IVUS Assessment of the Crossing Pathway of an Intraluminal Reentry Device Used in the Primary Treatment of Infrainguinal Chronic Total Occlusions

Abstract

Purpose: To examine with intravascular ultrasound (IVUS) the crossing pathways of the TruePath reentry device during primary antegrade recanalization of infrainguinal chronic total occlusions (CTOs). Methods: Between July 2017 and September 2018, a prospective multicenter study enrolled 143 consecutive patients (mean age 75±9 years; 101 men) with 146 CTOs treated in an antegrade approach using the TruePath reentry device with IVUS assessment of the crossing pathway in successful cases. Outcome measures were complete success (reentry device reached the distal true lumen), assisted success (reentry device use followed by a conventional guidewire to reach the distal true lumen), reentry device crossing route by IVUS assessment, and procedure- and device-related complications. Regression analyses were employed to identify any relevant associations between baseline patient variables and the outcome measures; results are presented as the odds ratio (ORs) and 95% confidence interval (CI). Results: Complete success was achieved in 82 (56.2%) lesions; any success (complete plus assisted) was documented in 117 (80.1%) lesions. Four (3%) perioperative device-related complications were observed. The crossing route was intraplaque for most of the total crossing distance in both complete success cases (95.3%±13.2%) and any success cases (94.8%±14.4%), with relatively short subintimal (3.6%±10.2% and 4.2%±11.2%, respectively) or intramedial (1.2%±5.8% and 1.0%±5.4%, respectively) crossing. CTO length was a significant risk factor for not achieving complete success (OR 1.74, 95% CI 1.13 to 2.68, p=0.012), and a history of failed revascularization was associated with not achieving any success (OR 6.40, 95% CI 1.28 to 28.9, p=0.038). Conclusion: The intraplaque route was the primary pathway taken by the TruePath reentry device as it crossed infrainguinal CTOs. Crossing rates were acceptable, with few device-related complications. However, a longer CTO length and a failed revascularization history negatively affected the success rate.

Keywords

chronic total occlusion endovascular therapy crossing device infrainguinal arteries intraluminal reentry device intravascular ultrasound

Introduction

The use of endovascular therapy (EVT) for peripheral artery disease (PAD) has expanded rapidly because of the less invasive nature of the procedure compared with bypass surgery and continued improvements in interventional devices.¹ However, technical success is not always satisfactory in cases of infrainguinal chronic total occlusion (CTO), which remains a challenging lesion.² If antegrade transluminal or subintimal CTO crossing fails conventionally, reentry devices are often deployed; however, these devices fail to reach the distal true lumen in up to 35% of cases.³

TruePath (Boston Scientific Corporation, Marlborough, MA, USA) is a unique device that facilitates antegrade crossing using a diamond-coated distal tip rotating at 13,000 rpm on a 0.018-inch guidewire with adjustable torque that permits distal tip adjustment up to 15°. The device is also equipped with an audiovisual feedback alarm that indicates high resistance at the device tip, which helps the operator avoid nonplaque areas and guides the tip to the distal true lumen.

The ReOpen study⁴ reported that the TruePath device was safe and effective for facilitating crossing of CTOs resistant to conventional guidewire maneuvers. Banerjee et al⁵ found that the successful lesion crossing rate was significantly lower using a primary wire catheter approach compared to a primary crossing device approach. Furthermore, several previous comparative studies were limited by operator experience and small samples sizes, so results may not necessarily reflect those in daily clinical practice.^4,6,7

The application of intravascular ultrasound (IVUS) for EVT evaluation is also growing.⁸ A previous report evaluating intraluminal wire crossing of CTOs with IVUS assessment found that the proportion of plaque crossings (relative to total route distance) may affect primary patency.⁹ Therefore, this study employed IVUS to fully assess the crossing pathway of an established transluminal crossing device used for primary antegrade recanalization of infrainguinal CTOs.

