洛和会病院医学雑誌

原Vol.30：79−85, 2019著

Effect of Predilatation Methods on Drug Coated Balloon
Treatment in In-Stent Restenosis Lesions
Ko Ko Soe¹, Phyo Htet Oo¹, Ayumu Fujioka², Toshihiro Iwasaku², Takeya Minami²,
Hiroaki Fujie², Naofumi Oyamada², Ichiro Hamanaka², Kinzo Ueda²¹No. (2), Defence Services General Hospital, Naypyitaw, Myanmar²Rakuwakai Kyoto Cardiovascular Intervention Center,
Rakuwakai Marutamachi Hospital【Abstract】
Background: Even in the modern drug eluting stent (DES) era, in stent restenosis (ISR) is still the problem
and existing treatment options are debatable. Among these, treatment with drug coated balloon (DCB) can bepromising on long term outcomes. However the predilatation methods before DCB are controversial.
Objective: The aim of this study is to evaluate whether the methods of predilatation (lesion preparation)
before DCB treatment can affect the outcomes in ISR cases.
Methods: Between 2014-2017, 101 patients were treated with DCB for ISR cases. Among these, 66 patients(65.3%) were followed up for CAG (coronary angiography) assessment. These patients were divided into twogroups; scoring balloon group (n = 40) and non-scoring balloon group (n= 26). Primary endpoint was thetarget lesion revascularization (TLR) at follow up. We also compared QCA (quantitative coronary angiography)
assessment for every procedure: before the procedure, after the procedure and during follow up. Then these
QCA parameters were compared thoroughly between two groups.
Results: Total seventeen cases (25.8%) were found to have TLR. These TLR rates were 20.0% in Scoring
balloon group and 34.6% in Non-scoring balloon group (p value = 0.18). In QCA analysis after the procedureand during follow up, minimal lumen diameter was higher, % diameter stenosis and % area stenosis weresignificantly lower in scoring balloon group than non-scoring balloon group. For the specific predilatation groups,
TLR rates were 16.1% in cutting balloon group, 33.3% in non-slip element (NSE) balloon group and 45.0% in
non-compliant (NC) balloon group respectively. In our subgroup analysis, TLR rates were 34.4% in hemodialysis
patients and 17.6% in non-hemodialysis patients (p value = 0.03). RCA (right coronary artery) proximal segment
had the highest TLR rate (53.8 %) compared with the other groups - RCA mid to distal, LCX (left circumflex)and LAD (left anterior descending) with 25.0%, 8.3% and 17.6% respectively (p value = 0.009).
Conclusions: Regarding the predilatation methods before DCB treatment in ISR cases, scoring balloon
especially cutting balloon is more superior to the non-scoring balloon in terms of TLR and QCA assessment.
Key words：In stent restenosis, Drug coated balloon, Lesion preparation, Predilatation methods,
  Cutting balloon angioplasty
Abbreviations：
CABG：Coronary artery bypass graft
CAG：Coronary angiography
CBA：Cutting balloon angioplasty
CVD：Cardiovascular diseases
DCB：Drug coated balloon
DES：Drug eluting stent
IHDF：Intermittent haemodiafiltration
ISR：In stent restenosis
IVUS：Intravascular ultrasound
LAD：Left anterior descending

LCX：Left circumflex
LLL：Late lumen loss
MLD：Minimal lumen diameter
NC：Non-complaint
NSE：Non-slip element
PCI：Percutaneous coronary intervention
QCA：Quantitative coronary angiography
RCA：Right coronary artery
TLR：Target lesion revascularization− 79 −

原【Background】

著

according to the usual standard of our catheterization

The development of stent is the turning point for thelaboratory either from femoral or radial approach. All

field of percutaneous coronary intervention (PCI). The

patients were receiving dual antiplatelet therapy with

progressive improvement of the modern DES makes good

aspirin and clopidogrel or prasugrel and other usual

clinical outcomes for the patients. But the penetration oftreatments for coronary artery disease. There was one

