Factors Affecting the Primary Patency of Tibial
Arteries post PTA in the Vascular Surgery
Department of Kaunas Clinics
Lamees Haytham Sa’ad HejaziFaculty of Medicine
Lithuanian University of Health Sciences Supervisor: Professor Aleksandras Antusevas
MD, PhD Vascular Surgery Department of Vascular Surgery
Kaunas, Lithuania 2018
TABLE OF CONTENTS
1. SUMMARY...3
2. ETHICS COMMITTEE CLEARANCE... 8
3. LIST OF ABBREVIATIONS...11
4. INTRODUCTION...13
5. AIM AND OBJECTIVES OF THE THESIS...16
6. LITERATURE REVIEW...18 7. RESEARCH METHODOLOGY...25 8. RESULTS...28 9. DISCUSSION...40 10. CONCLUSION...43 11. PRACTICAL RECOMMENDATIONS...45 12. REFERENCES...46 13. ANNEXES 48 2
SUMMARY
Author: Lamees Haytham Sa’ad Hejazi
Title: Factors Affecting the Primary Patency of Tibial Arteries post PTA in the Vascular Surgery Department of Kaunas Clinics.
Background: Tibial arterial atherosclerotic lesions have been an increasing problem today due to the aging population. Risk factors are similar to those of coronary artery disease. Treatment strategies include endovascular treatment of tibial arteries, yet there are risk factors affecting primary patency.
Aim: The aim of this prospective study is to evaluate the factors affecting primary patency of tibial arteries post percutaneous transluminal angioplasty.
Objectives:
1. Assess the demographic data and chronic diseases of the patients included in the study.
2. Assess endovascular treatment techniques and methods used for the management of tibial arterial atherosclerotic lesions and their complications.
3. Assess results of chosen methods by comparing primary patency and primary assisted patency and clinical outcomes.
4. Conclude the factors affecting primary patency.
Method: 75 patients (79 limbs) were included in this study. There was no age restriction. A questionnaire filled anonymously after the patient’s written consent was used to collect data and to gather information during a 12 month interval follow up. The study participants were patients in the vascular surgery department and Endocrinology department of Kaunas clinics who have undergone percutaneous transluminal angioplasty of the tibial arteries.
Results and Conclusion: The primary patency of tibial arteries post PTA in vascular surgery of Kaunas Clinics was 76%. The major risk factor affecting the primary patency was Diabetes Mellitus.
ACKNOWLEDGEMENTS
4My forever-beloved Grandfather, I wish you had been here to be proud of me.
Always in my heart. Mother, Your Excellency,
Without your continuous belief in my capabilities, your unconditional love and your endless support I would not be the woman I am today.
Father, My ever most love,
I will never be able to thank you enough for being wise, patient and pushing me to the limit to be a better me every day.
I am the pure hearted strong lady today because you are my tender hearted Dad.
Jordanian Special Armed Forces Lawyer and First Lieutenant Ahmad Al-Srour,
Thank you for always supporting me, telling me to never stop and to run full speed like the turbo I am. Thank you for waking up early to wish me luck before an exam and for staying up late till I finished
studying like a dynamo.
Near or far, I am truly blessed to even meet you.
Dr. Hitaf Issawi,
I am forever grateful and loyal to you, thank you for showing me the way when I was lost, Many times,
My angel sent from God.
To my inspirational supervisor Professor Aleksandras Antusevas
Thank you for choosing me to do this research, believing in me, for guiding me and for encouraging me throughout the process. Thank you for always making sure that I felt that I had all the support I
needed.
The author declares no conflict of interest.
ETHICS COMMITTEE APPROVAL
The study was performed in accordance with the medical Faculty rules and was approved by Lithuanian University of Health Sciences Bioethics Centre; Approval of Research Ethics Committee.
Reference number: BEC-MF-23. Date of issue: November 02th 2018.
Oral consent was obtained from the participants before conduction of the research and the oral interview. The questionnaire was filled not by the patient but by the doctors in charge of the research.
During the research, the points of interest were rediscussed and the research objectives refined in order to adjust to the number of patients.
The imaging has been reviewed by senior residents and doctors in the vascular surgery
department to measure the length of lesions of tibial arteries and to classify the lesions of tibial arteries according to TASC II.
