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ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 1  |  Page : 44-49

To evaluate the role of two-dimensional perfusion angiography as a predictor in wound healing outcomes in patients of critical limb ischemia


Department of Vascular and Endovascular Surgery, Institute of Vascular and Endovascular Sciences, Sir Ganga Ram Hospital, New Delhi, India

Date of Submission10-Sep-2019
Date of Acceptance21-Oct-2019
Date of Web Publication16-Mar-2020

Correspondence Address:
Dr. Ganesh Kumar Marada
Department of Vascular and Endovascular Surgery, Institute of Vascular and Endovascular Sciences, Sir Ganga Ram Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_62_19

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  Abstract 


Aim: The study was aimed to evaluate the role of two-dimensional (2D) perfusion angiography (PA) as a predictor in wound healing outcomes in patients of critical limb ischemia. Subject and Methods: It was a pilot study conducted over a period of 16 months after taking informed consent and institutional ethical clearance. The study included 40 patients of which 8 were lost to follow-up, hence the prospective data of 32 patients was collected and analyzed. Patients were subjected to endovascular intervention and 2D perfusion software was applied to the digital subtraction angiography images and its parameters were assessed. Transcutaneous oxygen tension (TcPO2) was measured pre- and postintervention and patients were closely followed up for the time taken for wound healing. Results: The median age was 62 years ranging from 30 to 85 years. Most common comorbidity was diabetes (21/32 patients). The mean Ankle–Brachial Index in the study was 0.55 and mean TcPO2 at admission was 26.5 mm of Hg. Most common involved angiosome was percutaneous transluminal angioplasty angiosome. Fifteen patients underwent direct, 9 indirect, and remaining 8 patients underwent revascularization in both territories. The mean percent improvement in TcPO2 was higher in indirect when compared to direct revascularization but it was not statistically significant. The time taken in wound healing was significantly higher in diabetics when compared to nondiabetics with P = 0.03. Most reliable parameter in 2D PA was area under the curve (AUC) which correlated with increase in volume of tissue perfusion. Patients with >100% improvement in AUC showed significantly better wound healing rates when compared to patients with <100% improvement (P = 0.04). Conclusion: This proved 2D PA as a reliable method for immediate assessment of improvement in microcirculation and as a predictor for wound healing. It can also be used as a real-time tool in optimizing the need and determining the end point for revascularization.

Keywords: Area under the curve, critical limb ischemia, transcutaneous oxygen tension, two-dimensional perfusion angiography, wound healing


How to cite this article:
Marada GK, Bedi VS, Agarwal S, Yadav A, Satwik A, Agarwal D, Srivastava A. To evaluate the role of two-dimensional perfusion angiography as a predictor in wound healing outcomes in patients of critical limb ischemia. Indian J Vasc Endovasc Surg 2020;7:44-9

How to cite this URL:
Marada GK, Bedi VS, Agarwal S, Yadav A, Satwik A, Agarwal D, Srivastava A. To evaluate the role of two-dimensional perfusion angiography as a predictor in wound healing outcomes in patients of critical limb ischemia. Indian J Vasc Endovasc Surg [serial online] 2020 [cited 2020 Apr 5];7:44-9. Available from: http://www.indjvascsurg.org/text.asp?2020/7/1/44/280679




  Introduction Top


Critical limb ischemia (CLI), the most severe clinical manifestation of peripheral artery disease, is characterized by ischemic rest pain or the presence of ischemic tissue loss with or without gangrene. Local perfusion problems in the foot, like a nonhealing ulcer, are often caused by macrovascular obstructions, sometimes in combination with disease at the level of the microcirculation of the foot. The latter is especially true for arterial diabetic foot disease.[1] In patients of diabetes and chronic kidney disease (CKD), calcification of the arterial wall, complete obstruction of the artery, and the presence of collateral circulation cause problems in Ankle–Brachial Index (ABI) determinations that exclude up to 30% of patients treated with endovascular intervention from the evaluation.[2]

Microcirculation is the most relevant indicator of skin health, and therefore, wound healing and an improvement of the oxygen pressure. Transcutaneous oxygen tension (TcPO2) is a good indicator for tissue perfusion; however, it cannot be done in cath lab setting. As there is a direct relation between flow through the capillaries and the oxygenation of the tissue, a direct and immediate measurement of flow through the capillaries, pre- and post-intervention in vascular cath lab, with perfusion angiography (PA) might be a good parameter for improved foot perfusion and tissue oxygenation. PA, which is a representation of the time-density curve of contrast volume flow in the foot, is a new imaging technique, using data from plain old digital subtraction angiography (DSA), for assessment of foot perfusion.[3]

In this study, we have assessed the tissue perfusion by two-dimensional (2D) PA (imaging modality) and its role in wound healing and compare the results with Tcpo2 levels before and after revascularization.