Materials and Methods

Study Design

A prospective, multicenter, observational study was begun in July 2017 in 14 hospitals in Japan to enroll symptomatic patients with an infrainguinal CTO assigned to primary treatment with the TruePath reentry device with IVUS examination of the crossing pathway following recanalization. Patients with symptoms of PAD were screened using noninvasive tests to detect limb ischemia and the presence of CTOs. Inclusion criteria were (1) age >20 years, (2) infrainguinal PAD (Rutherford category 2–5) with CTO (in-stent included), (3) ABI <0.9 or lower limb ischemia confirmed by other modalities if >0.9, (4) eligibility for EVT after a trial of exercise and/or drug therapy, (5) agreement to participate in clinical follow-up at 6 and 12 months after the procedure, and (6) signed informed consent. Exclusion criteria were (1) age <20 years, (2) pregnancy, (3) bleeding diathesis or coagulation disorder, (4) acute arterial occlusion or occlusion attributable to nonatherosclerotic or inflammatory diseases, (5) life expectancy <1 year, and (6) severe dementia that precluded informed consent.

The study was conducted in accordance with the principles of the Declaration of Helsinki, and the study protocol was approved by the ethics committee at each participating hospital. The study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (no. UMIN000026977) according to the guidelines of the International Committee of Medical Journal Editors. Written informed consent was obtained from every patient.

Procedure

A 5- or 6-F guiding sheath was inserted into the common femoral artery via a contralateral or ipsilateral antegrade approach at the operator’s discretion. Five thousand units of heparin were injected through the sheath; the activated clotting time was thereafter maintained at >200 seconds. The choice of microcatheter was at the operator’s discretion, as was the guidance method for the primary use of the reentry device during antegrade recanalization (fluoroscopy alone, IVUS, and/or duplex ultrasonography). If the feedback alarm of the reentry device was activated, the operator recorded the vessel location using plain fluoroscopy to perform IVUS assessments after recanalization. If it was not possible to cross the CTO using the reentry device, a conventional guidewire (antegrade), a retrograde approach via the tibial or popliteal artery, or the Outback reentry catheter (Cordis Corporation, Santa Clara, CA, USA) was used.

If antegrade guidewire navigation was successful, IVUS images were recorded by auto or manual pullback at a constant speed of 10 mm/s through the target segment to analyze the guidewire crossing route. IVUS images were acquired using commercially available consoles and a phased-array 20-MHz transducer (Eagle Eye Platinum; Volcano Corp, Rancho Cordova, CA, USA) or 30-MHz (Opticross 18; Boston Scientific Corporation) or 40-MHz [Opticross or AltaView (Terumo, Tokyo, Japan)] imaging catheters. If the IVUS catheter did not cross the lesion, a 2-mm-diameter balloon was inflated in the vessel prior to IVUS recording.

Conventional balloon dilation was then performed with an appropriately sized angioplasty balloon. For cases with optimal dilation [no major (≥grade D) flow-limiting dissection or residual stenosis <50%], a drug-coated balloon (IN.PACT Admiral; Medtronic, Santa Rosa, CA, USA) was used starting in January 2018 when this device first became available in Japan. No directional or rotational atherectomy devices were used as they are unavailable in Japan.

If a suboptimal result was obtained (≥grade D flow-limiting dissection or residual stenosis ≥50%), a stent approximately 1 mm larger than the vessel diameter was implanted. The stenting strategy (spot or full-covered stenting) and the choice of bare nitinol stent [S.M.A.R.T (Cordis Corporation, a Cardinal Health company, Santa Clara, CA, USA); Innova (Boston Scientific Corporation); or LifeStent (Bard Peripheral Vascular, Tempe, AZ, USA)], drug-eluting stent (Zilver PTX; Cook Medical, Bloomington, IN, USA), or covered stent (Viabahn; Gore Medical, Flagstaff, AZ, USA) was at the operator’s discretion. After stenting, routine postdilation was performed to achieve better stent expansion and apposition. At the end of the endovascular procedure, additional IVUS images were captured to evaluate the final outcome and stent apposition.

Dual antiplatelet therapy (DAPT) was prescribed for at least 1 month after procedures involving conventional balloon angioplasty, bare stent implantation, or DCB angioplasty. Patients receiving a drug-eluting stent were advised to continue DAPT for at least 2 months based on the package insert instructions.

IVUS Analysis

All IVUS images were reviewed, and a quantitative IVUS analysis was performed by an independent experienced investigator blinded to the clinical and angiographic information. The IVUS parameters measured or calculated were the crossing route of CTOs (intraplaque, subintimal, or intramedial); proximal, distal, and minimum external elastic membrane (EEM) areas; the presence of superficial calcification; maximum calcification arc; the presence of calcified nodules; minimum and maximum lumen areas; stent eccentricity; and stent edge dissection. The proportion of the total CTO route within the plaque was calculated based on the number of IVUS frames showing the guidewire and IVUS transducer along the intraplaque route divided by the total number of IVUS frames showing the entire CTO route. Subintimal and intramedial routes were calculated in the same manner.