DES is quite variable and patients with DES may also

case of Acute Coronary Syndrome in this study who was

suffer from in-stent restenosis1）. Revisiting to the historicaltreated with DCB. In every PCI case, an intravenous

background, in-stent restenosis were treated withunfractionated heparin 10000 units was used as soon as

conventional balloon angioplasty, stent in stent technique,after the arterial puncture and sheath insertion. In somebrachytherapy, debulking devices (rotational arthrectomy,

cases of Heparin Induced Thrombocytopenia (known

excimer laser coronary arthrectomy and directional

during the previous procedure), we used Argatroban (direct

coronary arthrectomy), cutting balloon angioplasty andthrombin inhibitors). In all cases, the anticoagulant (either

DCB . Among these treatments in ISR cases, DCB

heparin or Argatroban) dose was controlled according

treatment is the most outstanding and guidelines also

to the activated clotting time between 250 and 350

recommended to use in that situation 2）. Currently

seconds. In renal impairment cases (without under regularavailable DCB delivers Paclitaxel to the vessel wall duringhaemodialysis), we used the intermittent haemodiafiltration

balloon inflation, where the lipophilic nature of Paclitaxel(IHDF) method during the procedure as previously

enable it to partitions into the vessel walls, upon which

reported4）. In every case, in which we decided to treat

it exerts its anti-restenotic effect3）. However we have nowith DCB, predilatation methods (direct DCB, NC balloon,

data regarding the predilatation methods before DCB

Scoring balloon and Cutting balloon) were decided by thetreatment.

operator’s decision. Intravascular ultrasound (IVUS) was1）

performed for every procedure of PCI cases. In follow up【Methods】

CAG checkup, we used IVUS only in TLR cases.

We retrospectively analyzed 101 cases, in which

The DCB that we used in every procedure was

DCB treatments were used for ISR from 2014 to 2017.

SeQuent Please (NIPRO). This is a second generation DCB

Out of these cases, 66 patients (study patient populations)and has more efficient delivery of paclitaxel to the vessel

were followed up for CAG (follow up rate was 65.3%).

wall, which results in a longer persistence of the drug. It

The average follow up period was 9.7 ± 5.8 months. All ofhas the concentration of paclitaxel of 3.0 μg/mm² on thethese DCB treated cases were divided into two groups by

balloon surface. After the lesion modification, if there waspredilatation methods: scoring balloon group (NSE balloon

no significant dissection which was approved by IVUS,

and cutting balloon, n = 40) and non-scoring balloon group

we used the DCB. Inflation time was variable from 30(direct DCB, NC balloon and semi-compliance balloon, nseconds to 90 seconds. In every PCI procedure, after DCB= 26). During follow up, if the % stenosis was more thantreatment we checked IVUS again.

75%, these cases were retreated as ISR cases. No special
exclusion criteria were applied for this study. According

Angiographic analysis: Quantitative coronary angiography

to our usual standard procedure, informed consent was(QCA) was performed for every PCI case before andsigned by the patient and one responsible family member.

after the procedure and also during follow up (bothCAG and PCI cases). We measured percent (%) area

Procedure: Interventional procedures were performed

stenosis, percent (%) diameter stenosis, minimal lumen− 80 −

Effect of Predilatation Methods on Drug Coated Balloon Treatment in In-Stent Restenosis Lesions

diameter (MLD) and lesion length for every procedure.

70.5 years. Regarding the cardiovascular risk factors,

The calcification and tortuosity of the vessels were also

hypertension was common; 89.4 % of the study population.

classified angiographically.

The prevalence of other risk factors, dyslipidemia anddiabetes mellitus, were also very high; 75.8% and 69.7%

Definition: Restenosis was defined as more than 75%

respectively. Smoking was 31.8%, family history of CVD

stenosis of the luminal diameter compared to the reference

was 16.7% and previous history of CABG was found in

vessels. In-stent restenosis was defined as the restenosis

4.5% of the population. Chronic kidney disease underin stent (focal or diffuse) and stent edge restenosis (inroutine haemodialysis patient population, was also high insegment restenosis). Lesion length was defined as thethis study and it was 48.5%. Haemodialysis population was

distance from proximal edge of the lesion to the distal

higher in non-scoring balloon group in this study. It was

shoulder edge of the lesion.

because of the higher calcification burden in these patientsand scoring balloons were slightly difficult to use due toStatistical analysis: Continuous variables were mentioned

its low crossing profile. The other patient characteristics

as mean ± standard deviation and categorical variables

between scoring and non-scoring groups were notwere expressed as numbers with percentage. Continuous

significantly different.

variables were compared using the paired Student’s

The total involvement of the coronary vessels weret-test. Categorical variables were compared using the chi-

LAD 24.2%, LCX 18.1%, RCA proximal 19.6% and RCA

square test. Regarding the p value, < 0.05 was considered

mid to distal 36.3% and no significant difference between

significant.

