Research Article | Volume 23 Issue 1 (Jan - Mar, 2024) | Pages 55 - 64
Role of Tibial Acceleration Time in Predicting Limb Salvage in Critical Limb Ischemia
 ,
 ,
 ,
1
Al Hussain Medical city, Karbala, Iraq.
2
AlSader teaching city, Najaf, Iraq.
3
Najaf cardiac center, Najaf, Iraq.
Under a Creative Commons license
Open Access
Received
Dec. 1, 2023
Accepted
Feb. 17, 2024
Published
Feb. 29, 2024
Abstract

Introduction: The role of acceleration time in predicting limb salvage in critical limb ischemia is recently well described in the literature. Ankle-brachial index (ABI) is the traditional test for the diagnosis of lower extremity peripheral artery disease (PAD) and assessment of its severity while Duplex ultrasound (DUS) is used to localize the vascular lesion. ABI has a limited role in diabetic patients because of wall calcification, so it gives inaccurate readings. The place of DUS with waveforms (DWs) analysis to estimate distal perfusion remains poorly known even if many consider it a helpful tool to evaluate PAD severity through distal perfusion. Aim: To assess the role of Tibial Arteries Acceleration Time (TAT) measurement in the assessment of distal perfusion and in predicting healing in patients undergoing revascularization of the foot in critical limb ischemia. Methods: Duplex ultrasound was done for 40 consecutive adult patients with critical limb ischemia. All patients underwent a Doppler study with ultrasound. The study includes a color Doppler map and pulse wave Doppler for all lengths of the lower limbs concentrated on CFA, SFA, POPA, ATA, and PTA, the following measurement are recorded included PSV, EDV, and AT for the distal parts of PTA and ATA. The patients were categorized into different groups according to AT; class I AT = 40-120 ms, class II AT= 121- 180 ms, class III AT = 181 – 225, and class 1V AT more than 226 ms. Catheterization was done for those patients. After angioplasty, a second session of Doppler study of the affected limb was done, recording distal arterial PSV, EDV, and AT. Results: In this study, we found a significant correlation between Acceleration Time improvement and the clinical healing of patients. Limb salvage as complete improvement was achieved in 19 of 40 (47.5%), partial improvement was achieved in 8 of 40 (20%), and no improvement was seen in 13 of 40 (32.5%). Complete and partial improvement was seen in class I AT and class II AT and no improvement in class III AT and IV AT. Conclusions: Tibial Acceleration Time demonstrates a high correlation with clinical improvement in patients with critical limb ischemia and can be used as a prognostic predictor for limb salvage after revascularization.

Keywords
1. Introduction

Critical Limb Ischemia (CLI) is the most severe pattern of peripheral artery disease. It is defined by the presence of chronic ischemic rest pain, ulceration, or gangrene [1]. Limb pain at rest, or the imminent risk of amputation due to the inadequate blood supply, are hallmarks of critical limb ischemia [2]. Chronic limb ischemia (CLI) represents the "last stage" of Peripheral arterial disease (PAD) [3]. Chronic limb ischemia (CLI) is a disease process that develops over the course of months to years and, if left untreated, leads to limb loss due to a lack of blood flow and oxygenation in the limbs, this should not be confused with abrupt blockage of the distal arterial tree. Critical limb ischemia being a severe PAD symptom, these individuals would be placed in the most advanced stages of the Fontaine classification (stages III–IV) or the Rutherford classification (grades 4-6) [4] Table 1.

Although CLI patients may fall anywhere on the PAD spectrum, it is generally agreed that they experience the most severe type of PAD [5], and that the medical community should place the utmost emphasis on techniques to improve surgical and nonsurgical treatment and optimize early detection [6]. The vascular examination, the ankle-brachial index (ABI), and a number of imaging modalities make it easy to diagnose CLI, but it is less obvious how best to treat people who have CLI, whether surgically or therapeutically [7].

