Original Article
Effectiveness of Atherectomy and Drug-Coated Balloon Angioplasty in Femoropopliteal Disease: A Comprehensive Outcome Study
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Vasc Specialist Int (2024) 40:34
Published online September 30, 2024 https://doi.org/10.5758/vsi.240071
Copyright © The Korean Society for Vascular Surgery.
Abstract
Materials and Methods: From 2014 to July 2022, 85 limbs in 76 patients with FPOD underwent atherectomy with DCB angioplasty. We evaluated the efficacy of this procedure using primary patency (PP) and clinically driven target lesion revascularization (CD-TLR)-free survival. PP was defined as the duration of uninterrupted patency without occlusion or a peak systolic velocity ratio more than 2.5 at the target lesion. Lesion calcification was evaluated according to Peripheral Arterial Calcium Scoring System, and Grade 4 was classified as severe.
Results: Seventy-one (84%) cases were male, and 56 limbs (66%) were treated for claudication. Rotational and directional atherectomies were performed in 62 (73%) and 23 limbs, respectively. The improvement in the median ankle-brachial index was 0.36 (interquartile range, 0.25-0.48). Median follow-up duration was 19.4 months. The overall PP and CD-TLR-free survival rates were 77% and 93% at 1 year and 64% and 83% at 2 years, respectively. On multivariable analysis, female sex (adjusted hazard ratio [aHR], 3.77; 95% confidence interval (CI), 1.30-10.87, P=0.014), dialysis (aHR, 4.35; 95% CI, 1.33-13.22, P=0.015), and severe calcification (aHR, 2.42; 95% CI, 1.07-5.46, P=0.033) were independent risk factors for poor PP. Dialysis (aHR, 11.07; 95% CI, 3.72-32.92, P<0.001) and severe calcification (aHR, 3.19; 95% CI, 1.15-8.84, P=0.026) were identified as independent risk factors for CD-TLR.
Conclusion: Atherectomy with DCB angioplasty for FPOD did not work well in female patients, patients with lesions with severe calcification, and patients undergoing dialysis. Therefore, careful monitoring of these patients is crucial for patency loss and the requirement for revascularization. Additionally, for these patients requiring revascularization, surgical bypass may be appropriate for suitable candidates; whereas more proactive conservative management may be justified for claudicants.
Keywords
INTRODUCTION
Drug-coated balloons (DCBs) have emerged as an attractive treatment option for femoropopliteal occlusive disease (FPOD) under the “leave nothing behind” concept, considering the late failure modes and management difficulties after stent placement. However, achieving optimal outcomes with DCBs require proper vessel preparation. Therefore, the reduction and modification of atherosclerotic plaques by atherectomy have been reintroduced and gained worldwide popularity.
Various atherectomy devices have been introduced and utilized to ensure proper vessel preparation. Typically, combining atherectomy with DCBs have shown positive results in maximizing the luminal gain before balloon angioplasty and reducing the incidence of post-balloon flow-limiting dissection, subsequently lowering the need for stent placement. Notably, the calcium burden in FPOD is known to hinder the effect of antiproliferative drugs on the vessels, and atherectomy has been suggested to improve the outcome of DCB angioplasty by potentially reducing the calcium burden [1].
However, the reported outcomes of adding atherectomy to DCB angioplasty are controversial. Some studies have demonstrated the safety of atherectomy and sustained short-term improved patency [2,3]. Contrastingly, other reports suggested that initial atherectomy was associated with more reinterventions than non-atherectomy interventions and failed to show efficacy benefits compared with DCB and uncoated balloon angioplasty alone [4-6]. As the current evidence does not support the routine application of atherectomy for FPOD, it is necessary to identify the subset of patients who can benefit from atherectomy combined with DCB over the less expensive DCB angioplasty alone [7].
In this study, we aimed to evaluate the outcomes of atherectomy combined with DCB for FPOD treatment. Additionally, we sought to identify risk factors for patency loss and clinically driven target lesion revascularization (CD-TLR) to delineate the potential role of atherectomy.
MATERIALS AND METHODS
1) Study design and data collection
This study was approved by the Kyungpook National University Hospital Institutional Review Board (No. 2022-12-005). The requirement for informed consent was waived because of the retrospective nature of the study.
Between June 2014 and July 2022, 108 atherectomies for FPOD were consecutively performed in 94 patients. Among these, uncoated balloon angioplasty was performed in 12 limbs and drug-eluting stents were used in seven limbs as an adjunctive procedure after atherectomy. No further balloon angioplasty was performed on the four limbs after atherectomy. After excluding these 23 cases, 85 limbs of 76 patients who underwent DCB angioplasty post-atherectomy were included in the analysis. Cases with technical failure due to unsuccessful wire passage and patients who underwent below-the-knee atherectomy were excluded.
Patient characteristics, imaging findings, procedural details, and follow-up results were obtained through medical chart reviews and analysis of pre- and postoperative images. Patient demographics included age, sex, and the presence of other comorbidities. Lesion characteristics included the presence of occlusion, length of occlusion, Trans-Atlantic Inter-Society Consensus (TASC) II classification of FPOD [8], and severity of lesion calcification. The Peripheral Artery Calcium Scoring System (PACSS) was used to classify the calcium grade of each lesion. Lesions were assessed using high-intensity fluoroscopy in the anteroposterior projection and graded as 0 (no visible calcification), 1 (unilateral calcification <5 cm), 2 (unilateral calcification ≥5 cm), 3 (bilateral calcification <5 cm), or 4 (bilateral calcification ≥5 cm) [9]. Furthermore, perioperative complications were categorized as local/nonvascular, local/vascular, or systemic/remote and graded according to the recommended standards [10]. We recorded the patency of the femoropopliteal lesion, any reintervention of the index limb, amputation, and survival data during the follow-up period.
2) Operative details and follow-up protocol
Depending on the lesion location, access was achieved from the ipsilateral or contralateral common femoral artery under ultrasound guidance. After femoral artery puncture, intravenous heparin (3,000-5,000 IU) was administered in all cases to achieve systemic anticoagulation. If it was difficult to pass the femoropopliteal lesion through an antegrade approach, wire passage was attempted via popliteal or tibial artery puncture. After successful wire crossing of the lesion, a distal embolic protection device (EPD) was used in most cases, especially in patients with heavily calcified lesions or with only one infrapopliteal runoff vessel.
After EPD placement, rotational atherectomy (JetstreamTM, Boston Scientific) or directional atherectomy (TurboHawk or HawkOne, Medtronic Inc.) was performed according to the surgeon’s discretion. However, directional atherectomy was preferred for short and eccentric lesions, whereas rotational atherectomy was typically selected for longer lesions, owing to procedural time considerations. After atherectomy, preballooning of the lesion was performed using an uncoated balloon, followed by DCB angioplasty. Our protocol dictates preballooning for at least 2 minutes and DCB angioplasty for a minimum of 3 minutes to ensure adequate vessel preparation and optimal drug absorption. The DCB diameter was determined based on the diameter of the normal vessels near the lesion. The DCB was chosen to be sufficiently long to cover all lesions. Prolonged balloon inflation was performed first in a flow-limiting dissection or significant recoil event. If suboptimal results were achieved after prolonged balloon inflation, bail-out bare-metal stenting was performed.