LIST OF ABBREVIATIONS
ABI Ankle-Brachial-Index
ABG Artery Bypass Grafting
ALI Acute Limb Ischemia
AMA American Medical Association
CLI Critical Limb Ischemia
DEB Drug-eluted Balloon
DES Drug-eluted Stent
IC Intermittent Claudication
IGT Impaired Glucose Tolerance
IHD Ischemic Heart Disease
DM Diabetes Mellitus
FBG Fasting Blood Glucose
HBA1c Glycosylated hemoglobin
PAD Peripheral Artery Disease
PP Primary Patency
PAP Primary Assisted Patency
PTA Percutaneous Transluminal Angioplasty
TASC II Transatlantic Inter-Society Consensus II
INTRODUCTION
The anterior and posterior tibial arteries along with the peroneal artery are the main arteries irrigating the lower limb1. Injuries to those arteries are grouped under the term Peripheral Artery Disease (PAD), defined as the damage or the dysfunction of the artery resulting in reduced blood flow and to the obstruction of an artery2. There are several risk factors leading to PAD including, smoking, diabetes mellitus and dyslipidemia3. The main factor behind this disease is atherosclerosis (plaque buildup) in the arteries of the lower limbs4. PAD is a frequent pathology encountered in vascular surgery, where advanced critical limb ischemia – manifested by severe pain and tissue loss- is associated with a morbidity rate of 50% at 5 years and a mortality rate of approximately 20% within 6 months of diagnosis4,5. Transatlantic Inter-Society Consensus II (TASC II) is the classification system for lesions of arteries adopted in several studies, since it provides a framework for the comparison between therapeutic techniques and it divides lesions alphabetically from lower to higher lesion complexity into A,B,C and D. The choice of a specific surgical revascularization method over another depends on several factors such as lesion complexity, location of the anatomic lesion, the patient health condition and comorbidities, patient preference, as well as surgical expertise and technical resources and equipment available6. Treating tibial vascular disease has enhanced from exercise and medical therapy to invasive distal bypass surgery but the results were unsatisfactory7,8. Endovascular treatment is the lower risk option in patients with multiple comorbidities9. It comprises atherotomy, stents, balloons and drug eluting balloons6. The efficacy is high but the main complication of these procedures is the restenosis of the operated artery10. Several factors for restenosis include the length of the lesion, the position of the lesion, TASC II C/D lesions, the run-off (the number of patent arteries per procedure), Diabetes Mellitus, the non-use of Aspirin use post PTA6,11. The recurrence of symptoms and the complications post PTA such as hematoma or false aneurysms lead to either Target Lesion Revascularization- after which we assess what is called primary assisted patency (PAP) - or amputation9. The newer PTA methods using drug eluting balloons showed a significantly higher 1 year primary patency rate associated with significantly less Target Lesion Revascularization than conventional PTA, following endovascular recanalization of infrapopliteal arteries in patients presenting with CLI The primary patency rate at one year was around 80%12,13. The main aim of our study is to identify the major factors that affect the primary patency of tibial arteries post PTA in the department of vascular surgery in Kaunas
Clinics. Our question is “What are the major factors affecting the primary patency of tibial arteries post PTA in the department of vascular surgery in Kaunas Clinics?”
AIM AND OBJECTIVES
Aim
The aim of the study was to evaluate the major factors affecting the primary patency of tibial arteries post PTA in the department of vascular surgery in Kaunas Clinics.
Objectives
Objectives of the study:
1. Assess the demographic data and chronic diseases of the patients included in the study.
2. Assess endovascular treatment techniques and methods used for the management of tibial arterial atherosclerotic lesions and their complications.
3. Assess results of chosen methods by comparing primary patency and primary assisted patency of tibial arteries and clinical outcomes post PTA.
LITERATURE REVIEW
The lower limb receives its arterial supply from the common femoral artery, palpated at the groin. It divides into two branches: 1. The deep femoral artery, located between the adductor and the quadriceps muscles and 2. The superficial femoral artery, which passes through the adductor canal. The superficial femoral artery is then called the popliteal artery as it passes throught the popliteal fossa. From there, blood continues to flow in two main branches: 1. The anterior tibial artery, which accompanies the deep peroneal (fibular) nerve along the posterior margin of the tibia and 2. The tibioperoneal trunk, which in turn gives birth to the posterior tibial artery and peroneal artery. The peroneal artery passes adjacent the medial margin of the fibula throughout its course distally. The posterior tibial artery is accompanied by the tibial nerve within the deep posterior compartment1. Injury, mainly ischemia, to the peripheral arteries of the lower limb is known as peripheral arterial disease (PAD)14.
The major risk factor of peripheral arterial disease is atherosclerosis due to dyslipidemia. In Lithuania, dyslipidemia is the most frequent risk factor among
middle-aged Lithuanian subjects without cardiovascular disease and has been diagnosed in nine out of ten subjects15
.
Studies also show that atherosclerosis affects 12 million Americans16. Type II Diabetes Mellitus and smoking have also been listed as major risk factors for PAD, with an odds-ratio of 2.72 and 1.88, respectively17. Arterial Brachial index is a clinical exam used to diagnose PAD. It measures the blood pressure in the ankle and the arm. Then, the resultant ratio of ankle blood pressure to arm blood pressure is analyzed. A ratio of less than 0.9 indicates the presence of PAD18. Blood glucose intolerance or BGI has been proved to be associated with greater than 20% prevalence of an abnormal ankle-brachial index (ABI) relative to 7% in those with normal glucose tolerance. In addition, 20% of patients who present with PAD have Type II Diabetes Mellitus. Studies show that this percentage is underestimated due to the asymptomatic nature of less severe PAD and the altered pain perception in diabetic patients due to peripheral neuropathy A study conducted in the United Kingdom demonstrated that each 1% increase in glycosylated hemoglobin (HBA1c) was correlated with a 28% increase in incidence of PAD, microvascular complications, major amputation rates and higher rates of death and it was a stronger correlation amongst hypertensive and smoking males. Those patients with PAD who have Diabetes Mellitus (DM) have longer hospital stay periods which increases cost as compared to patients with PAD alone16. Moreover, another study showed that there were more women than men suffering from PAD after the age of 40 years19.The main symptoms of PAD are divided into several categories. The American College of Cardiology/American Heart Association Practice Guidelines divided peripheral arterial disease into four categories: asymptomatic, intermittent claudication (IC), critical limb ischemia (CLI), and acute limb ischemia (ALI)20. In the case of intermittent claudication of the lower limbs the symptoms felt are discomfort, cramping, pain and/or a sensation of fatigue, described by the patient, upon walking or climbing stairs. These symptoms are felt mainly in the calves and cease to bother the patient when the patient is at rest. In the case of critical limb ischemia, there is a chronic and rather significant obstruction of the artery’s lumen, the patient suffers from chronic pain which takes place even at rest and nocturnally as well. Skin discoloration, ulcers or even gangrene can
occur. The symptomatology lasts for two weeks and this helps doctors differentiate the above rather chronic cases from acute limb ischemia (ALI), which is sudden and mainly due to an embolism, a thrombus or a dissection and requires immediate intervention14.