Table 1. Shows the descriptive analysis of the demographic information of patients
Fontaine stage Symptoms Rutherford
Severity Category Symptoms
I Asymptomatic 0 0 Asymptomatic
II a Mild claudication I 1 Mild claudication
Iib Moderate-severe
claudication
I 2 Moderate claudication
3 Severe claudication      
III Ischemic rest pain II 4 Rest pain
IV Ulcer or gangrene III 5 Mild lesion
IV IV 6 Ulcer or gangrene

Diabetic complications in the lower extremity are common and diverse. These complications result from complex interactions between diabetic vasculopathy, neuropathy, structural deformity, and decreased immunity [8]. Diabetes mellitus is associated with 4–5 times increased likelihood of critical limb ischemia and lower limb amputation [9]. Lower limb atherosclerosis in patients with diabetes tends to occur more distally. Arteries below the knee are preferentially affected particularly the peroneal and posterior tibial arterie [10]. Atherosclerosis in DM: Classic atherosclerosis has been described in the proximal arteries of diabetic limbs, and it manifests itself as illnesses of the iliac, femoral, and popliteal arteries [11]. Conventional atherosclerotic lesions are found in diabetic patients’ proximal sites at the same frequency as they are in nondiabetic patients’ proximal sites [12]. The blockage is typically multisegmented and has inadequate growth of collateral vessels [13]. Diabetes patients typically experience the onset of atherosclerosis ten years earlier than people who do not have the condition [14].

Diabetic foot disease is one of the most feared complications of DM, refers to a collection of several pathologies, some of which include diabetic neuropathy, peripheral vascular disease, Charcot’s neuroarthropathy, foot ulceration, osteomyelitis, and limb amputation, which is an endpoint that may or may not be prevented. It is estimated that more than a million people with diabetes require limb amputation each year [15]. The lifetime of a person with diabetes developing foot ulceration is reported to be as high as 25% [16]. Ulcer Diabetic neuropathy, peripheral vascular disease, and traumas that occur in the foot are the most significant risk factors for foot ulcers. Even relatively minor injuries, especially when infection complicates the situation, can increase the demand for blood in the foot. If the blood supply is insufficient, this can result in foot ulceration, which can then potentially lead to amputation of the limb [17]. These injuries can eventually result in foot ulceration, which can then be followed by infection of the ulcer, which can ultimately result in foot amputation [18].

The measurement of the Ankle-Brachial Index (ABI) is based on comparing the blood pressure in the lower extremities to the blood pressure in the systolic blood pressure in the arm. The systolic blood pressure in the lower extremities should be equal to both the central systolic blood pressure in the aorta and the systolic blood pressure in the upper extremities under normal conditions, which is the basis for the test. This means that the ratio between the two values should be 1 [19]. After measuring the systolic blood pressure of both the brachial and lower extremity. After that, a ratio is obtained, and the two values are divided by one another [20]. The duplex ultrasound (DUS) method, a technology that allows direct observation of the artery, can both locate the anatomic site of arterial lesions and assess the hemodynamic effects of these lesions by measuring the speed at which blood flows across the affected areas [21]. According to this concept, the ultrasonic waveform. There is a correlation between the changes in the observed velocity of red blood cells and the degree of stenosis [22]. duplex ultrasound, in contrast to testing that is solely physiologic, can distinguish between occlusion and stenosis [23]. A healthy lower limb artery at rest, the arterial flow is pulsatile and laminar, and triphasic which consist of the sharp systolic upstroke, sharp descending systolic down stroke, Negative diastolic component, Positive diastolic rebound, and then Return to baseline [24] Figure 1.

Biphasic waveforms may be considered normal as long as they maintain a sharp systolic upstroke unless there is an abrupt change from triphasic waveforms. Also, the biphasic wave pattern is initially produced as atherosclerosis develops because the elastic and muscular recoil of the artery wall is lost. This causes a lack of forward flow during late diastole [24]. Figure 2.

Normal Doppler morphology in a lower limb artery at rest in a healthy subject is triphasic and comprises

(1) a rapid ascending branch (systolic rise time less than or equal to 70 ms, (2) a rapid descending branch, (3) a negative diastolic component, (4) a positive diastolic rebound, and (5) a return to baseline. The spectral window is clear. VMax systolic corresponds to the maximum systolic velocity and VEnd-diastolic corresponds to the end diastolic velocity, so multiphasic with rapid systolic acceleration, sharp systolic peak, reverse diastolic flow, and low, or absent, end-diastolic forward flow [25].