  Subject and Methods Top


Study description

The study was conducted in the Institute of Vascular and Endovascular Sciences, Sir Ganga Ram Hospital, New Delhi, India, on patients of chronic limb-threatening ischemia (CTLI).

Study type

This was a pilot study in which the data of the patients were prospectively collected.

Study design

The study included 40 patients of CTLI, of which 8 were lost to follow-up, hence the prospective data of 32 patients were collected and analyzed.

Inclusion criteria

  1. Patients who are >18 years of age
  2. Patients willing to participate and provide informed consent
  3. Patients having appropriate femoral arterial access
  4. Patients present with a Rutherford classification of 4–6.


Exclusion criteria

  1. Patient is unwilling or unable to comply with the protocol including all follow-up visits
  2. CLI due to acute arterial occlusion
  3. Patients with a history of or known reaction or sensitivity to contrast agent or any other condition that precludes an endovascular intervention and DSA
  4. Female participant of childbearing potential who is pregnant
  5. Participant life expectancy <3 months
  6. CKD patients not requiring dialysis.


Methodology

All patients with CTLI were subjected to endovascular intervention after obtaining informed consent and institutional ethical clearance. Postadmission history was obtained and examination was done. ABI, TcPO2, and all baseline investigations were done and recorded. Patients were subjected to endovascular intervention and 2D perfusion software was applied to the DSA images and its parameters were assessed. TcPO2 was measured postintervention at 2 weeks, and patients were closely followed up for the time taken for wound healing at 2, 4, and 12 weeks.

Technique

2D perfusion imaging PA which has been widely used neuroradiological interventions, also has major implications in peripheral vascular interventions. It utilizes high-resolution X-ray images to assess physiological changes in the parenchymal perfusion level. Acquisitions are made on the Philips Allura Xper FD20 system (Philips Healthcare, Best, The Netherlands).

There was no additional exposure to radiation or contrast agents. One run can be used to construct the perfusion image. 2D perfusion has a 3 frames/second (f/s) acquisition protocol, analyzing 30-s acquisition capturing 90 frames. The software captures contrast enhancement changes over time per pixel of the DSA image.

During the acquisition, a total of 9 mL radiographic contrast (Visipaque, 320 mg I/mL) at 3 mL/s is injected via a 5-Fr catheter. Within seconds, the 2D perfusion image is reconstructed and visualized on the workstation. Immobilization of the leg is crucial when performing perfusion runs, as well as standardization of the injection protocol.

With 2D perfusion, the flow of contrast through peripheral arteries and tissue enhancement can be visualized in a single color image, where different colors represent the corresponding blood perfusion levels. It also allows comparison of pre- and post-procedural perfusion levels. Within a user-defined region of interest, perfusion parameters can be appreciated. The reconstructed images can be evaluated for arrival time, time to peak, wash-in rate, width, area under the curve (AUC), and mean transit time. An operator-defined, freehand region of interest can be selected to determine a time-to-density curve, which is typically done at the level of the ulcer or wound.


  Results Top


[Figure 1] shows two-dimensional perfusion image of posterior tibial artery angiosome with healed wound in [Figure 2] while, [Figure 3] and [Figure 4] shows two-dimensional perfusion image with healed wound in anterior tibial artery angiosome territory respectively. The median age of the patients included in the study was 62 years (Range: 30–85). Out of 32 patients included in the study, there were 27 male (84%) and 5 female (16%), with a male:female ratio of 5.4:1. Most common comorbid condition in the study was diabetes mellitus which was seen in 21 patients.
Figure 1: Two-dimensional perfusion angiography with area under the curve of percutaneous transluminal angioplasty in posterior tibial artery angiosome

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Figure 2: Healed wound in percutaneous transluminal angioplasty in posterior tibial artery angiosome territory

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Figure 3: Two-dimensional perfusion image with area under the curve of anterior tibial artery angiosome

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Figure 4: Healed wound over anterior tibial artery angiosome territory

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Angiosome concept was utilized in categorizing the location of the wound in the foot as in [Figure 5] and type of revascularization as in [Figure 6], i.e., direct versus indirect revascularization was assessed. Most commonly involved angiosome was percutaneous transluminal angioplasty (PTA) territory and majority of the patients underwent direct revascularization. The primary goal was to improve perfusion at the site of the wound and revascularization of all the three below-knee arteries was attempted. Hence, good number of patients underwent indirect revascularization and rest underwent revascularization in both territories.
Figure 5: Location of gangrene based on angiosome distribution

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Figure 6: The type of vascularization compared in both diabetics and nondiabetics

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2D perfusion software was applied to the pre- and post-DSA data and time-density curve and perfusion parameters were assessed. Among all the 2D perfusion parameters, AUC was the most reliable parameter in indicating the tissue perfusion at the level of region of interest, i.e., at the location of wound. The value of the AUC varied among the patients, hence percentage improvement of AUC was calculated and a cutoff value of 100 was set for percent improvement in AUC.

