Impact of Kissing Balloon Inflation on the Main Vessel Stent Volume, Area, and Symmetry After Side-Branch Dilation in Patients With Coronary Bifurcation Lesions

JACC: CARDIOVASCULAR INTERVENTIONS

VOL. 6, NO. 9, 2013

ª 2013 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.

ISSN 1936-8798/$36.00 http://dx.doi.org/10.1016/j.jcin.2013.04.019

Impact of Kissing Balloon Inflation on the Main Vessel Stent Volume, Area, and Symmetry After Side-Branch Dilation in Patients With Coronary Bifurcation Lesions A Serial Volumetric Intravascular Ultrasound Study Shahid Rahman, MD,* Tara Leesar,* Mehmet Cilingiroglu, MD,* Mohamed Effat, MD,* Imran Arif, MD,* Tarek Helmy, MD,* Massoud A. Leesar, MDy Cincinnati, Ohio; and Birmingham, Alabama

Objectives Intravascular ultrasound (IVUS) was performed to investigate the impact of kissing balloon inflation (KBI) on the main vessel (MV) stent volume, area, and symmetry after side-branch (SB) dilation in patients with coronary bifurcation lesions (CBL). Background It remains controversial whether KBI would restore the MV stent area and symmetry loss after SB dilation. Methods A total of 88 serial IVUS examinations of the MV were performed after MV angioplasty, MV stenting, SB dilation, and KBI in 22 patients with CBL. The MV stent was divided into proximal, bifurcation, and distal segments; the stent volume index (SVI), minimal stent area (MSA), stent symmetry index (SSI), and external elastic membrane (EEM) volume index were measured in 198 stent segments and compared after MV stenting, SB dilation, and KBI. Results In the bifurcation segment, SVI, MSA, and SSI were significantly smaller after SB dilation than after MV stenting and KBI (SVI was 6.10  1.50 mm3/mm vs. 6.68  1.60 mm3/mm and 6.57  1.60 mm3/mm, respectively, p < 0.05; MSA was 5.15  1.30 mm2 vs. 6.08  1.40 mm2 and 5.86  1.50 mm2, respectively, p < 0.05; and SSI was 0.78  0.02 mm2 vs. 0.87  0.03 mm2 and 0.84  0.03 mm2, respectively, p < 0.05). KBI restored the MV SVI, MSA, and SSI after SB dilation. In the proximal segment, SVI, MSA, and EEM volume index were significantly larger, but SSI was smaller after KBI than after MV stenting and SB dilation. In the distal segment, neither SB dilation nor KBI had a significant impact on the MV stent volume or symmetry. Conclusions This is the first comprehensive volumetric IVUS analysis of CBL, to our knowledge, demonstrating that KBI restores the MV stent volume, area, and symmetry loss after SB dilation in the bifurcation segment, and induces asymmetric stent expansion in the proximal segment. (J Am Coll Cardiol Intv 2013;6:923–31) ª 2013 by the American College of Cardiology Foundation

From the *Division of Cardiology, University of Cincinnati College of Medicine, Cincinnati, Ohio; and the yDivision of Cardiology, University of Alabama, Birmingham, Alabama. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received January 21, 2013; revised manuscript received April 12, 2013, accepted April 25, 2013.

