- Email: [email protected]
The Impact of Femoropopliteal Artery Calcium Score after Endovascular Treatment
Clinical Research The Impact of Femoropopliteal Artery Calcium Score after Endovascular Treatment Takahiro Tokuda,1 Yasuhiro Oba,1 Ryoji Koshida,2 Yoriyasu Suzuki,1 Akira Murata,1 and Tatsuya Ito,1 Nagoya and Toyohashi, and Aichi, Japan
Background: The coronary artery calcium score is a widely known independent predictor of cardiac events. Tibial artery calcification had been reported as an amputation risk, but the femoropopliteal artery calcium score is rarely known. Methods: A retrospective analysis was performed using the data collected from the patients who underwent endovascular treatment for the femoropopliteal artery between January 2010 and December 2017. The femoropopliteal artery calcium scores on preprocedural computed tomography were calculated according to the Agatston definition. The mean value of total of femoropopliteal artery calcium scores was used to divide the scores into two groups. The prognostic value of the calcium score was analyzed based on primary patency, clinically driven target lesion revascularization, major amputation, and all-cause death. Results: In total, 132 consecutive limbs that underwent successful endovascular intervention were analyzed in this study; 44 and 88 limbs were assigned to the high and low calcium score groups, respectively. There were no significant differences between the two groups in terms of patient and lesion characteristics, except for chronic kidney disease (7% vs. 25%, P < 0.01), hemodialysis (80% vs. 25%, P < 0.01), and coronary artery disease (73% vs. 53%, P ¼ 0.03). Compared with the low calcium score group, the high calcium score group had a significantly higher rate of loss of primary patency and clinically driven target lesion revascularization at one year, based on the KaplaneMeier curve (55% vs. 81%, 44% vs. 8%, both P < 0.01). There were no significant differences between the two groups in terms of major amputation and death. Multivariate analysis revealed that hemodialysis [hazard ratio (HR): 1.9; 95% confidence interval (CI): 1.01e5.28; P ¼ 0.04] runoff grade 0 (HR: 2.9; 95% CI: 1.02e10.9; P ¼ 0.04), lesion length > 200 mm (HR: 3.9; 95% CI: 1.1e13.7; P ¼ 0.03), and calcium score per 100 increase (HR: 1.05; 95% CI: 1.02e1.08; P < 0.01) were predictors of clinically driven target lesion revascularization. As per receiver operating characteristic analysis, the best cutoff value of target lesion calcium score for target lesion revascularization was 206. Conclusions: A high femoropopliteal artery calcium score might increase loss of patency and the risk for clinically driven target lesion revascularization.
INTRODUCTION 1 Department of Cardiovascular Medicine, Nagoya Heart Center, Nagoya, Aichi, Japan. 2 Department of Cardiology, Toyohashi Heart Center, Toyohashi, Aichi, Japan.
Correspondence to: Takahiro Tokuda, Department of Cardiovascular Medicine, Nagoya Heart Center, 1-1-14Sunadabashi, Higashi-ku, Nagoya, Aichi, 461-0045, Japan; E-mail: [email protected] Ann Vasc Surg 2019; -: 1–11 https://doi.org/10.1016/j.avsg.2019.10.081 Ó 2019 Published by Elsevier Inc. Manuscript received: June 29, 2019; manuscript accepted: October 19, 2019; published online: - - -
Vascular calcification is sometimes encountered in patients with peripheral artery disease. A previous report revealed that vascular calcification made endovascular procedures difficult, especially in lesions that were 100% calcified.1 Another report showed that endovascular treatment (EVT) of heavily calcified lesions remained a technical challenge and that calcified lesions were generally difficult to cross with wires or balloons, rendering the affected vessel difficult to dilate.2 1
2 Tokuda et al.
The peripheral artery calcification scoring system (PACSS), which was first proposed by Rocha-Singh KJ et al., could be obtained and classified only by angiography.2 Okuno et al. reported that PACSS grade 4 was associated with loss of patency.3 This system enables the easy classification of lesion calcifications and quick performance of interventional procedures; however, it cannot always evaluate the accurate amount of calcification and might not reflect clinical outcomes. Tibial artery calcification has been shown to be an important risk factor for critical limb ischemia and limb amputation.4e6 One study reported that lower extremity arterial calcium score was associated with amputation and mortality.4 To the best of our knowledge, we are unaware of the detail of femoropopliteal artery calcium score. In this study, we aimed to determine the clinical relevance of the femoropopliteal artery calcium score to the clinical outcomes.
METHODS Study Design and Patients This retrospective observational study at a single institution evaluated 273 consecutive de novo patients who underwent endovascular procedures for femoropopliteal lesions between January 2010 and December 2017. All patients were on exercise and drug therapy and had symptoms corresponding to categories 2e6 of the Rutherford classification. When these treatments were ineffective, vascular specialists (including vascular surgeons and interventional cardiologists) decided whether EVT was appropriate. Patients who had available lower extremity computed tomography (CT) before the endovascular intervention were included. The patients were divided into two groups based on median of entire cohort of femoropopliteal artery calcium scores. We compared the two groups with respect to the patients, lesion, limb, and intervention results. The demographics of the patients, prior interventions, preoperative CT scans, intraoperative details and imaging, and follow-up records were collected and analyzed at 3, 6, and 12 months by assessment of any combination of symptoms, ankleebrachial index (ABI), duplex ultrasound, CT, or angiography. Computed Tomography The patients underwent noncontrast CT scan of the lower extremities on a single 128-slice CT scanner
Annals of Vascular Surgery
(definition AS+; Siemens, Forceheim, Germany) before endovascular procedure. Scans were performed using 3 mm increments, 200 mAs, and 120 kV with a field of view of 350 to 380 mm. The scan duration was approximately 15 sec. From the acquired raw data, the scan was reconstructed in 3 mm slices. Femoropopliteal Artery Calcium Score Using coronary artery calcium scoring software (Aquarius iNtuition, version 4.4.11; TeraRecon, Tokyo, Japan), two independent radiology experts who were blinded to the patients’ clinical information measured the femoropopliteal artery calcium score. On cross-sectional images through the lower extremities, areas of femoropopliteal artery calcification with a cross-sectional area greater than 1 mm2 and a density of >130 Hounsfield units were identified automatically. The regions of interest along the distal popliteal to the proximal superficial artery (SFA) were manually selected and labeled. We used 3 mm slices, measured calcium score of a cross-sectional area, and further summed across all calcium scores that started at the entry of the SFA and ended at the bottom of the patella. The calcium score at the site of target lesion was calculated and summed in contrast to angiography. Calcium scores were determined according to the method described by Agatston et al.7 This method was chosen because it is currently in widespread use, and it provides a simple transition from coronary calcium scoring. Interobserver variability was evaluated by two readers on a randomly selected list of 39 scans. The Spearman correlation coefficient was 0.96 (P < 0.01). The mean difference in the calcium score was 346. The study protocol was approved by the ethics committee and review board of our institution and was conducted in accordance with the Declaration of Helsinki. Consent of the patients was waived, given the nature of the study. Angioplasty Procedure and Follow-up All procedures were performed under local anesthesia, which was supplemented with intravenous sedation. Depending on the presence of combined proximal lesions, we chose an ipsilateral antegrade approach or a contralateral crossover approach. For the ipsilateral antegrade approach, a 5F or 6F sheath (Terumo, Tokyo, Japan) was introduced through the ipsilateral common femoral artery; a 6F destination (Terumo) or 6F Sheathless PV (Asahi intec, Aichi, Japan) was inserted through the