2 groups. In this study, one case was the SVG graft ISR.
Regarding the lesion characteristics, scoring balloon【Results 】

group and non-scoring balloon group were not different

Patient characteristics are shown in Table (1).

significantly. In procedural characteristics, the balloon

Average age distribution of the study population was

length used in scoring balloon group was shorter than non-Table (1). Patient characteristics of the study
Patient
Characteristics

All ISR cases(n = 66)

Scoring balloon group(n = 40)

Non-scoring balloon
group(n = 26)

p valueMale

84.8 %

90.0 %

76.9 %

0.15

Age

70.5 ± 11.0

71.1 ± 10.7

69.6 ± 11.2

0.56

Hypertension

89.4 %

85.0 %

96.1 %

0.15

Dyslipidaemia

75.8 %

75.0 %

76.9 %

0.86

Diabetes Mellitus

69.7 %

67.5 %

73.0 %

0.63

Haemodialysis

48.5 %

32.5 %

73.0 %

0.001

Smoking

31.8 %

45.0 %

11.5 %

0.004

Family History

16.7 %

12.5 %

23.0 %

0.26

Prior CABG

4.5 %

2.5 %

7.6 %

0.32

ACS

1.5 %

2.5 %

0%

0.42

− 81 −

原著

scoring balloon group (10.7 ± 1.3 v.s 14.5 ± 5.7, p =0.003). It% (p value = 0.18) (Table 3). For specific predilatation sub-was because scoring balloons we used were Flextome andgroups, TLR rate in cutting balloon group was significantly

NSE, their maximal length was only up to 13 mm. Therelower than NC balloon (16.1% v.s 45.0%, p value = 0.02).

was no difference between DCB size, length, inflation

There was no TLR rate in cases in which direct DCB

pressure and inflation duration between 2 groups (Table 2).

(n = 2) and semi-compliance balloon (n = 4) were used,

Before we retreated the ISR lesions with DCB, we decided

but these sub-groups were only small numbers in thethe predilatation methods – non-scoring or scoring balloon.

study. Concerning about the clinical outcomes in termsof TLR, predilatation methods by using cutting balloon【Clinical outcomes】

had significantly better than NC balloon group in DCB

Out of these 66 ISR cases with DCB treatment 17

treatment. (Figure 1).

cases had TLR during follow up (5 cases for CBA, 3 cases

Another finding with this study was that TLR rates

for NSE balloon and 9 cases for NC balloon). TLR rate inin haemodialysis group and non-haemodialysis groupscoring balloon was 20.0% and non-scoring balloon was 34.6

were 34.4% and 17.6% respectively and it was statistically

Table (2). Coronary artery involvement, lesion and procedural characteristics of the study
Scoring balloon

Non-scoring balloon

p valueCoronary Artery Involvement
LAD

16 (24.2 %)

10 (25.0 %)6 (23.1 %)

0.85

LCX

12 (18.1 %)

7 (17.5 %)

5 (19.2 %)0.85

RCA proximal

13 (19.6 %)7 (17.5%)

6 (23.1 %)0.57

RCA mid to distal

24 (36.3 %)

15 (37.5 %)

9 (34.6 %)

0.81

SVG

1 (1.5 %)

1 (2.5 %)

0 (0%)

0.41

Lesion Length (mm)10.6 ± 5.0

11.9 ± 5.6

0.36

Reference Vessel Diameter (mm)3.3 ± 0.6

3.3 ± 0.8

0.97

% Diameter Stenosis

72.2 ± 19.3

79.4 ± 21.8

0.18

Mild

47.5%

38.5%

0.47

Moderate

15.0%

30.8%

0.13

Severe

12.5%

19.2%

0.46

7.5%

23.1%

0.07

Predilatation Balloon Size (mm)2.9 ± 0.5

2.6 ± 0.7

0.06

Predilatation Balloon Length (mm)10.7 ± 1.3

14.5 ± 5.7

0.003

DCB Size (mm)3.2 ± 0.6

3.1 ± 0.6

0.65

DCB Length (mm)20.1 ± 4.4

22.0 ± 5.4

0.15

DCB Inflation Pressure (atm)13.2 ± 3.1

13.8 ± 3.4

0.44

DCB Inflation Duration (seconds)