High-resistant, biphasic waveform depicted with the forward flow in systole and reverse flow (late systole/early diastole), without a forward flow in late diastole

Normal monophasic waveforms following exercise or resulting from increased body temperature. The increased flow demand and decreased vascular resistance associated with exercising muscle, increased body temperature, or focal inflammation results in continuous forward flow with normal peak systolic velocity (PSV) and normal acceleration time [26] Figure 3.

Low-resistant (pulsed Doppler) monophasic waveform

Abnormal Monophasic Waveform: A monophasic waveform has an antegrade systolic flow that is blunted, slow, and persists into diastole. Monophasic arterial waveforms, which are frequently observed downstream from stenoses or in collateral arteries created around the occlusive illness, are always abnormal [27] Figure 4.

Abnormal monophasic flow

Normal Velocity in Lower Limb Arteries: In a control group of 68 patients with normal ABIs (1.08 \(\pm\) 0.09), PSVs in the anterior tibial artery varied from 69 to 71 cm/s. PSVs in the posterior tibial artery varied from 67 to 81 cm/s. In the peroneal artery, PSVs are lower and vary from 48 to 69 cm/s [28].

Acceleration Time (AT): Acceleration time is the time from the start of systole to peak systole. In a healthy subject rapid ascending branch (systolic rise time) less than or equal to 70 ms, Few recent studies, have established the accuracy of AT of distal arteries to diagnose severe peripheral arterial disease. As such, they recommend that PAT be added to the WIFI classification in the evaluation of ischemic limb disease [29] Figure 5.

The (A, B) represent the parameters measured manually on different duplex waveforms: (A) corresponds to a triphasic waveform, (B) is a monophasic attenuated (or “blunted”) waveform, Acceleration time is determined manually from the start of the systolic up-rise to the top of the systolic peak

The term "stenosis" should only be used to describe lesions that cause a change in hemodynamics [5]. If there is constriction following a specific reduction in lumen diameter, the arterial flow that is recorded will be altered. Alterations in the morphology of the Doppler waveforms are examples of what are recognized as direct indicators or signs of stenosis. [30].

Changes in the Doppler waveforms’ shape are recorded upstream and downstream from this point whenever there is a considerable amount of stenosis (which is traditionally defined as a diameter reduction of at least 70%). These shifts in the flow of water upstream and downstream are referred to as indirect signals [31]. If the collaterals are of high quality and efficiency, there may not be any indirect symptoms present. At the point where the artery lumen is reduced, the flow velocity begins to progressively increase, according to the schematic [32].

The degree to which the arterial lumen is reduced is directly correlated to the increase in flow velocity. Indirect indications will only become apparent further downstream when the stenosis is equal to or higher than 70% (decrease in diameter) and when there are no collaterals that are of a high grade or efficiency. When one moves further away from the stenosis, one sees a reduction in the severity of these alterations [33].

Regarding the decreased availability of oxygen further downstream from the stenosis, the downstream symptoms that have been seen include an increase in the systolic rise time (acceleration time) as well as an increase in the positive diastolic component. On the other hand, if the vasodilatation capacities of the region are pushed to their limits, this component might not be there. Last but not least, there is a substantial drop in the maximum systolic velocity. The indications that can be seen upstream include a reduction in systolic velocity as well as a lack of triphasic characteristics [34].

2. Patient and Methods

A. Patients

A prospective study includes 40 adult patients (31 male and 9 female), their age range (32y-78y), mean age 61.52\(\pm\) 9.49 years, after obtaining their informed written consents, who had been referred to AL-Najaf cardiology center in Al - Sadir medical city, Najaf – Iraq with signs and symptoms of critical limb ischemia. (rest pain, ulceration, and gangrene) for angiographic revascularization procedures. The study was carried out between 1/3/2022 -1/10/ 2022.

B. Inclusion Criteria

The patients with any symptoms including claudication, pain at rest, ulceration, and gangrene of more than 2 weeks duration were selected to enroll in our study. These symptoms are considered as critical limb ischemia.