Definitions and Outcomes

The severity of calcification was assessed according to the Peripheral Arterial Calcium Scoring System (PACSS).¹⁰ The angiographic morphology of CTOs (tapered/nontapered) at entry point and exit point was decided based on criteria from a previous study.¹¹ The IVUS parameters were measured according to a previous consensus.¹² Stent symmetry index was defined as the ratio of the minimum to maximum stent diameters. The wire passage route in CTOs was classified according to IVUS findings as intraplaque (inside the plaque), subintimal (between the plaque and tunica media), or intramedial (between the tunica media and adventitia).¹³ Stent edge dissection was defined as a dissection <5 mm proximal or distal to the stent margin.

The outcome measures were complete success, assisted success, procedure- and device-related complications, and successful antegrade crossing route with IVUS assessment. Complete success was defined as the TruePath reentry device reaching the distal true lumen. Assisted success was defined as initial reentry device usage followed by conventional wire usage to reach the distal true lumen. Procedure- and device-related complications included puncture site events (pseudoaneurysm, arteriovenous fistula, and hematoma), clinical wire perforation (any perforation requiring treatment), dissection, and any prolonged hospitalization.

Patient Population

Between July 2017 and September 2018, 143 symptomatic patients (mean age 75±9 years; 101 men) with a CTO in 146 limbs were enrolled prospectively in this multicenter observational study. The baseline characteristics of the study population and the CTOs are summarized in Tables 1 and 2, respectively. One-third of the target limbs (52, 35%) had critical limb ischemia, and 15 (10%) had infrapopliteal lesions. The mean CTO length was 11.0±7.8 cm (range 1.5–30) by quantitative vascular analysis. The vast majority of the lesions (130, 89%) were de novo CTOs; 8 (5%) were in-stent occlusions. Seven (5%) limbs had a history of failed revascularization. The majority of lesions (92, 63%) had a proximal-end tapered stump. Severe calcification (PACSS grade 4) was observed in 35 (24%) lesions.

Table 1.

Characteristics of the 143 Patients and 146 Lesions in the Study.^a

Patient variables
Age, y	75±9
Men	101 (71)
Body mass index, kg/m²	22.5±3.5
Nonambulatory status^b	27 (19)
Hypertension	127 (89)
Dyslipidemia	103 (72)
Diabetes mellitus	91 (64)
Chronic renal failure	46 (32)
Regular dialysis	38 (27)
Smoking
Never	34 (24)
Past	75 (52)
Current	34 (24)
Coronary artery disease	87 (61)
Aspirin use	120 (84)
Thienopyridine use	110 (77)
Cilostazol use	40 (28)
Anticoagulant use	21 (15)
Statin use	71 (50)
Lesion characteristics
Rutherford category
2	32 (22)
3	62 (42)
4	15 (10)
5	37 (25)
Infrapopliteal lesion target	15 (10)
Preprocedural ABI^c	0.52±0.25
Revascularization history
None	130 (89)
Angioplasty	8 (5)
Stent	8 (5)
Past failure	7 (5)
CTO length, cm^c	11.0±7.8
Proximal tapered stump	92 (63)
Distal tapered stump	52 (36)
PACSS classification
0	44 (30)
1	20 (14)
2	31 (21)
3	16 (11)
4	35 (24)
RVD, mm^c,d	4.8±1.0

Abbreviations: ABI, ankle-brachial index; CTO, chronic total occlusion; PACSS, Peripheral Arterial Calcium Scoring System; RVD, reference vessel diameter.

Continuous data are presented as the mean ± standard deviation; categorical data are given as the number (percentage).

Nonambulatory status was defined as bedridden or wheelchair use.

Data were missing on ABI in 2 cases and on distal RVD in 56 cases.

Calculated using quantitative vascular analysis.

Table 2.