In order to manage lesions of peripheral arteries, several classification systems have been created to divide the arterial lesions anatomically and surgically. Although there are several classification systems for the arterial lesions, each one has its limitations, its pros and its cons. Those include: Angiosomes Classification, WIfI Classification (wound, ischemia, and foot infection), American Medical Association (AMA) classification, Whole Person Impairment Classification, Rutherford Classification, Fontaine Classification, Bollinger Angiographic Classification, Graziani’s Morphologic Categorization and the Trans-Atlantic Inter-Society Consensus Document II (TASC II). The latter divides peripheral artery lesions anatomically into four subgroups: TASC A represents the simplest situation which is focal stenosis. It usually suggests excellent results from endovascular management alone. TASC B implies good results from endovascular management via endoluminal interventions. TASC C is designated to lesions suitable for surgical revascularization in patients suitable for surgery and with an available conduit. Surgeons are usually reserving endovascular techniques for surgically high risk patients. TASC D represents the most complex revascularization case, representing diffuse, occlusive lesions. Those lesions are managed by open surgery which involves artery bypass grafting or ABG.The TASC lesion classification for infrapopliteal lesions is illustrated in Fig. 121.
Figure 1. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) classification of infrapopliteal lesions. The unshaded area represents the target lesion; area inside the shaded rectangle represents typical background disease21.
As mentioned previously, the choice of a specific surgical revascularization method over another depends on factors like lesion complexity, location of the anatomic lesion, the patient health condition and comorbidities, patient preference, as well as surgical expertise and technical resources and equipment available6. Treating tibial vascular disease has enhanced from
exercise and medical therapy to invasive distal artery bypass surgery using the greater saphenous vein or prosthetic grafts. Nonetheless, the results were unsatisfactory7,8. Several inflow arteries have been used for the proximal anastomosis site of the grafts (common femoral artery, superficial femoral artery, popliteal artery) and the outflow arteries chosen were usually tibial arteries, depending on the vascular anatomy and the extent of atherosclerotic lesion21. Then newer methods such as endovascular treatment have shown to be the lower risk option in patients with multiple comorbidities9. Endovascular treatment option comprises atherotomy, stents, balloons and drug eluting balloons6. Progress in the field of endovascular surgical techniques, imaging and technology, including sheaths, wires, catheters, re-entry devices, stents, balloons, drug-eluted stents (DES) and debulking tools has been lately suggesting the use of endovascular treatment as a preference even in TASC C and D tibial lesions. Nevertheless, 50% of patients who have undergone PTA as a management of PAD have had restenosis or reocclusion within a year from the procedure. Restenosis is the most frequent problem encountered post PTA and has been a cause for revascularization22.
According to previous studies with numerous iliac interventions such as the one conducted by Roach A. N. et al., it was found that several factors were predictors for the loss of primary patency of iliac arteries. These factors included the younger age of patients, non-Caucasian race, and an external isolated artery occlusion23.
It was determined in a study by Lida O. et al. conducted in Japan that being underweight (BMI <18.5 kg/m2), having heart failure prior to PTA and a higher rate of wound infections have been risk factors for a higher restenosis rate and a higher amputation rate24.
Diabetes mellitus (DM) has been described, according to previous studies, as the utmost significant risk factor for the loss of patency post PTA. In a study led by Singh S. et al. in the University of California, more than 300 infrapopliteal lesions in patients with DM were treated with balloon angioplasty or DEB. The primary patency rate was 16% for patients with FBG above the median, compared to the rate of primary patency of 46% for patients with FBG below the median (p=0.005). Amputation rates were also higher amongst the latter group but without a significant difference (p=0.1). Patients with diabetes mellitus had lower primary patency rates after PTA and this was most likely due to the advanced stage of limb ischemia. They had higher rates of primary assisted patency
(PAP)25. Acutely elevated glucose levels have been found to induce inflammation, smooth muscle proliferation, abnormal matrix production, and inactivation of endothelium-derived relaxing factor. Additionally, hyperglycemia have been found to impact the expression of the fibroblast growth factor and the transforming growth factor-α, which in turn promotes proliferation of smooth muscle cells and the production of extracellular matrix. Increased expression of Tumor Necrosis Factor- alpha or TNF-α and C- reactive protein or CRP level, as well as oxidative stress and endothelial dysfunction, have a role in affecting the relatively high restenosis rates in patients with higher blood glucose values before endovascular intervention. Acute hyperglycemia has shown to induce the production of monocyte chemoattractant-protein-1, which has been linked with a higher risk of restenosis16.
