2020 Volume 84 Issue 11 Pages 1990-1998
Background: Duplex ultrasound scanning (DUS) plays a major role in less invasive diagnosis and assessment of lesion severity in lower extremity peripheral artery disease (PAD). In this study, we evaluated the efficacy of each DUS parameter measured in patients with PAD and established a simple method for PAD evaluation.
Methods and Results: We retrospectively investigated 211 patients (270 limbs) who underwent assessment with both angiography and DUS. During DUS of the common femoral artery (CFA) and popliteal artery, we measured 3 parameters: acceleration time (AcT), peak systolic velocity (PSV), and waveform contour. We compared these parameters with the degree of angiographic stenosis. AcT at the CFA had a significantly higher value in prediction of aortoiliac artery lesions with >50% stenosis (c-index, 0.85; 95% confidence interval (CI), 0.79–0.91), with a sensitivity of 0.82 and specificity of 0.76 at the best cutoff point, compared with PSV and waveform contour (P<0.001, respectively). For femoropopliteal lesions, the ratio of AcT at the popliteal artery to AcT at the CFA is the most predictive parameter, with sensitivity of 0.86 and specificity of 0.92 at the best cutoff point (c-index, 0.93; 95% CI, 0.90–0.97), compared with others (P<0.001, respectively).
Conclusions: For the assessment of PAD with DUS, AcT and AcT ratio are simple and reliable parameters for evaluating aortoiliac and femoropopliteal artery disease.
The number of patients with lower extremity peripheral artery disease (PAD) is increasing worldwide.1 Accurate diagnosis and assessment provide opportunities for treatment to relieve symptoms and improve quality of life in patients with symptomatic PAD. Therefore, clinical examination is important in the management of PAD.
Duplex ultrasound scanning (DUS) plays a major role in diagnosing and assessing the severity of PAD.2–4 Although noninvasive and serial examinations in patients with PAD can be performed using DUS, it is sometimes difficult to assess lesions directly in deep vessels or vessels with calcified walls. Furthermore, compared with other modalities such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA), DUS requires a longer examination time and the quality of the examination is examiner dependent.
In the assessment of patients with PAD using DUS, measurement of several parameters are recommended,4 but the relationship between those parameters and disease severity has not been fully evaluated and there is no consensus on a standard DUS method of screening for PAD. The purpose of this study was to evaluate the efficacy of parameters measured using DUS in patients with or suspected of having PAD and to establish a standard method for PAD evaluation.
A flow chart of the study population is presented in Figure 1. We investigated 281 patients who underwent assessment of lower extremity arteries with both angiography and DUS between January 2015 and December 2017 at the National Cerebral and Cardiovascular Center in Suita, Japan. In this study, patients were excluded if they had significant stenotic or occlusive lesions of the common femoral artery (CFA) or popliteal artery (PopA) or a history of a surgical procedure at the CFA or PopA. These patients were excluded because duplex flow patterns at these points could not be acquired or might be strongly affected by the lesions or prior procedures. After excluding 55 patients with CFA or PopA lesions and 15 patients with prior surgery, there were 162 aortoiliac lesions and 191 femoropopliteal lesions for which data from both imaging modalities were available in the remaining 211 patients. This study was approved by the National Cerebral and Cardiovascular Center Institutional Review Board for Clinical Research (M30-169).
Study enrollment flow chart. CFA, common femoral artery; DUS, duplex ultrasound scanning; PopA, popliteal artery.
DUS examinations were performed using Aplio 500, MX, or XG systems (Canon Medical Systems Co., Otawara, Japan) with a 5–10-MHz linear probe by sonographers with sufficient experience and expertise in performing ultrasound tests in patients with vascular disease. Sonographers were blinded to patients’ other data. Parameters in flow pattern analysis of the CFA and PopA were peak systolic velocity (PSV), acceleration time (AcT), and spectral Doppler waveform contour. Representative images illustrating these parameters are shown in Figure 2. PSV was defined as the velocity at peak flow during systole. AcT was defined as the time from systolic acceleration to peak flow. Waveform contour patterns were divided into 4 categories: triphasic, biphasic, monophasic, and continuous. A continuous pattern was defined as a monophasic pattern with continuous forward flow during diastole.