Details of the 146 Procedures Using the TruePath Reentry Device for Primary CTO Recanalization.^a

Approach
Contralateral	78 (53)
Ipsilateral	65 (45)
Bidirectional	3 (2)
Microcatheter
0.018-inch CX-1	32 (22)
0.018-inch Rubicon	14 (10)
LEONIS Mova	16 (11)
Prominent Raptor	30 (21)
Other	36 (25)
None	18 (12)
TruePath guidance
Fluoroscopy alone	141 (97)
IVUS	3 (2)
DUS	2 (1)
Any success^b	117 (80)
Conventional balloon use	51/117 (43)
Drug-coated balloon use	11/117 (10)
Stent type
BNS	40/117 (34)
DES	4/117 (3)
Viabahn	11/117 (9)
TruePath activation time, min	5.0 (3.0, 10.0)
Procedure time, min	71.0 (49.3, 101.8)
Fluoroscopy time, min	31.0 (20.3, 45.8)
Contrast volume, mL	90.0 (60.0, 130.8)
Perioperative complications	4 (3)
ABI within 1 week (n=82)	0.93±0.18

Abbreviations: ABI, ankle-brachial index; BNS, bare nitinol stent; CTO, chronic total occlusion; DES, drug-eluting stent; DUS, duplex ultrasonography; IVUS, intravascular ultrasound.

Continuous data are presented as the mean ± standard deviation or median (interquartile range Q1, Q3); categorical data are given as the number (percentage).

Any success refers to complete success (defined as the TruePath reentry device reaching the distal true lumen) plus assisted success (initial reentry device use followed by conventional wire usage to reach the distal true lumen).

Statistical Analysis

Continuous variables are presented as mean ± standard deviation, and discrete variables are presented as number (percentage) unless otherwise indicated. The 95% confidence interval (CI) for proportions was calculated using the Clopper-Pearson exact method. Risks of not achieving complete success (vs failure plus assisted success) and not achieving any success (vs failure) were calculated using binomial logistic regression models and expressed as the odds ratio (OR) with 95% CI. Sensitivity analyses for failure and assisted success individually vs complete success were conducted using multinomial logistic regression. The probability of complete success at a specific CTO length was assessed using the penalized cubic regression spline model with a logit link function. The threshold of statistical significance was a 2-tailed p<0.05. All statistical analyses were performed using R (version 3.1.0; R Development Core Team, Vienna, Austria).

Results

Complete success was achieved in 82 (56.2%) lesions (95% CI 47.7% to 64.4%), while any success (complete plus assisted) was documented in 117 (80.1%) lesions (95% CI 72.7% to 86.3%). Details of the EVT procedure are given in Table 2. EVT was performed mainly under fluoroscopic guidance using a microcatheter-supported TruePath reentry device. Stent implantation was required in 45 (38%) of the 117 successful cases; conventional balloons were used in 51 (43%) lesions and DCBs in 11 (10%). Four (3%) perioperative device-related complications were observed, including 2 puncture-site pseudoaneurysms, 1 distal embolization, and 1 wire perforation requiring treatment.

IVUS Findings in Successful Cases

Table 3 displays the proportional lengths of intraplaque, subintimal, and intramedial crossing (% of total) according to frame-by-frame IVUS assessment in successful cases. In completely successful cases, 95.3%±13.2% of the total crossing route was intraplaque compared with only 3.6%±10.2% subintimal and 1.2%±5.8% intramedial. Similarly, in cases with any success (complete plus assisted), 94.8%±14.4% of the route was intraplaque compared to only 4.2%±11.2% subintimal and 1.0%±5.4% intramedial. In 79.4% of cases achieving any success, the route was entirely intraplaque (95% CI 70.3% to 86.8%), and the route was entirely intraplaque in 80.6% of completely successful cases (95% CI 69.5% to 88.9%).

Table 3.

Proportion of Crossing Routes With IVUS Assessment.^a

	Any Success, %	Complete Success, %
Crossing route^b
Intraplaque	94.8±14.4	95.3±13.2
Subintimal	4.2±11.2	3.6±10.2
Intramedial	1.0±5.4	1.2±5.8
Totally intraplaque	79.4 (70.3 to 86.8)	80.6 (69.5 to 88.9)

Abbreviation: IVUS, intravascular ultrasound.

Data expressed as mean ± standard deviation or proportion (95% confidence interval).

Crossing route was assessed in 102 of 117 cases with any success and in 72 of 82 cases with complete success.

In the 117 cases with successful antegrade crossing, superficial calcification was found in 46 (45%) cases, the mean maximum calcification angle was 222.0°±120.1°, and calcified nodules were present in 20 (20%) of 97 cases (Table 4). No stent edge dissection was detected. The TruePath reentry device crossed the CTO without feedback alarm activation in nearly half of the cases. The alarm rang mainly in subintimal locations.