The increase in tissue perfusion was measured at 2 weeks after angioplasty and the percentage improvement in tcPO2 levels was higher in non-diabetics when compared to diabetics as shown in [Figure 7].
Figure 7: Percentage improvement in transcutaneous oxygen tension levels between diabetics and nondiabetics

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Patients were categorized into two groups: Group 1 included <100% improvement in AUC and Group 2 included patients with more than 100% improvement in AUC. Group 1 had 15 and Group 2 had 16 patients, their percentage improvement of TcPO2 and time taken for wound healing was compared and analyzed. The mean percentage improvement of TcPO2 was 116.7% in Group 2 when compared to Group 1 had 97.04%, but the difference was not statistically significant as seen in [Figure 8]. The time taken for wound healing was less in Group 2 (1.9 months) when compared to Group 2 (2.8 months) as seen in [Figure 9]. The difference was statistically significant with P = 0.04. The mean percentage improvement of AUC was also compared between the diabetic and nondiabetics which showed better improvement in nondiabetic patients, but the difference was not statistically significant.
Figure 8: The mean percent improvement of transcutaneous oxygen tension in Group 1 (≤100%) and Group 2 (>100%) of area under the curve

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Figure 9: Mean time taken for wound healing between Group 1 and Group 2 area under the curve

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  Discussion Top


CTLI [4] is the new terminology to include a wide spectrum and heterogeneous group of patients with varying degrees of ischemia that often delay wound healing and increase amputation risk.

The old term, CLI, did not include full spectrum of patients and excluded diabetes due to confounding factors such as neuropathy and susceptibility of infection. The wound healing into diabetic foot patients usually effected by both macrovascular and microvascular obstructions. Wound healing depended upon the local tissue perfusion, which was assessed by TcPO2 and 2D PA in our study.

The local tissue perfusion of the foot which is the important factor for wound healing correlates with the microcirculation of the foot. The microcirculation of the foot can be assessed using TcPO2 and was measured in all the patients pre- and postrevascularization.[5] The mean percentage improvement of improvement was higher in nondiabetic groups when compared to diabetic groups.

Angiosome concept was utilized in categorizing the location of the wound in the foot and type of vascularization, i.e., direct versus indirect revascularization was assessed.[6]

A study published by Spillerova et al. concluded that direct endovascular revascularization had better wound healing rates when compared to indirect revascularization.[7] On the contrary, we found that diabetics, who underwent indirect revascularization in our study had faster wound healing rates than who underwent direct revascularization, but it was not statistically significant (P = 0.11).

The wound healing rate was faster in nondiabetics when compared to diabetics in our study which was statistically significant with P = 0.03, and this is also correlated with more improvement in TcPO2 levels in nondiabetics when compared to diabetics which is a one of the predictors for wound healing.

Kabra et al.[8] also reported that, although direct revascularization helped in faster healing rates, the difference in the limb salvages rates was not statistically significant between direct and indirect groups suggesting that indirect revascularization should be attempted whenever direct revascularization was not possible. In similarity, our study also suggested that in diabetics, indirect revascularization was noninferior when compared to direct revascularization. However, we need larger subsets of patients to assess these findings.

The application of 2D PA principles is relatively new for assessing foot microcirculation in patients with ischemic foot. TcPO2 provided useful information on microcirculation of foot, but it was not feasible to assess TcPO2 immediately after intervention as many studies suggested that TcPO2 levels usually increase 2–3 weeks after intervention. In a study done in 2005 by Caselli et al. showed significant increase of TcPO2 levels immediately after successful angioplasty in the successful revascularization group, the percentage of successful revascularization patients with a TcPO2 ≥30 mmHg was 38.5% 1 week after PTA, while it increased to 75% 3 weeks later over the baseline level); P < 0.001].[9]

Therefore, assessing the microcirculation of foot was required to establish the completeness of the endovascular intervention. 2D PA was helpful, as it was able to quantify the amount of perfusion of the ischemic tissues postrevascularization.