Assessment of lower extremity arterial flow and lesions. (Left) Parameters for flow analysis with duplex ultrasound scanning: peak systolic velocity, acceleration time, and waveform contour. (Middle) Arterial supply of the lower extremities. White circles indicate sites of assessment with duplex ultrasound scanning. (Right) Representative images of lower extremity angiography and quantitative analysis of % vessel diameter stenosis.
Lesion severity was evaluated using quantitative angiography of the lower extremity, which is recommended by the consensus statement regarding assessment of lower limb intervention outcomes reported by Diehm et al.5 The degree of stenosis was expressed as % diameter stenosis (%DS), which was calculated using the validated QAngio XA image processing software (Medis, Leiden, The Netherlands) by persons who were blinded to the DUS assessment results. Greater than 50% stenosis on angiography was considered significant. A representative case is shown in Figure 2.
Comparison of DUS Analysis Parameters and Angiographic Lesion SeverityFirst, we compared 3 parameters measured for the CFA using DUS with the angiographic %DS in aortoiliac artery segments. Second, we compared parameters measured for the PopA using DUS to the angiographic %DS in femoropopliteal segments. In the assessment of the femoropopliteal artery, to eliminate the influence of proximal artery stenosis, we adopted 2 additional parameters, calculated as follows:
PSV ratio (PSVR) = PSV at PopA / PSV at CFA
AcT ratio (AcTR) = AcT at PopA / AcT at CFA
Subgroup AssessmentVarious factors can affect the DUS parameters, one of which is aortic valve stenosis (AS). We compared the predictive ability of the DUS parameters between patients with and without AS. We also investigated the influence of endovascular treatment (EVT) on DUS parameters. Furthermore, to assess the effect of proximal lesions on femoropopliteal lesions, we evaluated predictive ability in patients with and without significant aortoiliac lesions separately.
Statistical AnalysisContinuous variables are expressed as mean±standard deviation. Categorical variables are reported as numbers and percentages. Correlations between DUS parameters and lesion severity based on angiography were examined using Pearson correlation coefficients. The predictive ability and optimal cutoff value for each DUS parameter in predicting significant stenosis were calculated based on receiver-operating characteristic (ROC) analysis. The optimal cutoff value was determined as the point at which the sum of sensitivity and specificity was the highest. For all tests, a P value <0.05 was considered as statistically significant. Correction for multiple comparisons was made using the Bonferroni method as needed. Data were analyzed with the R software package, version 3.0.2 (http://www.r-project.org/).
The clinical characteristics of the study patients (mean age, 72.1±10.5 years; male, 77.3%) are shown in Table 1. Of 211 patients, 129 (61.1%) had Rutherford category ≤3 arteriosclerosis obliterans and 74 (35.1%) had Rutherford category ≥4 critical limb ischemia. DUS and angiographic findings of 270 lower extremities for which we were able to obtain both types of data are shown in Table 2. Significant stenosis was observed in 58.6% (95/162) of aortoiliac artery segments and 61.7% (118/191) of femoropopliteal artery segments.
| Age (years) | 72.1±10.5 |
| Male | 163 (77.3%) |
| Comorbidity | |
| Hypertension | 170 (80.6%) |
| Diabetes mellitus | 91 (43.1%) |
| Dyslipidemia | 128 (60.7%) |
| CAD | 68 (32.2%) |
| Cerebrovascular disease | 55 (26.1%) |
| ESRD on hemodialysis | 25 (11.9%) |
| Smoking status | |
| Current smoker | 72 (34.1%) |
| Previous smoker | 111 (52.6%) |
| Lower extremity disease | |
| ASO (Rutherford category ≤3) | 129 (61.1%) |
| CLI (Rutherford category ≥4) | 74 (35.1%) |
| ALI | 5 (2.4%) |
| Other | 3 (1.4%) |
Numeric values are expressed as n (%) or mean±standard deviation. ALI, acute limb ischemia; ASO, arteriosclerosis obliterans; CAD, coronary artery disease; CLI, critical limb ischemia; ESRD, endstage renal disease.