The postoperative follow-up protocol included (1) ankle-brachial index (ABI) measurement before discharge, (2) duplex ultrasonography (DUS) and ABI at 1 month, (3) clinical follow-up at 3 months, (4) ABI at 6 months, (5) DUS and ABI at 1 year, and (6) DUS and ABI annually. Physical examinations and evaluations of sustained symptom improvement were conducted during each follow-up visit. Additional DUS or computed tomography was performed for worsening symptoms or decreasing ABI values by >0.15. Patients who returned with symptoms before their scheduled follow-up were evaluated using the same protocol and other corrective procedures, as required.
Aspirin (100 mg/d), clopidogrel (75 mg/d), and statins were the standard postoperative medications. However, aspirin monotherapy with anticoagulants has been used in patients who have already been prescribed anticoagulants.
3) Study outcomes and definitions
This study evaluated primary patency (PP) and identified risk factors for PP loss after atherectomy with DCB angioplasty in FPOD. Additionally, we evaluated secondary patency (SP), CD-TLR, and risk factors for CD-TLR. The primary safety outcomes were perioperative morbidity and mortality rates within 30 days post-procedure, classified as grades 1, 2, or 3, according to the recommended reporting standard [10].
PP was defined as the duration of uninterrupted patency without occlusion or a peak systolic velocity ratio >2.5 at the femoropopliteal target segment. SP referred to femoropopliteal segment patency following occlusion after successful endovascular or surgical revascularization. CD-TLR was defined as revascularization of the treated femoropopliteal segment in a patient who returned with the clinical symptoms.
Regarding the calcification severity, Grade 4 in PACSS was defined as severe calcification. An inflow procedure was defined as an endovascular procedure for the iliac or common femoral artery; endarterectomy of the common femoral artery was also considered an inflow procedure. An infrapopliteal procedure was defined as a balloon angioplasty of the tibial arteries. No concomitant bypass procedure was performed.
Tissue loss was defined according to the Rutherford classification [10]. Minor tissue loss was defined as a non-healing ulcer or focal gangrene with diffuse pedal ischemia, whereas major tissue loss was defined as tissue loss extending above the transmetatarsal level. Major amputation was defined as an amputation at or above the ankle [10].
4) Statistical methods
Normally distributed continuous variables were reported as mean±standard deviation, whereas non-normally distributed variables were described using median and interquartile range (IQR). Categorical variables were presented as numbers and percentages. After normality testing, the Student t-test or Mann–Whitney U test was used to compare patient and lesion characteristics by revascularization indication (claudication vs. chronic limb threatening ischemia [CLTI]). Categorical variables were analyzed using the chi-squared test or Fisher exact test. PP, SP, and CD-TLR-free survival rates were evaluated using Kaplan–Meier plots. The log-rank test was used to ascertain the statistical significance of the differences between survival curves. Cox regression analysis identified the independent risk factors for PP loss and CD-TLR during follow-up. All statistical analyses were conducted using IBM SPSS Statistics (ver. 23.0, IBM Corp.), and a P-value of less than 0.05 was considered significant.
RESULTS
1) Characteristics of patient, lesion, and procedures
A total of 85 atherectomies with DCB angioplasty for FPOD were performed during the study period. The mean age of the participants was 68.0±9.4 years (range, 41-90 years), and 71 (84%) cases were male. The indications for revascularization were CLTI in 29 (34%) limbs (rest pain in 3, minor tissue loss in 20, and major tissue loss in 6) and disabling claudication in 56 (66%) limbs. Table 1 provides an overview of the patient characteristics.
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Table 1 . Baseline clinical characteristics (n=85).
Total limb (%) Male 71 (84) Age, mean±SD (y) 68.0±9.4 Indications for revascularization Claudication 56 (66) Chronic limb threatening ischemia 29 (34) Hypertension 54 (64) Diabetes mellitus 56 (66) Coronary artery disease 19 (22) Congestive heart failure 10 (12) Arrhythmia 10 (12) Cerebrovascular disease 21 (25) Smoking 26 (31) Chronic obstructive lung disease 2 (2.4) Renal insufficiency 37 (44) Dialysis 14 (17) Dyslipidemia 24 (28) Nine patients received bilateral limb interventions at different time points; age and comorbidity data reflected the status at the time of each treatment..
SD, standard deviation..
Table 2 details the lesion and procedural characteristics. Chronic total occlusion was present in 46 (54%) lesions. Regarding the TASC II classification, TASC C lesions (39%) were the most prevalent, followed by TASC B (28%), TASC D (24%), and TASC A (9%). Regarding the calcification severity, severe calcification defined as PACSS Grade 4 was most common in 28% (24/85). The lesion location was in the superficial femoral artery in 80 (94%) lesions, P1 segment of the popliteal artery in 36 (42%) lesions, and P2 or P3 segment in 9 (11%) lesions.
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Table 2 . Characteristic of femoropopliteal lesion and procedure (n=85).
Total limb (%) Chronic total occlusion 46 (54) Length, mean (mm) 140 TASC II classification A 8 (9) B 24 (28) C 33 (39) D 20 (24) PACSS classification 0 21 (25) 1 20 (24) 2 11 (13) 3 9 (11) 4 (severe) 24 (28) Lesion location Superficial femoral artery 80 (94) P1 segment of popliteal artery 36 (42) P2-P3 segment of popliteal artery 9 (11) Devices Rotational atherectomy 62 (73) Directional atherectomy 23 (27) Embolic protection device 61 (72) Bail-out stenting 3 (4) Inflow procedures 16 (19) Infrapopliteal procedures 24 (28) TASC, TransAtlantic Inter-Society Consensus; PACSS, Peripheral Artery Calcium Scoring System..
Rotational and directional atherectomies were performed in 62 limbs (73%) and 23 limbs (27%), respectively. EPD was used on 61 limbs (72%). Infrapopliteal procedures were performed on 24 limbs (28%); however, they were more commonly used in patients with CLTI than in those with claudication (claudicants: 9/56 limbs [16 %] vs. CLTI: 15/29 limbs [52%], P=0.001; Supplementary Table 1).
2) Perioperative outcomes
Although no in-hospital mortality occurred, one patient died of acute myocardial infarction within 30 days (early mortality). The mean preoperative and postoperative ABIs were 0.55±0.20 and 0.94±0.17, respectively. The median ABI increase was 0.36 (IQR, 0.25-0.48).
Supplementary Table 2 summarizes the device-related complications according to the grade. Overall, 14 complications occurred in 10 patients. Four complications were considered Grade 1 and did not require additional endovascular or surgical management. Additional endovascular management was necessary for 9 complications, including aspiration thrombectomy in 4 cases, bail-out stenting due to flow-limiting dissection in 3 cases, balloon angioplasty in 1 case, and balloon tamponade due to rupture in 1 case. One patient with a macroembolism underwent an open surgical embolectomy.
3) Patency and CD-TLR-free survival
The median follow-up duration was 19.4 months (IQR, 8.8-35.3 months). The overall PP rates after femoropopliteal atherectomy with DCB angioplasty were 77% at 1 year, 64% at 2 years, and 40% at 3 years (Fig. 1A). Additionally, the SP rates were 91%, 79%, and 59% at 1, 2, and 3 years, respectively (Fig. 1A).
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Figure 1.Patency and CD-TLR-free survival. (A) Overall primary and secondary patencies after atherectomy with drug-coated balloon angioplasty for femoropopliteal occlusive disease. (B) Overall CD-TLR-free survival. CD-TLR, clinically driven target lesion revascularization.