Volume
-, -
2019
contralateral femoral artery for the contralateral crossover approach. After insertion of the sheath, unfractionated heparin was administered to achieve an activated clotting time of >250 sec. Significant proximal inflow lesions were treated before EVT of the femoropopliteal lesions. For treatment of the femoropopliteal lesions, a 0.014, 0.018, or 0.035 inch guidewire was used, depending on the lesion characteristics and the operator’s preference. All lesions were treated with angioplasty using balloon catheters or stenting, depending on the lesion and the patient’s background. In case of flow-limiting dissection or residual stenosis >30%, prolonged balloon dilation (1e2 min longer than the initial dilation) was performed. If necessary, a slightly larger balloon was used according to the operator’s discretion. Bailout nitinol stent implantation was performed when flow-limiting dissection and recoil could not be resolved even after prolonged balloon dilation by angiographic assessment according to the operator’s discretion. All patients were followed-up clinically at one month and every three months thereafter. Antiplatelet therapy with aspirin (100 mg daily) and clopidogrel (75 mg daily), ticlopidine (100 mg twice daily), or cilostazol (100 mg twice daily) was started at least one week before the EVT and was continued for a minimum of four weeks after the procedure. Endpoints Primary patency, clinically driven target lesion revascularization (CD-TLR), major amputation (MA), and all-cause death were analyzed as endpoints. Definitions The procedure success was defined as residual stenosis of <30% without a suboptimal result. CDTLR was performed if >50% stenosis was found at follow-up with symptomatic peripheral artery disease (PAD) or critical limb ischemia (CLI). Loss of primary patency was defined as a peak systolic velocity ratio of >2.4, >50% stenosis, or occlusion on angiography, duplex ultrasound, or CT, or a decrease in the resting ABI of 0.2.8 Hypertension was defined as a systolic blood pressure of 140 mm Hg and/or a diastolic blood pressure of 90 mm Hg or an ongoing therapy for hypertension. Diabetes was defined as a glycated hemoglobin level of >6.5%, random plasma glucose level of >200 mg/dL, or treatment with oral hypoglycemic agents or insulin injection. Dyslipidemia was regarded as a low-density lipoprotein cholesterol of >140 mg/dL, a triglyceride level of >150 mg/dL,
Impact of femoropopliteal calcium score 3
a high-density lipoprotein cholesterol of <40 mg/ dL, or when a patient was under medical treatment for dyslipidemia. Coronary artery disease was defined as stable angina, history of percutaneous coronary intervention, history of coronary artery bypass graft surgery, or previous myocardial infarction. Cerebral infarction was defined as cerebral stroke that persisted for at least 24 hr and resulted in a neurological deficit. Runoff grade 0 was defined as no antegrade flow beyond a certain point below the knee.8 A major amputation above the ankle was defined as an MA. The PACSS was used to categorize the degree of lesion calcification on angiography.2 To evaluate the limb status of CLI, we used the society for vascular surgery (SVS) wound, ischemia, and foot infection (WIfI) system, which provided an objective classification for nonwound healing and limb amputation based on the following three independent risk factors: wound extent (e.g., size, depth, and presence of gangrene), degree of ischemia, and extent of foot infection. A detailed description of the SVS WIfI grading system has been presented in the previous report.9
Statistical Analysis All statistical analyses were performed using JMP version 14.0.0 software (SAS Institute Inc., Cary, NC). Data were analyzed based on limb and presented as number and percentage, mean ± standard deviation, or median (interquartile range). Categorical variables were compared between groups using the c2 test or the Fisher’s exact test, as appropriate. Continuous variables were compared between groups using the Manne Whitney U-test. To reveal the relationship between PACSS and the calcium score, Spearman correlation analysis was performed. Predictors of CD-TLR were evaluated via Cox regression analysis; the results were presented as the hazard ratio (HR) and 95% confidence interval (CI). A subsequent multivariate model, which included all the significant variables, was established to estimate the HR and 95% CI. The rates of CD-TLR, MA, and all-cause death were compared using the KaplaneMeier method, followed by the log-rank test. A probability ( p) value of <0.05 was considered statistically significant. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff value of target lesion calcium score to predict CD-TLR, with cutoff point being selected to yield the highest for the sum of sensitivity and specificity. The area under the ROC
4 Tokuda et al.
Annals of Vascular Surgery
Fig. 1. Study flow chart.
curve (AUC) was used as a measurement of the accuracy of the parameter.
RESULTS The mean calcium score was 2236 ± 2790, and its range was 0e13,859. A flowchart of the patient selection process is presented in Figure 1. Of all patients, 135 patients were excluded because of no available preprocedural CT. A total of four patients were excluded because of EVT failure, whereas eight patients were excluded because of acute limb ischemia or being lost to follow-up. Of these patients with EVT failure, one patient underwent MA and one patient died because of infection. The femoropopliteal artery bypass was performed for the other two patients. The average of calcium score for these patients was 7,434. A total of 132 patients and 163 limbs were analyzed in this study. Of these, 31 patients experienced bilateral limb ischemia, and thus, these patients were enrolled at the initial EVT. Of the 132 limbs included for analysis, 44 limbs were divided into the high calcium score group, and 88 were divided into the low calcium score group with mean calcium score. The mean follow-up duration was 816 ± 656 days. The follow-up rates were 80.3% and 68.8% at 6 months and 12 months, respectively. The complete baseline clinical and
demographic characteristics of the included patients are presented in Tables IeIII. No significant difference was observed in the baseline clinical data between the two groups, except for hemodialysis (80% vs. 25%, P < 0.01) and coronary artery disease (73% vs. 53%, P < 0.01). Compared with the low calcium score group, the high calcium score group had higher Rutherford classification grade, PACSS class, and below the knee lesions as other target lesions. The rate of CLI was significantly higher in the high calcium score group. (45.5% vs. 17.1%, P < 0.01) However, the limb status evaluated using the WIfI classification did not differ between the two groups. In treatment strategies, there were no significant differences between the two groups (Table III). The same result was obtained in terms of using cutting balloon. There was no significant difference between the two groups on the Rutherford grade after EVT (Table IV). Spearman correlation analysis revealed that the PACSS and calcium score were relatively correlated (r ¼ 0.72, P < 0.01; Fig. 2). There was no significant difference between the two groups in terms of MA and all-cause death, but loss of primary patency and CD-TLR were more frequent in the high calcium score group than in the low calcium score group (55% vs. 81%, 56% vs. 92%, both P < 0.01) (Figs. 3e6). According to the quartile of calcium score, the rate of CD-TLR gradually increased as the calcium score increased (Fig. 7). The result of ROC analysis is
Volume
-, -
2019
Impact of femoropopliteal calcium score 5
Table I. Patient background
Age (years) Male no. (%) Hypertension no. (%) Diabetes mellitus no. (%) Dyslipidemia no. (%) CKD no. (%) Hemodialysis no. (%) CI no. (%) Ejection fraction < 30%, no. (%) CAD no. (%) Current smoking no. (%) Cilostazole no. (%)
High calc
Low calc
44
88
72.1 ± 8.1 30 (68.2) 38 (86.4) 30 (68.2)
71.0 ± 8.0 64 (72.7) 78 (88.6) 55 (62.5)
24 3 35 9 4
62 22 22 14 12
(54.6) (6.8) (79.6) (20.5) (9.1)
P-value
0.48 0.59 0.71 0.52
(70.5) (25.0) (25.0) (15.9) (14.3)
0.07 <0.01 <0.01 0.52 0.38
32 (72.7) 6 (13.6)
47 (53.4) 22 (25.0)
0.03 0.12
16 (36.4)
31 (35.2)
0.90
CKD, chronic kidney disease; CI, cerebral infarction; CAD, coronary artery disease.
