Endovascular Intervention for Critical Lower Limb Ischemia; a Review of Outcomes after Percutaneous Transluminal Angioplasty using Balloon Catheter

Peripheral Arterial Disease (PAD) of lower limb with variable morbidity can be manifested as an asymptomatic, sever or life threatening disease. It is also a major cause of disability in many cases. The management of patients with PAD can be defined from a number of different treatment options in the terms of conservative-, interventionaland surgical therapies. Percutaneous Transluminal Angioplasty (PTA) using balloon catheter as a revascularization procedure has been used with acceptable outcomes. The method results are highlighted with comparable success—and patency rates, low complications, improving the quality of life and survival. We reviewed published studies and found that PTA is an appropriate alternative in the management of patient with Critical Limb Ischemia (CLI). Better outcomes have been achieved using Drug Coated Balloons (DCB) as well as Drug Eluting Stents (DES). Atherectomy remains with controversial results. Patient characteristics, the presence of associated risk factors, characteristics of lesions and accompanied cardiopulmonary disease may be the main challenges to use of these treatment options in the future.


Review Design
This article was formulated with the aim of literature review on treated patient with CLI using PTA.
Searches were conducted via the following databases, covering the period from their commencement to 01/10/2018: Medline, Pre MEDLINE, EMBASE, Cochrane Library and other databases. In this review, are outlined the outcome of this technique and the authors' views on the current status of treatments.

Definition of Procedure
Percutaneous Transluminal Angioplasty (PTA) of lower limb using balloon catheter has evolved since the 1960s (Becker & Dake, 2013). This procedure is a well-established treatment for Critical Limb Ischemia (CLI). It is indicated for documented stenosis > 50% of the vessel diameter, single stenosis and occlusions lesser than 10 cm in length, short consecutive multiple stenosis and also calcified occlusions (Pentecost et al., 1994;Athanasoulis, 1980). It should be not offered in active inflammation of a luminal stricture, sepsis, severe coagulopathy and recent surgical anastomotic stricture (Athanasoulis, 1980). Standard angiography and Magnetic Resonance Angiography (MRA) can provide a definition of occlusion anatomically and preoperative planning of revascularization but MRA could be considerable in patient with previously operation clips or endovascular stent and other MR imaging contraindications. Under local anesthesia and an antegrade puncture of the common femoral artery, a five or six French gauge sheath is positioned to perform a preliminary angiographic study using diluted (50%) non-ionic contrast medium (Gates et al., 2000).
A guide wire and a French balloon catheter are used for the dilatation of 2-8 mm diameter arteries. Due to increase the risk of thrombosis especially in the infra popliteal arteries, stents are employed if dissection or suboptimal results occurred. During the procedure, 5000-7000 IU of sodium heparin is infused into the arterial lumen. If vessel spasm occurred, 0.1-0.2 mg of nitroglycerine is infused as an intra-arterial bolus. Intra-arterial thrombus is managed by catheter aspiration and/or urokinase and heparin infusion (Papavassiliou et al., 2003).
A nephroprotection protocol is used in all non-dialyzed patients: 1500 ml salin is infused the day before and the day after the procedure. Creatinine value is determined the day before and after the PTA. In subjects with creatinine > 110 mg/dl, dopamine 2 mg/Kg/min is infused 24 h before and after the procedure. In patients with an ejection fraction < 40%, 20 mg of furosemide are injected intravenously at the beginning and the end of the daily hydration. Hospital stay can be 3 days. All the patients are prescribed either ticlopidine 500 mg/day or clopidogrel 75 mg/day for 30 days and subsequently acetyl salicylic acid 100 mg/day or ticlopidine 250 mg/day (Papavassiliou et al., 2003).
This method offers faster recovery and requires shorter hospital stay. It requires no general anesthesia and maintains all option for extremity revascularization. PTA may be repeated if necessary and may be combined with surgery improving inflow or outflow of surgically placed graft. This method also may be considerable due to lower primary patency rate, multiple stenosis and may be limited due to cost-benefit ration and necessary to reintervention (Mazari et al., 2012).