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Coronary bifurcation lesions (CBL) represent 1 of the most difficult technical challenges in percutaneous coronary intervention (PCI) (1–5). Thus far, no uniform strategy has been established for the optimal management of CBL (6). The challenges of CBL treatment with PCI include a relatively high rate of restenosis, risk of myocardial infarction, and risk of stent thrombosis (7,8). Approximately 15% to 20% of PCIs performed in the United States involve CBL, and such lesions are also commonly referred for bypass surgery, particularly when they are located in either the left main or left anterior descending coroAbbreviations nary artery (4,9). In a large and Acronyms meta-analysis (10), CBL were an independent predictor of stent CBL = coronary bifurcation lesions thrombosis, which was associated with a 45% rate of mortality. DES = drug-eluting stent(s) A recent large registry study of EEM = external elastic membrane drug-eluting stents (DES) (11) demonstrated that the 2-year EES = everolimus-eluting stent(s) follow-up major adverse cardiac ISA = incomplete stent events in patients with CBL were apposition significantly higher than in nonIVUS = intravascular bifurcation lesions (18.9% vs. ultrasound 12.9%). KBI = kissing balloon In the era of DES, the 2 inflation(s) primary interventional strategies MLD = minimal lumen for managing CBL include the diameter complex strategydstenting of MSA = minimal stent area both the main vessel (MV) and side MV = main vessel branch (SB)dand the simple P&M = plaque plus media strategydstenting of the MV and provisional stenting of the SB. PCI = percutaneous coronary intervention Recent meta-analyses (6,12) of POT = proximal optimization randomized trials (13–18) comtreatment paring these 2 strategies demonQCA = quantitative coronary strated no significant differences in angiography terms of death or target lesion RD = reference diameter revascularization, but the rate of SB = side branch myocardial infarction was significantly higher in the complex stratSES = sirolimus-eluting stent(s) egy. However, these meta-analyses SSI = stent symmetry index provided limited information because stenting techniques were SVI = stent volume index not uniform among the trials. In the simple strategy, after stenting of the MV, SB dilation shifts the carina to the MV, distorts the MV stent, and induces a stenosis in the MV stent. However, it remains controversial whether kissing balloon inflation (KBI) would restore the MV stent area and symmetry loss after SB dilation. In this respect, in a phantom model of a bifurcation lesion (19), SB dilation with a balloon catheter through the struts of a stent distorted the stent and induced a stenosis in the stent immediately distal to the SB, which were restored by KBI of the MV and SB. In contrast, an in vivo intravascular

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ultrasound (IVUS) study of CBL (20) demonstrated that KBI did not restore the MV stent area or symmetry loss after SB dilation. The reduction in the stent area after SB dilation may increase the incidence of in-stent restenosis or event rates, but the aforementioned IVUS study is limited because the authors did not perform volumetric IVUS analysis, and the minimal stent area (MSA) was determined by visual estimate. We, therefore, performed serial volumetric IVUS analysis after MV angioplasty, MV stenting, SB dilation, and KBI to investigate the impact of KBI on the MV stent volume, area, and symmetry after SB dilation in patients with CBL. Methods Study population. Between April 2008 and January of 2009, 88 serial IVUS examinations of the MV were performed after MV angioplasty, MV stenting, SB dilation, and KBI in 22 patients with CBL. All patients underwent stenting using the simple strategy (stenting of the MV with provisional stenting of the SB). The study was approved by the institutional review board, and informed consent was obtained from all patients. The inclusion criteria were as follows: patients with unstable angina or documented ischemia who were eligible to undergo stenting of a bifurcation lesion in the coronary artery; and bifurcation lesions with stenoses >50% in both the MV 2.5 mm and/or the ostium of the SB 2.25 mm based on visual estimate, as reported in the BBC-ONE (British Bifurcation Coronary Study: Old, New, and Evolving Strategies) trial (17). The exclusion criteria were as follows: acute myocardial infarction or the presence of hemodynamic instability; distal vessels that were totally occluded; patients with renal failure (serum creatinine >2.0 mg/dl); and patients with severe left ventricular dysfunction (left ventricular ejection fraction 30). Experimental protocol. All patients were pre-treated with aspirin (325 mg) and clopidogrel (600 mg). Heparin (60 U/kg) and glycoprotein IIb/IIIa receptor inhibitors were used in all patients. After engaging the coronary artery with a 6-F or a 7-F guiding catheter, 100 mg of intracoronary nitroglycerin were administered. A 0.014-inch Terumo guidewire (Terumo Interventional Systems, Somerset, New Jersey) was used to cross the stenosis of the MV and then positioned in the distal part of the artery. In addition, a 0.014-inch hydrophilic wire (Whisper guidewire, Abbott Vascular, Santa Clara, California) was positioned in the SB. The MV angioplasty was performed using an undersized balloon to permit baseline IVUS examination. Next, IVUS imaging of the MV was performed using an Atlantis SR Pro Imaging catheter (Boston Scientific, Natick, Massachusetts). The IVUS catheter was advanced at least 10 mm distal to the bifurcation lesion in the MV, and pullback imaging was obtained automatically at a speed of 0.5 mm/s. Before MV stenting, the diameter of the stent in the MV was determined by using the average distal reference lumen diameter measured by IVUS. After MV stenting, the second