Table II. Lesion and limb characteristics
Reference diameter (mm) Lesion length (mm) Total occlusion, no. (%) Run off Run off grade 0, no. (%) TASC, no. (%) A B C D CLI, no. (%) WIfI class, no. (%) Very low Low Moderate High PACSS no. (%) 0 1 2 3 4 Calcium score Calcium score at treated lesion
High calc
Low calc
44
88
4.8 ± 0.8
4.8 ± 0.6
0.73
78.6 ± 68.0 14 (31.8) 1.73 ± 0.73 6 (13.6)
91.4 ± 72.9 39 (44.3) 1.82 ± 0.67 7 (8.0)
0.33 0.16 0.48 0.31
22 15 2 5 20
(50.0) (34.1) (4.6) (11.4) (45.5)
40 24 12 12 15
(45.5) (27.3) (13.6) (13.6) (17.1)
1 8 5 6
(5.0) (40.0) (25.0) (30.0)
3 3 5 4
(20.0) (20.0) (33.3) (26.7)
2 (4.6) 2 (4.6) 2 (4.6) 19 (43.2) 19 (43.2) 5482 ± 392 1977 ± 1577
P-value
29 (33.0) 34 (38.6) 6 (6.8) 15 (17.1) 4 (4.6) 613 ± 65 285 ± 396
0.34
<0.01
0.38
<0.01 <0.01 <0.01
TASC, transatlantic intersociety consensus; CLI, critical limb ischemia; WIfI, Wound, Ischemia, and foot Infection classification; PACSS, Proposed Peripheral Arterial Calcium Scoring System.
6 Tokuda et al.
Annals of Vascular Surgery
Table III. Procedure results
Balloon angioplasty only, no. (%) Use of cutting balloon, no.(%) Stent implantation, no.(%) Stent reference (mm) Number of stent Stent length (mm) Other target lesion, no. (%) Iliac CFA BTK Pre ABI Post ABI at the time of first follow-up
High calc
Low calc
44
88
20 (45.5)
28 (31.8)
0.13
9 (20.5)
14 (15.9)
0.52
24 (54.5)
60 (68.2)
0.13
6.1 ± 0.5 1.2 ± 0.4 115.1 ± 52.6
6.2 ± 0.5 1.4 ± 0.6 146.8 ± 74.3
0.48 0.06 0.07
1 (9.1) 2 (18.2) 8 (72.7) 0.62 ± 0.19 0.90 ± 0.12
12 (70.6) 0 (0) 5 (29.5) 0.58 ± 0.20 0.93 ± 0.13
P-value
<0.01 0.20 0.22
CFA, common femoral artery; BTK, below the knee; ABI, ankleebrachial index.
presented in Figure 8. The AUC was 0.85, and the best cutoff value was 206 (P < 0.01).
Table IV. The shift to lower Rutherford categories
Predictor of Target Lesion Revascularization The multivariate Cox regression analysis revealed that hemodialysis (HR: 1.9; 95% CI: 1.01e5.28; P ¼ 0.04) runoff grade 0 (HR: 2.9; 95% CI: 1.02e 10.9; P ¼ 0.04), lesion length > 200 mm (HR: 3.9; 95% CI: 1.1e13.7; P ¼ 0.03), and calcium score per 100 increase (HR: 1.05; 95% CI: 1.02e1.08; P < 0.01) were the independent predictors of CDTLR (Table V).
Baseline Rutherford, no. (%) 2 3 4 5 6
High calc
Low calc
44
88
0 23 3 16 2
(0) (52.3) (6.8) (36.4) (4.6)
41
DISCUSSION The present study is the first report to evaluate the impact of femoropopliteal artery calcium score after EVT. The main findings were as follows:
1) In patients with a high calcium score, loss of primary patency and the CD-TLR rate were higher, compared with those in the lower calcium score group. 2) The cutoff value of target lesion calcium score was 206. Our results implied that a higher calcium score was independently associated with the loss of primary patency and CD-TLR rate.
Rutherford at first follow-up, no. (%) 0 1 2 3 4 5 6
23 9 0 3 0 5 1
6 66 3 13 0
P-value
(6.8) (75.0) (3.4) (14.8) (0)
<0.01
83
(56.1) (22.0) (0) (7.3) (0) (12.2) (2.4)
56 19 2 1 1 4 0
(67.5) (22.9) (2.4) (1.2) (0.9) (4.8) (0)
0.13
Previous work on chronic coronary artery occlusion showed that vessel calcification was a predictor of technical failure of catheter-based treatment, and this result was first reported by Mollet et al., who described calcification of the coronary arteries on preoperative CT angiography.10 In the field of
Volume
-, -
2019
Fig. 2. Relationship between the calcium score of the femoropopliteal artery and the Proposed Peripheral Arterial Calcium Scoring System.
Impact of femoropopliteal calcium score 7
the high calcium score group; however, the majority of the lesions had type A or B transatlantic intersociety consensus II classification.11 The result that the freedom from the rate of CDTLR at one year was approximately 55% may not be feasible, even if our study included only balloon angioplasty strategy, because the previously reported rates of CD-TLR after EVT for the femoropopliteal artery were 10%e20%.12,13 As an explanation for high rate of CD-TLR, we assumed that vessel calcification was one of the reasons for the loss of patency because balloon dilatation or stent implantation might have been insufficient to secure an adequate lumen diameter, as reported by Fujihara et al.14 Also, our results revealed that a calcium score was a stronger predictor than the PACSS classification with Cox regression analysis.
Fig. 3. KaplaneMeier curve for MA according to the calcium score.
peripheral intervention, the concept of using the calcium score was first applied to the tibial arteries, as described by Guzman et al.5 In addition, a recent report described the usefulness of CT angiography and that 100% calcification was the best predictor of technical failure of EVT in the femoropopliteal artery.1 In this study, we noted that the femoropopliteal artery calcium score might be a predictive factor for clinical outcomes. We revealed that the freedom from the rate of CD-TLR at one year was approximately 55% in
This result implies that calcium score is an accurate evaluation tool, although the measurement of femoropopliteal artery calcium score could be a complex procedure, compared with that of the PACSS classification. The previous study demonstrated that a higher calcium score was associated with a higher Rutherford grade.6 As the present study implied, baseline Rutherford grade was different between the two groups in our study. However, there was no significant difference between the two groups on the
8 Tokuda et al.
Annals of Vascular Surgery
Fig. 4. KaplaneMeier curve for all-cause death according to the calcium score.
Fig. 5. KaplaneMeier curve for primary patency according to the calcium score.
