Factors in Sufficient Endovascular Vessel Preparation for Severely Calcified Femoropopliteal Lesions

Abstract

Background: Vessel preparation for endovascular treatment (EVT) is important but because the contributory factors for favorable outcomes are not yet known, we conducted the present study to elucidate the factors associated with sufficient vessel preparation for severely calcified femoropopliteal (FP) lesions.

Methods and Results: This was a single-center retrospective observational study of 97 patients (mean age, 75±8 years, 76% male) with 106 de novo severely calcified FP lesions who underwent EVT under intravascular ultrasound (IVUS) evaluation. The lesion definition was 360° of superficial calcification on IVUS. The primary outcome measure was sufficient vessel preparation, which was defined as successful cracking of severely calcified lesions evaluated by IVUS after predilation. The mean lesion length was 200±103 mm, and chronic total occlusion was present in 38% of patients. According to the greater difference between the preballoon size and the lumen diameter of the severely calcified lesion, the frequency of sufficient vessel preparation increased (odds ratio, 4.68; 95% confidence interval, 2.09–10.49; P<0.01). Balloon type (noncompliant, P=0.80; scoring: P=0.25) and pressure (P=0.27) were non-contributory.

Conclusions: The difference between the lumen diameter at the severely calcified FP lesion site and the preballoon dilatation diameter was the sole factor contributing to sufficient vessel preparation.

Approximately half of all symptomatic patients with lower extremity arterial disease (LEAD) have femoropopliteal (FP) lesions,¹ with half of such cases complicated by vessel calcification (2). The presence of vessel calcification affects the occurrence of restenosis after endovascular therapy (EVT) with stents,^2–4 mainly due to insufficient dilation and consequent recoil during the initial treatment.^3,4 Although atherectomy devices can effectively treat severely calcified FP lesions, they are not routinely used in contemporary FP practice because of their high cost, risk of complications including distal embolization, and insufficient results of combined use.^5–7 Although the importance of vessel preparation was recently reported,^8,9 the factors contributing to sufficient vessel preparation for severely calcified FP lesions have not been elucidated, which became the aim of our study.

Methods

Study Participants

This was a single-center retrospective observational study conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Kansai Rosai Hospital (reference no. 19 16D008g). From July 2012 to April 2021, intravascular ultrasound (IVUS)-supported EVT under a provisional stenting strategy was performed for 955 de novo FP lesions in 773 patients with symptomatic LEAD. Of them, 849 lesions were excluded for the following reasons: (1) no calcification (n=275); (2) not total circumferential calcification (n=499); (3) lack of IVUS data after preballoon dilatation (n=72); and (4) lack of postprocedural IVUS data (n=3). The remaining 106 de novo FP lesions in 97 patients were analyzed in this study. The study flowchart is shown in Figure 1. Because this was an noninvasive observational study without intervention and not using human biological specimens, the requirement for written informed consent was waived in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan. Instead, relevant information about the study was made publicly available.

Figure 1.

Participant flow chart.

Intervention Procedure and Follow-up Protocol

An ipsilateral or contralateral approach was used to achieve vascular access via the common femoral artery under local anesthesia, and a 6- or 7-Fr guiding sheath was used. After placement of the guiding sheath above the target FP lesion, 5,000 units of heparin was routinely injected via arterial access. Guidewires (0.035”, 0.018”, or 0.014”) were selected by the physician. After successful passage of the guidewire through the entire lesion, the lumen, external elastic membrane (EEM) diameter, and area at the distal healthy sites and severely calcified FP lesion site were evaluated using IVUS (OptiCross or Atlantis SR Pro, Boston Scientific, Marlborough, MA, USA; or AltaView, Terumo Corp., Tokyo, Japan). Based on the IVUS findings, the predilatation balloon type, size, and pressure were determined by each physician. The size of the nitinol stent with or without paclitaxel was determined as 1 : 1 relative to the distal EEM diameter. When an interwoven stent or stent graft was indicated, stent size was determined by the distal lumen based on the 1:1 strategy. Stent type was determined by each physician. Bare-nitinol stents included the S.M.A.R.T. Control^TM (Cordis, Miami Lakes, FL, USA), INNOVA (Boston Scientific), Life stent (Bard Peripheral Vascular, Tempe, AZ) and Misago (Terumo Corporation). The interwoven stent was a Supera stent (Abbott Vascular, Santa Clara, CA, USA), the stent graft was a Viabahn covered stent (W. L. Gore & Associates, Flagstaff, AZ, USA), and the drug-eluting stents were ELUVIA stents (Boston Scientific) and Zilver PTX (Cook Medical, Bloomington, IN, USA). When multiple stents were required, the margin of overlap was at least 10 mm. Post-dilatation was performed using a balloon of similar size to or 1 mm smaller than the stent diameter. Procedural success was defined as the absence of a limiting flow. All participants were scheduled to visit for follow-up, and evaluations of ischemic symptoms and ankle-brachial index were regularly conducted, as well as duplex ultrasonography (DUS). The patients were scheduled for follow-up at 1 and 3 months postoperative and every 3 months thereafter. If restenosis was identified on DUS assessment, follow-up angiography was scheduled. Dual-antiplatelet therapy (aspirin 100 mg/day with clopidogrel 75 mg/day or prasugrel 3.75 mg/day) was prescribed for at least 1 week prior to EVT and continued based on the use instructions for each.