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IVUS imaging of the MV was performed followed by SB dilation. After SB dilation, the third IVUS imaging of the MV was performed followed by KBI of the MV and SB. After KBI, the fourth IVUS imaging of the MV was performed. Intracoronary nitroglycerin was administered before each IVUS run. The study flow chart is shown in Figure 1. For KBI, the diameter of balloon in the SB was determined by the visual estimation of the SB, and the diameter of the balloon in the MV was determined by using the average distal reference lumen diameter measured by IVUS. Before KBI, high-pressure balloon inflation was performed in the MV to expand the MV stent followed by the KBI of the MV and SB using 2 noncompliant balloons. IVUS analysis. All IVUS data were stored on CD-ROM (compact disk), and quantitative analysis was performed offline by a single experienced investigator (M.A.L.) at the IVUS core laboratory at the University of Cincinnati. After MV stenting, the stent was divided into 3 segments, using a previously reported method (21) (Fig. 2): 1) the proximal segment, the segment between the proximal edge of the stent and the tip of the carina; 2) the bifurcation segment, the segment between the tip of the carina and 5.0 mm distal from the carina; and 3) the distal segment, the segment between the distal edge of the stent and >5.0 mm distal from the tip of the carina. For quantitative IVUS analysis, the stent and external elastic membrane (EEM) contours in the proximal, bifurcation, and distal segments of the IVUS images were manually traced at every 0.5-mm cross-sectional frame using commercially available planimetry software (echoPlaque, INDEC Medical Systems, Santa Clara, California).

Rahman et al. Bifurcation Lesions and Kissing Inflations

Volumetric data were calculated using Simpson’s rule. To standardize for different lengths, the stent volume index (SVI), plaque plus media (P&M) volume index, and EEM volume index were calculated as their volume data divided by length as previously described (22,23). P&M volume was calculated as EEM volume minus stent volume. The MSA within each stent segment was defined as the smallest lumen cross-sectional area. The stent symmetry index (SSI) was calculated by dividing the minimal stent diameter by the maximal stent diameter at a cross section with the smallest lumen cross-sectional area in the proximal, bifurcation, and distal stent segments, as previously described (24,25). SVI, MSA, SSI, EEM volume index, and P&M volume index were measured by quantitative IVUS analysis in 198 stent segments and compared after MV stenting, SB dilation, and KBI. The representative images of IVUS and coronary angiography from a study patient are shown in Figure 3. Quantitative coronary angiography. The angiograms of the MV and SB were analyzed off-line after the MV angioplasty, MV stenting, SB dilation, and KBI by an experienced investigator (M.A.L.) using validated, commercially available, edge detection software (QCA-CMS, version 5.2, Medis Medical Imaging Systems, Leiden, the Netherlands) (26,27). For the MV, the reference diameter (RD) was the average of the proximal and distal reference lumen diameters. For the SB, the RD was the distal reference lumen diameter as previously reported (21,28). Diameter stenosis (DS) was calculated by: 100  (RD  MLD)/RD, where MLD ¼ minimal lumen diameter. Statistical analysis. Statistical analysis was performed with SPSS version 21 (SPSS, Chicago, Illinois). IVUS and quantitative coronary angiography (QCA) parameters were compared after MV stenting, SB dilation, and KBI using the

Figure 2. Schematic Diagram of IVUS Analysis Figure 1. Study Flowchart IVUS ¼ intravascular ultrasound.

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BIF ¼ bifurcation; IVUS ¼ intravascular ultrasound; MV ¼ main vessel; SB ¼ side branch.

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Figure 3. Images of IVUS and Angiography From a Study Patient Panel 1: (A) Baseline IVUS image of the LAD and diagonal bifurcation; lumen area of the LAD ¼ 2.95 mm2; (B) the angiogram of the LAD demonstrating a stenosis at bifurcation segment; and (C) 3D IVUS image at baseline. Panel 2: (D) IVUS of the LAD after stenting with a stent area ¼ 7.11 mm2; (E and F) angiogram of the LAD during and after stenting demonstrates a significant stenosis at the ostium of diagonal after stenting of the LAD; and (G) 3D IVUS image of the proximal (P), bifurcation (B), and distal (D) stent segments demonstrating stent expansion in the LAD and carina shift to the diagonal. Panel 3: (H) IVUS of the LAD after SB dilation demonstrates reduced stent area and asymmetry with a stent area ¼ 6.17 mm2; (I and J) angiogram of the LAD and diagonal during and after balloon dilation of diagonal; and (K) 3D IVUS image demonstrates that the carina is shifted to the LAD. Panel 4: (L) IVUS of the LAD after KBI demonstrates that stent is well expanded in the bifurcation segment with a stent area ¼ 7.35 mm2; (M and N) angiogram of the LAD and diagonal during and after KBI; and (O) 3D IVUS image of the LAD demonstrates that the carina is in the middle and the stent in the LAD is well expanded. 3D ¼ 3-dimensional; DA ¼ diagonal coronary artery; KBI ¼ kissing balloon inflation; LAD ¼ left anterior descending coronary artery; other abbreviations as in Figure 2.