Rutherford grade at the time of first follow-up after EVT. One of the treatment strategies to overcome the calcification is to use a scoring balloon, although a recent study did not demonstrate the efficacy using
scoring balloon.15 The use of an atherectomy device should be considered as another treatment strategy; however, Foley et al. reported that the efficacy of the atherectomy device was similar to that of the conventional treatment strategy.16 Based on these
Volume
-, -
2019
Impact of femoropopliteal calcium score 9
Fig. 6. KaplaneMeier curve for CD-TLR according to the calcium score.
Fig. 7. The rate of CD-TLR according to the quartile of calcium score.
results, a bypass surgery may need to be considered in cases with a high femoropopliteal artery calcium score, depending on the patient and lesion characteristics. Previous studies demonstrated a significant correlation between vascular calcification and the coronary artery calcification score on CT in end stage renal disease patients.17,18 In the present study, the number of hemodialysis patients was higher in the high calcium score group. The rate of MA was similar between the groups studied in this report. We assumed that the amount of calcific disease in the tibial vessels, rather than the femoropopliteal vessels, would most strongly reflect the degree of
Fig. 8. Receiver operating characteristics analysis of target lesion calcium score for developing target lesion revascularization.
blood flow impairment to the foot. In addition, there was no significant difference in all-cause death between the two groups; this was probably because of the short observation period of only one year, although majority in the high calcium score group were hemodialysis patients. Data on the direct relationship between femoropopliteal artery calcium score and the immediate or late outcomes of EVT are limited. However, this study demonstrated that a high calcium score was independently associated with loss of patency and rate of CD-TLR.
10 Tokuda et al.
Annals of Vascular Surgery
Table V. Univariate and multivariate Cox regression analyses of the predictors of target lesion revascularization Univariate
Multivariate
Variables
HR
95% CI
P
Female Diabetes mellitus Chronic kidney disease Hemodialysis Critical limb ischemia Low EF Current smoking Total occlusion Runoff grade 0 Reference diameter Lesion length of >200 mm PACSS 4 Calcium score (per 100 increase)
1.71 1.48 1.27 3.51 2.93 1.57 1.01 1.47 2.57 1.01 2.97 3.85 1.02
0.85e3.37 0.73e3.25 0.58e3.16 1.76e7.22 1.35e5.98 0.56e6.57 0.43e2.14 0.72e2.90 1.29e5.07 0.15e7.24 1.26e6.28 1.78e7.86 1.01e1.03
0.13 0.30 0.58 <0.01 <0.01 0.46 0.98 0.28 <0.01 0.96 0.02 <0.01 <0.01
HR
95% CI
P
1.93 1.57
1.01e5.28 0.52e4.75
0.04 0.42
2.89
1.02e10.9
0.04
3.88 1.06 1.05
1.10e13.7 0.33e3.36 1.02e1.08
0.03 0.92 <0.01
EF, ejection fraction; PACSS, Proposed Peripheral Arterial Calcium Scoring System.
This study had several limitations that should be addressed. The retrospective, single-center cohort design of this study and the small number of patients are the inherent limitations. Because of the nature of this study, this study did not consist of consecutive patients. Second, and most importantly, the two patient groups differed in baseline clinical and angiographic characteristics, and there might be a type 2 error; nevertheless, we compensated for the influence of the confounding factors with the use of multivariate regression analyses. Third, the treatment strategy varied according to the operator’s discretion. Finally, the study cohort was limited to Japanese patients with physical constitutions, muscle strengths, and lipid metabolisms that often differ from those of Western patients. Therefore, further prospective studies are warranted to confirm these results in other populations.
2.
3.
4.
5.
6.
7.
CONCLUSION A high femoropopliteal artery calcium score might increase the loss of primary patency and risk for CD-TLR.
8.
9.
The authors thank the staff in the catheterization laboratory of the Nagoya Heart Center for their assistance in this work. REFERENCES 1. Itoga NK, Kim T, Sailer AM, et al. Lower extremity computed tomography angiography can help predict
10.
technical success of endovascular revascularization in the superficial femoral and popliteal artery. J Vasc Surg 2017;66:835e43. Rocha-Singh KJ, Zeller T, Jaff MR. Peripheral arterial calcification: prevalence, mechanism, detection, and clinical implications. Catheter Cardiovasc Interv 2014;83:E212e20. Okuno S, Iida O, Shiraki T, et al. Impact of calcification on clinical outcomes after endovascular therapy for superficial femoral artery disease: assessment using the peripheral artery calcification scoring system. J Endovasc Ther 2016;23: 731e7. Huang CL, Wu IH, Wu YW, et al. Association of lower extremity arterial calcification with amputation and mortality in patients with symptomatic peripheral artery disease. PLoS One 2014;9:e90201. Guzman RJ, Brinkley DM, Schumacher PM, et al. Tibial artery calcification as a marker of amputation risk in patients with peripheral arterial disease. J Am Coll Cardiol 2008;51: 1967e74. Ohtake T, Oka M, Ikee R, et al. Impact of lower limbs’ arterial calcification on the prevalence and severity of PAD in patients on hemodialysis. J Vasc Surg 2011;53:676e83. Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827e32. Ranke C, Creutzig A, Alexander K. Duplex scanning of peripheral arteries: correlation of the peak velocity ratio with angiographic diameter reduction. Ultrasound Med Biol 1992;18: 433e40. Seiichi H, Yoshimitsu S, Yusuke T, et al. Impact of runoff grade after endovascular therapy for femoropopliteal lesions. J Vasc Surg 2014;59:720e7. Mills JL, Conte MS, Armstrong DG, et al. The society for vascular surgery lower extremity threatened limb classification system: risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg 2014;59:220e34. Mollet NR, Hoye A, Lemos PA, et al. Value of preprocedure multislice computed tomographic coronary angiography to predict the outcome of percutaneous recanalization of chronic total occlusions. Am J Cardiol 2005;95:240e3.
Volume
-, -
2019
11. Norgren L, Hiatt WR, Dormandy JA, et al., TASC II Working Group. Inter-society consensus for the management of peripheral arterial disease (TASC II). Eur J Vasc Surg 2007;33:S1e75. 12. Bunte MC, Cohen DJ, Jaff MR, et al. Long-term clinical and quality of life outcomes after stenting of femoropopliteal artery stenosis: 3-year results from the STROLL study. Catheter Cardiovasc Interv 2018;92:106e14. 13. Rocha-Singh KJ, Beckman JA, Ansel G, et al. Patient-level meta-analysis of 999 claudicants undergoing primary femoropopliteal nitinol stent implantation. Catheter Cardiovasc Interv 2017;89:1250e6. 14. Fujihara M, Higashimori A, Kato Y, et al. Nitinol stent implantation for femoropopliteal disease in patients on hemodialysis: results of the 3-year retrospective multicenter APOLLON study. Heart Vessels 2016;31:1476e83.
Impact of femoropopliteal calcium score 11
15. Lugenbiel I, Grebner M, Zhou Q, et al. Treatment of femoropopliteal lesions with the AngioSculpt scoring balloonresults from the Heidelberg PANTHER registry. Vasa 2018;47:49e55. 16. Foley TR, Cotter RP, Kokkinidis DG, et al. Mid-term outcomes of orbital atherectomy combined with drug-coated balloon angioplasty for treatment of femoropopliteal disease. Catheter Cardiovasc Interv 2017;89:1078e85. 17. Tenenbaum A, Shemesh J, Fisman EZ, et al. Advanced mitral annular calcification is associated with severe coronary calcification on fast dual spiral computed tomography. Invest Radiol 2000;35:193e8. 18. Pohle K, M€affert R, Ropers D, et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation 2001;104: 1927e32.