C. Exclusion Criteria

1. Patients who refused any revascularization due to personal issues.

2. Patients with renal impairment and drug allergy who are contraindicated for iodine contrast.

3. Patients with signs and symptoms of infection.

4. Patients who had not been followed by Doppler ultrasound after the re- vascularization or missed clinical follow-up.

D. Methods

All patients undergo a Doppler study with a single ultrasound machine (VOLUSON, S10, GE, AUSTRIA) by the same expert radiologist. The Doppler study includes a color Doppler map and pulse wave Doppler for all lengths of the lower limbs concentrated on CFA, SFA, POPA, ATA, and PTA, the following measurement are recorded including PSV, EDV, and AT for the distal parts of PTA, and ATA (at the level of the ankle); all the data were collected in CD and printed photographs. The patients were categorized into different groups according to Acceleration Tim (AT); class I AT = 40-120 ms, class II AT= 121- 180 ms, class III AT = 181-225, and class 1V more than 225 ms. The procedures of the Doppler study were done in the supine position after resting for 10 minutes to avoid increased diastolic flow due to exercise, using lubricating gel with a high-frequency linear probe. On the same day, all patients enrolled were subjected to interventional procedures of the stenotic segment.

E. Procedure of Angioplasty

All patients undergone catheterization under local anesthesia starting with access selection either antegrade or retrograde approach, followed by diagnostic angiography for proper visualization of the lesion then putting a plan of intervention which include balloon dilatation, only two patients need stenting in addition to balloon dilatation, 38 patients out of 40 were catheterized through femoral arteries, only two patients the catheterization done through the brachial artery. After finishing the catheterization, the patient was admitted to the recovery ward center for 8 hours with dressing at the site of the arterial puncture. Within the first 2-3 hours of the angioplasty, a second session of doppler study of the affected limb was done, recording distal arterial PSV, EDV, and AT. All patients were followed for three months after the procedures, asking them for clinical improvement regarding pain, ulcer healing, and state of gangrene.

F. Statistical Analysis

Data were entered and analyzed using the statistical package for social sciences (SPSS) version 22. All categorical and ordinal variables were determined by their frequencies in each subgroup. The scale variables were defined by mean and standard deviation. Comparison between values of acceleration time of pre- and post- revascularization was done by paired T-test and the p-value of less than 0.05 was considered significant. Correlation between values of acceleration times and improvement of the limb affected was done by Pearson correlation which the p-value of less than 0.05 was considered significant.

3. Result

A total of 40 patients were enrolled in this study, the mean age of the patients was 61.52\(\pm\) 9.49 years. Figure 6 shows the histogram of the patient’s age, the dispersion of age which is demonstrating that the dispersion is higher in the ages of above 61.52. Out of 40 patients, 31 were male and 9 were female and 30 patients had DM, 31 hypertensives, 11 with IHD, 1 patient with IHD and HT, 1 patient with IHD, H, T, and DM and 1 patient had IHD and DM. Out of 40 patients; 19 were nonsmokers, and 25 patients had a family history of PAD Table 2.

Table 2. Shows the descriptive analysis of the demographic information of patients
Variable Subgroups Frequency
Gender Male 31(77.5%)
Female 9(22.5%)
DM Yes 30(75%)
No 10(25%)
Diabetic foot Yes 27(67.5%)
No 13(32.5%)
HT Yes 31(77.5%)
No 9(22.5%)
Other systemic disease No 26(65%)
IHD 11(27.5%)
IHD, HT 1(2.5%)
IHD, HT, DM 1(2.5%)
IHD, DM 1(2.5%)
Hyperlipidemia Yes 17(42.5%)
No 23(57.5%)
Smoking Yes 21(52.5%)
No 19(47.5%)
Family history of PAD Yes 25(62.5%)
No 15(37.5%)

The left limb is affected more with CLI representing 65% while the RT limb represents 35%, 30 patients not complaining of claudication, 25 limbs had ulceration and 4 patients had gangrene, out of the 40 patients 9 of them had a previous vascular intervention Table 3.