In a study by Min P. et al. where PTA was performed on 144 limbs, classified as TransAtlantic Inter-Society consensus (TASC). TASC A or B showed tendency of better patency rates than those classified as TASC C or D (p=0.099). However, there was no significant difference in the primary patency between lesions with good runoff and lesions with poor runoff26.
Spreen M.I. et al. conducted in patients undergoing revascularization it was found that revascularization with drug eluted stenting had a higher primary patency rate and a lower amputation rate27. The ACHILLES trial had randomized 200 patients who underwent infrapopliteal revascularization and it was found that revascularization with drug eluted stents had higher primary patency rates than revascularization with standard PTA. Nonetheless, the studies did not show significant differences for death, amputation rates, or the clinical status21. The study DESTINY conducted by Bosiers M. et al. on 140 patients with infrapopliteal disease who underwent revascularization and the results showed a higher primary patency rate and lower primary assisted patency rate in patients who underwent DEB compared to those undergoing PTA alone. Nonetheless, there was no significant difference found between major amputations which were rare or mortality rates which represented 12.9% of a total of 178 patients28.
According to Spreen M.I. et al., lesion lengths superior or equal to 10cm had a statistically superior patency if drug eluted stents were used in endovascular intervention
procedure compared with the use of standard PTA alone in femoral lesions given that it included patients with lesion lengths up to 17 cm27.
The research was conducted over an interval of one year. This was between September 2016 and September 2017. The object of the study was the patients who underwent percutaneous transluminal angioplasty (PTA) of tibial arteries after presenting with symptoms of lower limb ischemia.
A total of 95 patients (99 limbs) were included in the study. In our clinics, the majority of patients were presenting from the Department of Endocrinology (diabetic) with PAD. Patients in Vascular Surgery Department were not mainly diabetic but had similar lesions of tibial arteries as those patients with PAD presenting from the Department of Endocrinology. They were followed up over a period of one year following the date of the procedure.
After receiving the patients’ consent a questionnaire was used to collect data about the patients such as demographic data and clinical data: gender, age, symptoms of limb ischemia like intermittent claudication and pain at rest, chronic diseases of the patients especially diabetes since it is thought to be, according to literature, a major risk factor for restenosis and loss of patency, anatomy of the lesions of the studied arteries according to TASC – collected and analyzed from the angiographic data, the method used to re-vascularize the arteries occluded or stenosed - PTA or DEB.
The patients’ symptoms and clinical findings, as well as the incidence of restenosis was followed up during one year from the date of endovascular treatment of the tibial arteries. Radiological testing using angiography was repeated when needed according to data such as clinical data post procedure.
Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) 12.0 statistical software for Windows (SPSS Inc, Chicago, IL, USA). Primary patency rates were calculated according to the Kaplan-Meier life-table. P value less than or equal to 0.05 was considered statistically significant.
95 patients
99 limbs
PTA
93 limbs
Excluded
12
PTA did not work
Allocated
79 limbs
Died
4 patients
Amputation
indicaticating loss of
patency
12 limbs
Primary patency after
12 months
63 limbs
Primary assisted
patency
12 limbs
DEB
6 limbs
RESULTS
Table 1: Demographic Data
Gender Male : 58.23% Female : 41.77%
Age 30-49 years : 3.8% 50-69 years : 17.72% >=70 years : 78.48% Table 1 demonstrates the age and gender of the patients in the study.
Table 2: Symptoms before and after the Endovascular Treatment
Symptom Before After
Claudication 59.5% 20.3%
Pain at rest 91.1% 55.7%
Ulcers 68.4% 21.5%
Table 2 compares the percentage of ischemic lower limb symptoms encountered by patients before and after endovascular treatment.
Table 3: Percentage of Chronic diseases amongst participants as risk factors affecting primary patency of tibial arteries post PTA
Chronic Disease Percentage
Diabetes Mellitus 67.1%
Hypertension 55.7%
Obesity 6.3%
Smoking 5.3%
History of PTA procedure 13.9%
Ischemic Heart Disease 27.8%
Table 3 shows the chronic diseases to be studied as risk factors for restenosis of tibial arteries.
Table 4: Angiography findings according to the following classifications
Number of
stenotic/occluded arteries
25.32% 39.24% 35.44%
Length of Lesion < 5 cm 5-10 cm > 10 cm
11.39% 51.90% 36.71%
TASC II A B C D
7.59% 29.11% 35.44% 27.85%
Table 4 represents the lesions observed during angiography of the tibial arteries.
TASC II type A
Figure 1. TASC II type A lesion. Figure 1a illustrates a single focal stenosis less than 5cm in length of the anterior tibial artery with stenosis of the peroneal and posterior tibial artery as shown on the left. The second figure 1b is taken during the PTA of the anterior tibial artery. 1c is during the PTA of the posterior tibial artery. 1d is after the endovascular treatment.