repeated-measures analysis of variance. Significance was determined after multiple pairwise comparisons with the Bonferroni post tests. Data are presented as mean  SD; a p value <0.05 was considered statistically significant. Intraobserver variability was assessed by the evaluation of 60 random SVI, MSA, and SSI measurements after MV stenting, SB dilation, and KBI by the same reader at 2 separate time points. The correlation between 2 cross-sectional IVUS measurements was regarded as intraobserver correlations. The intraobserver correlations were tested using Pearson regression analysis. Results Patient characteristics. All patients underwent MV stenting, SB dilation, and KBI of the MV and SB. All patients

underwent 4 serial IVUS examinations after MV angioplasty, MV stenting, SB dilation, and KBI of the MV and SB. The baseline clinical and angiographic characteristics of patients are shown in Table 1. The procedural characteristics of the study are displayed in Table 2. IVUS analysis. After MV angioplasty, the minimum lumen area, lumen volume index, P&M volume index, and EEM volume index of the bifurcation segment were 2.80  1.53 mm2, 5.5  1.8 mm3/mm, 4.9  2.8 mm3/mm, and 10.40  3.4 mm3/mm, respectively. The results of quantitative IVUS analysis after MV stenting, SB dilation, and KBI in the bifurcation, proximal, and distal stent segments are shown in Table 3. In the bifurcation segment, SVI, MSA, and SSI were significantly smaller after SB dilation compared with after MV stenting (Table 3, Figs. 4 to 6). KBI restored SVI, MSA, and SSI

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Table 1. Baseline Clinical and Angiographic Characteristics (N = 22)

Table 2. Procedural Characteristics (N = 22) Stent diameter, mm

3.20  0.30

Male/female

14/8

Stent length, mm

21.3  5.2

Previous MI

6 (22)

Post-stent dilation balloon size in the main vessel, mm

3.16  0.30 16.5  0.30

Age, yrs

61  12

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Ejection fraction

50  11

Post-stent dilation balloon length in the main vessel, mm

Hypertension

16 (73)

Side-branch balloon diameter, mm

Diabetes

16 (73)

Side-branch balloon length, mm

2.51  0.17 15.85  2.20

Radiation exposure time, mm

20.3  8.80

Hyperlipidemia

19 (86)

Procedure time, min

106  24

Unstable angina

13 (59)

The amount of contrast used, ml

289  93

Previous PCI

6 (22)

Angiographic characteristics Left anterior descending/diagonal artery Circumflex/obtuse marginal artery

Stent type 18 (82)

Sirolimus-eluting stents

11

4 (18)

Paclitaxel-eluting stents

8

Everolimus-eluting stents

1

Type of bifurcation according to Medina’s classification 1,1,1

9 (41)

1,1,0

7 (32)

Glycoprotein IIb/IIIa use

22

1,0,1

4 (18)

Heparin

22

1,0,0

2 (9)

Guiding catheter used

Angulation between MV and SB Angle <70%

17 (77)

Angle >70%

5 (13)

Single-vessel disease Two-vessel disease

Bare-metal stents

2

6-F

20

7-F

2

Values are mean  SD or n.