Background: The coronary artery calcium score is a widely known independent predictor of cardiac events. Tibial artery calcification had been reported as an amputation risk, but the femoropopliteal artery calcium score is rarely known. Methods: A retrospective analysis was performed using the data collected from the patients who underwent endovascular treatment for the femoropopliteal artery between January 2010 and December 2017. The femoropopliteal artery calcium scores on preprocedural computed tomography were calculated according to the Agatston definition. The mean value of total of femoropopliteal artery calcium scores was used to divide the scores into two groups. The prognostic value of the calcium score was analyzed based on primary patency, clinically driven target lesion revascularization, major amputation, and all-cause death. Results: In total, 132 consecutive limbs that underwent successful endovascular intervention were analyzed in this study; 44 and 88 limbs were assigned to the high and low calcium score groups, respectively. There were no significant differences between the two groups in terms of patient and lesion characteristics, except for chronic kidney disease (7% vs. 25%, P < 0.01), hemodialysis (80% vs. 25%, P < 0.01), and coronary artery disease (73% vs. 53%, P ¼ 0.03). Compared with the low calcium score group, the high calcium score group had a significantly higher rate of loss of primary patency and clinically driven target lesion revascularization at one year, based on the KaplaneMeier curve (55% vs. 81%, 44% vs. 8%, both P < 0.01). There were no significant differences between the two groups in terms of major amputation and death. Multivariate analysis revealed that hemodialysis [hazard ratio (HR): 1.9; 95% confidence interval (CI): 1.01e5.28; P ¼ 0.04] runoff grade 0 (HR: 2.9; 95% CI: 1.02e10.9; P ¼ 0.04), lesion length > 200 mm (HR: 3.9; 95% CI: 1.1e13.7; P ¼ 0.03), and calcium score per 100 increase (HR: 1.05; 95% CI: 1.02e1.08; P < 0.01) were predictors of clinically driven target lesion revascularization. As per receiver operating characteristic analysis, the best cutoff value of target lesion calcium score for target lesion revascularization was 206. Conclusions: A high femoropopliteal artery calcium score might increase loss of patency and the risk for clinically driven target lesion revascularization.
INTRODUCTION 1 Department of Cardiovascular Medicine, Nagoya Heart Center, Nagoya, Aichi, Japan. 2 Department of Cardiology, Toyohashi Heart Center, Toyohashi, Aichi, Japan.
Correspondence to: Takahiro Tokuda, Department of Cardiovascular Medicine, Nagoya Heart Center, 1-1-14Sunadabashi, Higashi-ku, Nagoya, Aichi, 461-0045, Japan; E-mail: [email protected] Ann Vasc Surg 2019; -: 1–11 https://doi.org/10.1016/j.avsg.2019.10.081 Ó 2019 Published by Elsevier Inc. Manuscript received: June 29, 2019; manuscript accepted: October 19, 2019; published online: - - -
Vascular calcification is sometimes encountered in patients with peripheral artery disease. A previous report revealed that vascular calcification made endovascular procedures difficult, especially in lesions that were 100% calcified.1 Another report showed that endovascular treatment (EVT) of heavily calcified lesions remained a technical challenge and that calcified lesions were generally difficult to cross with wires or balloons, rendering the affected vessel difficult to dilate.2 1
2 Tokuda et al.
The peripheral artery calcification scoring system (PACSS), which was first proposed by Rocha-Singh KJ et al., could be obtained and classified only by angiography.2 Okuno et al. reported that PACSS grade 4 was associated with loss of patency.3 This system enables the easy classification of lesion calcifications and quick performance of interventional procedures; however, it cannot always evaluate the accurate amount of calcification and might not reflect clinical outcomes. Tibial artery calcification has been shown to be an important risk factor for critical limb ischemia and limb amputation.4e6 One study reported that lower extremity arterial calcium score was associated with amputation and mortality.4 To the best of our knowledge, we are unaware of the detail of femoropopliteal artery calcium score. In this study, we aimed to determine the clinical relevance of the femoropopliteal artery calcium score to the clinical outcomes.
METHODS Study Design and Patients This retrospective observational study at a single institution evaluated 273 consecutive de novo patients who underwent endovascular procedures for femoropopliteal lesions between January 2010 and December 2017. All patients were on exercise and drug therapy and had symptoms corresponding to categories 2e6 of the Rutherford classification. When these treatments were ineffective, vascular specialists (including vascular surgeons and interventional cardiologists) decided whether EVT was appropriate. Patients who had available lower extremity computed tomography (CT) before the endovascular intervention were included. The patients were divided into two groups based on median of entire cohort of femoropopliteal artery calcium scores. We compared the two groups with respect to the patients, lesion, limb, and intervention results. The demographics of the patients, prior interventions, preoperative CT scans, intraoperative details and imaging, and follow-up records were collected and analyzed at 3, 6, and 12 months by assessment of any combination of symptoms, ankleebrachial index (ABI), duplex ultrasound, CT, or angiography. Computed Tomography The patients underwent noncontrast CT scan of the lower extremities on a single 128-slice CT scanner
Annals of Vascular Surgery
(definition AS+; Siemens, Forceheim, Germany) before endovascular procedure. Scans were performed using 3 mm increments, 200 mAs, and 120 kV with a field of view of 350 to 380 mm. The scan duration was approximately 15 sec. From the acquired raw data, the scan was reconstructed in 3 mm slices. Femoropopliteal Artery Calcium Score Using coronary artery calcium scoring software (Aquarius iNtuition, version 4.4.11; TeraRecon, Tokyo, Japan), two independent radiology experts who were blinded to the patients’ clinical information measured the femoropopliteal artery calcium score. On cross-sectional images through the lower extremities, areas of femoropopliteal artery calcification with a cross-sectional area greater than 1 mm2 and a density of >130 Hounsfield units were identified automatically. The regions of interest along the distal popliteal to the proximal superficial artery (SFA) were manually selected and labeled. We used 3 mm slices, measured calcium score of a cross-sectional area, and further summed across all calcium scores that started at the entry of the SFA and ended at the bottom of the patella. The calcium score at the site of target lesion was calculated and summed in contrast to angiography. Calcium scores were determined according to the method described by Agatston et al.7 This method was chosen because it is currently in widespread use, and it provides a simple transition from coronary calcium scoring. Interobserver variability was evaluated by two readers on a randomly selected list of 39 scans. The Spearman correlation coefficient was 0.96 (P < 0.01). The mean difference in the calcium score was 346. The study protocol was approved by the ethics committee and review board of our institution and was conducted in accordance with the Declaration of Helsinki. Consent of the patients was waived, given the nature of the study. Angioplasty Procedure and Follow-up All procedures were performed under local anesthesia, which was supplemented with intravenous sedation. Depending on the presence of combined proximal lesions, we chose an ipsilateral antegrade approach or a contralateral crossover approach. For the ipsilateral antegrade approach, a 5F or 6F sheath (Terumo, Tokyo, Japan) was introduced through the ipsilateral common femoral artery; a 6F destination (Terumo) or 6F Sheathless PV (Asahi intec, Aichi, Japan) was inserted through the
Volume
-, -
2019