| Laterality | |
| Right | 127 |
| Left | 143 |
| Duplex findings | |
| Parameters for the common femoral artery | 270 |
| Peak systolic velocity (cm/s) | 71.3±31.0 |
| Acceleration time (ms) | 103.0±43.7 |
| Waveform contour | |
| Triphasic | 27 (10.2%) |
| Biphasic | 98 (37.0%) |
| Monophasic | 91 (34.3%) |
| Continuous | 49 (18.5%) |
| Parameters for the popliteal artery | 191 |
| Peak systolic velocity (cm/s) | 32.5±21.4 |
| Acceleration time (ms) | 135.0±50.5 |
| Waveform contour | |
| Triphasic | 17 (7.9%) |
| Biphasic | 48 (19.6%) |
| Monophasic | 77 (31.4%) |
| Continuous | 103 (42.0%) |
| Angiographic findings | |
| % aortoiliac artery diameter stenosis | 162 |
| 0–50% | 67 (41.4%) |
| 51–75% | 41 (25.3%) |
| 76–100% | 54 (33.3%) |
| % femoropopliteal artery diameter stenosis | 191 |
| 0–50% | 73 (38.2%) |
| 51–75% | 27 (14.1%) |
| 76–100% | 91 (47.6%) |
Numeric values are expressed as n (%) or mean±standard deviation.
Scatterplots of angiographic aortoiliac arterial stenosis and DUS parameters of the CFA and ROC curves for predicting angiographic binary stenosis are shown in Figure 3. Predictive ability results are shown in the Supplementary Table. Among the 3 DUS parameters of the CFA, AcT had a significantly higher predictive value (c-index, 0.85; 95% confidence interval (CI), 0.79–0.91), with a sensitivity of 0.82 and specificity of 0.76 at the best cutoff point, compared with PSV (c-index, 0.75; 95% CI, 0.68–0.83; P<0.001) and waveform contour (c-index, 0.77; 95% CI, 0.71–0.84; P<0.001).
Relationships between parameters at the common iliac artery and % diameter stenosis of aortoiliac artery lesions and receiver-operating characteristic curves for duplex ultrasound scanning parameters. (A) Peak systolic velocity, (B) acceleration time, and (C) waveform contour. CFA, common femoral artery.
For clinical use, we determined cutoff values in round numbers for predicting aortoiliac lesions. Although AcT for the CFA had the highest performance, the discriminative ability of the c-index was moderate. Therefore, we adopted 2 values of AcT for the CFA: 85 ms for negative prediction and 120 ms for positive prediction. The former value had a sensitivity of 0.90 (95% CI, 0.82–0.95) and the latter value had a specificity of 0.91 (95% CI, 0.82–0.97).
Assessment of Femoropopliteal Artery LesionsScatterplots of angiographic stenosis in the femoropopliteal artery and DUS parameters for the PopA and ROC curves are presented in Figure 4. During the assessment of femoropopliteal artery lesions, PSVR and AcTR were also assessed as DUS parameters. Their predictive values are shown in the Supplementary Table. In this assessment, AcTR had a significantly higher c-index value (0.93; 95% CI, 0.90–0.97), with a sensitivity of 0.86 and specificity of 0.92 at the best cutoff point, compared with AcT (c-index, 0.79; 95% CI, 0.72−0.87, P<0.001), PSV (c-index, 0.69; 95% CI, 0.61−0.76, P<0.001), PSV ratio (c-index, 0.72; 95% CI, 0.65−0.80, P<0.001), and waveform contour (c-index, 0.72; 95% CI, 0.65−0.79, P<0.001).
Relationships between parameters of the popliteal artery and % diameter stenosis of femoropopliteal artery lesions and receiver-operating characteristic curves for duplex ultrasound scanning parameters. (A) Peak systolic velocity. (B) Ratio of peak systolic velocity at the femoropopliteal artery to peak systolic velocity at the common femoral artery. (C) Acceleration time. (D) Ratio of acceleration time at the femoropopliteal artery to acceleration time at the common femoral artery. (E) Waveform contour. PopA, popliteal artery.
For screening femoropopliteal lesions, we adopted a single number of 1.25 as the cutoff value, which had a sensitivity of 0.88 (95% CI, 0.81–0.93) and a specificity of 0.90 (95% CI, 0.81–0.96). A proposed assessment chart for aortoiliac arteries and femoropopliteal arteries is shown in Figure 5.
Chart for screening of aortoiliac and femoropopliteal artery lesions. CFA, common femoral artery; PopA, popliteal artery.
The distribution of AS based on echocardiography was as follows: no AS (PSV <2 m/s) in 173 patients; mild AS (2 m/s ≤ PSV < 3 m/s) in 21 patients; moderate AS (3 m/s ≤ PSV < 4 m/s) in 5 patients; severe AS (4 m/s ≤ PSV) in 1 patient; and missing echocardiography data in 11 patients. ROC curves in patients with AS (PSV ≥ 2 m/s) and without AS (PSV < 2 m/s) for AcT in the CFA and AcTR were not significantly different (Figure 6A).