18 (82) 4 (18)

Values are mean  SD, n , or n (%). MI ¼ myocardial infarction; MV ¼ main vessel; PCI ¼ percutaneous coronary intervention; SB ¼ side branch.

losses after SB dilation such that after KBI, SVI, MSA, and SSI were no longer significantly different compared with after MV stenting (Table 3, Figs. 4 to 6). The EEM volume index and P&M volume index were not significantly different after MV stenting, SB dilation, and KBI (Table 3). The correlation coefficients of SVI, MSA, and SSI measurements were 98%, 97%, and 94%, respectively, p < 0.001. In the proximal segment, SVI, SMA, and EEM volume index were significantly larger after KBI compared with after MV stenting and SB dilation (Table 3, Figs. 4 and 5). By contrast, SSI was significantly smaller after KBI compared with after MV stenting (Fig. 6). Furthermore, after MV stenting, incomplete apposition of the MV stent to the vessel wall was observed in 5 patients (22%), which resolved after KBI in 4 patents. The P&M volume index was not significantly different after KBI, MV stenting, and SB dilation. In the distal segment, SVI, MSA, EEM volume index, P&M volume index, and SSI were not significantly different after MV stenting, SB dilation, and KBI (Table 3, Figs. 4 to 6). Angiographic results. Quantitative angiographic analysis at baseline and after MV stenting, SB dilation, and KBI in the MV and SB is shown in Table 4. In the MV, MLD was significantly smaller after SB dilation compared with after MV stenting and KBI. By contrast, DS was significantly greater after SB dilation compared with after MV stenting and KBI (Table 4).

In the SB, MLD was significantly smaller after MV stenting compared with after SB dilation and KBI. By contrast, DS was significantly greater after MV stenting compared with after SB dilation and KBI (Table 4). Procedural and clinical outcomes. After SB dilation, there was no incidence of SB dissection, therefore, no stent was deployed to the SB. There were no complications related to stenting, including dissection, perforation, or stent thrombosis. All patients were discharged on the next day of the procedure. Serial electrocardiograms, performed at baseline, after PCI, and at discharge, demonstrated no significant changes. Discussion To our knowledge, this is the first comprehensive volumetric IVUS trial to investigate the impact of KBI on the MV stent volume, area, and symmetry after SB dilation in patients with bifurcation lesions. The salient findings of the present study are summarized as follows: 1) in the bifurcation segment, after MV stenting, SB dilation significantly reduced the MV stent volume and area, and distorted the MV stent symmetry, which were restored after KBI; 2) in the proximal segment, KBI significantly increased the MV stent volume and area, and induced asymmetric stent expansion; and 3) in the distal segment, SB dilation or KBI had no significant impact on the MV stent volume, area, or symmetry. The present data extend the observation of Ormiston et al. (19) in their study using an in vitro model, in which they demonstrated that balloon dilation through the struts of a stent distorted the stent and induced a stenosis in the stent

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Table 3. Quantitative IVUS After MV Stenting (IVUS RUN 2)

After SB Dilation (IVUS RUN 3)

After KBI (IVUS RUN 4)

Stent volume index, mm3/mm

6.68  1.60

6.10  1.50*

6.57  1.60

Minimal stent area, mm2

6.08  1.40

5.15  1.30*

Bifurcation segment

EEM volume index, mm3/mm

11.71  3.0

11.53  2.60

5.86  1.50 11.62  3.0

P&M volume index, mm3/mm

5.37  3.6

5.46  3.3

5.37  3.8

Stent symmetry index

0.87  0.03

0.78  0.04*

0.84  0.03

Stent volume index, mm3/mm

7.34  1.6

7.06  1.75

8.62  1.9y

Minimal stent area, mm2

6.30  1.7

5.96  1.6

7.4  2.0y

12.77  3.15

12.51  2.87

13.96  2.93y

Proximal segment

EEM volume index, mm3/mm P&M volume index, mm3/mm

5.43  1.9

5.47  1.8

5.34  1.5

Stent symmetry index

0.88  0.04

0.84  0.06

0.81  0.06z

Distal segment Stent volume index mm3/mm

5.82  1.3

5.68  1.2

5.74  1.2

Minimal stent area mm2

5.56  1.0

5.48  0.9

5.63  0.8

EEM volume index mm3/mm

10.40  2.7

10.50  2.9

10.63  2.9

P&M volume index mm3/mm

4.58  2.0

4.82  2.2

4.89  2.2

Stent symmetry index

0.86  0.04

0.84  0.08

0.87  0.05

Values are mean  SD. *p < 0.05 versus after MV stenting and KBI. yp < 0.01 versus after MV stenting and SB dilation. zp < 0.01 versus after MV stenting. EEM ¼ external elastic membrane; IVUS ¼ intravascular ultrasound; KBI ¼ kissing balloon inflation; P&M ¼ plaque plus media; other abbreviations as in Table 1.