Definitions

Chronic limb-threatening ischemia was diagnosed when patients had (1) chronic ischemic foot pain at rest with an ankle pressure <50 mmHg, toe pressure <30 mmHg, or skin perfusion pressure ≤30 mmHg; (2) ischemic foot ulcer/gangrene with an ankle pressure <70 mmHg, toe pressure <40 mmHg, or skin perfusion pressure ≤40 mmHg (ankle pressure/toe pressure/skin perfusion pressure-proven critical ischemia); or (3) ischemic foot pain at rest or ulcer/gangrene with critical ischemia indicated by other modalities.¹⁰ A severely calcified lesion was defined as 360° of superficial calcification on IVUS evaluation (Figure 2), and sufficient vessel preparation was defined as a calcified site that was cracked on IVUS evaluation after predilatation¹¹ (Figure 2). Cracks in the calcified lesions were characterized by a gap in the calcium and direct exposure of calcium to the lumen at the gap.

Figure 2.

Definition of sufficient vessel preparation and classification of severely calcified femoropopliteal (FP) lesion sites according to the difference between the preballoon dilatation diameter and the mean lumen diameter ([long-axis diameter + short-axis diameter] / 2). (A) Intravascular ultrasound (IVUS) image of the lumen diameter of a severely calcified FP lesion site at the initial pullback. The long- and short-axis diameters were 4.3 mm and 3.3 mm, respectively, and the average lumen diameter was 3.8 mm. (B) IVUS image of a severely calcified FP lesion site after preballoon dilatation. Cracking of the calcification is visible (arrowheads), which indicated sufficient vessel preparation.

Procedure-related complications were defined as vessel injury occurring after predilatation. Vessel complications were defined as vessel rupture after the predilatation procedure, development of an arteriovenous fistula, and overstretching the vessel larger than the native diameter. The difference in mean lumen diameter ([long-axis + short-axis] / 2) between the preballoon dilatation diameter and that of the severely calcified lesion site was classified into 4 groups: 0 (< +0.5 mm), +1 (> +0.5 mm but < +1.5 mm), +2 (> +1.5 mm but < +2.5 mm), and +3 (> +2.5 mm) (Figure 2). Restenosis was defined as a peak systolic velocity ratio >2.4 assessed using DUS.

IVUS Analysis

The mean lumen and EEM diameters were calculated from the long- and short-axis diameters. Proximal and distal reference segments were selected as the most normal-looking sections within 10 mm either side of the lesion. The plaque burden was defined as the area occupied by plaque between these leading edges and was calculated as the proportion of the entire EEM occupied by atherosclerotic plaque throughout the segment of interest.¹² Plaque burden was used for analysis, with the more severe values at the proximal and distal sites as representative values. Stent edge dissection was defined as disruption of the vessel’s luminal surface into the media at the stent edges (within margins of ≈5 mm at the proximal and distal sides of the stent).¹² The stent symmetry index was calculated as the short-axis diameter/long-axis diameter at the site of minimal stent area (MSA).¹²

Outcomes

The primary outcome measure was sufficient vessel preparation, which was defined as the successful cracking of severely calcified lesions evaluated by IVUS after predilatation. The secondary outcomes included MSA according to the identified factors and procedure-related complications.

Statistical Analysis

Continuous variables are described as mean±standard deviation, and discrete variables are described as frequencies (percentages). Continuous and discrete data were compared between groups using the unpaired t-test and Fisher’s exact test. A receiver-operating characteristic (ROC) curve analysis was performed to delineate cutoff points. Factors associated with cracking were investigated using logistic regression analysis, and the results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). The cutoff value was determined using ROC curve analysis. Pearson’s correlation coefficient was used to explore the correlation coefficients. The Kaplan-Meier method was used to calculate the restenosis rate after EVT. For all analyses the significance level was set at P<0.05 and SPSS Statistics package version 27 (IBM, Armonk, NY, USA) was used.

