Ann Thorac Surg 2008;86:1249. doi:10.1016/j.athoracsur.2008.07.041
© 2008 The Society of Thoracic Surgeons
Original Articles: Adult Cardiac
Invited Commentary
Torsten Doenst, MD, PhD
Department of Cardiac Surgery, University of Leipzig-Heart Center, Struempellstr 39, Leipzig, 04289 Germany
(Email: torsten.doenst{at}med.uni-leipzig.de).
Left ventricular remodeling (ie, the global hypertrophic and dilatory response of the heart to a local infarct) is one of the main and still growing causes for heart failure. It is characterized by an imbalance of extracellular matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitor of MMPs [TIMPs]). Therapeutic approaches are being developed and tested to prevent or even reverse remodeling, but pharmacologic options are still in their experimental stage. In contrast, surgical ventricular reconstruction has been advocated as a potential therapeutic tool to stop the remodeling process. However, so far its efficacy has not been demonstrated. The Surgical Treatment of IsChemic Heart failure (STICH) trial has reactivated this discussion and will provide outcomes soon.
In this article, Hsu and colleagues [1] provide important experimental evidence that left ventricular aneurysm resection improves cardiac function and prevents remodeling, possibly by reducing wall tension and readjusting the balance of MMPs and TIMPs. The authors demonstrate consistent left ventricular (LV) aneurysm formation after left anterior descending coronary artery (LAD) ligation. Resection of the aneurysm by tying a pursestring suture around the apex was associated with normal LV size, normal ejection fraction, decreased expression of TIMPs and MMPs, and less fibrosis 10 weeks after surgery. These findings are promising because they provide experimental evidence for the efficacy of surgical ventricular reconstruction on the cellular and extracellular matrix level. It also provides a potential link to the underlying mechanism of surgical action.
However, in humans, only 20% of patients develop aneurysms and global remodeling after infarction. This observation suggests caution in transferring the results to the clinical scenario. Thus, identifying the mechanisms of post-infarct remodeling in both rodents and humans is key. A role for MMPs and TIMPs is undeniable, but to establish mechanisms, one has to go further. Two important questions remain to be addressed. First, is the MMP–TIMP system cause or effect for aneurysm formation and remodeling? A time course of post-infarct TIMP and MMP activity and external modulation of their activity levels by inhibitors or activators would be required. Second, does aneurysm resection stop or even reverse the remodeling process? This question is critical for the clinical setting, because it would help to address whether aneurysm surgery may not only be helpful in patients with limited remodeling effects, but also in patients with grossly remodeled ventricles. Hsu and colleagues [1] have performed an intelligent and important study representing a step in the right direction. It remains to wish that further steps will follow.
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- Hsu C-P, Huang C-Y, Wang J-S, Sun P-C, Shih C-C. Extracellular matrix remodeling attenuated after experimental postinfarct left ventricular aneurysm repair Ann Thorac Surg 2008;86:1243-1249.[Abstract/Free Full Text]
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Extracellular Matrix Remodeling Attenuated After Experimental Postinfarct Left Ventricular Aneurysm Repair
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