During the follow-up period, 20 CD-TLR events occurred in 17 limbs and major amputation was performed in one limb. The types of CD-TLR included repeated endovascular intervention in 10 cases (repeated atherectomy with DCB angioplasty in 4 cases, DCB angioplasty alone in 4 cases, atherectomy with uncoated balloon angioplasty in 1 case, and stent placement in 1 case), surgical bypass in 9 cases, and hybrid operation in 1 case. The overall CD-TLR-free survival rates were 93%, 83%, and 63% at and 1, 2, and 3 years, respectively (Fig. 1B).
4) Risk factors for PP loss and CD-TLR
Table 3 summarizes the risk factors for PP loss after univariable and multivariable analyses. Based on the results of the univariable analysis, female sex (P<0.001), CLTI (P=0.049), TASC C/D lesions (P=0.017), severe calcification (P=0.001), renal insufficiency (P=0.018), and dialysis (P<0.001) were associated with poor PP. The multivariable analysis further elucidated that female sex (adjusted hazard ratio [aHR], 3.77; 95% confidence interval [CI], 1.30-10.87, P=0.014), dialysis (aHR, 4.35; 95% CI, 1.33-13.22, P=0.015), and severe calcification (aHR, 2.42; 95% CI, 1.07-5.46, P=0.033) remained independent risk factors for PP loss. Fig. 2 demonstrates the PP of the femoropopliteal segment stratified by these independent risk factors.
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Figure 2.Primary patency of the femoropopliteal segment stratified by independent risk factors. (A) Primary patency by sex. (B) Primary patency according to presence of severe calcification. Severe calcification was defined as Grade 4 in the PACSS. (C) Primary patency according to dialysis. CI, confidence interval; N/A, not available; PACSS, Peripheral Artery Calcium Scoring System.
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Table 3 . Risk factors for primary patency loss after univariable and multivariable analyses.
Univariable analysis Multivariable analysis HR (95% CI) P-value aHR (95% CI) P-value Sex, female 7.01 (3.14-15.65) <0.001 3.77 (1.30-10.87) 0.014 CLTI 2.20 (1.00-4.83) 0.049 TASC II C/D vs. A/B 3.24 (1.23-8.52) 0.017 Severe calcification 3.46 (1.67-7.21) 0.001 2.42 (1.07-5.46) 0.033 Chronic total occlusion 1.40 (0.67-2.95) 0.372 Diabetes mellitus 1.85 (0.76-4.54) 0.178 Congestive heart failure 2.25 (0.85-5.96) 0.105 Renal insufficiency 2.45 (1.17-5.15) 0.018 Dialysis 9.62 (3.96-23.38) <0.001 4.35 (1.33-14.22) 0.015 Rotational atherectomy 2.24 (0.78-6.42) 0.134 aHR, adjusted hazard ratio; CLTI, chronic limb-threatening ischemia; TASC, Trans-Atlantic Inter-Society Consensus..
Table 4 outlines the risk factors for CD-TLR following both univariable and multivariable analyses. The risk factors for CD-TLR and those for PP loss were similar. In the univariable analysis, female sex (P=0.001), CLTI (P=0.007), TASC C/D lesions compared with TASC A/B lesions (P=0.042), severe calcification (P=0.011), diabetes mellitus (P=0.043), renal insufficiency (P=0.034), and dialysis (P<0.001) were significantly associated with an increased risk of CD-TLR. The multivariable analysis highlighted dialysis (aHR, 11.07; 95% CI, 3.72-32.92, P<0.001) and severe calcification (aHR, 3.19; 95% CI, 1.15-8.84, P=0.026) as independent risk factors for CD-TLR.
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Table 4 . Risk factors for clinically driven target lesion revascularization after univariable and multivariable analyses.
Univariable analysis Multivariable analysis HR (95% CI) P-value aHR (95% CI) P-value Sex, female 5.52 (2.03-15.04) 0.001 CLTI 3.84 (1.44-10.24) 0.007 TASC II C/D vs. A/B 4.63 (1.05-20.33) 0.042 Severe calcification 3.49 (1.34-9.11) 0.011 3.19 (1.15-8.84) 0.026 Outflow procedure 1.95 (0.72-5.28) 0.189 Diabetes mellitus 8.06 (1.07-60.76) 0.043 Congestive heart failure 3.11 (0.99-9.66) 0.051 Renal insufficiency 2.87 (1.08-7.64) 0.034 Dialysis 11.13 (4.01-30.86) <0.001 11.07 (3.72-32.92) <0.001 aHR, adjusted hazard ratio; CLTI, chronic limb-threatening ischemia; TASC, Trans-Atlantic Inter-Society Consensus..
DISCUSSION
This study demonstrated the outcomes of atherectomy combined with DCB angioplasty for FPOD, with 77% PP and 93% CD-TLR-free survival rates at 12 months. A significant finding of this study was that atherectomy with DCB angioplasty for FPOD was less effective in female patients, those with severe calcification, and patients on dialysis. The 12-month PP rates were 30.0% in female patients, 54.7% in patients with severe calcification, and 20.0% in patients on dialysis. Additionally, the freedom from CD-TLR rates was significantly lower in patients with severe calcification or those on dialysis than in those without these risk factors. Therefore, this study provides crucial insights that can significantly influence the choice of revascularization method and predict the outcomes after atherectomy combined with DCB angioplasty in patients with FPOD.
Overall, the rates of PP and freedom from CD-TLR in our study were comparable with those reported in other studies. For example, a study using directional atherectomy followed by DCB angioplasty for FPOD reported a 1-year PP rate of 80.8% and a freedom from CD-TLR rate of 92.2% [11]. Similarly, after rotational atherectomy with DCB angioplasty, 12-month PP and freedom from CD-TLR rates were reported to be 81.6% and 90.1%, respectively [12]. However, as mentioned in the Introduction section, the reported outcomes of adding atherectomy to DCB angioplasty are controversial. It has been suggested that initial atherectomy was associated with more reinterventions than non-atherectomy interventions [5]. Compared with DCB and uncoated balloon angioplasty alone, initial atherectomy failed to show efficacy benefits, including patency and freedom from CD-TLR, except for intraoperative bail-out stenting [6]. Therefore, it is crucial to determine the specific patient and lesion characteristics for which atherectomy can add value, considering its high-cost burden [13,14].
Although numerous studies have analyzed the risk factors for PP loss and CD-TLR after balloon angioplasty, relatively few have specifically examined these risk factors following atherectomy combined with DCB angioplasty for the femoropopliteal artery. A report using directional atherectomy determined a total length of chronic total occlusion >10 cm as an independent risk factor for PP loss and CD-TLR within one year [11]. Additionally, recently published large data on atherectomy for FPOD, consisting of approximately 60% of patients in a total cohort of 955 receiving DCB angioplasty after atherectomy, identified more calcified lesions and a vessel diameter of 4 mm or smaller as independent risk factors for TLR [15]. Findings of our study and those of this recently published report are similar [15]. In our study, female sex was associated with poor PP rates, which may be due to the generally smaller vessel diameter in females than that in males. Additionally, severe calcification and dialysis were associated with poor PP and CD-TLR-free survival rates in our series, which can be explained by the relation between heavy calcification in the peripheral arteries and dialysis. Moreover, the correlation analysis in our series showed that the correlation coefficients between female sex and dialysis was 0.658 (P<0.01), between female sex and severe calcification was 0.356 (P<0.01), and between dialysis and severe calcification was 0.356 (P<0.01). These results indicated the interrelation between sex, dialysis, and calcification levels in our study.