TASC II type B
a b c d e Figure 2. TASC II type B. Multiple stenosis are seen each less than 5 cm in length with a total length of less than 10cm in the anterior tibial artery, with worse severity lesions in the posterior tibial artery and peroneal artery as shown in 2a. 2 b, c and d are taken during PTA and 2e after PTA.
TASC II type C
Figure 3. TASC II type C. Multiple stenoses are shown in the anterior tibial artery with a total length superior to 10 cm as well as similar lesions in the peroneal artery and worse lesions in the posterior tibial artery. 3a and 3b are before PTA. 3c and 3d are during proximal PTA. 3e and f distal PTA of the anterior tibial artery.
TASC II type D
a b c d e Figure 4. TASC II type D. Multiple occlusions are seen with a total lesion length of more than 10 cm on the anterior tibial artery, no visualization of collaterals as illustrated in 4a. 4b and c are during PTA. 4d and e are after PTA.
Table 5: Antiaggregants/Anticoagulants/Cilostazole used before and after Endovascular Treatment
Medication Before After
Aspirin/Plavix/Warfarin 22.8% 100%
Table 5 demonstrates the main antiaggregants or anticoagulants and or Cilostazole used before and after the revascularization procedure. According to hospital protocol 100% of patients used Aspirin 100mg 1 tablet per day for life and Plavix 75 mg 1 tablet per day for three months. Cilostazole use to alleviate symptoms of intermittent claudication after the procedure was nearly doubled (12.7%).
Table 6: Incidence of complications, Amputations and death during 1 year follow up
Event Percentage
Complications 8.8%
Amputation 15.2%
Death 5.1%
Table 6 represents the incidence of complications (hematoma: 6.3%, false aneurysm: 2.5%), amputations (15.2%) as well as the incidence of death during the 12 month follow up which was 5.1%. Of the 12 patients with major post PTA amputations 10 had DM. Death was not associated with complications of PTA. General Primary Patency was hence 76%.
Graph 1 represents the percentage of the revascularization procedure adopted for the management of arterial lesions. 92% was percutaneous transluminal angioplasty (PTA) and 7% drug eluted balloon (DEB).
Graph 2 shows the percentage of restenosis within one year of the procedure. 68% of patients had restenosis within one year follow up. It was noticed that the most factor with significant effect on the restenosis rate was DM. In fact, 49 of the 54 patients who had restenosis were diabetic. Restenosis was measured using the sum of several factors: complaints of patients post PTA (persistence of symptoms), follow up echography or follow up angiography post PTA. In this case it did not at all mean that PTA was unsuccessful or that repetition of the procedure was necessary. In addition, It was found that of the 5 patients taking Cilostazole before the procedure 1 only had restenosis (p=0.033) and of the 10 who were prescribed Cilostazole, 7 did not have any restenosis (p=0.009). Several factors were considered as major risk factors for restenosis and are further illustrated.
Graph 3: Kaplan Meier curve estimates for the primary patency rates in patients with DM and in patients without DM treated by Endovascular Treatment
Graph 3 graph represents the Kaplan Meier curve estimates for the primary patency rates in patients without DM and in patients with DM treated by endovascular treatment, which were 81% and 74% respectively with a significantly lower primary patency rate in diabetic patients (p<0.05). A rt er y P at en cy R at es 26 26 24 24 24 24 24 24 24 24 24 24 21 53 49 48 48 47 43 43 42 42 42 41 40 39
Graph 4: Kaplan Meier curve estimates for the primary patency rates after Endovascular treatment according to the number of stenosed/occluded arteries
Graph 4 represents the Kaplan Meier curve estimates for the primary patency after endovascular treatment according to the number of stenosed/occluded arteries seen on angiography. There was no significant effect on primary patency noted according to the above classification.
Time
Number of Arteries Stenosed/Occluded
A rt er y P at en cy R at es 20 20 20 18 18 16 16 16 16 16 16 16 16 16 31 30 28 28 27 25 25 24 24 24 23 22 20 19 28 25 25 25 25 25 25 25 25 25 25 25 24 24 P value Log Rank 0.383 Breslow 0.383
Graph 5: Kaplan Meier curve estimates for the primary patency rates according to the total length of the lesion of the artery affected
Graph 5 demonstrates the Kaplan Meier curve estimates for the primary patency rates classified according to the total length of the arterial lesion. The maximum lesion length in our study was around 17cm. There was no significant effect found on the primary patency rate.
Time
Total Number of Arteries Affected
A rt er y P at en cy R at es 9 8 8 8 8 8 8 6 6 6 6 6 6 41 40 38 37 37 37 37 37 37 37 36 36 36 29 26 26 26 26 22 22 22 22 22 22 20 20 P value Log rank : 0.217 Breslow: 0.229
Graph 6: Kaplan Meier curve estimates for primary patency rates according to TASC II
Graph 6 represents the Kaplan Meier curve estimates for the tibial arteries’ primary patency rates according to TASC II. Our results show that following endovascular treatment there was no significant difference between TASC A, B, C or D in primary patency rates of tibial arteries.
