분지병변에서 측부간지 폐쇄의 기전에 대한 혈관내 초음파 연구

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분지병변에서 측부간지 폐쇄의 기전에 대한 혈관내 초음파 연구

굿모닝병원 순환기내과¹, 국민건강보험 일산병원 심장내과²

이원경

¹

, 오성진

²

, 문용선

²

, 전동운

²

, 양주영

²

Mechanisms of Side Branch Jailing with Stenting at Bifurcation Lesions:

Volumetric Intravascular Ultrasound Analysis

Won Kyung Lee

¹

, Seung Jin Oh

²

, Yong Seon Moon

²

, Dong Woon Jeon

²

, Joo Young Yang

²

1Division of Cardiology, Good Morning Hospital, Pyeongtaek,

2Division of Cardiology, Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea

Background: Although plaque shift is believed to be the principal mechanism of side branch (SB) jailing in the percutaneous coronary intervention (PCI) of bifurcation lesions, objective evidence is lacking.

Methods: We analyzed volumetric intravascular ultrasound parameters before and after PCI in 55 bifurcation lesions. The lesions were classified into jailed (n=23) or patent group (n=32) according to SB jailing occurrence. Cross sections were analyzed by 1 mm intervals in segments that were 5 mm proximal and distal to the SB ostium, and were analyzed separately (proximal vs.

distal portion).

Results: Before PCI, the distal portion of the jailed group showed significantly smaller lumen and external elastic lamina (EEM) volume than the patent group (19.8±6.8 vs. 28.4±11.0 mm³, 43.8±11.1 vs. 53.6±13.4 mm³, respectively; p=0.006, 0.002), whereas plaque and media (P&M) volume did not differ between groups (24.0±11.8 vs. 25.1±11.2 mm³, p=0.73). All parameters related to the proximal portion were similar in both groups. After PCI, lumen volume of the distal portion increased significantly more in the jailed group than the patent group (+16.7±10.0 vs. +11.0±8.5 mm³, p=0.026). This was mainly derived from EEM volume expansion (49.5 to 60.4 mm³, p<0.001) than from P&M volume reduction (24.7 to 22.3 mm³, p=0.012). The proximal portion showed no significant differences in mean changes of EEM, lumen, and P&M volume between groups.

Conclusion: Instead of plaque shift, over-expansion of the distal relative to the proximal portion of a bifurcation lesion, which shifts the carina toward the SB, may be the main mechanism of SB jailing.

Key Words: Intravascular ultrasound, Percutaneous coronary intervention, Bifurcation

책임저자: 오성진

10444 경기도 고양시 일산동구 일산로 100 국민건강보험 일산병원 심장내과 전화 : (031)900-3164, 팩스 : (031)900-0639 E-mail : osjwsa@naver.com

INTRODUCTION

Percutaneous coronary intervention (PCI) of bifurcation lesions has always been challenging. Despite the initial expecta- tion that drug-eluting stents would finally address this longs- tanding problem, various techniques involving complex two- stent strategies have failed to prove their superiority over the single-stent strategy in terms of short- and long-term out-

comes.^1,2 Thus, the single-stent strategy remains the standard treatment for these lesions despite its consistent association with a high incidence of procedural complications, such as side branch (SB) jailing and peri-procedural myocardial infarction.^3,4 Also, Side branch predilatation before main vessel stenting may be associated with an increased risk of repeat revasculari- zation in patients with true nonleft main bifurcation.⁵ Several studies aimed at identifying the mechanism and predictors of SB jailing have been based solely on angiographic quantitative coronary analysis (QCA) despite the fact that intravascular ultrasound (IVUS) has already provided in-depth information in other various lesion subsets.^6,7 Therefore, we investigated the underlying mechanism and potential predictors of SB jailing by means of volumetric IVUS analysis.

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Fig. 1. Schematic representation of study segments within the proximal and distal portions in a bifurcation lesion. The proximal and distal slices of the side branch ostium (‘P’ and ‘D’) are shown.

