Negative Remodeling at the Ostium of the Left Anterior
Descending Artery Induced Myocardial Ischemia

Negative remodeling is a condition in which the vessel area decreases in size, often as a result of a structural change in the coronary vessel wall. It is a major factor in restenosis following balloon angioplasty, but its contribution to myocardial ischemia in a de novo lesion has not been clearly shown. We report on a patient with exertional angina that was caused by negative remodeling at the ostium of left anterior descending artery (LAD).

Case Report. A 48-year-old female with exertional angina was admitted to our hospital. Electrocardiography revealed inverted T-waves in the aVL and V1–5 leads, and myocardial scintigraphy showed exercise-induced myocardial ischemia in the LAD territory (Figure 1). Thus, coronary angiography was performed, revealing a severe stenosis at the ostium of the LAD (Figure 2). To rule out vasospasm, we administered 2.0 mg of isosorbide dinitrate in the left coronary artery and started an intravenous infusion of nitroglycerin. The degree of stenosis at the ostium did not improve, thus preprocedural intravascular ultrasound (IVUS) was performed. Interestingly the image demonstrated that the lesion had only mild plaque burden and negative remodeling, with a 0.66 ratio of external elastic membrane area of the lesion to the distal site (Figure 3). Though the cross-sectional narrowing percentage was insignificant, we decided to treat the lesion with stenting because negative remodeling caused the myocardial ischemia. Stenting of the ostial LAD was successful (Figure 4), and relieved the patient’s angina.

Discussion. The number of in vivo IVUS reports examining positive remodeling has been increasing, but that of negative remodeling is limited, especially for ostial lesions,because they were excluded in these studies. Case reports of negative remodeling at ostial lesions are also limited. Kobayashi et al presented a case with a 60% stenosis at the ostium of the left circumflex artery and IVUS revealed mild plaque burden and negative remodeling.¹ The minimum luminal area was 5.3 mm² and fractional flow reserve was 0.95, thus the lesion was insignificant and did not require intervention. A small percentage of angiographic stenoses have been demonstrated to develop by negative remodeling without the presence of a large amount of plaque.^2,3 Nishioka et al reported that a reduction of the external elastic membrane area contributed to 39% luminal reduction.⁴ Compared to these reports, including those that excluded ostial lesions in their analyses, our case demonstrated a very small volume of plaque burden, thus it is interesting that negative remodeling contributed to almost all the luminal reduction in our patient.A recent study of serial assessments with IVUS demonstrated that there was an increase in the external elastic membrane area, both at the reference site and at the lesion site at 18- month follow up, and the increase at the reference site was greater than that at the lesion site.⁵ These increases indicate that the coronary lesion remodeled expansively; in contrast, the remodeling index decreased during the follow-up period. Therefore, some lesions classified as having negative remodeling could be lesions with positively remodeled reference segments. Moreover, Shimada et al showed negative remodeling in a bifurcation lesion located distal to the side branch.⁶ Burke et al also reported the lack of association between plaque size and lumen area for the proximal coronary arteries, while there was a significant negative relationship between them for the smaller arteries.⁷ These results suggest that the LAD or circumflex artery ostial lesion just distal to the left main bifurcation may have increased in external elastic membrane area, but the rate of increase was smaller than what occurred at the distal site. As a result, it was classified as negative remodeling. This is one explanation for the negative remodeling at the ostial lesion, but in our patient, the external elastic membrane area at the ostium was too small for a normal vessel, thus the ostial lesion must have shrunk. Though we were unable to determine why a de novo lesion remodeled so constrictively without significant plaque, the case presented here suggests that negative remodeling at the ostial lesion, even without significant plaque burden, could be the main cause of myocardial ischemia.

References

1. Kobayashi Y, Mehran R, Moussa I, et al. Negative remodeling at the ostium of the left circumflex artery. J Invasive Cardiol 2001;13:805–807.

2. Mintz GS, Kent KM, Pichard AD, et al. Contribution of inadequate arterial remodeling to the development of focal coronary artery stenoses: An intravascular ultrasound study. Circulation 1997;95:1791–1798.

3. Hong MK, Mintz GS, Lee CW, et al. Intravascular ultrasound assessment of patterns of arterial remodeling in the absence of significant reference segment plaque burden in patients with coronary artery disease. J Am Coll Cardiol 2003;42:806–810.

4. Nishioka T, Luo H, Eigler NL, et al. Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: An in vivo intravascular ultrasound study. J Am Coll Cardiol 1996;27:1571–1576.

5. Sipahi I, Tuzcu M, Schoenhagen P, et al. Static and serial assessments of coronary arterial remodeling are discordant: An intravascular ultrasound analysis from the reversal of atherosclerosis with aggressive lipid lowering (REVERSAL) trial. Am Heart J 2006;152:544–550.

6. Shimada Y, Courtney BK, Nakamura M, et al. Intravascular ultrasonic analysis of atherosclerotic vessel remodeling and plaque distribution of stenotic left anterior descending coronary arterial bifurcation lesions upstream and downstream of the side branch. Am J Cardiol 2006;98:193–196.

7. Burke AP, Kolodgie FD, Farb A, et al. Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 2002;105:297–303.