contralateral femoral artery for the contralateral crossover approach. After insertion of the sheath, unfractionated heparin was administered to achieve an activated clotting time of >250 sec. Significant proximal inflow lesions were treated before EVT of the femoropopliteal lesions. For treatment of the femoropopliteal lesions, a 0.014, 0.018, or 0.035 inch guidewire was used, depending on the lesion characteristics and the operator’s preference. All lesions were treated with angioplasty using balloon catheters or stenting, depending on the lesion and the patient’s background. In case of flow-limiting dissection or residual stenosis >30%, prolonged balloon dilation (1e2 min longer than the initial dilation) was performed. If necessary, a slightly larger balloon was used according to the operator’s discretion. Bailout nitinol stent implantation was performed when flow-limiting dissection and recoil could not be resolved even after prolonged balloon dilation by angiographic assessment according to the operator’s discretion. All patients were followed-up clinically at one month and every three months thereafter. Antiplatelet therapy with aspirin (100 mg daily) and clopidogrel (75 mg daily), ticlopidine (100 mg twice daily), or cilostazol (100 mg twice daily) was started at least one week before the EVT and was continued for a minimum of four weeks after the procedure. Endpoints Primary patency, clinically driven target lesion revascularization (CD-TLR), major amputation (MA), and all-cause death were analyzed as endpoints. Definitions The procedure success was defined as residual stenosis of <30% without a suboptimal result. CDTLR was performed if >50% stenosis was found at follow-up with symptomatic peripheral artery disease (PAD) or critical limb ischemia (CLI). Loss of primary patency was defined as a peak systolic velocity ratio of >2.4, >50% stenosis, or occlusion on angiography, duplex ultrasound, or CT, or a decrease in the resting ABI of 0.2.8 Hypertension was defined as a systolic blood pressure of 140 mm Hg and/or a diastolic blood pressure of 90 mm Hg or an ongoing therapy for hypertension. Diabetes was defined as a glycated hemoglobin level of >6.5%, random plasma glucose level of >200 mg/dL, or treatment with oral hypoglycemic agents or insulin injection. Dyslipidemia was regarded as a low-density lipoprotein cholesterol of >140 mg/dL, a triglyceride level of >150 mg/dL,
Impact of femoropopliteal calcium score 3
a high-density lipoprotein cholesterol of <40 mg/ dL, or when a patient was under medical treatment for dyslipidemia. Coronary artery disease was defined as stable angina, history of percutaneous coronary intervention, history of coronary artery bypass graft surgery, or previous myocardial infarction. Cerebral infarction was defined as cerebral stroke that persisted for at least 24 hr and resulted in a neurological deficit. Runoff grade 0 was defined as no antegrade flow beyond a certain point below the knee.8 A major amputation above the ankle was defined as an MA. The PACSS was used to categorize the degree of lesion calcification on angiography.2 To evaluate the limb status of CLI, we used the society for vascular surgery (SVS) wound, ischemia, and foot infection (WIfI) system, which provided an objective classification for nonwound healing and limb amputation based on the following three independent risk factors: wound extent (e.g., size, depth, and presence of gangrene), degree of ischemia, and extent of foot infection. A detailed description of the SVS WIfI grading system has been presented in the previous report.9
Statistical Analysis All statistical analyses were performed using JMP version 14.0.0 software (SAS Institute Inc., Cary, NC). Data were analyzed based on limb and presented as number and percentage, mean ± standard deviation, or median (interquartile range). Categorical variables were compared between groups using the c2 test or the Fisher’s exact test, as appropriate. Continuous variables were compared between groups using the Manne Whitney U-test. To reveal the relationship between PACSS and the calcium score, Spearman correlation analysis was performed. Predictors of CD-TLR were evaluated via Cox regression analysis; the results were presented as the hazard ratio (HR) and 95% confidence interval (CI). A subsequent multivariate model, which included all the significant variables, was established to estimate the HR and 95% CI. The rates of CD-TLR, MA, and all-cause death were compared using the KaplaneMeier method, followed by the log-rank test. A probability ( p) value of <0.05 was considered statistically significant. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff value of target lesion calcium score to predict CD-TLR, with cutoff point being selected to yield the highest for the sum of sensitivity and specificity. The area under the ROC
4 Tokuda et al.
Annals of Vascular Surgery
Fig. 1. Study flow chart.
curve (AUC) was used as a measurement of the accuracy of the parameter.
RESULTS The mean calcium score was 2236 ± 2790, and its range was 0e13,859. A flowchart of the patient selection process is presented in Figure 1. Of all patients, 135 patients were excluded because of no available preprocedural CT. A total of four patients were excluded because of EVT failure, whereas eight patients were excluded because of acute limb ischemia or being lost to follow-up. Of these patients with EVT failure, one patient underwent MA and one patient died because of infection. The femoropopliteal artery bypass was performed for the other two patients. The average of calcium score for these patients was 7,434. A total of 132 patients and 163 limbs were analyzed in this study. Of these, 31 patients experienced bilateral limb ischemia, and thus, these patients were enrolled at the initial EVT. Of the 132 limbs included for analysis, 44 limbs were divided into the high calcium score group, and 88 were divided into the low calcium score group with mean calcium score. The mean follow-up duration was 816 ± 656 days. The follow-up rates were 80.3% and 68.8% at 6 months and 12 months, respectively. The complete baseline clinical and
demographic characteristics of the included patients are presented in Tables IeIII. No significant difference was observed in the baseline clinical data between the two groups, except for hemodialysis (80% vs. 25%, P < 0.01) and coronary artery disease (73% vs. 53%, P < 0.01). Compared with the low calcium score group, the high calcium score group had higher Rutherford classification grade, PACSS class, and below the knee lesions as other target lesions. The rate of CLI was significantly higher in the high calcium score group. (45.5% vs. 17.1%, P < 0.01) However, the limb status evaluated using the WIfI classification did not differ between the two groups. In treatment strategies, there were no significant differences between the two groups (Table III). The same result was obtained in terms of using cutting balloon. There was no significant difference between the two groups on the Rutherford grade after EVT (Table IV). Spearman correlation analysis revealed that the PACSS and calcium score were relatively correlated (r ¼ 0.72, P < 0.01; Fig. 2). There was no significant difference between the two groups in terms of MA and all-cause death, but loss of primary patency and CD-TLR were more frequent in the high calcium score group than in the low calcium score group (55% vs. 81%, 56% vs. 92%, both P < 0.01) (Figs. 3e6). According to the quartile of calcium score, the rate of CD-TLR gradually increased as the calcium score increased (Fig. 7). The result of ROC analysis is
Volume
-, -
2019
Impact of femoropopliteal calcium score 5
Table I. Patient background
Age (years) Male no. (%) Hypertension no. (%) Diabetes mellitus no. (%) Dyslipidemia no. (%) CKD no. (%) Hemodialysis no. (%) CI no. (%) Ejection fraction < 30%, no. (%) CAD no. (%) Current smoking no. (%) Cilostazole no. (%)
High calc
Low calc
44
88
72.1 ± 8.1 30 (68.2) 38 (86.4) 30 (68.2)
71.0 ± 8.0 64 (72.7) 78 (88.6) 55 (62.5)
24 3 35 9 4
62 22 22 14 12
(54.6) (6.8) (79.6) (20.5) (9.1)
P-value
0.48 0.59 0.71 0.52
(70.5) (25.0) (25.0) (15.9) (14.3)
0.07 <0.01 <0.01 0.52 0.38
32 (72.7) 6 (13.6)
47 (53.4) 22 (25.0)
0.03 0.12
16 (36.4)
31 (35.2)
0.90
CKD, chronic kidney disease; CI, cerebral infarction; CAD, coronary artery disease.