Time A rt er y P at en cy R at es TASC II 6 6 6 6 6 6 6 6 6 6 6 6 6 23 22 22 21 21 21 21 20 20 20 20 20 20 22 21 20 20 19 19 19 19 19 19 18 18 18 28 26 26 26 26 22 22 22 22 22 22 21 21 P value Log Rank 0.383 Breslow 0.383
Table 7: The Main Independent Factors Affecting Primary Patency of Tibial Arteries Post Endovascular Treatment
Variable HR 95% CI p-value
DM 0.019-0.059 10.804-12.436 0.038
Table 7 represents the main independent risk factors affecting primary patency of tibial arteries post PTA. Diabetes Mellitus was found to be a significant factor affecting the primary patency rate of tibial arteries post PTA whilst the length of the lesion alone and the TASC alone were not found to be factors affecting primary patency rates of tibial arteries post PTA. However, when crosstabled with DM, they did.
Graph 7: Primary Assisted Patency
Graph 7 shows the need for the repetition of endovascular procedure if clinical or radiological symptoms of restenosis/re-occlusion were significant during the 1 year follow up period. The repetition rate is 15% which signifies a general Primary Assisted Patency Rate of 85%.
Graph 8: Kaplan Meier curve estimates for the primary assisted patency rates in Diabetic Patients and Non Diabetic Patients
Graph 8 represents the Kaplan Meier curve estimates for the primary assisted patency rates in non-diabetic patients and diabetic patients during a 12 month period, which were 96% and 79% respectively (p<=0.05).
DISCUSSION
Primary Assisted PatencyTime A rt er y P at en cy R at es 26 26 26 26 26 26 26 26 26 26 26 26 25 53 52 51 51 50 48 46 45 45 45 44 43 42 P value Log rank 0.05 Breslow 0.054
Tibial artery percutaneous transluminal angioplasty (PTA) and drug eluted balloon (DEB) endovascular procedures are considered today as alternative therapeutic options to older methods such as arterial bypass surgery (ABG) for patients with
symptomatic tibial artery stenosis or tibial artery occlusion. After endovascular procedure, the major problem is restenosis and in our study, the restenosis rate was 68%. In a previous study it was as high as 50%22. It was measured using the sum of several factors such as the complaints and symptoms of patients post PTA, clinical follow up, follow up echography and/or follow up angiography post PTA. We observed that the factor with the most significant effect on the restenosis rate was diabetes mellitus, which is in high accordance with what we have found in literature25. In fact, 49 of the 54 patients who had restenosis in our study were diabetic. Although the restenosis rate was high, it did not reflect the loss of patency or the need for re-vascularization since the degree of restenosis varied from mild asymptomatic restenosis of the artery lumen with a good run-off seen on angiography to major re-occlusion which usually needed medical or endovascular re-intervention depending on each case. In addition, it was found that of the 5 patients taking Cilostazole before the procedure 1 only had restenosis (p=0.033) and of the 10 who were prescribed Cilostazole, 7 did not have any restenosis (p=0.009).
In our study the primary patency rate after one year was 76% (n= 79). Assisted primary patency (PAP) rate was 85%. We have evaluated several symptoms related to the restenosis of tibial arteries post PTA and assessed the relation to several risk factors. We have looked at demographic data: age and gender. We had more males than females in our study (58% and 42% respectively). 4% of patients were between 30 and 39 years of age, 18% between 50 and 69 years of age and 78% were 70 years old and above.
We have evaluated the risk factors in previous studies such as DM, obesity and others. 67% of our patients had DM, 55% had HT, 6.3% were obese, 5.3% only smoked, 14%had a previous PTA and 28% had ischemic heart disease. Amongst the above risk factors evaluated DM was the one found to have a significant effect on primary patency (p=0.038) and primary assisted patency (p=0.05) of tibial arteries in our study. This finding was in accordance with previous studies that evaluated DM as a risk factor for restenosis25. Our study does not show a significant effect of the other factors on the restenosis rate.
The symptoms evaluated before the procedure were the following: pain at rest, claudication of more than and less than 200m as well as the ulcers of lower limbs and the amputation rate. After the revascularization procedure, those symptoms were reevaluated.
Our results showed the following: since a large number of our patients were above the age of 70, our results of symptoms before and after endovascular treatment contradicts a previous study in 2015 which found that being of lower age was a risk factor for restenosis23. As for the symptoms, we found that there was a significant decrease from 91% to 55% of pain at rest, a decrease in claudication from 59% to 20% and a decrease in the occurrence of ulcers from 68% to 21%.
The number of stenosed/occluded arteries seen on the angiography before PTA were as follows: 1 artery affected 25%, 2 arteries affected 39%, 3 arteries affected 35%. The lengths of lesions of the tibial arteries were also studied and were divided into three categories : <5cm: 11%, 5-10cm: 52%, >10cm: 37%. Lesions were also divided according to TASC II as A, representing only 8%, B: 29%, C: 35%, D: 28%. These differences in percentages amongst number of arteries affected, length of lesion of arteries affected and TASC II were suspected to have a major alteration of p-value in studying them as risk factors of restenosis post PTA. But this was not the case in our study although all patients undergoing endovascular treatment of tibial arteries in the time period specified were included.
We have found previous studies such as the ACHILLES study comparing endovascular procedures and showing that drug eluted stents showed higher patency rates21. Unfortunately we were unable to compare the PTA method to that of DEB in our study since the DEB procedure represented only 8% of the endovascular procedures adopted.