51.3 ± 14.3

52.3 ± 10.2

0.73

Lesion Characteristics

Calcification

Tortuosity

Procedural Characteristics− 82 −

Effect of Predilatation Methods on Drug Coated Balloon Treatment in In-Stent Restenosis Lesions

significant (p value = 0.03). The underlying pathological47.1 ± 30.8 %, p value = 0.02; 44.8 ± 26.2 % v.s 63.1 ±mechanism of calciphylaxis in chronic kidney disease make27.5 %, p value = 0.01) and minimal lumen diameter was

heavily calcified lesion in coronary arteries and thesesignificantly higher (2.3 ± 1.0 v.s 1.8 ± 1.2, p value < 0.05)

patients had higher chance of restenosis in comparisonin scoring balloon group compared with the non-scoringwith the other patients although the interventional

balloon group at follow up. There was no difference inprocedures were relatively same. So we sub-analyzed

acute gain (2.0 ± 0.8 mm v.s 1.9 ± 0.7 mm, p value = 0.59)

the predilatation methods in haemodialysis patient (nand late lumen loss (0.7 ± 0.8 mm v.s 0.9 ± 1.0 mm, p value= 32) between scoring and non-scoring balloon groups.  

= 0.22) between scoring balloon group and non-scoring

Although the TLR rate was higher in non-scoring balloon

balloon group.

group (42.1% in non-scoring and 30.8% in scoring group), it
was statistically non-significant. It might be due to small
number of population in the study.

Table (3). TLR rates of scoring balloon and non-scoring
balloon group

3.5

TLR rate

2.5

Scoring balloon

Non-scoring balloon

P value

20.0 %

34.6 %

0.18

Minimal Lumen Diamerer (mm)

4

3.0

3

2.6

2

1.8 P value−0.05

1.5

0.9

1

0.7

0.5
0

(％)
50
40

p value − 0.02
p value − 0.55

Baseline

Post procedure
Scoring45.0

Follow up

Non-scoring

p value − 0.25

Figure (2). Comparison of the minimal lumen diameter
between scoring balloon group and nonscoring balloon group

33.3

30
20

2.3

16.1

10
0

0

0

% Diameter Stenosis

120

CBA
NSE
NC
Semi
None
（n=31） （n=9） （n=20） （n=4） （n=2）

100
80Figure (1). TLR rates of specific predilatation groups

60

79.4
72.2
47.1

40

24.9

30.2

20

Angiographic results: QCA was performed totally 3 times

0for every procedure – before and immediately after
there were no significant differences in baseline and postprocedure between 2 groups, the % diameter stenosis, %area stenosis were significantly reduced (30.2 ± 25.5 % v.s

16.1

Baseline

Post procedure
Scoring

the procedure and at follow up (Figure 2 - 4). Although

P value−0.02

Follow up

Non-scoring

Figure (3). Comparison of the % diameter stenosis
between scoring balloon group and nonscoring balloon group− 83 −

原著

before DCB treatment in ISR cases. By using the scoring% Area Stenosis

120

diameter stenosis, % area stenosis, MLD) had better results

100
80

balloon for lesion preparation, QCA measurements (%91.0

than the non-scoring balloon and statistically significant.

88.5
63.1

60

42.2

44.8

40

before DCB, we were able to have the better clinicaloutcomes by reducing TLR rates although the expenses

28.5

20
0

Furthermore, with the cutting balloon for predilatation
P value−0.01

were approximately same as the other lesion preparation
Baseline

Post procedure
Scoring

Follow up

methods. Before the development of DCB, such ISR cases

Non-scoring

were treated with another stent implantation (stent instent), but the two metallic layer of the stents make the

Figure (4). Comparison of the % area stenosis between
scoring balloon group and non-scoring balloon
groupfurther chances of restenosis and thrombosis higher.
With the progressive development of DCB, we can havethe stent like treatment without new metallic layer withgood clinical outcome and also has the benefit for shorter
duration of the dual antiplatelet therapy. But most of theAnother important point from this study was the

ISR cases have many cardiovascular risk factors and theiranatomical site of ISR. In our study of 66 ISR patients,

coronary arterial walls have high burden of calcification.

one case was the vein graft ISR and the other 65 cases

To get the uniform delivery of the drug over the vessel

were native coronary ISR cases. By comparison of thewall, we must perform the plaque modification effectively.