Evaluation Parameters
In the current review, success-and patency rates, complications, quality of life and survival rate were as the available evaluation parameters.
Two forms of success rates include technical and clinical success. Technical success is defined as the substantial relief of stenosis or occlusion with residual narrowing of 20% or less, significant hemodynamic improvement, and no major morbidity (Society of Interventional Radiology Standards of Practice Committee, Guidelines for Percutaneous Transluminal Angioplasty, 2003).
Clinical success in the femoropopliteal segment is defined as relief of or substantial improvement in symptoms, increase in the ankle-brachial index of at least 0.15 (Thom et al., 2011)  Primary patency implies uninterrupted patency following the revascularization procedure being evaluated. Assisted primary patency expresses cases in which a revision of the revascularization method is applied to prevent impending occlusion or progression of stenosis. Secondary patency refers to patency of the initially treated vessel following a re-intervention to restore patency after occlusion (Dormandy et al., 2000).
Complications parameters include; the amputation of treated limb with assessment of yearly evaluation of patient charts, surgical bypass of the trial leg, peri-procedural (within 30 days) complications, endovascular or surgical re-intervention of target lesion and death. Quality of life can be defined as an emotional well-being of satisfaction with a multidimensional construct comprising physical, psychological, social, and functional domains (Korolija et al., 2004). It can be measured by some methods such as McGill quality of life measurement questionnaire (McGill, 2004).
Intermittent claudication is associated with a significant reduction in quality of life. Treatment of claudicants aims to reduce mortality from cardio-and cerebrovascular events and to improve quality of life. PTA is now widely used in the treatment of intermittent claudication (Cassar et al., 2003).
To consider 1-, 2-and 3-years survival rates in patients with PAD using PTA versus stent or surgical treatment methods can clarify the role of PTA as an alternative therapy in the management of these patients.  More than any other vascular segment, technical success and patency in the femoropopliteal artery depend on the characteristics of the lesion treated. Lesion classification has been defined by Society of Interventional Radiology Standards of Practice Committee according to the length, location of stenosis or occlusion and single or multiple lesions. The mean of technical success in reviewed studies was noted for 90.42% with sample Standard Deviation (SD) for 7.43% and Confidence Interval (CI) Approximations in level of 95% between 57.56% and 93.27% of patients with PAD (range 77-100%)

Survival Rate
The mean of survival rate at 1 year (

Developed Endovascular Techniques
In recently years many different endovascular techniques have been used for the management of peripheral artery diseases such as Drug-Coated Balloons (DCB), Bare Metal Stents (BMS) and Drug-Eluting Stents (DES) as well as numerous atherectomy devices.

Drug Coated Balloon (DCB)
The DCB delivers an anti-proliferative drug to the arterial wall during balloon angioplasty, 6-month primary patency of PTA in femoropopliteal disease with Drug-Coated (DCB) and Uncoated Balloons has been reviewed by Zhen Y et al. in 2018. They reported that DCB may improve early primary patency by inhibiting inflammation. A higher postoperative Neutrophil-Lymphocyte Ratio (NLR) was associated with early restenosis. Through a randomized trials in 2018 Chou HH et al. suggested that superior 2-year outcomes using DCB compared with uncoated balloon angioplasty and similar safety profiles in dialysis patients with femoropopliteal disease.

Bare-Metal Stent (BMS) and Drug Eluting Stent (DES)
Bare-metal stent is a stent with or without covering. Stent placement has been used with an acceptable success rate. Yang X et al. suggested that primary stent implantation had no advantage over balloon angioplasty in reducing restenosis or revascularization for infrapopliteal disease. Primary stent implantation seems to be a promising treatment for focal infrapopliteal lesions. Publication bias could not be ruled out, and the results should be treated with caution (Yang et al., 2014).
Cejna M et al. reported that after stent placement, the primary success rate was significantly higher than after PTA. However, 1-year angiographic and clinical/hemodynamic success was not improved.

Discussion
Percutaneous transluminal angioplasty using balloon catheter can be performed as the first choice in treatment of the CLI with high success-and patency rates, low complication rate, increase the quality of life and providing an acceptable survival.  reported that diabetic patients with CLI have high risks of amputation and death. In a dedicated diabetic foot center, the major amputation, ulcer recurrence, and major contralateral limb amputation rates were low. Coronary Artery Disease (CAD) is the leading cause of death and in patients with CAD history the impaired ejection fraction is the major independent prognostic factor.
Fagila et al. in 2009 also evaluated the feasibility of peripheral revascularization by PTA or By Pass Grafting (BPG) in diabetic patients with Critical Limb Ischemia (CLI). They presented that revascularization by PTA is highly feasible in diabetics with CLI. The feasibility of revascularization