Table 4.

IVUS Findings in the Successful Antegrade Crossings.^a

EEM area, mm² (n=102)
Minimum	16.3±9.0
Distal	23.2±9.4
Proximal	29.2±10.5
Calcification (n=102)
Nonsuperficial	19 (19)
Superficial	46 (45)
None	37 (36)
Maximum arc, deg (n=46)	222.0±120.1
Calcified nodule (n=97)	20 (21)
Feedback alarm location (n=100)
Intramedial	10 (9)
Intraplaque	8 (7)
Subintimal	34 (29)
None	48 (48)
Lumen area, mm² (n=99)
Minimum	14.6±6.3
Maximum	21.9±7.4
Stent eccentricity (n=54)	0.78±0.14
Stent edge dissection (n=53)	0 (0)

Abbreviations: EEM, external elastic membrane; IVUS, intravascular ultrasound.

Continuous data are presented as the mean ± standard deviation; categorical data are given as the number (percentage).

Association of Baseline Characteristics With Procedural Success (Table 5)

A long CTO lesion was a risk factor for not achieving complete success (OR 1.74, 95% CI 1.13 to 2.68 per 10-mm increase in occlusion length, p=0.012). In addition, a history of failed revascularization was a risk factor for not achieving any success (OR 6.08, 95% CI 1.28 to 28.9, p=0.023).

Table 5.