Results

Patients’ Characteristics

Patient characteristics are summarized in Table 1. The mean age was 75±8 years and 76% (n=76) were male. Notable comorbidities included diabetes mellitus (76% [n=74]), renal failure (84% [n=81]), and coronary artery disease (64% [n=62]). Chronic limb-threatening ischemia was observed in 37% (n=36) of the patients. No significant difference was noted in background factors between patients with and without cracks.

Table 1. Patients’ Characteristics

	All (n=97)	Cracking (+) (n=69)	Cracking (−) (n=28)	P value
Age (years)	75±8	75±8	75±7	0.91
Male sex	74 (76)	54 (78)	20 (71)	0.48
Body mass index (kg/m2)	23±4	23±6	22±4	0.48
Hypertension	64 (66)	49 (71)	15 (54)	0.10
Dyslipidemia	42 (43)	27 (39)	15 (54)	0.20
Diabetes mellitus	74 (76)	53 (77)	21 (75)	0.85
Renal failure	81 (84)	58 (84)	23 (82)	0.82
Hemodialysis	65 (67)	48 (70)	17 (61)	0.41
Current smoking status	23 (24)	18 (26)	15 (18)	0.39
Coronary artery disease	62 (64)	41 (59)	21 (75)	0.15
Chronic limb-threatening ischemia	36 (37)	23 (33)	13 (46)	0.23

Data are presented as mean±standard deviation or n (%).

Lesion Characteristics

Table 2 shows the characteristics of the lesions evaluated using angiography and IVUS. Trans-Atlantic Inter-Society Consensus Document II C/D and chronic total occlusion were found in 70% (n=74) and 38% (n=40) of patients, respectively. The mean lesion length was significantly more and the lumen diameter at the severely calcified site was significantly greater in the group with vs. without cracks (lesion length: 212±100 vs. 166±104 mm, P=0.04; lumen diameter at severely calcified site: 4.0±0.5 vs. 3.6±0.6 mm, P<0.01). The plaque burden was significantly greater in the group without vs. with cracks (54±11% vs. 48±10%, P<0.01).

Table 2. Lesion Characteristics Evaluated by Angiography and IVUS

	All (n=106)	Cracking (+) (n=77)	Cracking (−) (n=29)	P value
Angiographic findings
TASC II classification
A	14 (13)	12 (16)	2 (7)	0.058
B	18 (17)	12 (16)	6 (21)
C	40 (38)	24 (31)	16 (55)
D	34 (32)	29 (37)	5 (17)
Chronic total occlusion, (n)	40 (38)	29 (38)	11 (38)	0.98
Lesion length, (mm)	200±103	212±100	166±104	0.04
Run-off vessels
0	5 (5)	3 (4)	2 (7)	0.46
1	60 (57)	41 (53)	19 (66)
2	34 (32)	28 (36)	6 (20)
3	7 (7)	5 (7)	2 (7)
IVUS findings
Lumen diameter at proximal site, (mm)	5.4±1.1	5.5±1.1	5.1±1.0	0.08
EEM diameter at proximal site, (mm)	7.4±1.2	7.5±1.2	7.2±1.2	0.22
Lumen diameter at severe calcified site	3.7±0.6	4.0±0.5	3.6±0.6	<0.01
Lumen diameter at distal site, (mm)	5.0±0.8	5.1±0.7	4.8±0.9	0.07
EEM diameter at distal site, (mm)	6.7±0.9	6.7±0.8	6.8±1.0	0.42
Plaque burden, (%)	50±10	48±10	54±11	<0.01

EEM, external elastic membrane; IVUS, intravascular ultrasound; TASC, Trans-Atlantic Inter-Society Consensus.

Procedural Characteristics and Post-EVT Findings

Procedural characteristics are listed in Table 3. Semicompliant, noncompliant, and scoring balloon types for vessel preparation with and without cracks were used by 13% (n=10) vs. 14% (n=4), 45% (n=35) vs. 66% (n=19), and 42% (n=32) vs. 20% (n=6) (P=0.06), respectively. The distribution of preballoon dilatation diameters differed between the groups (P<0.01). The difference between the lumen diameter at the severely calcified site and the preballoon dilatation diameter and MSA was significantly larger in the with cracks group (difference between lumen diameter at the severely calcified site and preballoon dilatation diameter: 2.3±0.8 vs. 1.3±0.8 mm, P<0.01; MSA: 17.3±3.3 vs. 13.9±3.2 mm², P<0.01).