Among the multiple parameters derived from the 2D perfusion methods, the most reliable parameter was found to be AUC. Reeker's et al. reported that the mean percentage improvement of AUC represented the increase in volume flow of the contrast.[10] Increased volume flow of contrast postintervention represented successful revascularization, but, in their study, they did not correlate this percentage improvement of AUC with rates of wound healing.

In our study, AUC which is the most reliable parameter for microcirculation of foot was measured, and percentage improvement in AUC was calculated. Our study showed that ≤100% increase in AUC (Group 1) had slower rates of wound healing when compared to patients with >100% increase in AUC (Group 2) which was statistically significant with P = 0.04.

The percentage improvement of TcPO2 between the two groups was compared, although it was higher in Group 2 than Group 1, the difference between the two was not statistically significant.

Our study suggests that 2D PA can be a reliable tool in immediate intraprocedural assessment of level of improvement of microcirculation in the cath lab. It can helpful assessing the need for more intervention required for maintaining optimal tissue perfusion for wound healing.

Therefore, the percentage improvement in AUC can be used as new end point for revascularization, but for defining the cutoff limit of revascularization, we still need studies with larger subset of patients and close follow-up.


  Conclusion Top


Microcirculation in the foot is as much important as macrocirculation for wound healing in diabetics.[11] The predictors for wound healing in an ischemic wound at the level of microcirculation are TcPO2 and 2D PA, but TcPO2 usually is reliable only after 2–3 weeks of endovascular interventional procedure.

2D PA is more reliable method in the immediate assessment of improvement in microcirculation in the cath lab during intervention and as a predictor for wound healing.

It can be used as a real-time tool in optimizing the need for revascularization and determining the end point for revascularization.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
de Graaff JC, Ubbink DT, van der Spruit JA, Lagarde SM, Jacobs MJ. Influence of peripheral arterial disease on capillary pressure in the foot. J Vasc Surg 2003;38:1067-74.  Back to cited text no. 1
    
2.
Pardo M, Alcaraz M, Bernal FL, Felices JM, Achel GD, Canteras M, et al. Transcutaneous oxygen tension measurements following peripheral transluminal angioplasty procedure has more specificity and sensitivity than ankle brachial index. Br J Radiol 2015;88:20140571.  Back to cited text no. 2
    
3.
Jens S, Marquering HA, Koelemay MJ, Reekers JA. Perfusion angiography of the foot in patients with critical limb ischemia: Description of the technique. Cardiovasc Intervent Radiol 2015;38:201-5.  Back to cited text no. 3
    
4.
Conte MS, Bradbury AW, Kolh P, White JV, Dick F, Fitridge R, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg 2019;69:3S-125, e40.  Back to cited text no. 4
    
5.
White RA, Nolan L, Harley D, Long J, Klein S, Tremper K, et al. Noninvasive evaluation of peripheral vascular disease using transcutaneous oxygen tension. Am J Surg 1982;144:68-75.  Back to cited text no. 5
    
6.
Dilaver N, Twine CP, Bosanquet DC. Editor's choice – Direct vs. indirect angiosomal revascularisation of infrapopliteal arteries, an updated systematic review and meta-analysis. Eur J Vasc Endovasc Surg 2018;56:834-48.  Back to cited text no. 6
    
7.
Spillerova K, Biancari F, Leppäniemi A, Albäck A, Söderström M, Venermo M. Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization. Eur J Vasc Endovasc Surg 2015;49:412-9.  Back to cited text no. 7
    
8.
Kabra A, Suresh KR, Vivekanand V, Vishnu M, Sumanth R, Nekkanti M. Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia. J Vasc Surg 2013;57:44-9.  Back to cited text no. 8
    
9.
Caselli A, Latini V, Lapenna A, Di Carlo S, Pirozzi F, Benvenuto A, et al. Transcutaneous oxygen tension monitoring after successful revascularization in diabetic patients with ischaemic foot ulcers. Diabet Med 2005;22:460-5.  Back to cited text no. 9
    
10.
Reekers JA, Koelemay MJ, Marquering HA, van Bavel ET. Functional imaging of the foot with perfusion angiography in critical limb ischemia. Cardiovasc Intervent Radiol 2016;39:183-9.  Back to cited text no. 10
    
11.
Prompers L, Schaper N, Apelqvist J, Edmonds M, Jude E, Mauricio D, et al. Prediction of outcome in individuals with diabetic foot ulcers: Focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE study. Diabetologia 2008;51:747-55.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]



 

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