Traditionally, the presence of severe calcification elevates the dissection risk and may lessen the anti-mitotic effect of paclitaxel by impeding its absorption and distribution in the artery wall [16-18]. Fanelli et al. [19] supported this by reporting that lesions with circumferential calcification, determined using computed tomography angiography, had a higher 12-month late lumen loss and a higher occurrence of CD-TLR following DCB angioplasty. Therefore, atherectomy before DCB angioplasty is considered an effective approach for vessel preparation in calcified lesions to reduce the calcification burden and thus mitigate the risk [20].
However, only small randomized and single-arm studies have reported the use of atherectomy to treat heavily calcified lesions [21-23] because randomized clinical trials often exclude femoropopliteal lesions with severe calcification because of the challenges of safe and effective treatment of these complex lesions. Compared to DCB angioplasty alone, adjuvant atherectomy for heavily calcified femoropopliteal lesions demonstrated some benefits, including higher patency and lower CD-TLR rates [23]. However, the results are limited, and long-term follow-up data are scarce in the literature.
In our study, severe calcification, defined as a PACSS Grade 4, was identified as an independent risk factor for poor PP and higher CD-TLR rates during follow-up. The PP and freedom from CD-TLR rates in patients with severe calcification were 54.7% and 82.3% at 1 year, and 41.0% and 54.9% at 2 years, respectively, which were significantly lower than those in patients without severe calcification (87.4% and 95.9% for PP and freedom from CD-TLR at 1 year, and 71.7% and 91.0% for PP and freedom from CD-TLR at 2 years). Therefore, although atherectomy is theoretically effective and can be applied for vessel preparation in severe calcification cases, the expected outcomes are considered poor compared to lesions without severe calcification. In addition, other treatment methods such as bypass surgery in feasible patients, should be considered for this group of patients [24]. Two-thirds of our patients presented with lifestyle-limiting claudication. Considering the inferior PP rates and higher CD-TLR rates observed in female patients, as well as in those with severe calcification and on dialysis, more proactive conservative management, including medical treatment and supervised exercise, may be justified for these groups of patients.
This study had several limitations. First, the study had a single-center retrospective design with a small number of patients; therefore, the statistical power may be low and bias may be present. Small number of patients were identified as having risk factors, including female sex, severe calcification, and dialysis, and the standard error in the Kaplan–Meier analysis was significant. Furthermore, our variables for risk factor analysis suggested some interrelation between sex, dialysis, and calcification levels. Therefore, a large-scale study is necessary to address these interrelations and confirm the findings, thereby mitigating the potential confounding effects. Second, we did not include a control group, such as patients who underwent endovascular therapy with DCB alone. The results of endovascular treatments with DCB alone should be evaluated and compared to determine the precise role of atherectomy in DCB angioplasty. Third, the absence of an independent core laboratory to review calcification grading and follow-up patency may have influenced the objectivity and accuracy of the results, potentially introducing variability in the assessment of calcification severity and patency outcomes. Fourth, we did not accurately measure vessel diameter. Although we could not directly measure vessel diameters in this study, previous research has reported that female patients generally have smaller vessel diameters than male patients [25]. This may explain the observed differences in PP rates between the sexes. However, our study did not confirm this hypothesis with precise measurements, and future research should include direct measurements of the vessel diameter to validate this hypothesis. Therefore, our sample may not represent the overall cohort of patients with femoropopliteal disease and the study results require cautious interpretation.
CONCLUSION
Although the PP and CD-TLR-free survival rates in our study were comparable to those in other reports, atherectomy combined with DCB angioplasty for femoropopliteal disease did not work well in female patients, patients with lesions with severe calcification, and patients on dialysis. Therefore, it is crucial to carefully monitor these patients for the development of patency loss and the need for revascularization. Additionally, for these patients requiring revascularization, surgical bypass may be appropriate for suitable candidates; whereas more proactive conservative management, including medical treatment and supervised exercise, may be justified for claudicants.
Supplemental Materials
FUNDING
None.
CONFLICTS OF INTEREST
Hyung-Kee Kim has been the editor-in-chief of the VSI since 2023. Woo-Sung Yun has been the senior editor of the VSI since 2023.
AUTHOR CONTRIBUTIONS
Conception and design: HKK. Analysis and interpretation: HJK, HKK. Data collection: HJK, DH, WSY, HKK. Writing the article: HJK, HKK. Critical revision of the article: WSY, SH, HKK. Final approval of the article: all authors. Statistical analysis: HJK, HKK. Obtained funding: none. Overall responsibility: HKK.
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- Noory E, Böhme T, Steinhauser Y, Salm J, Beschorner U, de Forest A, et al. Acute and mid-term results of atherectomy in femoropopliteal lesions. J Endovasc Ther 2024. https://doi.org/10.1177/15266028241240898 [Epub ahead of print]
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- Zeller T, Langhoff R, Rocha-Singh KJ, Jaff MR, Blessing E, Amann-Vesti B, et al; DEFINITIVE AR Investigators. Directional atherectomy followed by a paclitaxel-coated balloon to inhibit restenosis and maintain vessel patency: twelve-month results of the DEFINITIVE AR study. Circ Cardiovasc Interv 2017;10:e004848. https://doi.org/10.1161/circinterventions.116.004848
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Related articles in VSI
Article
Original Article
Vasc Specialist Int (2024) 40:34
Published online September 30, 2024 https://doi.org/10.5758/vsi.240071
Copyright © The Korean Society for Vascular Surgery.
Effectiveness of Atherectomy and Drug-Coated Balloon Angioplasty in Femoropopliteal Disease: A Comprehensive Outcome Study
Hyeon Ju Kim1 , Deokbi Hwang2 , Woo-Sung Yun2 , Seung Huh2 , and Hyung-Kee Kim1
1Division of Vascular and Endovascular Surgery, Department of Surgery, Kyungpook National University Chilgok Hospital, Daegu,
2Division of Vascular and Endovascular Surgery, Department of Surgery, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
Correspondence to:Hyung-Kee Kim
Division of Vascular and Endovascular Surgery, Department of Surgery, Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu, Daegu 41404, Korea
Tel: 82-53-200-5605
Fax: 82-53-421-0510
E-mail: hkkim6260@knu.ac.kr
https://orcid.org/0000-0002-4436-7424
The main findings of this study were presented at the 74th Annual Congress of The Korean Surgical Society in Seoul, Korea, in 2022.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Purpose: Atherectomy has been reintroduced for debulking calcified atheroma to enhance the efficacy of drug-coated balloons (DCBs); however, its efficacy in severe calcification and related outcomes have not been fully evaluated. This study aimed to evaluate the outcomes of atherectomy and DCB angioplasty for treating femoropopliteal occlusive disease (FPOD).
Materials and Methods: From 2014 to July 2022, 85 limbs in 76 patients with FPOD underwent atherectomy with DCB angioplasty. We evaluated the efficacy of this procedure using primary patency (PP) and clinically driven target lesion revascularization (CD-TLR)-free survival. PP was defined as the duration of uninterrupted patency without occlusion or a peak systolic velocity ratio more than 2.5 at the target lesion. Lesion calcification was evaluated according to Peripheral Arterial Calcium Scoring System, and Grade 4 was classified as severe.