Subgroup assessments of acceleration time (AcT) and acceleration time ratio (AcTR). (A) Receiver-operating characteristic curves in patients with and without aortic valve stenosis. (Left) AcT in the common femoral artery (CFA) for assessment of an aortoiliac artery segment. (Right) AcTR for assessment of a femoropopliteal artery segment. (B) Assessments of aortoiliac segments in patients who underwent endovascular treatment (EVT). (Left) Aortoiliac artery diameter stenosis before and after EVT. (Middle) AcT in the CFA before and after EVT. (Right) Scatterplots for reduction in % aortoiliac artery diameter stenosis and reduction in AcT for the CFA. (C) Assessment of femoropopliteal segments in patients who underwent EVT. (Left) % femoropopliteal artery diameter stenosis before and after EVT. (Middle) AcTR before and after EVT. (Right) Scatterplots for reduction in % femoropopliteal artery diameter stenosis and reduction of AcTR. (D) Receiver-operating characteristic curves for assessment of femoropopliteal segments in patients with and without aortoiliac lesions. (Left) Patients without aortoiliac artery lesions. (Right) Patients with aortoiliac artery lesions. AS, aortic valve stenosis; CFA, common femoral artery; EVT, endovascular treatment; PopA, popliteal artery.
Among the study lesions, 106 aortoiliac and 70 femoropopliteal lesions were treated with EVT just after lower extremity angiography. %DS and DUS parameters (AcT at CFA and AcTR) before and after EVT are shown in Figure 6B,C, which also depicts scatterplots between reductions in the %DS and DUS parameters. Angiographic changes after EVT were significantly positively correlated with changes in DUS parameters in aortoiliac segments (r=0.41; 95% CI, 0.23–0.55; P<0.001) and femoropopliteal segments (r=0.27; 95% CI, 0.04–0.48; P=0.02).
Finally, we evaluated femoropopliteal arterial lesions in patients with and without aortoiliac lesions (Figure 6D). Regarding the predictive ability of AcT vs. AcTR, in patients without aortoiliac artery stenosis, there was no significant difference between the c-index for AcT and AcTR (0.96; 95% CI, 0.89–1.00 vs. 0.94; 95% CI, 0.86–1.00; P=0.46). In patients with aortoiliac artery stenosis, AcTR had a significantly higher c-index than AcT (0.90; 95% CI, 0.81–0.99 vs. 0.70; 95% CI, 0.54–0.86; P=0.003).
Although DUS is an excellent, easy-to-use modality for evaluating lesions of the lower extremities, it is less sensitive for stenosis identification than CTA or MRA,6–8 which means that DUS could overlook significant stenosis more frequently than other modalities. Therefore, it is desirable to improve the diagnostic ability of DUS. In this study, we found that AcT is a superior parameter for predicting significant stenosis in aortoiliac and femoropopliteal arteries compared with PSV and waveform contour. For evaluating femoropopliteal lesions, the predictability of AcT in the PopA could be affected by the presence of a proximal stenotic lesion, whereas AcTR between the CFA and PopA allowed us to evaluate femoropopliteal artery stenosis more accurately, eliminating the influence of a proximal lesion. Although DUS has been highly recommended in the clinical management of lower extremity PAD,4 some conditions, such as severe calcification, make it difficult to evaluate lesion severity accurately. The occurrence of stenosis in multiple regions has also been reported to decrease the sensitivity of DUS assessment.9 In this study, we established a simple assessment chart using DUS with AcT and AcTR cutoff points for positive and negative prediction of arterial lesions. This method requires examiners to scan only 2 points (CFA and PopA) and not all of the lower extremity arteries. As both the CFA and PopA run near the body surface, it is generally easier to measure blood flow at these points than in arteries running deep in the pelvis and thigh. These aspects of our method could contribute to shorter examination time and higher diagnostic accuracy.