Table 3. Procedural Characteristics and Post-Lesion Assessment by Angiography and IVUS

	All (n=106)	Cracking (+) (n=77)	Cracking (−) (n=29)	P value
Procedure
Balloon type for predilatation, (n)
Semicompliant	14 (12)	10 (13)	4 (14)	0.06
Noncompliant	54 (51)	35 (45)	19 (66)
Scoring	38 (36)	32 (42)	6 (20)
Balloon diameter for predilatation, (mm)
4	11 (10)	5 (6)	5 (17)	<0.01
5.0 or 5.5	28 (26)	17 (22)	12 (41)
6.0 or 6.5	45 (42)	35 (45)	10 (34)
7.0	21 (20)	19 (25)	2 (7)
8.0	1 (1)	1 (1)	0
Balloon pressure, (atm)	16±4	16±3	17±4	0.25
Balloon length, (mm)	82±62	81±62	84±62	0.84
Difference between lumen diameter at the severely calcified site and preballoon diameter, (mm)	2.0±0.9	2.3±0.8	1.3±0.8	<0.01
Difference between lumen diameter at the distal site and preballoon diameter, (mm)	0.8±1.0	0.9±1.0	0.5±1.0	0.15
Stent type
Bare-nitinol	22 (21)	18 (23)	3 (10)	0.04
Interwoven	12 (11)	6 (8)	11 (38)
Drug-eluting	27 (25)	24 (31)	3 (10)
Stent graft	38 (36)	29 (38)	9 (31)
Stent diameter	6.5±0.8	6.6±0.8	6.4±0.8	0.16
Stent length, (mm)	229±110	243±107	192±111	0.03
Post-balloon diameter, (mm)	6.1±0.8	5.9±0.8	6.2±0.7	0.10
Post-EVT findings
Minimum stent area, (mm2)	16.3±3.6	17.3±3.3	13.9±3.2	<0.01
Stent symmetry index	0.77±0.14	0.78±0.13	0.74±0.15	0.21
Edge dissection	9 (8)	6 (8)	3 (10)	0.68

EVT, endovascular therapy; IVUS, intravascular ultrasound.

Univariate and Multivariate Analyses of Factors Contributing to Sufficient Vessel Preparation

Table 4 shows the univariate and multivariate analyses of the factors associated with sufficient vessel preparation, which was observed in 73% (n=77) of patients. Balloon type (semicompliant vs. noncompliant: OR, 0.84; 95% CI, 0.23–3.10; P=0.80; semicompliant vs. scoring: OR, 2.37; 95% CI, 0.55–10.26; P=0.25) and pressure (OR, 0.94; 95% CI, 0.83–1.05; P=0.27) did not contribute to sufficient vessel preparation, whereas the difference between the lumen diameter of the severely calcified lesion and the preballoon dilatation diameter did have an effect (OR, 4.68; 95% CI, 2.09–10.49; P<0.01). For severely calcified FP lesions, the cutoff value for the difference between the preballoon dilatation diameter for the achievement of sufficient vessel preparation and the lumen diameter of the severely calcified lesion site was 1.9 mm (AUC, 0.80; 95% CI, 0.71–0.89; sensitivity, 74%; specificity, 76%) (Figure 3). In this study, restenosis occurred in 22% (n=21) of the lesions during the mean follow-up period of 19±14 months. The Kaplan-Meier curve of sufficient vs. insufficient vessel preparation showed that the sufficient vessel preparation group had significantly better primary stent patency than the insufficient group (85±5% vs. 53.0±13.0%, P<0.01). Stent type did not differ between the sufficient and insufficient vessel preparation groups (P=0.054).