Results: Seventy-one (84%) cases were male, and 56 limbs (66%) were treated for claudication. Rotational and directional atherectomies were performed in 62 (73%) and 23 limbs, respectively. The improvement in the median ankle-brachial index was 0.36 (interquartile range, 0.25-0.48). Median follow-up duration was 19.4 months. The overall PP and CD-TLR-free survival rates were 77% and 93% at 1 year and 64% and 83% at 2 years, respectively. On multivariable analysis, female sex (adjusted hazard ratio [aHR], 3.77; 95% confidence interval (CI), 1.30-10.87, P=0.014), dialysis (aHR, 4.35; 95% CI, 1.33-13.22, P=0.015), and severe calcification (aHR, 2.42; 95% CI, 1.07-5.46, P=0.033) were independent risk factors for poor PP. Dialysis (aHR, 11.07; 95% CI, 3.72-32.92, P<0.001) and severe calcification (aHR, 3.19; 95% CI, 1.15-8.84, P=0.026) were identified as independent risk factors for CD-TLR.
Conclusion: Atherectomy with DCB angioplasty for FPOD did not work well in female patients, patients with lesions with severe calcification, and patients undergoing dialysis. Therefore, careful monitoring of these patients is crucial for patency loss and the requirement for revascularization. Additionally, for these patients requiring revascularization, surgical bypass may be appropriate for suitable candidates; whereas more proactive conservative management may be justified for claudicants.
Keywords: Atherectomy, Drug-coated balloon, Peripheral arterial disease, Vascular patency, Revascularization
INTRODUCTION
Drug-coated balloons (DCBs) have emerged as an attractive treatment option for femoropopliteal occlusive disease (FPOD) under the “leave nothing behind” concept, considering the late failure modes and management difficulties after stent placement. However, achieving optimal outcomes with DCBs require proper vessel preparation. Therefore, the reduction and modification of atherosclerotic plaques by atherectomy have been reintroduced and gained worldwide popularity.
Various atherectomy devices have been introduced and utilized to ensure proper vessel preparation. Typically, combining atherectomy with DCBs have shown positive results in maximizing the luminal gain before balloon angioplasty and reducing the incidence of post-balloon flow-limiting dissection, subsequently lowering the need for stent placement. Notably, the calcium burden in FPOD is known to hinder the effect of antiproliferative drugs on the vessels, and atherectomy has been suggested to improve the outcome of DCB angioplasty by potentially reducing the calcium burden [1].
However, the reported outcomes of adding atherectomy to DCB angioplasty are controversial. Some studies have demonstrated the safety of atherectomy and sustained short-term improved patency [2,3]. Contrastingly, other reports suggested that initial atherectomy was associated with more reinterventions than non-atherectomy interventions and failed to show efficacy benefits compared with DCB and uncoated balloon angioplasty alone [4-6]. As the current evidence does not support the routine application of atherectomy for FPOD, it is necessary to identify the subset of patients who can benefit from atherectomy combined with DCB over the less expensive DCB angioplasty alone [7].
In this study, we aimed to evaluate the outcomes of atherectomy combined with DCB for FPOD treatment. Additionally, we sought to identify risk factors for patency loss and clinically driven target lesion revascularization (CD-TLR) to delineate the potential role of atherectomy.
MATERIALS AND METHODS
1) Study design and data collection
This study was approved by the Kyungpook National University Hospital Institutional Review Board (No. 2022-12-005). The requirement for informed consent was waived because of the retrospective nature of the study.
Between June 2014 and July 2022, 108 atherectomies for FPOD were consecutively performed in 94 patients. Among these, uncoated balloon angioplasty was performed in 12 limbs and drug-eluting stents were used in seven limbs as an adjunctive procedure after atherectomy. No further balloon angioplasty was performed on the four limbs after atherectomy. After excluding these 23 cases, 85 limbs of 76 patients who underwent DCB angioplasty post-atherectomy were included in the analysis. Cases with technical failure due to unsuccessful wire passage and patients who underwent below-the-knee atherectomy were excluded.
Patient characteristics, imaging findings, procedural details, and follow-up results were obtained through medical chart reviews and analysis of pre- and postoperative images. Patient demographics included age, sex, and the presence of other comorbidities. Lesion characteristics included the presence of occlusion, length of occlusion, Trans-Atlantic Inter-Society Consensus (TASC) II classification of FPOD [8], and severity of lesion calcification. The Peripheral Artery Calcium Scoring System (PACSS) was used to classify the calcium grade of each lesion. Lesions were assessed using high-intensity fluoroscopy in the anteroposterior projection and graded as 0 (no visible calcification), 1 (unilateral calcification <5 cm), 2 (unilateral calcification ≥5 cm), 3 (bilateral calcification <5 cm), or 4 (bilateral calcification ≥5 cm) [9]. Furthermore, perioperative complications were categorized as local/nonvascular, local/vascular, or systemic/remote and graded according to the recommended standards [10]. We recorded the patency of the femoropopliteal lesion, any reintervention of the index limb, amputation, and survival data during the follow-up period.
2) Operative details and follow-up protocol
Depending on the lesion location, access was achieved from the ipsilateral or contralateral common femoral artery under ultrasound guidance. After femoral artery puncture, intravenous heparin (3,000-5,000 IU) was administered in all cases to achieve systemic anticoagulation. If it was difficult to pass the femoropopliteal lesion through an antegrade approach, wire passage was attempted via popliteal or tibial artery puncture. After successful wire crossing of the lesion, a distal embolic protection device (EPD) was used in most cases, especially in patients with heavily calcified lesions or with only one infrapopliteal runoff vessel.
After EPD placement, rotational atherectomy (JetstreamTM, Boston Scientific) or directional atherectomy (TurboHawk or HawkOne, Medtronic Inc.) was performed according to the surgeon’s discretion. However, directional atherectomy was preferred for short and eccentric lesions, whereas rotational atherectomy was typically selected for longer lesions, owing to procedural time considerations. After atherectomy, preballooning of the lesion was performed using an uncoated balloon, followed by DCB angioplasty. Our protocol dictates preballooning for at least 2 minutes and DCB angioplasty for a minimum of 3 minutes to ensure adequate vessel preparation and optimal drug absorption. The DCB diameter was determined based on the diameter of the normal vessels near the lesion. The DCB was chosen to be sufficiently long to cover all lesions. Prolonged balloon inflation was performed first in a flow-limiting dissection or significant recoil event. If suboptimal results were achieved after prolonged balloon inflation, bail-out bare-metal stenting was performed.
The postoperative follow-up protocol included (1) ankle-brachial index (ABI) measurement before discharge, (2) duplex ultrasonography (DUS) and ABI at 1 month, (3) clinical follow-up at 3 months, (4) ABI at 6 months, (5) DUS and ABI at 1 year, and (6) DUS and ABI annually. Physical examinations and evaluations of sustained symptom improvement were conducted during each follow-up visit. Additional DUS or computed tomography was performed for worsening symptoms or decreasing ABI values by >0.15. Patients who returned with symptoms before their scheduled follow-up were evaluated using the same protocol and other corrective procedures, as required.
Aspirin (100 mg/d), clopidogrel (75 mg/d), and statins were the standard postoperative medications. However, aspirin monotherapy with anticoagulants has been used in patients who have already been prescribed anticoagulants.
3) Study outcomes and definitions
This study evaluated primary patency (PP) and identified risk factors for PP loss after atherectomy with DCB angioplasty in FPOD. Additionally, we evaluated secondary patency (SP), CD-TLR, and risk factors for CD-TLR. The primary safety outcomes were perioperative morbidity and mortality rates within 30 days post-procedure, classified as grades 1, 2, or 3, according to the recommended reporting standard [10].