MATERIALS AND METHODS

1. Patient population

We identified in our institutional database a total of 98 con- secutive de novo bifurcation lesions that were treated with single-stent implantation in the main vessel across the SB and that underwent both pre- and post-stenting (before additional intervention, such as kissing balloon dilatation or SB stenting) IVUS imaging. We exclusively included lesions without SB ostial disease (reference diameter >2.5 mm and % diameter stenosis

<50% on QCA of SB) to rule out the influence of SB ostial plaque and to assess the pure effects of main vessel plaque movement. After reviewing IVUS images, lesions with inade- quate image quality secondary to severe calcification, insuffi- cient stented length to cover the study segments by protocol (5 mm proximal and distal to the SB ostium), or other side branch arising within the study segments were excluded. The remaining 55 lesions in 53 patients were included in this analysis. Prespecified clinical and procedural data were obtained from hospital charts. Written informed consent was obtained from all patients, and the study was conducted with the app- roval of the Institutional Review Board.

2. IVUS Image Analysis and Measurements IVUS imaging was performed in a standard fashion with commercially available equipment (Galaxy, Boston Scientific Inc., USA) and 3.0 Fr Atlantis imaging catheters (40 MHz).

Pre- and post-PCI IVUS analysis was performed using images acquired before pre-dilation and after high-pressure adjuvant ballooning (before final kissing balloon dilation, if conducted), respectively. Quantitative IVUS analysis was performed using computerized planimetry (Echo Plaque, Indec Systems, USA)

as follows. First, the pre-PCI image was reviewed to select the SB ostium of interest on the longitudinal view. The proximal and distal ends of the ostium were designated as slice ‘P’ and

‘D’, respectively. Then, the longitudinal view of the post-PCI image was reviewed side-by-side with the pre-PCI image to identify the corresponding slice ‘P’ and ‘D’. Finally, the study segment (from 5 mm proximal to the slice ‘P’ through 5mm distal to the slice ‘D’) was divided into 1mm intervals in both pre- and post-PCI images. Five proximal slices were numbered from the closest to slice ‘P’ as ‘+1’ to ‘+5’ and designated as the ‘proximal portion’ as a whole. Five distal slices were numbered from the closest to slice ‘D’ as ‘-1’ to ‘-5’ and designated as the ‘distal portion’ (Fig. 1). In each slice, the external elastic membrane (EEM) and lumen area were mea- sured and plaque and media (P&M) area, defined as EEM area minus lumen area, was calculated. Changes in EEM, lumen, and P&M areas before and after PCI were also calculated.

Volumetric analysis of these measurements was performed in the proximal and distal portions separately using Simpson’s rule according to recent AHA/ACC guidelines.⁸ IVUS studies were reviewed separately by the independent personnel (Y.S.M.), who had no knowledge of the occurrence of SB jailing.

3. Statistical Analysis

Statistical analysis was performed using SPSS, version 18.0.

(SPSS Inc., USA). Continuous variables are presented as mean values±SD and compared using paired or unpaired student t- tests, and Categorical variables are presented as frequency (%) and compared with Fisher’s exact test. Correlations between parameters were evaluated using the Pearson’s correlation analysis. A p<0.05 was accepted as significant.

RESULTS

A total of 55 lesions in 53 patients were included in this study. SB jailing after stent implantation occurred in 23 lesions, which comprised the jailed group, and they were compared with 32 lesions in the patent group. The clinical characteristics of the patients are shown in Table 1. Overall, mean age of patients was 65.5±10.7 years and most were male (72%). The target lesions were mainly located at the left anterior descending/diagonal branch (92%). In two patients, more than one bifurcation lesion were treated in the same patient and analyzed separately. The two groups were comparable in terms of clinical characteristics statistically. Results of Volumetric IVUS analysis are summarized in Table 2. Before PCI, the jailed group showed significantly smaller lumen and EEM volume at the distal portion than the patent group (19.8±6.8 vs. 28.4

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Table 1. Clinical and angiographic characteristics