Associations of Baseline Characteristics With Procedural Success.^a

	Binomial Logistic Regression Model		Multinomial Logistic Regression Model
	No Complete Success (Failure + Any Success vs Complete Success)	No Success (Failure vs Complete Success + Assisted Success)	Assisted vs Complete Success	Failure vs Complete Success
Male sex	1.28 (0.62 to 2.65), p=0.50	1.40 (0.55 to 3.56), p=0.48	1.16 (0.49 to 2.77), p=0.74	1.46 (0.55 to 3.85), p=0.44
Age (per 10-year ↑)	1.11 (0.76 to 1.63), p=0.58	1.17 (0.73 to 1.88), p=0.52	1.06 (0.67 to 1.67), p=0.81	1.19 (0.72 to 1.95), p=0.50
BMI (per 5-kg/m² ↑)	0.97 (0.61 to 1.55), p=0.90	0.81 (0.45 to 1.47), p=0.50	1.09 (0.62 to 1.93), p=0.76	0.84 (0.45 to 1.55), p=0.57
Nonambulatory status	1.24 (0.54 to 2.86), p=0.62	2.48 (0.97 to 6.29), p=0.06	0.63 (0.19 to 2.06), p=0.44	2.19 (0.82 to 5.79), p=0.12
Hypertension	1.00 (0.35 to 2.86), p=0.99	1.83 (0.39 to 8.57), p=0.44	0.74 (0.23 to 2.39), p=0.61	1.66 (0.34 to 8.20), p=0.53
Dyslipidemia	0.82 (0.39 to 1.69), p=0.58	0.66 (0.27 to 1.57), p=0.34	0.99 (0.40 to 2.46), p=0.99	0.65 (0.26 to 1.63), p=0.36
Diabetes mellitus	0.86 (0.44 to 1.71), p=0.67	0.74 (0.32 to 1.69), p=0.47	0.99 (0.43 to 2.29), p=0.99	0.73 (0.31 to 1.75), p=0.49
Chronic renal failure	1.44 (0.71 to 2.90), p=0.31	0.97 (0.40 to 2.34), p=0.95	1.71 (0.75 to 3.92), p=0.21	1.15 (0.46 to 2.90), p=0.76
Regular dialysis	1.40 (0.67 to 2.94), p=0.37	1.10 (0.44 to 2.76), p=0.83	1.52 (0.63 to 3.66), p=0.35	1.26 (0.48 to 3.31), p=0.63
Smoking (vs never)	1.00 (Ref)	1.00 (Ref)	1.00 (Ref)	1.00 (Ref)
Past	1.49 (0.66 to 3.37), p=0.34	0.97 (0.36 to 2.64), p=0.95	1.88 (0.66 to 5.34), p=0.24	1.15 (0.41 to 3.24), p=0.79
Current	1.34 (0.51 to 3.50), p=0.56	1.04 (0.32 to 3.35), p=0.95	1.54 (0.45 to 5.25), p=0.49	1.16 (0.34 to 3.90), p=0.81
CAD	1.90 (0.96 to 3.77), p=0.07	1.60 (0.67 to 3.82), p=0.29	1.88 (0.82 to 4.34), p=0.14	1.92 (0.78 to 4.71), p=0.16
Aspirin use	1.02 (0.41 to 2.50), p=0.97	1.21 (0.38 to 3.88), p=0.75	0.91 (0.32 to 2.63), p=0.86	1.18 (0.35 to 3.95), p=0.79
Thienopyridine use	0.99 (0.45 to 2.13), p=0.97	0.60 (0.24 to 1.49), p=0.27	1.46 (0.53 to 4.03), p=0.47	0.67 (0.26 to 1.71), p=0.40
Cilostazol use	0.76 (0.36 to 1.59), p=0.46	0.78 (0.30 to 1.99), p=0.60	0.79 (0.32 to 1.93), p=0.60	0.73 (0.27 to 1.92), p=0.52
Anticoagulant use	1.49 (0.59 to 3.78), p=0.40	0.94 (0.29 to 3.04), p=0.92	1.80 (0.62 to 5.20), p=0.28	1.15 (0.33 to 4.00), p=0.82
Statin use	0.68 (0.35 to 1.31), p=0.25	0.75 (0.33 to 1.69), p=0.48	0.69 (0.31 to 1.53), p=0.36	0.67 (0.29 to 1.57), p=0.35
Rutherford category	1.10 (0.81 to 1.48), p=0.54	1.32 (0.91 to 1.91), p=0.15	0.95 (0.66 to 1.38), p=0.80	1.30 (0.88 to 1.91), p=0.19
ABI (per 0.1-unit ↑)	1.05 (0.91 to 1.20), p=0.51	1.05 (0.89 to 1.25), p=0.55	1.03 (0.88 to 1.22), p=0.70	1.06 (0.89 to 1.27), p=0.50
History of failed revascularization	3.39 (0.64 to 18.1), p=0.15	6.08 (1.28 to 28.9), p=0.023	1.18 (0.10 to 13.4), p=0.90	6.40 (1.11 to 37.0), p=0.038
CTO length (per 10-mm ↑)	1.74 (1.13 to 2.68) p=0.012	1.37 (0.83 to 2.28), p=0.22	1.79 (1.08 to 2.99) p=0.025	1.68 (0.97 to 2.89), p=0.06
Proximal tapered stump	0.96 (0.49 to 1.89), p=0.91	0.79 (0.35 to 1.82), p=0.58	1.11 (0.48 to 2.54), p=0.81	0.82 (0.34 to 1.94), p=0.65
Distal tapered stump	0.91 (0.46 to 1.80), p=0.78	0.51 (0.20 to 1.29), p=0.15	1.30 (0.58 to 2.91), p=0.52	0.55 (0.21 to 1.44), p=0.23
Presence of calcification	1.79 (0.86 to 3.73), p=0.12	1.45 (0.57 to 3.70), p=0.43	1.85 (0.74 to 4.59), p=0.19	1.72 (0.66 to 4.51), p=0.27
PACSS type (vs 0)	1.00 (Ref)	1.00 (Ref)	1.00 (Ref)	1.00 (Ref)
1	1.93 (0.66 to 5.67), p=0.23	0.93 (0.21 to 4.05), p=0.93	2.54 (0.73 to 8.80), p=0.14	1.24 (0.27 to 5.75), p=0.78
2	1.59 (0.62 to 4.09), p=0.33	1.02 (0.29 to 3.56), p=0.98	1.92 (0.62 to 5.91), p=0.26	1.22 (0.33 to 4.45), p=0.76
3	1.50 (0.47 to 4.84), p=0.49	1.76 (0.44 to 7.08), p=0.42	1.21 (0.26 to 5.54), p=0.81	1.84 (0.44 to 7.76), p=0.41
4	2.05 (0.82 to 5.09), p=0.12	2.11 (0.71 to 6.30), p=0.18	1.71 (0.54 to 5.38), p=0.36	2.44 (0.78 to 7.59), p=0.12
Distal RVD (per 1-mm ↑)	1.07 (0.70 to 1.63), p=0.77	0.95 (0.58 to 1.55), p=0.83	1.16 (0.67 to 1.99), p=0.60	0.99 (0.59 to 1.65), p=0.97

Abbreviations: ↑, increase; ABI, ankle-brachial index; BMI, body mass index; BTK, below-the-knee lesions; CAD, coronary artery disease; CTO, chronic total occlusion; FP, femoropopliteal lesions; PACSS, Peripheral Arterial Calcium Scoring System; Ref, reference; RVD, reference vessel diameter.