PP was defined as the duration of uninterrupted patency without occlusion or a peak systolic velocity ratio >2.5 at the femoropopliteal target segment. SP referred to femoropopliteal segment patency following occlusion after successful endovascular or surgical revascularization. CD-TLR was defined as revascularization of the treated femoropopliteal segment in a patient who returned with the clinical symptoms.
Regarding the calcification severity, Grade 4 in PACSS was defined as severe calcification. An inflow procedure was defined as an endovascular procedure for the iliac or common femoral artery; endarterectomy of the common femoral artery was also considered an inflow procedure. An infrapopliteal procedure was defined as a balloon angioplasty of the tibial arteries. No concomitant bypass procedure was performed.
Tissue loss was defined according to the Rutherford classification [10]. Minor tissue loss was defined as a non-healing ulcer or focal gangrene with diffuse pedal ischemia, whereas major tissue loss was defined as tissue loss extending above the transmetatarsal level. Major amputation was defined as an amputation at or above the ankle [10].
4) Statistical methods
Normally distributed continuous variables were reported as mean±standard deviation, whereas non-normally distributed variables were described using median and interquartile range (IQR). Categorical variables were presented as numbers and percentages. After normality testing, the Student t-test or Mann–Whitney U test was used to compare patient and lesion characteristics by revascularization indication (claudication vs. chronic limb threatening ischemia [CLTI]). Categorical variables were analyzed using the chi-squared test or Fisher exact test. PP, SP, and CD-TLR-free survival rates were evaluated using Kaplan–Meier plots. The log-rank test was used to ascertain the statistical significance of the differences between survival curves. Cox regression analysis identified the independent risk factors for PP loss and CD-TLR during follow-up. All statistical analyses were conducted using IBM SPSS Statistics (ver. 23.0, IBM Corp.), and a P-value of less than 0.05 was considered significant.
RESULTS
1) Characteristics of patient, lesion, and procedures
A total of 85 atherectomies with DCB angioplasty for FPOD were performed during the study period. The mean age of the participants was 68.0±9.4 years (range, 41-90 years), and 71 (84%) cases were male. The indications for revascularization were CLTI in 29 (34%) limbs (rest pain in 3, minor tissue loss in 20, and major tissue loss in 6) and disabling claudication in 56 (66%) limbs. Table 1 provides an overview of the patient characteristics.
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Table 1 . Baseline clinical characteristics (n=85).
Total limb (%) Male 71 (84) Age, mean±SD (y) 68.0±9.4 Indications for revascularization Claudication 56 (66) Chronic limb threatening ischemia 29 (34) Hypertension 54 (64) Diabetes mellitus 56 (66) Coronary artery disease 19 (22) Congestive heart failure 10 (12) Arrhythmia 10 (12) Cerebrovascular disease 21 (25) Smoking 26 (31) Chronic obstructive lung disease 2 (2.4) Renal insufficiency 37 (44) Dialysis 14 (17) Dyslipidemia 24 (28) Nine patients received bilateral limb interventions at different time points; age and comorbidity data reflected the status at the time of each treatment..
SD, standard deviation..
Table 2 details the lesion and procedural characteristics. Chronic total occlusion was present in 46 (54%) lesions. Regarding the TASC II classification, TASC C lesions (39%) were the most prevalent, followed by TASC B (28%), TASC D (24%), and TASC A (9%). Regarding the calcification severity, severe calcification defined as PACSS Grade 4 was most common in 28% (24/85). The lesion location was in the superficial femoral artery in 80 (94%) lesions, P1 segment of the popliteal artery in 36 (42%) lesions, and P2 or P3 segment in 9 (11%) lesions.
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Table 2 . Characteristic of femoropopliteal lesion and procedure (n=85).
Total limb (%) Chronic total occlusion 46 (54) Length, mean (mm) 140 TASC II classification A 8 (9) B 24 (28) C 33 (39) D 20 (24) PACSS classification 0 21 (25) 1 20 (24) 2 11 (13) 3 9 (11) 4 (severe) 24 (28) Lesion location Superficial femoral artery 80 (94) P1 segment of popliteal artery 36 (42) P2-P3 segment of popliteal artery 9 (11) Devices Rotational atherectomy 62 (73) Directional atherectomy 23 (27) Embolic protection device 61 (72) Bail-out stenting 3 (4) Inflow procedures 16 (19) Infrapopliteal procedures 24 (28) TASC, TransAtlantic Inter-Society Consensus; PACSS, Peripheral Artery Calcium Scoring System..
Rotational and directional atherectomies were performed in 62 limbs (73%) and 23 limbs (27%), respectively. EPD was used on 61 limbs (72%). Infrapopliteal procedures were performed on 24 limbs (28%); however, they were more commonly used in patients with CLTI than in those with claudication (claudicants: 9/56 limbs [16 %] vs. CLTI: 15/29 limbs [52%], P=0.001; Supplementary Table 1).
2) Perioperative outcomes
Although no in-hospital mortality occurred, one patient died of acute myocardial infarction within 30 days (early mortality). The mean preoperative and postoperative ABIs were 0.55±0.20 and 0.94±0.17, respectively. The median ABI increase was 0.36 (IQR, 0.25-0.48).
Supplementary Table 2 summarizes the device-related complications according to the grade. Overall, 14 complications occurred in 10 patients. Four complications were considered Grade 1 and did not require additional endovascular or surgical management. Additional endovascular management was necessary for 9 complications, including aspiration thrombectomy in 4 cases, bail-out stenting due to flow-limiting dissection in 3 cases, balloon angioplasty in 1 case, and balloon tamponade due to rupture in 1 case. One patient with a macroembolism underwent an open surgical embolectomy.
3) Patency and CD-TLR-free survival
The median follow-up duration was 19.4 months (IQR, 8.8-35.3 months). The overall PP rates after femoropopliteal atherectomy with DCB angioplasty were 77% at 1 year, 64% at 2 years, and 40% at 3 years (Fig. 1A). Additionally, the SP rates were 91%, 79%, and 59% at 1, 2, and 3 years, respectively (Fig. 1A).
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Figure 1. Patency and CD-TLR-free survival. (A) Overall primary and secondary patencies after atherectomy with drug-coated balloon angioplasty for femoropopliteal occlusive disease. (B) Overall CD-TLR-free survival. CD-TLR, clinically driven target lesion revascularization.
During the follow-up period, 20 CD-TLR events occurred in 17 limbs and major amputation was performed in one limb. The types of CD-TLR included repeated endovascular intervention in 10 cases (repeated atherectomy with DCB angioplasty in 4 cases, DCB angioplasty alone in 4 cases, atherectomy with uncoated balloon angioplasty in 1 case, and stent placement in 1 case), surgical bypass in 9 cases, and hybrid operation in 1 case. The overall CD-TLR-free survival rates were 93%, 83%, and 63% at and 1, 2, and 3 years, respectively (Fig. 1B).