Table 4. Univariate and Multivariate Analyses of Factors for Sufficient Vessel Preparation

	Unadjusted OR [95% CI]	P value	Adjusted OR [95% CI]	P value
Diabetes mellitus	0.91 [0.34–2.44]	0.85
Hemodialysis	1.53 [0.62–3.75]	0.36
Chronic limb-threatening ischemia	0.59 [0.25–1.42]	0.24
Lesion length (per 10 mm increased)	1.05 [1.00–1.09]	0.04	1.04 [0.99–1.10]	0.13
Plaque burden	0.94 [0.90–0.99]	0.01	0.95 [0.90–1.00]	0.07
Balloon type for predilatation
Semicompliant	Ref.
Noncompliant	0.84 [0.23–3.10]	0.80
Scoring	2.37 [0.55–10.26]	0.25
Balloon pressure, (atm)	0.94 [0.83–1.05]	0.27
Balloon length	1.00 [0.99–1.01]	0.57
Difference between lumen diameter at the severely calcified lesion site and preballoon diameter	5.50 [2.56–11.83]	<0.01	4.68 [2.09–10.49]	<0.01
Difference between lumen diameter at the distal site and preballoon diameter	1.34 [0.87–2.02]	0.20

CI, confidence interval; OR, odds ratio.

Figure 3.

Cutoff value for the difference between preballoon dilatation diameter for sufficient vessel preparation and lumen diameter of severely calcified FP lesion site was 1.9 mm (area under the curve, 0.80; 95% confidence interval, 0.71–0.89; sensitivity, 74%; specificity, 76%).

Rate of Sufficient Vessel Preparation According to the Difference Between the Lumen Diameter of the Severely Calcified Lesion Site, Preballoon Dilatation Diameter, and MSA

Figure 4A shows the sufficient vessel preparation rate divided into 4 groups according to the difference between the lumen diameter of the severely calcified lesion site and the preballoon dilatation diameter. The sufficient vessel preparation rate was 0% (0/5) in the 0 mm group, 48% (11/23) in the +1 mm group, 79% (37/47) in the +2 mm group, and 94% (29/31) in the ≥+3 mm group. Figure 4B shows the MSA divided into 4 groups according to the difference between the lumen diameter of the severely calcified lesion site and the preballoon dilatation diameter. No significant intergroup difference was noted in the distal EEM diameter (all P>0.10) or stent size (all P>0.010), but the MSA was 12.8±2.1 mm² in the 0 mm group, 14.5±2.8 mm² in the +1 mm group, 16.3±3.6 mm² in the +2 mm group, and 18.3±3.3 mm² in the ≥+3 mm group (Figure 4B). A weak correlation was noted between MSA and the difference in the lumen and predilatation balloon diameters at the site of severely calcified lesions (R=0.42, P<0.01).

Figure 4.

(A) Rate of sufficient vessel preparation divided into 4 groups according to the difference between the lumen diameter of the severely calcified femoropopliteal (FP) lesion site and the preballoon dilatation diameter. The sufficient vessel preparation rate was 0% (0/5) in the 0 mm group, 48% (11/23) in the +1 mm group, 79% (37/47) in the +2 mm group, and 94% (29/31) in the ≥+3 mm group. (B) Minimal stent area (MSA) according to difference between lumen diameter of severely calcified FP lesion site and preballoon dilatation diameter was 12.8±2.1 mm² in the 0 mm group, 14.5±2.8 mm² in the +1 mm group, 16.3±3.6 mm² in the +2 mm group, and 18.3±3.3 mm² in the ≥+3 mm group. (C) Rate of vessel complications divided into 4 groups according to difference between lumen diameter of severely calcified FP lesion site and preballoon dilatation diameter. The procedure-related complication rates were 0% (0/5) in the 0 mm group, 0% (0/23) in the +1 mm group, 23% (11/47) in the +2 mm group, and 52% (16/31) in the ≥+3 mm group.

Vessel Complication Rate According to the Difference Between the Lumen Diameter of the Severely Calcified Lesion Site and the Preballoon Dilatation Diameter

Figure 4C shows the vessel complication rate divided into 4 groups according to the difference between the lumen diameter of the severely calcified lesion site and the preballoon dilatation diameter. The vessel complications were 0% (0/5) in the 0 mm group, 0% (0/23) in the +1 mm group, 23% (11/47) in the +2 mm group, and 52% (16/31) in the ≥+3 mm group. In addition, the only factors examined for procedure-related vessel complications were the difference in lumen diameter at the severely calcified site and preballoon dilatation diameter (OR, 9.80; 95% CI, 1.79–53.56; P<0.01) (Supplementary Table). Overall, vessel rupture occurred in 74% of patients (n=20/27), and an arteriovenous fistula developed in 26% (n=7/27). In the +2 mm group, vessel rupture occurred in 63% (n=7/11), and arteriovenous fistula developed in 37% (n=4/11). In the ≥+3 mm group, vessel rupture occurred in 81% (n=13/16), and arteriovenous fistula developed in 19% (n=3/16).