Odds ratios presented with 95% confidence intervals in parentheses. Boldfaced values indicate statistical significance.

For CTO length, a sensitivity analysis using the multinomial logistic regression model yielded an OR of 1.79 (95% CI 1.08 to 2.99, p=0.025) for assisted success vs complete success and an OR of 1.68 (95% CI 0.97 to 2.89, p=0.063) for failure vs complete success. For a history of failed revascularization, the corresponding values were OR 1.18 (95% 0.10 to 13.4, p=0.90) and OR 6.40 (95% CI 1.11 to 37.0, p=0.038). The spline model indicated that the proportion of complete success was almost linearly related to CTO length (Figure 1). Figure 2 illustrates the proportion of any success in subgroups with and without a history of failed revascularization.

Figure 1.

Association of chronic total occlusion (CTO) length and complete success rate. The bold solid line and thin dotted lines represent the probability of complete success at a specific CTO length and associated 95% confidence interval, respectively.

Figure 2.

Comparison of the rate of any success in patients with vs without a history of failed revascularization. Error bars represent 95% confidence intervals.

Discussion

In this study, the majority of cases (89%) were intermediate-length de novo lesions, which reflects the routine clinical situation better than a previous study assessing the efficacy of secondary reentry device use, in which only 55% of cases were de novo lesions.⁴ Although the TruePath reentry device proved relatively successful in recanalizing infrainguinal CTOs, the primary reentry device approach appears limited in some situations, such as especially long CTOs and patients with previous revascularization failure. For long femoropopliteal CTOs (mean lesion length 246±42 mm), a 0.035-inch looped subintimal wire was reported to achieve an antegrade success rate of 74% to 90%.¹³ In the current study, the target CTO length was shorter, indicating the need for subintimal wire use. In addition, the route was almost entirely intraplaque in successful (complete or complete plus assisted) cases using the antegrade approach according to frame-by-frame IVUS assessment. In a study of cases with long occlusive length (mean of 177 mm), however, the intraplaque route accounted for only 73% of the total distance.⁹

Nonetheless, even in cases with longer CTO length, the reentry device achieved a predominantly intraplaque route. One possible explanation is the inclusion of an alarm system, which rang mainly in subintimal locations according to IVUS assessment. A retrospective analysis from the XLPAD registry reported that a primary crossing device approach to CTOs provides significantly higher technical success with lower reintervention and amputation rates.⁵ The proportion of total distance within the plaque may affect the final CTO patency.⁹ Specifically, a primary crossing device approach with a high proportion of intraplaque crossing may improve patency and reduce the risk of reintervention. However, the aforementioned report was from a retrospective registry,⁵ so additional follow-up of the present study cohort is required to verify whether the primary reentry device approach for CTOs improves patency, freedom from reintervention, and amputation rates.

In nearly half of the successful antegrade crossing cases, no alarm was activated, suggesting that the operator should subsequently proceed without changing the shape of the guidewire tip until or unless the alarm is activated. On the other hand, the distal tip of the reentry device is not tapered, so it may easily follow a previous wire route and be guided away from the intraplaque region. Therefore, a long CTO lesion and history of failed revascularization might be risk factors for not achieving complete or any success.

From previous registry data, initial simple guidewire use was a significantly less expensive procedure than initial use of the crossing device (p<0.001).⁵ Although an experienced operator does not really need the reentry device for intermediate-length de novo CTOs, a reentry device might be valued by a less experienced operator from the viewpoint of getting decent results. In addition, the reentry device would not work well in adverse lesions (long CTOs and history of failed revascularization). However, this study had a single-arm design that did not compare primary reentry device use with an initial guidewire strategy for CTOs. A randomized controlled trial (RCT) would be needed to prove the advantage of primary reentry device use over the guidewire alone.