4) Risk factors for PP loss and CD-TLR
Table 3 summarizes the risk factors for PP loss after univariable and multivariable analyses. Based on the results of the univariable analysis, female sex (P<0.001), CLTI (P=0.049), TASC C/D lesions (P=0.017), severe calcification (P=0.001), renal insufficiency (P=0.018), and dialysis (P<0.001) were associated with poor PP. The multivariable analysis further elucidated that female sex (adjusted hazard ratio [aHR], 3.77; 95% confidence interval [CI], 1.30-10.87, P=0.014), dialysis (aHR, 4.35; 95% CI, 1.33-13.22, P=0.015), and severe calcification (aHR, 2.42; 95% CI, 1.07-5.46, P=0.033) remained independent risk factors for PP loss. Fig. 2 demonstrates the PP of the femoropopliteal segment stratified by these independent risk factors.
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Figure 2. Primary patency of the femoropopliteal segment stratified by independent risk factors. (A) Primary patency by sex. (B) Primary patency according to presence of severe calcification. Severe calcification was defined as Grade 4 in the PACSS. (C) Primary patency according to dialysis. CI, confidence interval; N/A, not available; PACSS, Peripheral Artery Calcium Scoring System.
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Table 3 . Risk factors for primary patency loss after univariable and multivariable analyses.
Univariable analysis Multivariable analysis HR (95% CI) P-value aHR (95% CI) P-value Sex, female 7.01 (3.14-15.65) <0.001 3.77 (1.30-10.87) 0.014 CLTI 2.20 (1.00-4.83) 0.049 TASC II C/D vs. A/B 3.24 (1.23-8.52) 0.017 Severe calcification 3.46 (1.67-7.21) 0.001 2.42 (1.07-5.46) 0.033 Chronic total occlusion 1.40 (0.67-2.95) 0.372 Diabetes mellitus 1.85 (0.76-4.54) 0.178 Congestive heart failure 2.25 (0.85-5.96) 0.105 Renal insufficiency 2.45 (1.17-5.15) 0.018 Dialysis 9.62 (3.96-23.38) <0.001 4.35 (1.33-14.22) 0.015 Rotational atherectomy 2.24 (0.78-6.42) 0.134 aHR, adjusted hazard ratio; CLTI, chronic limb-threatening ischemia; TASC, Trans-Atlantic Inter-Society Consensus..
Table 4 outlines the risk factors for CD-TLR following both univariable and multivariable analyses. The risk factors for CD-TLR and those for PP loss were similar. In the univariable analysis, female sex (P=0.001), CLTI (P=0.007), TASC C/D lesions compared with TASC A/B lesions (P=0.042), severe calcification (P=0.011), diabetes mellitus (P=0.043), renal insufficiency (P=0.034), and dialysis (P<0.001) were significantly associated with an increased risk of CD-TLR. The multivariable analysis highlighted dialysis (aHR, 11.07; 95% CI, 3.72-32.92, P<0.001) and severe calcification (aHR, 3.19; 95% CI, 1.15-8.84, P=0.026) as independent risk factors for CD-TLR.
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Table 4 . Risk factors for clinically driven target lesion revascularization after univariable and multivariable analyses.
Univariable analysis Multivariable analysis HR (95% CI) P-value aHR (95% CI) P-value Sex, female 5.52 (2.03-15.04) 0.001 CLTI 3.84 (1.44-10.24) 0.007 TASC II C/D vs. A/B 4.63 (1.05-20.33) 0.042 Severe calcification 3.49 (1.34-9.11) 0.011 3.19 (1.15-8.84) 0.026 Outflow procedure 1.95 (0.72-5.28) 0.189 Diabetes mellitus 8.06 (1.07-60.76) 0.043 Congestive heart failure 3.11 (0.99-9.66) 0.051 Renal insufficiency 2.87 (1.08-7.64) 0.034 Dialysis 11.13 (4.01-30.86) <0.001 11.07 (3.72-32.92) <0.001 aHR, adjusted hazard ratio; CLTI, chronic limb-threatening ischemia; TASC, Trans-Atlantic Inter-Society Consensus..
DISCUSSION
This study demonstrated the outcomes of atherectomy combined with DCB angioplasty for FPOD, with 77% PP and 93% CD-TLR-free survival rates at 12 months. A significant finding of this study was that atherectomy with DCB angioplasty for FPOD was less effective in female patients, those with severe calcification, and patients on dialysis. The 12-month PP rates were 30.0% in female patients, 54.7% in patients with severe calcification, and 20.0% in patients on dialysis. Additionally, the freedom from CD-TLR rates was significantly lower in patients with severe calcification or those on dialysis than in those without these risk factors. Therefore, this study provides crucial insights that can significantly influence the choice of revascularization method and predict the outcomes after atherectomy combined with DCB angioplasty in patients with FPOD.
Overall, the rates of PP and freedom from CD-TLR in our study were comparable with those reported in other studies. For example, a study using directional atherectomy followed by DCB angioplasty for FPOD reported a 1-year PP rate of 80.8% and a freedom from CD-TLR rate of 92.2% [11]. Similarly, after rotational atherectomy with DCB angioplasty, 12-month PP and freedom from CD-TLR rates were reported to be 81.6% and 90.1%, respectively [12]. However, as mentioned in the Introduction section, the reported outcomes of adding atherectomy to DCB angioplasty are controversial. It has been suggested that initial atherectomy was associated with more reinterventions than non-atherectomy interventions [5]. Compared with DCB and uncoated balloon angioplasty alone, initial atherectomy failed to show efficacy benefits, including patency and freedom from CD-TLR, except for intraoperative bail-out stenting [6]. Therefore, it is crucial to determine the specific patient and lesion characteristics for which atherectomy can add value, considering its high-cost burden [13,14].
Although numerous studies have analyzed the risk factors for PP loss and CD-TLR after balloon angioplasty, relatively few have specifically examined these risk factors following atherectomy combined with DCB angioplasty for the femoropopliteal artery. A report using directional atherectomy determined a total length of chronic total occlusion >10 cm as an independent risk factor for PP loss and CD-TLR within one year [11]. Additionally, recently published large data on atherectomy for FPOD, consisting of approximately 60% of patients in a total cohort of 955 receiving DCB angioplasty after atherectomy, identified more calcified lesions and a vessel diameter of 4 mm or smaller as independent risk factors for TLR [15]. Findings of our study and those of this recently published report are similar [15]. In our study, female sex was associated with poor PP rates, which may be due to the generally smaller vessel diameter in females than that in males. Additionally, severe calcification and dialysis were associated with poor PP and CD-TLR-free survival rates in our series, which can be explained by the relation between heavy calcification in the peripheral arteries and dialysis. Moreover, the correlation analysis in our series showed that the correlation coefficients between female sex and dialysis was 0.658 (P<0.01), between female sex and severe calcification was 0.356 (P<0.01), and between dialysis and severe calcification was 0.356 (P<0.01). These results indicated the interrelation between sex, dialysis, and calcification levels in our study.
Traditionally, the presence of severe calcification elevates the dissection risk and may lessen the anti-mitotic effect of paclitaxel by impeding its absorption and distribution in the artery wall [16-18]. Fanelli et al. [19] supported this by reporting that lesions with circumferential calcification, determined using computed tomography angiography, had a higher 12-month late lumen loss and a higher occurrence of CD-TLR following DCB angioplasty. Therefore, atherectomy before DCB angioplasty is considered an effective approach for vessel preparation in calcified lesions to reduce the calcification burden and thus mitigate the risk [20].
However, only small randomized and single-arm studies have reported the use of atherectomy to treat heavily calcified lesions [21-23] because randomized clinical trials often exclude femoropopliteal lesions with severe calcification because of the challenges of safe and effective treatment of these complex lesions. Compared to DCB angioplasty alone, adjuvant atherectomy for heavily calcified femoropopliteal lesions demonstrated some benefits, including higher patency and lower CD-TLR rates [23]. However, the results are limited, and long-term follow-up data are scarce in the literature.