Discussion

This study investigated factors associated with sufficient vessel preparation for FP lesions complicated by severely calcified lesions. In the multivariate analysis, the difference between the lumen diameter of the severely calcified FP lesion site and the preballoon dilatation diameter was the only factor. The cutoff value for the difference between the lumen diameter of the severely calcified FP lesion site and the preballoon dilatation diameter, a factor contributing to sufficient vessel preparation for severely calcified FP lesions, was 1.9 mm.

Comparison With Calcified Lesions in Coronary Arteries

The preballoon dilatation diameter relative to vessel diameter is a known factor contributing to sufficient vessel preparation in coronary lesions with calcification.^13,14 In this study, the factor contributing to sufficient vessel preparation for severely calcified FP lesion sites was the preballoon dilatation diameter, and the cutoff value was 1.9 mm for severely calcified FP lesion sites (AUC, 0.80; 95% CI, 0.71–0.89; sensitivity, 74%; specificity, 76%) (Figure 3). Torii et al reported that calcification associated with lower-extremity arteries has various patterns and is thicker than that associated with coronary artery lesion.¹⁵ A preballoon with a diameter +1.9 mm larger than the lumen diameter of the severely calcified FP lesion site is recommended to use for sufficient lesion preparation. If the IVUS findings after predilatation do not show successful cracking of the calcification, we believe that the use of an atherectomy device should be considered to achieve sufficient vessel preparation. In the future, optical coherence tomography and optical frequency domain imaging will be used to evaluate calcification in more detail, particularly regarding the relationship between calcification thickness and vessel preparation success.

Advantages and Disadvantages of Aggressive Vessel Preparation

An association between vessel complications and pre-balloon dilatation diameter has been reported.^16,17 We also found that the frequency of vessel complications increased as the difference between the preballoon dilatation diameter and the lumen diameter of the severely calcified lesion increased (0% [0/5], 0% [0/23], 23% [11/47], and 52% [16/31] in the 0, +1, +2, and ≥+3 mm groups, respectively) (Figure 4C). In actual clinical practice, the vessel preparation rate and the incidence of vessel complications should be considered when selecting a preballoon dilatation diameter. The MSA was greater in the sufficient vessel preparation group than in the insufficient vessel preparation group in this study (17.3±3.3 vs. 13.9±3.2 mm², P<0.01). An association has been noted between MSA and long-term primary patency after stenting.^18,19 In the present study, the sufficient vessel preparation group showed better primary patency after stenting than the insufficient vessel preparation group, although no significant difference was noted in stent type used between the groups (sufficient vs. insufficient vessel preparation: 85±5% vs. 53.0±13.0%, P<0.01). Sufficient vessel preparation according to the IVUS findings reduced the long-term stent restenosis rate.

Clinical Implications

Our findings suggest that, for severely calcified FP lesions assessed by IVUS, a preballoon dilatation diameter ≥1.9 mm larger than the lumen diameter of the severely calcified FP lesions site is important for sufficient vessel preparation, larger lumen diameter after stenting, and improved long-term results.

Study Limitations

First, it was a single-center retrospective study with a small sample size, which may have involved selection bias. Because of the small number of patients, we were unable to detect the association between several procedural factors and successful cracking. Further studies are required to evaluate the effect of these factors on successful cracking. A prospective multicenter study with a larger sample size is required to resolve this issue. Second, the IVUS analysis was not conducted in an independent core laboratory. Analyses performed by a single observer may lack generalizability, and there may have been an unintentional lack of blinding. Third, balloon type and pressure used for the predilatation were chosen by the surgeons and may have influenced the results. Finally, the capability of IVUS was only used for intravascular assessment, especially arterial surface conditions, but it cannot measure calcification thickness. It is unclear in this study how calcification thickness affected cracking. Further studies using optical coherence tomography/optical frequency domain imaging are necessary to examine calcification in detail, including thickness.

Conclusions

The only factor that contributed to sufficient vessel preparation for severely calcified FP lesions associated with FP lesions was the difference between the preballoon dilatation diameter and the lumen diameter of the severely calcified FP lesion site. Balloon type and pressure were non-contributory.

Disclosures

All authors declare no conflicts of interest.

Acknowledgments

We express our sincere appreciation of our staff for their continuing support and constant encouragement for this work.

Funding / Conflicts of Interest

None.

IRB Information

This study was approved by Kansai Rosai Hospital (reference no. 16D008g).

Data Availability

The identified participant data will not be shared.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-22-0444

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