Patent Group (n=36) Jailed Group (n=30) p-value Age, years

Male gender, n (%) Diabetes mellitus, n (%) Acute coronary syndrome, n (%) LAD location, n (%)

60.8±11.1 26 (72.2) 10 (27.8) 18 (50.0) 33 (88.9)

62.3±10.2 22 (73.3) 8 (26.7) 16 (53.3) 27 (90.0)

0.61 0.78 0.60 0.35 0.81

Bifurcation type, n (%) 0.69

(1, 1, 0) (1, 0, 0) (0, 1, 0) Stent/Artery ratio

Stent implantation pressure, atm

10 (27.8) 10 (27.8) 13 (36.1) 1.1 14.8±3.2

9 (30.0) 13 (43.3) 11 (36.7) 1.1 14.7±2.9

0.95 0.88 Before stenting

MV RVD, mm MV MLD, mm SB RVD, mm SB MLD, mm After stenting MV MLD, mm MV RS, % SB MLD, mm SB RS, %

3.18±0.68 1.72±0.49 2.61±0.53 1.28±0.57 2.91±0.68 11.6±6.43 2.12±0.51 18.8±9.96

3.01±0.98 1.82±1.24 2.55±0.31 1.23±0.91 2.81±0.51 10.0±7.32 1.12±0.69 56.1±14.60

0.41 0.56 0.63 0.76 0.56 0.42 0.005 <0.001 Values are presented as n (%) or mean±SD.

LAD, left anterior descending; MV, main vessel; SB, side branch; RVD, reference vessel diameter; MLD, minimal luminal diameter;

RS, residual stenosis.

Table 2. Results of Volumetric IVUS analysis

Volume, mm³ Patent Group (n=32) Jailed Group (n=23) p-value

Before stenting

Proximal EEM Proximal L Proximal P&M Distal EEM Distal L Distal P&M

69.13±15.43 34.02±11.11 35.12±14.42 53.55±13.35 28.42±10.96 25.13±11.15

63.03±15.05 28.39±12.58 34.64±9.76 43.83±11.06 19.80±6.78 24.04±11.76

0.15 0.09 0.89 0.006 0.002 0.73

After stenting

77.47±14.57 43.85±8.66 33.62±11.50 62.52±12.23 39.37±8.14 23.14±8.88

73.23±12.29 39.71±7.77 33.52±8.90 57.51±14.58 36.45±8.58 21.06±7.77

0.26 0.07 0.97 0.17 0.20 0.37

Volume change

+8.34±7.34 +9.83±12.21 -1.49±9.27 +8.97±7.31 +10.95±8.45 -1.99±7.46

+10.20±7.55 +11.32±12.18 -1.12±7.80 +13.68±6.76 +16.65±10.00 -2.97±6.11

0.36 0.66 0.88 0.019 0.026 0.61 Values are presented as mean ± SD.

EEM, external elastic lamina; L, lumen; P&M, plaque and media.

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Fig. 2. The results of sub-segmental IVUS analysis. Panel A shows the pre-PCI measurements of EEM, lumen, and P&M CSA in the proximal and distal portions. In each stacked column, lumen is shown in black and P&M in white. EEM is represented by the total column. Panel B shows post-PCI measurements (^*p<0.01 vs. Patent group; ^†p<0.05 vs. Patent group).

±11.0 mm³, 43.8±11.1 vs. 53.6±13.4 mm³, respectively; p=

0.006, 0.002). All parameters related to the proximal portion did not differ between groups and had no predictive value for SB jailing. After PCI, lumen and EEM volume of the distal portion increased significantly (24.8±10.3 to 38.1±8.4 mm³, 49.5±13.2 to 60.4±13.4 mm³, respectively; p<0.001) to a significantly greater extent in the jailed group compared with the patent group (+16.7±10.0 vs. +11.0±8.5 mm³, +13.7±