In our study, severe calcification, defined as a PACSS Grade 4, was identified as an independent risk factor for poor PP and higher CD-TLR rates during follow-up. The PP and freedom from CD-TLR rates in patients with severe calcification were 54.7% and 82.3% at 1 year, and 41.0% and 54.9% at 2 years, respectively, which were significantly lower than those in patients without severe calcification (87.4% and 95.9% for PP and freedom from CD-TLR at 1 year, and 71.7% and 91.0% for PP and freedom from CD-TLR at 2 years). Therefore, although atherectomy is theoretically effective and can be applied for vessel preparation in severe calcification cases, the expected outcomes are considered poor compared to lesions without severe calcification. In addition, other treatment methods such as bypass surgery in feasible patients, should be considered for this group of patients [24]. Two-thirds of our patients presented with lifestyle-limiting claudication. Considering the inferior PP rates and higher CD-TLR rates observed in female patients, as well as in those with severe calcification and on dialysis, more proactive conservative management, including medical treatment and supervised exercise, may be justified for these groups of patients.
This study had several limitations. First, the study had a single-center retrospective design with a small number of patients; therefore, the statistical power may be low and bias may be present. Small number of patients were identified as having risk factors, including female sex, severe calcification, and dialysis, and the standard error in the Kaplan–Meier analysis was significant. Furthermore, our variables for risk factor analysis suggested some interrelation between sex, dialysis, and calcification levels. Therefore, a large-scale study is necessary to address these interrelations and confirm the findings, thereby mitigating the potential confounding effects. Second, we did not include a control group, such as patients who underwent endovascular therapy with DCB alone. The results of endovascular treatments with DCB alone should be evaluated and compared to determine the precise role of atherectomy in DCB angioplasty. Third, the absence of an independent core laboratory to review calcification grading and follow-up patency may have influenced the objectivity and accuracy of the results, potentially introducing variability in the assessment of calcification severity and patency outcomes. Fourth, we did not accurately measure vessel diameter. Although we could not directly measure vessel diameters in this study, previous research has reported that female patients generally have smaller vessel diameters than male patients [25]. This may explain the observed differences in PP rates between the sexes. However, our study did not confirm this hypothesis with precise measurements, and future research should include direct measurements of the vessel diameter to validate this hypothesis. Therefore, our sample may not represent the overall cohort of patients with femoropopliteal disease and the study results require cautious interpretation.
CONCLUSION
Although the PP and CD-TLR-free survival rates in our study were comparable to those in other reports, atherectomy combined with DCB angioplasty for femoropopliteal disease did not work well in female patients, patients with lesions with severe calcification, and patients on dialysis. Therefore, it is crucial to carefully monitor these patients for the development of patency loss and the need for revascularization. Additionally, for these patients requiring revascularization, surgical bypass may be appropriate for suitable candidates; whereas more proactive conservative management, including medical treatment and supervised exercise, may be justified for claudicants.
Supplemental Materials
FUNDING
None.
CONFLICTS OF INTEREST
Hyung-Kee Kim has been the editor-in-chief of the VSI since 2023. Woo-Sung Yun has been the senior editor of the VSI since 2023.
AUTHOR CONTRIBUTIONS
Conception and design: HKK. Analysis and interpretation: HJK, HKK. Data collection: HJK, DH, WSY, HKK. Writing the article: HJK, HKK. Critical revision of the article: WSY, SH, HKK. Final approval of the article: all authors. Statistical analysis: HJK, HKK. Obtained funding: none. Overall responsibility: HKK.
Fig 1.
Fig 2.
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Table 1 . Baseline clinical characteristics (n=85).
Total limb (%) Male 71 (84) Age, mean±SD (y) 68.0±9.4 Indications for revascularization Claudication 56 (66) Chronic limb threatening ischemia 29 (34) Hypertension 54 (64) Diabetes mellitus 56 (66) Coronary artery disease 19 (22) Congestive heart failure 10 (12) Arrhythmia 10 (12) Cerebrovascular disease 21 (25) Smoking 26 (31) Chronic obstructive lung disease 2 (2.4) Renal insufficiency 37 (44) Dialysis 14 (17) Dyslipidemia 24 (28) Nine patients received bilateral limb interventions at different time points; age and comorbidity data reflected the status at the time of each treatment..
SD, standard deviation..
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Table 2 . Characteristic of femoropopliteal lesion and procedure (n=85).
Total limb (%) Chronic total occlusion 46 (54) Length, mean (mm) 140 TASC II classification A 8 (9) B 24 (28) C 33 (39) D 20 (24) PACSS classification 0 21 (25) 1 20 (24) 2 11 (13) 3 9 (11) 4 (severe) 24 (28) Lesion location Superficial femoral artery 80 (94) P1 segment of popliteal artery 36 (42) P2-P3 segment of popliteal artery 9 (11) Devices Rotational atherectomy 62 (73) Directional atherectomy 23 (27) Embolic protection device 61 (72) Bail-out stenting 3 (4) Inflow procedures 16 (19) Infrapopliteal procedures 24 (28) TASC, TransAtlantic Inter-Society Consensus; PACSS, Peripheral Artery Calcium Scoring System..
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Table 3 . Risk factors for primary patency loss after univariable and multivariable analyses.
Univariable analysis Multivariable analysis HR (95% CI) P-value aHR (95% CI) P-value Sex, female 7.01 (3.14-15.65) <0.001 3.77 (1.30-10.87) 0.014 CLTI 2.20 (1.00-4.83) 0.049 TASC II C/D vs. A/B 3.24 (1.23-8.52) 0.017 Severe calcification 3.46 (1.67-7.21) 0.001 2.42 (1.07-5.46) 0.033 Chronic total occlusion 1.40 (0.67-2.95) 0.372 Diabetes mellitus 1.85 (0.76-4.54) 0.178 Congestive heart failure 2.25 (0.85-5.96) 0.105 Renal insufficiency 2.45 (1.17-5.15) 0.018 Dialysis 9.62 (3.96-23.38) <0.001 4.35 (1.33-14.22) 0.015 Rotational atherectomy 2.24 (0.78-6.42) 0.134 aHR, adjusted hazard ratio; CLTI, chronic limb-threatening ischemia; TASC, Trans-Atlantic Inter-Society Consensus..
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Table 4 . Risk factors for clinically driven target lesion revascularization after univariable and multivariable analyses.
Univariable analysis Multivariable analysis HR (95% CI) P-value aHR (95% CI) P-value Sex, female 5.52 (2.03-15.04) 0.001 CLTI 3.84 (1.44-10.24) 0.007 TASC II C/D vs. A/B 4.63 (1.05-20.33) 0.042 Severe calcification 3.49 (1.34-9.11) 0.011 3.19 (1.15-8.84) 0.026 Outflow procedure 1.95 (0.72-5.28) 0.189 Diabetes mellitus 8.06 (1.07-60.76) 0.043 Congestive heart failure 3.11 (0.99-9.66) 0.051 Renal insufficiency 2.87 (1.08-7.64) 0.034 Dialysis 11.13 (4.01-30.86) <0.001 11.07 (3.72-32.92) <0.001 aHR, adjusted hazard ratio; CLTI, chronic limb-threatening ischemia; TASC, Trans-Atlantic Inter-Society Consensus..
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