Table II. Lesion and limb characteristics
Reference diameter (mm) Lesion length (mm) Total occlusion, no. (%) Run off Run off grade 0, no. (%) TASC, no. (%) A B C D CLI, no. (%) WIfI class, no. (%) Very low Low Moderate High PACSS no. (%) 0 1 2 3 4 Calcium score Calcium score at treated lesion
High calc
Low calc
44
88
4.8 ± 0.8
4.8 ± 0.6
0.73
78.6 ± 68.0 14 (31.8) 1.73 ± 0.73 6 (13.6)
91.4 ± 72.9 39 (44.3) 1.82 ± 0.67 7 (8.0)
0.33 0.16 0.48 0.31
22 15 2 5 20
(50.0) (34.1) (4.6) (11.4) (45.5)
40 24 12 12 15
(45.5) (27.3) (13.6) (13.6) (17.1)
1 8 5 6
(5.0) (40.0) (25.0) (30.0)
3 3 5 4
(20.0) (20.0) (33.3) (26.7)
2 (4.6) 2 (4.6) 2 (4.6) 19 (43.2) 19 (43.2) 5482 ± 392 1977 ± 1577
P-value
29 (33.0) 34 (38.6) 6 (6.8) 15 (17.1) 4 (4.6) 613 ± 65 285 ± 396
0.34
<0.01
0.38
<0.01 <0.01 <0.01
TASC, transatlantic intersociety consensus; CLI, critical limb ischemia; WIfI, Wound, Ischemia, and foot Infection classification; PACSS, Proposed Peripheral Arterial Calcium Scoring System.
6 Tokuda et al.
Annals of Vascular Surgery
Table III. Procedure results
Balloon angioplasty only, no. (%) Use of cutting balloon, no.(%) Stent implantation, no.(%) Stent reference (mm) Number of stent Stent length (mm) Other target lesion, no. (%) Iliac CFA BTK Pre ABI Post ABI at the time of first follow-up
High calc
Low calc
44
88
20 (45.5)
28 (31.8)
0.13
9 (20.5)
14 (15.9)
0.52
24 (54.5)
60 (68.2)
0.13
6.1 ± 0.5 1.2 ± 0.4 115.1 ± 52.6
6.2 ± 0.5 1.4 ± 0.6 146.8 ± 74.3
0.48 0.06 0.07
1 (9.1) 2 (18.2) 8 (72.7) 0.62 ± 0.19 0.90 ± 0.12
12 (70.6) 0 (0) 5 (29.5) 0.58 ± 0.20 0.93 ± 0.13
P-value
<0.01 0.20 0.22
CFA, common femoral artery; BTK, below the knee; ABI, ankleebrachial index.
presented in Figure 8. The AUC was 0.85, and the best cutoff value was 206 (P < 0.01).
Table IV. The shift to lower Rutherford categories
Predictor of Target Lesion Revascularization The multivariate Cox regression analysis revealed that hemodialysis (HR: 1.9; 95% CI: 1.01e5.28; P ¼ 0.04) runoff grade 0 (HR: 2.9; 95% CI: 1.02e 10.9; P ¼ 0.04), lesion length > 200 mm (HR: 3.9; 95% CI: 1.1e13.7; P ¼ 0.03), and calcium score per 100 increase (HR: 1.05; 95% CI: 1.02e1.08; P < 0.01) were the independent predictors of CDTLR (Table V).
Baseline Rutherford, no. (%) 2 3 4 5 6
High calc
Low calc
44
88
0 23 3 16 2
(0) (52.3) (6.8) (36.4) (4.6)
41
DISCUSSION The present study is the first report to evaluate the impact of femoropopliteal artery calcium score after EVT. The main findings were as follows:
1) In patients with a high calcium score, loss of primary patency and the CD-TLR rate were higher, compared with those in the lower calcium score group. 2) The cutoff value of target lesion calcium score was 206. Our results implied that a higher calcium score was independently associated with the loss of primary patency and CD-TLR rate.
Rutherford at first follow-up, no. (%) 0 1 2 3 4 5 6
23 9 0 3 0 5 1
6 66 3 13 0
P-value
(6.8) (75.0) (3.4) (14.8) (0)
<0.01
83
(56.1) (22.0) (0) (7.3) (0) (12.2) (2.4)
56 19 2 1 1 4 0
(67.5) (22.9) (2.4) (1.2) (0.9) (4.8) (0)
0.13
Previous work on chronic coronary artery occlusion showed that vessel calcification was a predictor of technical failure of catheter-based treatment, and this result was first reported by Mollet et al., who described calcification of the coronary arteries on preoperative CT angiography.10 In the field of
Volume
-, -
2019
Fig. 2. Relationship between the calcium score of the femoropopliteal artery and the Proposed Peripheral Arterial Calcium Scoring System.
Impact of femoropopliteal calcium score 7
the high calcium score group; however, the majority of the lesions had type A or B transatlantic intersociety consensus II classification.11 The result that the freedom from the rate of CDTLR at one year was approximately 55% may not be feasible, even if our study included only balloon angioplasty strategy, because the previously reported rates of CD-TLR after EVT for the femoropopliteal artery were 10%e20%.12,13 As an explanation for high rate of CD-TLR, we assumed that vessel calcification was one of the reasons for the loss of patency because balloon dilatation or stent implantation might have been insufficient to secure an adequate lumen diameter, as reported by Fujihara et al.14 Also, our results revealed that a calcium score was a stronger predictor than the PACSS classification with Cox regression analysis.
Fig. 3. KaplaneMeier curve for MA according to the calcium score.
peripheral intervention, the concept of using the calcium score was first applied to the tibial arteries, as described by Guzman et al.5 In addition, a recent report described the usefulness of CT angiography and that 100% calcification was the best predictor of technical failure of EVT in the femoropopliteal artery.1 In this study, we noted that the femoropopliteal artery calcium score might be a predictive factor for clinical outcomes. We revealed that the freedom from the rate of CD-TLR at one year was approximately 55% in
This result implies that calcium score is an accurate evaluation tool, although the measurement of femoropopliteal artery calcium score could be a complex procedure, compared with that of the PACSS classification. The previous study demonstrated that a higher calcium score was associated with a higher Rutherford grade.6 As the present study implied, baseline Rutherford grade was different between the two groups in our study. However, there was no significant difference between the two groups on the
8 Tokuda et al.
Annals of Vascular Surgery
Fig. 4. KaplaneMeier curve for all-cause death according to the calcium score.
Fig. 5. KaplaneMeier curve for primary patency according to the calcium score.
Rutherford grade at the time of first follow-up after EVT. One of the treatment strategies to overcome the calcification is to use a scoring balloon, although a recent study did not demonstrate the efficacy using
scoring balloon.15 The use of an atherectomy device should be considered as another treatment strategy; however, Foley et al. reported that the efficacy of the atherectomy device was similar to that of the conventional treatment strategy.16 Based on these
Volume
-, -
2019
Impact of femoropopliteal calcium score 9
Fig. 6. KaplaneMeier curve for CD-TLR according to the calcium score.