QCA measurement, % diameter stenosis, % area stenosis,

When treating in-stent restenosis with balloon angioplasty,

MLD and acute gain were not relatively different between

luminal gain is achieved by a combination of additional

segment 1(RCA proximal) and other segments of coronary

stent expansion and neointimal tissue compression

arteries, but late lumen loss was more in segment 1 than

through the stent. Although satisfactory initial clinicalother segments (1.3 ± 1.1 mm v.s 0.6 ± 0.8 mm, p value

and angiographic results were obtained with balloon= 0.05). During the follow up period, the TLR rate inangioplasty, a significant early late lumen loss was also

segment 1 (53.8%) was the highest, compared with theobserved shortly after in stent restenosis treatment due toother segments (segment 2-4 was 25.0%, segment 5-10

recoil and re-intrusion of neointimal tissue in the lumen6）.

was 17.6%, and segment 11-15 was 8.3%) and it was also

Cutting balloon has 3 or 4 longitudinal blades alongsidestatistically significant (p value – 0.009). While reanalysis

the balloon and it makes the longitudinal focused forceof the segment 1 TLR cases, the comparison between theto effectively modify the atherosclerotic plaque. Cutting

cutting balloon and NC balloon as predilatation methods

balloon present several advantages for the treatment of

were 42.9% and 80.1% respectively (p value = 0.19. TLR)

severe calcified lesions, allowing a larger luminal gain at

rates seemed to be lower in cutting balloon group than inlower pressure compared to balloon angioplasty alone andNC balloon group.

preventing late recoil due to the incisions created by theblades7）8）. Furthermore cutting balloon anchors the lesion【Discussion】

during inflation and reduce the risks of displacements andIn our single center retrospective study, we compareddissections at the stent margins1）. Scoring balloon also has

the different predilatation methods (lesion preparation)

the spiral shape blade over the balloon but the height of− 84 −

Effect of Predilatation Methods on Drug Coated Balloon Treatment in In-Stent Restenosis Lesions

the blade is shorter and the breaking power of the plaque2018 ESC guidelines for myocardial revascularization.

is lower than the cutting balloon with similar crossing

European Heart Journal, ehy 394, 25th August 2018.

profile. NC balloons have the better crossing profile than3）Kern MJ, Seto AH et al. Chapter 32 – Thoracic aortic,

the others but its plaque modification effect will be lower.

Abdominal aortic and Lower extremities intervention.

Although the study population in this study was small, theSCAI Interventional Cardiology Review, 3rd edition,effectiveness of cutting balloon treatment prior to DCB

2018

was disclosed, may be due to such specific mechanism of4）Shiota Y, Miyoshi Y, Hadano K et al. Prevention of

cutting balloon angioplasty.

contrast-induced nephropathy by the high flow-volume
CHDF during and after the angiography/PPI/PCI.

【Conclusions】

CVIT Jpn Ed 2013, 5: 117 – 123

Although the treatments for in-stent restenosis are5）Mehran R, Mintz GS, Popma JJ, Pichard AD, Satler LF,

still challenging for the interventionists, drug coatedKent KM, Griffin J, Leon MB. Mechanisms and results

balloon has the promising effect and also has the classof balloon angioplasty for the treatment of in-stent

IA recommendation in European Society of Cardiology

restenosis. Am J Cardiol. 78: 618-22, 1996

guideline2）. Before the DCB treatment, lesion preparation6）Shiran A, Mintz GS, Waksman R, Mehran R, Abizaid A,

by cutting balloon angioplasty has the satisfactory clinical

Kent KM, Pichard AD, Satler LF, Popma JJ, Leon MB.

and angiographic results in comparison with the other

Early lumen loss after treatment of in-stent restenosis:

lesion preparation methods like NSE balloon and NC

an intravascular ultrasound study. Circulation. 98: 200-3,

balloon.

19987）Secco GG, Foin N, Viceconte N, Borgia F, De Luca G, Di【References】

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Eurointervention, 2011: 7: 828-34  
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