Table 3. Demonstrate Clinical Picture of Affected Limb
Limb affected Right 14 (35%)
  Left 26%
Pain at rest Yes 35 (87 .5 %)
No 5 (12.5 %)
Ulceration yes 25 (62.5%)
No 15(37.5%)
Gangrene Yes 4 (10%)
No 36 (90%)
Previous vascular intervention Yes 9 (22.5 %)
No 31(77.5 %)

The mean AT of the anterior tibial artery was 120 .72 ms pre angioplasty while post angioplasty it was 90.52 ms with a significant difference, P = 0.006. PSV of ATA was 17.47 cm/s in pre angioplasty in post angioplasty the velocity was higher 28.72 highly significant, p = 0.0001 while the EDV of ATA was 4.97 pre-angioplasty and 5.25 post-angioplasty with no significant difference = 0.792 Table 4.

Table 4. Doppler Measurement of Pre and Post angioplasty of both ATA and PTA
Variable Pre (mean \(\pm\)SD) Post (mean\(\pm\)SD) p-value
ATA-AT 120.72\(\pm\)14.92 90.52\(\pm\)9.88 0.006
ATA-PSV 17.47\(\pm\)2.60 28.72\(\pm\)3.58 0.000
ATA-EDV 4.97\(\pm\)1.09 5.25\(\pm\)0.93 0.792
PTA-AT 169.17\(\pm\)10.83 115.65\(\pm\)8.88 0.000
PTA-PSV 24.87\(\pm\)2.41 33.25\(\pm\)2.68 0.000
PTA-EDV 8.36\(\pm\)1.10 8.67\(\pm\)1.19 0.766
MEAN-AT 176.72\(\pm\)9.84 118.95\(\pm\)8.47 0.000
MEAN-PSV 21.30\(\pm\)10.90 31.55\(\pm\)2.69 0.000
MEAN-EDV 6.92\(\pm\)0.93 6.85\(\pm\)0.94 0.933

Regarding the PTA, the mean of AT was 169.17 pre-angioplasty and 115.65 post-angioplasty with a highly significant difference, P=0.0001. Also, there is a significant difference in the PSV in pre- and post-angioplasty with P= 0.0001, while there was no significant difference in the EDV, P=0.76. The mean value of AT of both ATA and PTA shows a significant difference, P = 0.0001as well as there was a significant difference in the mean value of PSV of both ATA and PTA between pre- and post-angioplasty, while there was no significant difference in the mean value of EDV of both ATA and PTA. The common site of stenosis was the SFA seen in 21 patients out of 40. Out of 40 patients, 32 showed total occlusion, 7 showed subtotal, and one patient with mild occlusion. During the revascularization based on the site of occlusion (Table 5) two methods of approach were used, in 24 patients (60%) retrograde approach and 16 (40%) antegrade approaches were used. In 10 of 40 (25%) a stent was used and 30 0f 40 (75%) underwent revascularization without any stent.

Table 5. Demonstrate sites of arterial occlusion
Variable Artery Frequency  
Site of Occlusion Left iliac artery 1(2.5%)
SFA 21(52.5)
Tibial (ATA and PTA) 1(2.5%)
Tibioperinoeal, ATA 1(2.5%)
POP 4(10%)
EIA 3(7.5%)
PTA 1(2.5%)
ATA 1(2.5%)
POP and peroneal 1(2.5%)
LEI 1(2.5%)
SFA and PTA 1(2.5%)
SFA, POPATA and
Peroneal
1(2.5%)
CIA 1(2.5%)
SFA, PTA, ATA 1(2.5%)
SFA and ATA 1(2.5%)
Degree of occlusion Total 32 ( 80%) Subtotal 7 (17%) Mild 1 (2.5%)
Approach Retrograde 24(60%)  
Antegrade 24(16%  
Variable Class Frequency  
Pre angioplasty.
AT class
I (40-120 ms) 9(22.5%)
II (121-180 ms) 11(27.5%)
III (181-224 ms) 11(27.5%)
IV (>224 ms ) 9(22.5%)
Post-angioplasty
AT class
I 24(60%)
II 9(22.5%)
III 7(17.5%)

Eleven patients were in class 2, nine of them remain in class 2 and two of them became in class I. Eleven patients were in class III, seven remained in class III and four patients became in class I. Nine patients were in class IV after intervention all became in class III and II. After the revascularization, the improvement of the patients was evaluated based on three categories: no improvement, partial and complete improvement Tables 6,7 and 8.