6.8 vs. +9.0±7.3 mm³, respectively; p=0.019). P&M volume of the distal portion was reduced (24.7±11.3 to 22.3±8.4 mm³, p=0.012), but the extent was not significantly different between groups (-2.97±6.11 vs. -1.99±7.46, p=0.61). The relative contribution of vessel expansion to lumen enlarge-

ment was 82.2%, and plaque reduction only accounted for 17.8% of luminal gain in the jailed group. Although lumen and EEM volume of the proximal portion were also increased (31.7±12.0 mm³ to 42.1±8.5 mm³, 66.6±15.4 mm³ to 75.7

±13.7 mm³, respectively; p<0.0001), P&M volume did not change and there were no significant differences in mean changes of EEM, lumen, and P&M volume between groups. The sub-segmental IVUS analysis results are shown in Fig. 2. When pre-PCI IVUS images were analyzed by 1-mm intervals, significantly smaller lumen and EEM CSA were noted uniformly over the entire distal portion segments of the jailed group (p=0.98 by ANOVA). P&M CSA did not significantly differ between groups and it did not vary over the proximal through distal

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portion. The changes in lumen, EEM and P&M volume after PCI were uniform over the length of the study segments in the patent group. In the jailed group, the increase in lumen volume was greatest in the 2 segments nearest from the SB ostium in the proximal portion and did not vary in the distal portion.

DISCUSSION

The present study demonstrates that vessel stretch at the distal portion of bifurcation is the major determinant of SB jailing after stenting in the false bifurcation lesions. Previous IVUS studies have reported that stent implantation expands coronary lumen not only by vessel stretch but also by plaque redistribution leading to plaque reduction at the center of lesion.^9,10,11 This plaque moves longitudinally toward both ends of the lesion(plaque shift.¹² However, conclusive data to con- firm the presence of plaque shift have not been reported. Most of the luminal gain was attributable to vessel stretch after stenting, and its extent at distal portion was related to occurrence of SB jailing. The discrepancy is most likely derived from several morphological differences unique to bifurcation lesions.

Unlike the non-bifurcation lesions, which usually have maxi- mum plaque at the center of lesion, atheroma usually exists at the opposite side of SB and spares the carina.^13-15 In addi- tion, vessel dimension decreases abruptly after SB comes out, and “stepping down” of the luminal border exclusively locates at the side of carina.¹⁶ Consequently, as shown by the present data, stenting expands the lumen unequally and relatively over- expands the distal portion of the lesion. Another compelling source of evidence stems from the observation that small pre- PCI vessel and lumen dimension at the distal portion of the bifurcation lesion were the only identifiable predictors for SB jailing in the present study. On the other hand, the amount of plaque, either at the proximal or distal portion, was not predictive for SB jailing. Therefore, it is not surprising that stenting shifts the carina towards the SB ostium without any notable redistribution of plaque. Recently, a consensus document from the expert meeting focused on bifurcation lesion has proposed a tentative theory involving carina displacement as the main mechanism of SB jailing.¹⁷ This is based on several observational data including an angiographic study showing that carina displacement from stent struts is a major mechanism governing changes in coronary bifurcations after main vessel stenting.¹⁸IVUS and fractional flow reserve measurements done by Koo et al also reported that lumen increase in the distal MB is primarily due to enlargement of the vessel and not plaque shift, supporting carina shift.¹⁹ However, these studies did not compare changes according to the presence of SB jailing so that it remained unclear whether carina shift

was an immediate cause of SB jail. Our IVUS analysis supports this theory by exclusively enrolling false bifurcation lesions and showing that the main component which compromises the SB ostium may be the outer margin of the distal portion, that is, the carina itself. The results from the present study have several clinical implications. Because lesions with smaller lumen on the distal portion of the bifurcation tend to be over- expanded with stenting and are vulnerable to SB jailing, side branch protection with another guide wire will be helpful as further intervention. Also, stent size determination according to the distal reference diameter may be reasonable to avoid SB jailing in those cases. Considering that the carina shift may be the main mechanism of SB jailing, expansion of the proximal portion with the kissing balloon technique or POT (proximal optimization technique)²⁰ may be the best way to restore SB patency and maintain the stent dimension of the main vessel in case of SB jailing.

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