Although IVUS may contribute to EVT success,⁸ it is not necessarily covered by medical insurance. In addition, high success rates have been reported only in some institutions, with more variable results in others.^4,6,7 Therefore, it is difficult to apply these earlier findings to daily clinical practice. In the current prospective multicenter study, over 90% of the total route was intraplaque in successful crossing cases using the reentry device and IVUS. Therefore, the use of the TruePath reentry device for CTOs without IVUS may make more aggressive vessel preparation possible. Additional studies are required to assess the benefits of IVUS and to identify the remedial procedures needed if the reentry device is used without IVUS.

Limitations

First, this was a single-arm observational study, not an RCT comparing an initial reentry device strategy to an initial simple guidewire. Second, the mean CTO length was relatively short (11 cm), so selection bias may have influenced the results. Third, the accuracy of route proportion estimates may be affected by the manual pullback used for IVUS examination. Also, it was difficult to exactly match the location of the alarm activation with the same IVUS frame. Fourth, assessments of angiographic morphology (proximal and distal CTO type), PACSS grade, and IVUS findings were not evaluated by independent core laboratory review. Fifth, although the investigators perform EVT routinely as part of their daily practice, institutional differences in operator experience and procedures were not included in the analysis because it was limited in sample size. Finally, a cost-effectiveness analysis of the reentry device was not performed because of the relatively small number of cases and the single-arm study design. Therefore, further investigations, including RCTs, are needed to confirm the utility of the TruePath reentry device compared to conventional guidewire recanalization for CTOs.

Conclusion

The intraplaque route was the primary pathway taken by the TruePath reentry device as it crossed infrainguinal CTOs. Crossing rates were acceptable, with few device-related complications. However, CTO length and a history of revascularization failure decreased success, suggesting that the TruePath crossing device is most appropriate for intermediate-length de novo lesions.

Footnotes

Acknowledgements

The authors would like to acknowledge the study investigators and the catheterization laboratory medical staff. The authors also thank Enago ( www.enago.jp ) for the English language review.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Yusuke Tomoi

Masahiko Fujihara

Yoshimitsu Soga

References

Aboyans

Ricco

Bartelink

MEL

, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Endorsed by: the European Stroke Organization (ESO), The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39:763–816.

Norgren

Hiatt

Dormandy

, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45(suppl S):S5–S67.

Shin

Baril

Chaer

, et al. Limitations of the Outback LTD re-entry device in femoropopliteal chronic total occlusions. J Vasc Surg. 2011;53:1260–1264.

Bosiers

Diaz-Cartelle

Scheinert

, et al. Revascularization of lower extremity chronic total occlusions with a novel intraluminal recanalization device: results of the ReOpen study. J Endovasc Ther. 2014;21:61–70.

Banerjee

Jeon-Slaughter

Tsai

, et al. Comparative assessment of procedure cost and outcomes between guidewire and crossing device strategies to cross peripheral artery chronic total occlusions. JACC Cardiovasc Interv. 2016;9:2243–2252.

Soga

Nakamura

Hirose

, et al. Primary use of the TruePath crossing device for infrainguinal chronic total occlusions with intravascular ultrasound evaluation. J Endovasc Ther. 2018;25:592–598.

Banerjee

Sarode

Das

, et al. Endovascular treatment of infrainguinal chronic total occlusions using the TruePath device: features, handling, and 6-month outcomes. J Endovasc Ther. 2014;21:281–288.

Iida

Takahara

Soga

, et al. Efficacy of intravascular ultrasound in femoropopliteal stenting for peripheral artery disease with TASC II class A to C lesions. J Endovasc Ther. 2014;21:485–492.

Mori

Hirano

Ito

, et al. Clinical outcomes of the intraluminal approach for long occlusive femoropopliteal lesions assessed by intravascular ultrasound. J Atheroscler Thromb. 2017;24:477–486.

10.

Rocha-Singh

Zeller

Jaff

MR.

Peripheral arterial calcification: prevalence, mechanism, detection, and clinical implications. Catheter Cardiovasc Interv. 2014;83:212–220.

11.

Morino

Abe

Morimoto

, et al. Predicting successful guidewire crossing through chronic total occlusion of native coronary lesions within 30 minutes: the J-CTO (Multicenter CTO Registry in Japan) score as a difficulty grading and time assessment tool. JACC Cardiovasc Interv. 2011;4:213–221.

12.

Mintz

Nissen

Anderson

, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001;37:1478–1492.

13.

Kawasaki

Iida

Fukunaga

, et al. Wire passages of 0.035-inch looped wire technique for femoropopliteal long total occlusions. J Atheroscler Thromb. 2015;22:1071–1079.