Table 6. Shows changes in the mean acceleration time after angioplasty
Class Pre-cath Post-cath Number
      I II III IV
I 9 24 9 11 4  
II 11 9 11 11 7 2
III 11 7 4 6 11(1pt no change) 6
IV 9 0   3 6 9
Variable Subgroups Frequency
Improvement Complete 19(47.5%)
Partial 8(20%)
No 13(32.5%)
Table 7. Classification of Pre-Catheterization AT in Correlation with improvement
Class Class I (40-120ms) Class II (121-180ms) Class III (181-224ms) Class IV >225
Pre-catheterization Pre-catheterization Pre-catheterization Pre-catheterization Pre-catheterization Pre-catheterization Pre-catheterization Pre-catheterization  
n 9 24 11 9 11 7 9 0
Complete
improvement
9 (100%) 18 (75%) 9 (81.8%) 1 (11.1%) 2 (18%) 0 (0%) 0 (0%) 0 (0%)
Partial impro 0 4 (16.7%) 1 (9.1%) 4 (44.4 %) 3 (27%) 0 (0%) 2 (22%) 0 (0%)
No 0 2 (8.3%) 1 (9.1%) 4 (44.4%) 5 (45%) 7 (100%) 7 (77%) 0 (0%)
Table 8. One Class Change in Post Angioplasty study
Number One class descend
Class II-class I Class III-Class II Class IV- class III
11 6 6
Improve me N (%)
Compel e 9 (81.8%) 1 (16.6%) 0 (0%)
Parti al 2 (18.1%) 3 (50%) 0 (0%)
No. 0 (0%) 2 (33.3%) 6 (100%)
Comment Beneft because already
low class
Beneft from angioplasty No beneft

Post angioplasty Doppler study showed improvement in tibial flow, the AT changed from class II to class I in eleven patients while in class III to class II in six patients and the change from class IV to class III had been seen in six patients, as shown in the above table. In class II -class I AT,81% of this change showed complete improvement versus 18% showing partial improvement and no patient showed no improvement. In a change from class III-II,16% showed complete improvement 50% showed partial improvement and 33% had non-any improvement. unfortunately, class IV-III changes show no partial or complete improvement Table 9.


Table 9. Two class change post catheterization
Number Two Class descend
  Class III- class I Class IV- class II
  4 3
Improvement Complete Partial no Complete Partial no
Number and percentage 1 25% 2 (50%) 1 (25%) 0 (0%) 2 (66.6%) 1 (33.3%)

Post angioplasty Doppler study showed improvement in tibial flow, the AT changed from class III to class I in four patients while in class IV to class II in three patients, as shown in the above table. In class III -class I,25% of this change showed complete improvement versus 50% showed partial improvement and 25% of patients show no improvement. In a change from class IV-class II,0% showed complete improvement versus 66% showed partial improvement and 33% had non any improvement Table 10.

Table 10. Correlation of patient AT >225 with improvement
Patient number and percentage Pre -catheterization AT >225
  Improvement and percentage
9 comp partial no
Percentage 0 (0%) 2(22.2 %) 7 (78.7%)

A. Illustrated cases

  1. Case 1: 63Y old female presented with CLI and requested for revascularization. Figure 6 and 7 showed the angiography before and after re-vascularization, Rt fem a show multiple total occlusions along tibioperoneal, ATA & peroneal arteries and total occlusion at mid-PTA.

    Angiography before and after re-vascularization. C post catheterization DUS showing with prolonged AT; showing ATA AT= 227 ms. A:Before re-vascularization, B: After re-vascularization, C:Monophasic Flow
    Photographs of the foot before (A) and after (B) re-vascularization
  2. Case 2: 55 y old male presented with CLI and requested for angioplasty Figure 8 and 9.

    Showing pre- catheterization monophasic flow with prolonged AT, figure A showing pre-cath PTA AT= 120 ms, figure C shows that post-cath PTA AT= 80 ms; figure B shows abnormal monophasic pre-cath ATA AT=89 ms; figure D showing abnormal post -cath ATA=70 ms. Mean AT pre cath =104 ms , Mean AT post cath = 75 ms