Abstract 12628: Late Repair of Ischemic Mitral Regurgitation does not Prevent Left Ventricular Remodeling: Importance of Timing for Beneficial Repair
Introduction: Ischemic mitral regurgitation (MR) is a frequent complication of myocardial infarction (MI) associated with left ventricular (LV) dilatation and reduced contractility that doubles mortality. At the molecular level, moderate volume overload after MI is characterized by a biphasic response with initial compensatory rise in pro-hypertrophic and anti-apoptotic signals followed by their exhaustion. We have shown that early MR repair 30 days after MI is associated with LV reverse remodeling. It is not known if MR repair performed after the exhaustion of compensatory mechanisms is also beneficial. We hypothesised that late MR repair will not result in LV reverse remodeling.
Methods: Twelve sheep underwent distal left anterior descending coronary artery ligation to create apical MI, and implantation of a LV to left atrium shunt to create standardized moderate volume overload. At 90 days, animals were randomized to shunt closure (late MR repair) vs sham surgery (no repair). LV remodeling was assessed by 3D echocardiography, dP/dt, preload recruitable stroke work (PRSW) and myocardial biopsies.
Results: At 90 days, both groups had moderate volume overload, increased LV volume and reduced ejection fraction (all p<0.01 vs baseline, p=NS between groups). Shunt closure at 90 days corrected the volume overload (regurgitant fraction 6±5% vs 27±16% for late MR repair vs sham, p<0.01). However, late repair was not associated with changes in LV volume (end-diastolic volume 106±15 vs 110±22 ml; end-systolic volume 35±6 vs 36±6 ml), PRSW (41±7 vs 39±13 ml•mmHg) or dP/dt (803±210 vs 732±194 mmHg/sec) at 120 days (all p=NS). Levels of activated akt, central in the hypertrophic process, and STAT3, a critical node in the hypertrophic stimulus by cytokines, were depressed equally in both groups.
Conclusion: Late correction of moderate volume overload after MI did not improve LV volume or contractility. Up-regulation of pro-hypertrophic intra-cellular pathways was not observed. These results contrast with previously reported identical models in which early repair at 30 days resulted in marked LV reverse remodeling. This suggests a “window of opportunity” to repair ischemic MR, after which no beneficial effect on LV is observed despite successful repair.
- © 2012 by American Heart Association, Inc.