Fig. 7. The rate of CD-TLR according to the quartile of calcium score.
results, a bypass surgery may need to be considered in cases with a high femoropopliteal artery calcium score, depending on the patient and lesion characteristics. Previous studies demonstrated a significant correlation between vascular calcification and the coronary artery calcification score on CT in end stage renal disease patients.17,18 In the present study, the number of hemodialysis patients was higher in the high calcium score group. The rate of MA was similar between the groups studied in this report. We assumed that the amount of calcific disease in the tibial vessels, rather than the femoropopliteal vessels, would most strongly reflect the degree of
Fig. 8. Receiver operating characteristics analysis of target lesion calcium score for developing target lesion revascularization.
blood flow impairment to the foot. In addition, there was no significant difference in all-cause death between the two groups; this was probably because of the short observation period of only one year, although majority in the high calcium score group were hemodialysis patients. Data on the direct relationship between femoropopliteal artery calcium score and the immediate or late outcomes of EVT are limited. However, this study demonstrated that a high calcium score was independently associated with loss of patency and rate of CD-TLR.
10 Tokuda et al.
Annals of Vascular Surgery
Table V. Univariate and multivariate Cox regression analyses of the predictors of target lesion revascularization Univariate
Multivariate
Variables
HR
95% CI
P
Female Diabetes mellitus Chronic kidney disease Hemodialysis Critical limb ischemia Low EF Current smoking Total occlusion Runoff grade 0 Reference diameter Lesion length of >200 mm PACSS 4 Calcium score (per 100 increase)
1.71 1.48 1.27 3.51 2.93 1.57 1.01 1.47 2.57 1.01 2.97 3.85 1.02
0.85e3.37 0.73e3.25 0.58e3.16 1.76e7.22 1.35e5.98 0.56e6.57 0.43e2.14 0.72e2.90 1.29e5.07 0.15e7.24 1.26e6.28 1.78e7.86 1.01e1.03
0.13 0.30 0.58 <0.01 <0.01 0.46 0.98 0.28 <0.01 0.96 0.02 <0.01 <0.01
HR
95% CI
P
1.93 1.57
1.01e5.28 0.52e4.75
0.04 0.42
2.89
1.02e10.9
0.04
3.88 1.06 1.05
1.10e13.7 0.33e3.36 1.02e1.08
0.03 0.92 <0.01
EF, ejection fraction; PACSS, Proposed Peripheral Arterial Calcium Scoring System.
This study had several limitations that should be addressed. The retrospective, single-center cohort design of this study and the small number of patients are the inherent limitations. Because of the nature of this study, this study did not consist of consecutive patients. Second, and most importantly, the two patient groups differed in baseline clinical and angiographic characteristics, and there might be a type 2 error; nevertheless, we compensated for the influence of the confounding factors with the use of multivariate regression analyses. Third, the treatment strategy varied according to the operator’s discretion. Finally, the study cohort was limited to Japanese patients with physical constitutions, muscle strengths, and lipid metabolisms that often differ from those of Western patients. Therefore, further prospective studies are warranted to confirm these results in other populations.
2.
3.
4.
5.
6.
7.
CONCLUSION A high femoropopliteal artery calcium score might increase the loss of primary patency and risk for CD-TLR.
8.
9.
The authors thank the staff in the catheterization laboratory of the Nagoya Heart Center for their assistance in this work. REFERENCES 1. Itoga NK, Kim T, Sailer AM, et al. Lower extremity computed tomography angiography can help predict
10.
technical success of endovascular revascularization in the superficial femoral and popliteal artery. J Vasc Surg 2017;66:835e43. Rocha-Singh KJ, Zeller T, Jaff MR. Peripheral arterial calcification: prevalence, mechanism, detection, and clinical implications. Catheter Cardiovasc Interv 2014;83:E212e20. Okuno S, Iida O, Shiraki T, et al. Impact of calcification on clinical outcomes after endovascular therapy for superficial femoral artery disease: assessment using the peripheral artery calcification scoring system. J Endovasc Ther 2016;23: 731e7. Huang CL, Wu IH, Wu YW, et al. Association of lower extremity arterial calcification with amputation and mortality in patients with symptomatic peripheral artery disease. PLoS One 2014;9:e90201. Guzman RJ, Brinkley DM, Schumacher PM, et al. Tibial artery calcification as a marker of amputation risk in patients with peripheral arterial disease. J Am Coll Cardiol 2008;51: 1967e74. Ohtake T, Oka M, Ikee R, et al. Impact of lower limbs’ arterial calcification on the prevalence and severity of PAD in patients on hemodialysis. J Vasc Surg 2011;53:676e83. Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827e32. Ranke C, Creutzig A, Alexander K. Duplex scanning of peripheral arteries: correlation of the peak velocity ratio with angiographic diameter reduction. Ultrasound Med Biol 1992;18: 433e40. Seiichi H, Yoshimitsu S, Yusuke T, et al. Impact of runoff grade after endovascular therapy for femoropopliteal lesions. J Vasc Surg 2014;59:720e7. Mills JL, Conte MS, Armstrong DG, et al. The society for vascular surgery lower extremity threatened limb classification system: risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg 2014;59:220e34. Mollet NR, Hoye A, Lemos PA, et al. Value of preprocedure multislice computed tomographic coronary angiography to predict the outcome of percutaneous recanalization of chronic total occlusions. Am J Cardiol 2005;95:240e3.
Volume
-, -
2019
11. Norgren L, Hiatt WR, Dormandy JA, et al., TASC II Working Group. Inter-society consensus for the management of peripheral arterial disease (TASC II). Eur J Vasc Surg 2007;33:S1e75. 12. Bunte MC, Cohen DJ, Jaff MR, et al. Long-term clinical and quality of life outcomes after stenting of femoropopliteal artery stenosis: 3-year results from the STROLL study. Catheter Cardiovasc Interv 2018;92:106e14. 13. Rocha-Singh KJ, Beckman JA, Ansel G, et al. Patient-level meta-analysis of 999 claudicants undergoing primary femoropopliteal nitinol stent implantation. Catheter Cardiovasc Interv 2017;89:1250e6. 14. Fujihara M, Higashimori A, Kato Y, et al. Nitinol stent implantation for femoropopliteal disease in patients on hemodialysis: results of the 3-year retrospective multicenter APOLLON study. Heart Vessels 2016;31:1476e83.
Impact of femoropopliteal calcium score 11
15. Lugenbiel I, Grebner M, Zhou Q, et al. Treatment of femoropopliteal lesions with the AngioSculpt scoring balloonresults from the Heidelberg PANTHER registry. Vasa 2018;47:49e55. 16. Foley TR, Cotter RP, Kokkinidis DG, et al. Mid-term outcomes of orbital atherectomy combined with drug-coated balloon angioplasty for treatment of femoropopliteal disease. Catheter Cardiovasc Interv 2017;89:1078e85. 17. Tenenbaum A, Shemesh J, Fisman EZ, et al. Advanced mitral annular calcification is associated with severe coronary calcification on fast dual spiral computed tomography. Invest Radiol 2000;35:193e8. 18. Pohle K, M€affert R, Ropers D, et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation 2001;104: 1927e32.