Complications post PTA represented 8.8% and were hematoma and false aneurysm, which were found to be the most common complications post PTA. The amputation level was already high (22.8%) since most of our patients were referred from the department of endocrinology with high levels of FBG. Nonetheless, the amputation rate also decreased post PTA with a percentage of 15%. The mortality rate in our study was 5.1% but it was not related to the endovascular procedure and it was less compared to previous studies27.
1. There were more males than females in our study. The highest age group was represented by patients whose age was 70 years or more. Diabetes Mellitus was the most common chronic disease the patients had.
2. The main endovascular method used for tibial artery revascularization was PTA. The major complications post PTA were encountered in less than 10% of patients (hematoma, false aneurysm).
3. The PTA procedure showed to be quite effective in the management of tibial artery lesions of all lengths and all TASC types with a general primary patency of 76%. The primary patency was 81% in non-diabetic patients and 74% in diabetic patients, as well as a general primary assisted patency of 84.81%. In non-diabetic patients the PAP was 96% and in diabetic patients it was 79%. The clinical symptoms have all diminished after endovascular treatment.
4. According to our study which comprised only 79 limbs, the major factor affecting primary patency was found to be diabetes Mellitus.
Tibial arterial disease has been a medical issue today due to the aging population. It has various risk factors similar to those promoting coronary artery disease, some of which can be modified. Patient education remains the number one aspect in this regard in both primary and secondary prevention. Furthermore, different specialists in medicine should collaborate and use a multidisciplinary approach to improve the clinical outcomes and follow up post endovascular treatment. Although diabetic patients have a higher risk of loss of primary patency compared to nondiabetic patients, recent advances in pharmacology and endovascular treatment techniques have contributed to favorable outcomes. Nonetheless, further work remains necessary. For instance, a better understanding of the mechanisms responsible for restenosis of tibial arteries post PTA would ultimately improve results.
1. Mills J L. Classification of acute and chronic lower extremity ischemia [Internet]. Uptodate. 2019 [cited 1 April 2019]. Available from: https://www.uptodate.com/contents/classification-of-acute-and-chronic-lower-extremity-ischemia
2. Peripheral arterial disease [Internet]. Merriam-webster. 2019 [cited 1 April 2019]. Available from:
https://www.merriam-webster.com/medical/peripheral%20arterial%20disease 3. Hardman R. et al. Overview of Classification Systems in Peripheral Artery Disease. –
PubMed – NCBI [Internet]. Ncbi.nlm.nih.gov. 2014 [cited 1 April 2019]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232437/
4. Clair D. et al. Current state of diagnosis and management of critical limb ischemia. -PubMed - NCBI [Internet]. Ncbi.nlm.nih.gov. 2012 [cited 1 April 2019]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22311595
5. Faglia E. et al. Long-term prognosis of diabetic patients with critical limb ischemia: a population-based cohort study. – PubMed - NCBI [Internet]. Ncbi.nlm.nih.gov. 2009 [cited 1 April 2019]. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/19223609
6. Stoner M. Reporting standards of the Society for Vascular Surgery for endovascular treatment of chronic lower extremity peripheral artery disease. Journal of Vascular Surgery. 2016; 64(1):1-21. Available from:
https://www.jvascsurg.org/article/S0741-5214(16)30002-7/pdf
7. Adam D, Bradbury A. TASC II Document on the Management of Peripheral Arterial Disease. European Journal of Vascular and Endovascular Surgery [Internet]. 2007 [cited 1
April 2019]; 33(1):1-2. Available from:
https://www.sciencedirect.com/science/article/pii/S1078588406006575?via%3Dihub 8. Jeffrey W. O. et al. Peripheral Artery Disease: Evolving Role of Exercise, Medical
Therapy and Endovascular Options. Journal of the American College of Cardiology [Internet]. 2015 [cited 1 April 2019]; 67(11): 1338-1357. Available from:
https://www.sciencedirect.com/science/article/pii/S0735109716001558
9. Thukkani A, Kinlay S. Endovascular Intervention for Peripheral Artery Disease [Internet]. Pubmed - NCBI. 2015 [cited 1 April 2019]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504240
10. Baumann F. et al. The Importance of Patency in Patients with Critical Limb Ischemia Undergoing Endovascular Revascularization for Infrapopliteal Arterial Disease [Internet]. PubMed - NCBI. 2014 [cited 1 April 2019]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668862/
11.Yu J. S et al. Midterm Outcome of Femoral Artery Stenting and Factors Affecting Patency [Internet]. Pubmed – NCBI. 2015 [cited 1 April 2019]. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694182/
12.Tepe G. et al. Drug-Coated Balloon Versus Standard Percutaneous Transluminal Angioplasty for the Treatment of Superficial Femoral and Popliteal Peripheral Artery Disease. American Heart Association Journals. Circulation [Internet]. 2014 [cited 1 April 2019]; 131(5): 495-502. Available from :
