n=22)sham. Moderate-to-severe MR was introduced by perforating the anterior mitral leaflet with a needle via the LV apex (Fig A1-3) and MI was created via left coronary ligation (Fig A4). All the rats underwent bi-weekly cardiac echo for 20 weeks, and invasive hemodynamics were measured at 2, 10 and 20 weeks.
RESULTS: Moderate-to-severe MR was reproducible and infarction sizes were comparable. End-diastolic volume was largest in MR+MI at 20 weeks (171% vs. sham, p<0.05), followed by MR only (157% vs. sham, p<0.05), and then MI (129% vs. sham, p<0.05) (Fig B1). Similarly, end-systolic volume was highest in MR+MI (266% vs. sham, p<0.05), followed by MI only (202% vs. sham, p<0.05), and then MR (202% vs. sham, p<0.05) (Fig B2). Ejection fraction 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, MR and MI. End diastolic pressure was significantly elevated in the all experimental groups after introduction of either infarction and regurgitation compared to sham.CONCLUSIONS: MR induced LV dilatation but preserved LV contraction. MI disturbed systolic function, and MR+MI caused systolic dysfunction and dilatation. This data indicates that earlier repair of MR associated with ventricular ischemia may be recommended compared to MR only with ventricular disease.
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