How Should We Define Inadequate Coronary Arterial Remodeling?
To the Editor:
After our report1 showing the contribution of “inadequate compensatory enlargement” to the development of coronary narrowing, Mintz et al2 in their recently published report confirmed this concept in a larger study population by using a different definition of “inadequate arterial remodeling.” However, the assessment of the relative importance of “inadequate arterial remodeling” is highly dependent on the definition used.
As pointed out by Mintz et al, the assessment of the true effect of vessel remodeling on the progression of coronary narrowing would require serial or longitudinal intravascular ultrasound studies (IVUS) over a long time period. However, such longitudinal, serial studies are time consuming and impractical. Consequently, we compared the size of the external elastic lamina (EEL) area (the area within the outer border of the sonolucent zone considered to represent EEL) at the lesion site with those at the reference sites. The proximal and distal reference sites were defined as the sites with minimal narrowing by angiography and the largest lumen area and <50% area stenosis as determined by IVUS. In our study,1 the EEL area of all arteries was larger at the proximal reference sites than at the distal reference sites, and “inadequate compensatory enlargement” was defined when there was a smaller EEL area at the lesion site than at the distal reference site. This definition is based on two factors: (1 ) nonatherosclerotic coronary arteries taper from the proximal to the distal portion of the coronary artery and (2 ) “adequate arterial remodeling” at the lesion site should result in the same or more prominent compensatory enlargement of the vessel compared with the distal reference site that has less luminal narrowing. Our definition resulted in a frequency of “inadequate compensatory enlargement” of 26% or approximately 1 in 4 patients.
Mintz et al defined “inadequate arterial remodeling” as a ratio of the lesion EEL area over the proximal reference EEL area ≤0.78 and found that 15% of the lesions they studied met this criteria.2 By applying these criteria to our study population, we found that 14% of the coronary lesions (1 in 7 patients) had “inadequate arterial remodeling,” which reflects an excellent agreement between our studies. Hence the apparent discrepancy between the studies (1 in 4 [26%] versus 1 in 7 [14%]) concerning the relative importance of “inadequate arterial remodeling” seems to be due to different definitions. We, like Pasterkamp et al,3 Mintz et al, and others, hypothesize that a substantial proportion of arterial stenoses are due to not only plaque accumulation but also to the failure to develop compensatory arterial enlargement. In this context we believe that it is essential to carefully assess the rationale behind the definitions of this new entity. Mintz et al based their definition of normal tapering of the coronary artery on their previous study, in which among 146 coronary arteries with focal, hemodynamically significant stenoses, no artery developed EEL area tapering exceeding 21% over a 10-mm arterial length4 from the proximal to the distal reference site. However the proximal and the distal reference sites used for the definition of normal tapering also had atherosclerosis and exhibited an area stenosis of ≈50%, and these “normal sites,” as pointed out by the authors, may be affected by a variable type and degree of vessel remodeling. Moreover, the significant lesion located between both reference sites may have also influenced coronary remodeling at the reference sites. Hence the prevalence of “inadequate coronary arterial remodeling,” suggested by the data presented by Mintz et al are hampered by the fact that they did not use “ideal” reference segments in their definition. Our definition is not based on idealized segments either; rather, we use the coronary artery being imaged as its own “control.” Our criteria use on-line assessment and require no complex calculations or assumptions. IVUS imaging is used to directly assess whether “inadequate compensatory enlargement” at the lesion site is present in the specific coronary artery being assessed for intervention. Should “inadequate compensatory enlargement” have an impact on which coronary interventions are preferable in a given clinical situation, we believe our definition may serve as an appropriate and practical tool for the coronary interventionalist.
- Copyright © 1998 by American Heart Association
Mintz GS, Kent KM, Pichard AD, Satler LF, Popma JJ, Leon MB. Contribution of inadequate arterial remodeling to the development of focal coronary artery stenoses: an intravascular ultrasound study. Circulation. 1997;95:1791–1798.
Pasterkamp G, Wensing PJ, Post MJ, Hillen B, Mali WP, Borst C. Paradoxical arterial wall shrinkage may contribute to luminal narrowing of human atherosclerotic femoral arteries. Circulation. 1995;91:1444–1449.
The reports from Nishioka et al,R1 Pasterkamp et al,R2 and our laboratoryR3 all confirm that inadequate arterial remodeling contributes importantly to the process of atherosclerotic stenosis formation in some lesions.
We agree with Nishioka and colleagues that the definition used in our report required a number of assumptions and was, perhaps, cumbersome. However, all of the studies (including ours) had flaws. Either the sample size was small,R1 R2 the results were potentially biased by lesion selection,R1 R2 R3 or the prevalence was definition dependent.R1 R2 R3
In the report by Nishioka et al,R1 the lesion was compared with a distal reference segment.R1 This comparison also has limitations. First, the ultrasound catheter must be advanced far enough past the lesion into the distal vessel to identify a distal reference segment, something not always possible. Second, the authors did not define the axial distal between their lesion image slice and their distal reference segment. (Because vessels taper, distal reference segment selection will also affect identification of inadequate remodeling.) Third, it has been our experience that crossing a stenosis with the ultrasound catheter, especially a tight stenosis (ie, stenoses most likely to require intervention), causes the distal vessel to become underperfused, (1 ) making identification of the distal reference segment difficult and (2 ) causing the cross-sectional measurements to be unreliably small. Fourth, the distal reference must contain enough of a plaque burden with positive remodeling.
We believe that remodeling is a spectrum and that many stenoses fitting none of the definitions in these three studies may also have an element of inadequate remodeling. Also, none of these studies adequately address whether these findings are present during the early stages of lesion formation in some vessels or whether plaque and arterial shrinkage are late events.
Finally, we believe that the pathologic concepts outlined in all three of these studies are more important than the exact prevalence of the findings and the definitions used.
Nishioka T, Luo H, Eigler NL, Berglund H, Kim CJ, Siegel RJ. 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.
Pasterkamp G, Wensing PJ, Post MJ, Hillen B, Mali WP, Borest C. Paradoxical arterial shrinkage may contribute to luminal narrowing of human atherosclerotic femoral arteries. Circulation. 1995;91:1444–1449.
Mintz GS, Kent KM, Pichard AD, Satler LF, Popma JJ, Leon MB. Contribution of inadequate arterial remodeling to the development of focal artery stenoses: an intravascular ultrasound study. Circulation. 1997;95:1791–1798.