AcT for the Assessment of Peripheral Arterial Blood FlowThe American Society of Echocardiography guidelines provide diagnostic criteria for lower extremity PAD based on waveform contour, PSV ratio, and presence of spectral broadening.4 Measurement of AcT corresponds to a quantitative assessment of spectral broadening. Although studies have shown the effectiveness of AcT for assessing peripheral arteries, including the carotid and renal arteries,10,11 it has not been fully investigated for DUS assessment of arteries in the lower extremities. In our study, AcT had the most favorable predictive ability, and a possible reason would be that PSV and waveform contour can be substantially affected by the Doppler angle. Although blood flow in the CFA and PopA can be evaluated with DUS relatively easily, the horizontal course of these arteries can make it difficult to match the direction of the Doppler. The discordance between the direction of the artery and the Doppler leads to inaccurate evaluation of PSV and the waveform contour,4 whereas AcT is not substantially affected by the Doppler angle. Waveform analysis is easy to apply because it is not necessary to measure parameters. The waveform can be recognized by visual inspection of the duplex flow shape; however, it is sometimes difficult to distinguish one pattern from another because subsequent backward flow or second forward flow can often be too small to be distinguished between patterns. Therefore, compared with PSV and waveform contour, AcT seems to be a more objective and reliable parameter for evaluating duplex flow. In this study, we also investigated the influence of AS on the predictive ability of these parameters, and we that it did not seem to affect our method. However, as the number of patients with AS in this study was small, further studies are required.
Assessment of Aortoiliac and Femoropopliteal LesionsSeveral methods for assessment of aortoiliac lesions have been reported.12–14 Compared with them, assessment of AcT in the CFA is simple and sufficiently predictive. On the other hand, methods to screen for femoropopliteal lesions using duplex flow patterns have not been fully reported, which could be partly because femoropopliteal lesions can be affected by the presence of a proximal flow-limiting lesion. One solution for eliminating the influence of proximal lesions is to calculate the ratio between the proximal and distal parameters in the target segment. Representative examples included the ankle-brachial pressure index and PSVR, which are recommended as screening for PAD in the guideline mentioned before.4 In our study, AcTR was more favorable for screening femoropopliteal lesions than PSVR. It has become even more important to assess femoropopliteal lesions because of the recent development of various EVT devices.15–18 We evaluated the influence of revascularization with EVT on DUS parameters. The reduction in angiographic stenosis was significantly related to changes in AcT and AcTR, which suggested that these parameters could be used for efficient evaluation after EVT.
Study LimitationsFirst, this was a single-center, retrospective study. Second, this method cannot be applied in patients with CFA or PopA lesions because such lesions would preclude accurate evaluation of flow patterns. In addition, in patients with a lesion just proximal to the CFA or PopA, which can affect the flow pattern at the point of DUS assessment, examiners need to consider the influence of flow acceleration secondary to the lesion. It also remains unknown whether these parameters can be applied to the assessment of below-the-knee arteries. Results might differ because below-the-knee arteries are smaller than above-the-knee arteries and can develop rich collateral networks. These factors can affect flow patterns in distal peripheral arteries. As this study was not planned to evaluate such situations, further studies are required. Third, in this study we used %DS to assess lesion severity with angiography. Lesion severity could have been underestimated in cases of eccentric stenosis. Fourth, arterial flow can be affected by arterial stiffness. In general, patients with elevated arterial stiffness have low AcT.19 The cutoff value for AcT in the CFA defined in this study could be inappropriate in patients with high arterial stiffness (e.g., patients on hemodialysis) or low arterial stiffness (e.g., young patients). However, predictions of lesions in the femoropopliteal artery were evaluated based on relative, not absolute AcT values, which would not be affected by arterial stiffness. Therefore, in aortoiliac artery assessment, additional evaluation at a proximal point (such as the abdominal aorta) could help to reduce the influence of arterial stiffness and improve the predictive value. Considering these perspectives, it may be possible to evaluate lower extremity flow more accurately.
AcT in the CFA and the ratio between AcT in the CFA and at PopA are simple and reliable parameters for evaluating lesions in aortoiliac and femoropopliteal arteries in patients with PAD.
The authors gratefully acknowledge Yutaka Demura and Fujiko Nakamoto of the Vascular Laboratory at the National Cerebral and Cardiovascular Center.
The deidentified participant data will not be shared because the dataset contains sensitive and potentially identifying patient information.
The authors received no specific funding for this work.
S. Yasuda is a member of Circulation Journal ’ Editorial Team. The others report no relationships that could be construed as a conflict of interest.
This study was approved by the National Cerebral and Cardiovascular Center Institutional Review Board for Clinical Research (reference no. M30-169).
Please find supplementary file(s);
http://dx.doi.org/10.1253/circj.CJ-20-0427