immediately distal to the SB, which were restored by simultaneous KBI of the MV and SB. However, Suarez de Lezo et al. (20) performed IVUS cross-sectional analysis in patients with CBL and demonstrated that SB dilation significantly reduced the MV stent area and distorted the

stent, which were not restored after KBI. In contrast our data demonstrate that KBI restored the MV stent volume, area, and symmetry after SB dilation in the bifurcation segment. It is worth noting that the diameter of balloon catheter used for SB dilation in the Suarez de Lezo et al.

Figure 4. Stent Volume Index

Figure 5. Minimal Stent Area

Stent volume index in the proximal, bifurcation, and distal stent segments after MV stenting, SB dilation, and kissing balloon inflation. Abbreviations as in Figures 2 and 3.

Minimal stent area in the proximal, bifurcation, and distal stent segments after MV stenting, SB dilation, and kissing balloon inflation. Abbreviations as in Figures 2 and 3.

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Figure 6. Stent Symmetry Index Stent symmetry index in the proximal, bifurcation, and distal stent segments after MV stenting, SB dilation, and kissing balloon inflation. Abbreviations as in Figures 2 and 3.

(20) study was comparable to the present study; however, their study is limited because the authors did not perform volumetric IVUS analysis, and MSA was determined by visual estimate. On the other hand, in the present study, MSA was determined by computerized volumetric analysis. In the present study, KBI significantly increased the MV stent volume and area in the proximal segment. Furthermore, KBI restored the MV stent volume and area in the bifurcation segment, though the MV stent volume and area after KBI was not significantly different compared with after MV stenting. In this respect, it is conceivable to infer that the expansion of the MV stent in the proximal segment or the restoration of the MV stent area in the bifurcation

Table 4. Quantitative Coronary Angiography After PCI Baseline

After MV Stenting

After SB Dilation

After KBI

MLD, mm

0.90  0.48

2.92  0.63

2.44  0.66*

2.94  0.56

RVD, mm

2.89  0.33

3.24  0.60

3.06  0.65

3.26  0.68

68  14

9.87  3.80

MLD, mm

1.35  0.43

1.09  0.50y

1.76  0.36

1.56  0.39

RVD, mm

2.30  0.36

2.25  0.30

2.20  0.30

2.20  0.30

41  18

52  20y

22  9.0

28  11

Main vessel

DS, %

20.05  10*

9.4  8.40

Side branch

DS, %

Values are mean  SD. *p < 0.05 versus after MV stenting and KBI. yp < 0.05 versus after SB dilation and KBI. DS ¼ diameter stenosis; MLD ¼ minimal lumen diameter; RVD ¼ reference vessel diameter; other abbreviations as in Tables 1 and 3.

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segment by KBI might reduce the rate of in-stent restenosis. However, concerns have been raised that such benefits might be outweighed by stent asymmetry leading to variation of the drug concentration in the vessel wall with a consequent increased incidence of neointima hyperplasia (29,30). In this respect, a number of studies (24,25,31,32) reported that stent asymmetry per se was not associated with an increased incidence of neointima hyperplasia. Another concern was raised by Foin et al. (33) that KBI, compared with sequential post-dilation of the SB and MV after MV stenting in a bench coronary model, induced higher rates of asymmetric stent expansion and incomplete stent apposition (ISA) at the proximal edge of stents. In addition, asymmetric stent expansion increased stress concentration proximal to the SB as assessed by computational fluid dynamics; however, further studies are needed to investigate the correlation between increased stress concentration and clinical outcomes. In our study, 5 patients developed ISA at the proximal edge of stents after MV stenting, which resolved after KBI in 4 patients owing to stent expansion. Such a difference in the incidence of ISA after KBI, comparing the Foin et al. (33) study with the present study, is probably linked to the fact that Foin et al. used an in vitro coronary bifurcation model, which did not have any lesions. By contrast, in the present study, coronary plaque reduced the incidence of ISA as a result of filling the gap between stent struts and the vessel wall. The majority of stents used in our study were the firstgeneration stents such as sirolimus-eluting stents (SES), which are characterized by thick (0.0055-inch) stainless steel struts and a cell design with limited side-cell expansion. By contrast, the second-generation stents, such as everolimuseluting stents (EES) are based on thin (0.0032-inch) cobalt chromium struts and a cell design that achieves larger side cells after SB balloon dilation. In this respect, Burzotta et al. (34) randomized 150 patients with bifurcation lesions to EES versus SES and demonstrated that the MLA of the MV stent and the clinical outcomes did not differ significantly when comparing SES with EES; however, the MLD at the ostium of the SB was larger in the EES than in the SES. If we had used the second-generation DES, the MLA of the MV stent would have been comparable to the present study, but the MLD at the ostium of the SB would have been larger after SB dilation. In our study, over 40% of bifurcation lesions were not true bifurcation lesions, and the SB was not involved significantly, and therefore, KBI or SB dilation could have been deferred. Likewise, the European Bifurcation Club (35) recommends that in the absence of a tight lesion at the ostium of the SB, KBI may not be routinely required. Furthermore, when a tight lesion (>75% stenosis by angiography) is present at the ostium of the SB after MV stenting, the European Bifurcation Club suggests measuring the fractional flow reserve of the SB to determine the significance of SB stenosis,