13.Haddad S. E. et al. One Year Primary Patency of Infrapopliteal Angioplasty Using Drug – Eluting Balloons: Single Center Experience at King Hussein Medical Center [Internet]. 2017 [cited 1 April 2019]. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559924/
14.Neschis D. G., Golden M. A. Clinical features and diagnosis of lower extremity peripheral artery disease [Internet]. 2018 [cited 1 April 2019]. Available from:
https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-lower-extremity-peripheral-artery-disease?topicRef=16740&source=see_link
15.Rinkuniene E. et al. The prevalence of dyslipidemia and its relation to other risk factors: a nationwide survey of Lithuania. Clinical Lipidology [Internet]. 2015 [cited 1 April 2019]; 10(3): 219-225. Available from:
https://www.tandfonline.com/doi/pdf/10.2217/clp.15.16
16.Thiruvoipati T. et al. Peripheral artery disease in patients with diabetes: Epidemiology, mechanisms, and outcomes. World Journal of Diabetes [Internet]. 2015 [cited 1 April 2019]; 6(7): 961-969. Available from:
https://www.wjgnet.com/1948-9358/full/v6/i7/961.htm
17.Fowkes F. G. et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis [Internet]. Pubmed – NCBI. 2013 [cited 1 April 2019]. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/23915883/
18.Crawford F. et al. Ankle brachial index for the diagnosis of lower limb peripheral arterial disease [Internet]. Cochrane Library. 2016 [cited 1 April 2019]. Available from:
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010680.pub2/full 19. Jelani Q. et al. Peripheral Arterial Disease in Women: an Overview of Risk Factor Profile,
Clinical Features, and Outcomes [Internet]. PubMed – NCBI. 2018 [cited 1 April 2019]. Available from:
20.Gerhard-Herman M. D. et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. American Heart Journals. Circulation [Internet]. 2016 [Cited 1 April 2019]; 135(12):686–725. Available from:
https://www.ahajournals.org/doi/10.1161/CIR.0000000000000501
21.Jaff M. R. et al. An update on Methods for Revascularization and Expansion of the TASC Lesion Classification to include Below-the-Knee Arteries: A supplement to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). PubMed – NCBI [Internet]. 2015 [cited 1 April 2019]. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691515/
22.Silingardi R. et al. Durability and Efficacy of Tibial Arterial Stent Placement for Critical Limb Ischemia. Journal of Vascular and Interventional Radiology [Internet]. 2015 [cited 1 April 2019]; 26(4): 475-483. Available from:
https://www.sciencedirect.com/science/article/pii/S1051044314011701?via%3Dihub 23.Roach A. N. et al. The effect of demographic factors and lesion severity on iliac stent
patency. Journal of Vascular Surgery [Internet]. 2015 [cited 1 April 2019]; 62(3): 645-653. Available from:
https://www.sciencedirect.com/science/article/pii/S0741521415009520?via%3Dihub 24.Lida O. et al. Endovascular treatment for infrainguinal vessels in patients with critical
limb ischemia: OLIVE registry, a prospective, multicenter study in Japan with 12-month follow-up. PubMed – NCBI [Internet]. 2013 [cited 1 April 2019]. Available from:
25.Singh S. et al. Association of elevated fasting glucose with lower patency and increased major adverse limb events among patients with diabetes undergoing infrapopliteal balloon angioplasty. SAGE Journals. Vascular Medicine [Internet]. 2014 [cited 1 April 2019]; 19(4): 307-314. Available from:
https://journals.sagepub.com/doi/pdf/10.1177/1358863X14538330
26.Min P. K. et al. Impact of infrapopliteal run-off on the primary patency after femoro-popliteal intervention. European Society of Cardiology. European Heart Journal. [Internet]. 2017 [cited 1 April 2019]; 38(1): 5204
https://academic.oup.com/eurheartj/article/38/suppl_1/ehx493.P5204/4086557
27.Spreen M. I. et al. Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial. American Heart Association. Circulation: Cardiovascular Interventions [Internet]. 2016 [cited 1 April 2019]; 9(2): 1-10. Available from:
https://www.ahajournals.org/doi/pdf/10.1161/CIRCINTERVENTIONS.114.002376 28.Bosiers M. et al. Randomized comparison of everolimus-eluting versus bare-metal stents
in patients with critical limb ischemia and infrapopliteal arterial occlusive disease. Journal of Vascular Surgery [Internet]. 2012 [cited 1 April 2019]; 55(2): 390-398. Available from:
https://www.sciencedirect.com/science/article/pii/S0741521411020787?via%3Dihub
Questionnaire
I- Sociodemographic Data :
1. Age
20-29 30-39
40-49 50-59 60-69 ≥70 2. Gender Male Female
II- Anamnesis/patient’s risk factors affecting primary patency
3. Date of first Admission :
4. Symptoms/clinical characteristics /chronic limb ischemia/Rutherford Symptom s /Time (months) Pain at Rest (Y/N) Claudicatio n (meters) Wounds (ulcers) (Y/N) Amputation
(Y/N) Treatmentwith Cilostazol e (Y/N) Before procedure 1 3 6 12 24 5. Smoking Diabetes Mellitus Obesity Hypertension Second PTA
Family history of PTA Ischemic Heart Disease
III- Procedural and lesion-specific factors
7. Angiographic findings
-TASC lesion type and location
A B C D 8. Procedure adopted PTA
Drug eluted balloon PTA
9. Post procedure treatment plan