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or alternatively, performing KBI because KBI will reduce the physiologically significant stenoses from 30% to 5% (36). However, it is worth noting that deferring KBI in patients with no significant SB stenosis will leave stent struts unopposed. In this respect, a number of studies (37,38) reported that stenting with a DES across the SB, and leaving struts unopposed, would lead to incomplete stent coverage, and that this was the most common cause of late stent thrombosis in the post-mortem exams. Likewise, an optical coherence study (39) reported that the neointimal coverage of stent struts across the SB was less frequently observed in patients who underwent stenting with DES. On the other hand, 2 recent randomized trials (40,41) compared KBI with no KBI in patients with bifurcation lesions and reported that the clinical outcomes of patients were not significantly different at 6-month follow-up. In this context, because the long-term follow-up of adverse events, including the incidence of late stent thrombosis after KBI, is lacking, its long-term role in the outcomes of patients would need to be investigated in future trials. In the current study, the post-dilation strategy differs from that recommended by the European Bifurcation Club (35) that suggests the following: 1) the stent is sized to the MB vessel distally just beyond the bifurcation; 2) there should be “proximal optimization treatment” (POT), defined as postdilation of the MV stent proximal to the SB and up to the SB with a balloon sized to the proximal vesseldthis strategy makes it more likely that the crossing to the SB will be close to the carina, hence optimizing struts in relation to the SB; and 3) if KBI is needed after POT, it should be performed with short balloons that do not extend back to the proximal MV stent, therefore, the proximal MV stent will not be asymmetric in cross section. In the present study, the use of the POT strategy after MV stenting would have expanded stents symmetrically in the proximal segments. Likewise, an improvement in the symmetry of the proximal MV stent could have been achieved by final postdilation of the proximal MV stent with an appropriately sized balloon. Study limitations. First, we included a relatively small number of patients to determine the impact of SB dilation and KBI on the MV stent volume, area, and symmetry; second, we included a relatively high number of patients with non-true bifurcation lesions (i.e., no significant SB involvement), and KBI could have been deferred in those patients; and third, the diameter of the SB vessel was underestimated in the present study because QCA was not performed with a dedicated bifurcation analysis system. As reported previously (21,28), we performed QCA of the SB using the distal vessel diameter to determine the reference vessel diameter instead of using the average of the proximal and distal reference vessel diameters, because the ostial SB was diseased and that led to underestimation of the diameter of the SB vessel.

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Conclusions We demonstrated that in patients with bifurcation lesions, SB dilation reduced the MV stent volume and distorted the MV stent symmetry in the bifurcation segment, which were restored after KBI. We also demonstrated that KBI increased the MV stent volume and area, and induced asymmetric stent expansion in the proximal segment. Although KBI is commonly being performed, its long-term impact on patient outcomes cannot be ascertained based on current studies and requires further investigation. Reprint requests and correspondence: Dr. Massoud A. Leesar, UAB Heart and Vascular Center, University of Alabama– Birmingham, 510 20th Street South, FOT-920, Birmingham, Alabama 35294. E-mail: [email protected].

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Key Words: bifurcation lesions - IVUS inflation - stenting.

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kissing balloon