**3.2 The anatomic distribution and severity of lower limb arterial occlusive disease related to perioperative MACE**

A reduction in arterial lumen more than 75% of cross-sectional area or 50% of luminal diameter causes the significant stenosis which are limiting blood flow to

*Cardiovascular Complications Related to Lower Limb Revascularization and Drug-Delivering… DOI: http://dx.doi.org/10.5772/intechopen.107973*

#### **Figure 5.**

*The energy losses in the arterial stenotic lesion according to Poiseuille's law and the reduction in blood flow across an arterial stenosis due to the inertial energy losses by the turbulent flow in entrance and exit effects. Q, flow rate; ΔP, pressure gradient (P1-P2); r, radius; L, length; η, fluid viscosity.*

lower limbs [3, 35]. From the Poiseuille's law [44, 45], the flow rate (Q ) of the fluid in a hollow cylindrical shape tube is a direct variation of the fluid pressure (ΔP) and tube's radius (r) whereas the tube's length (L) and fluid viscosity (η) is indirect variation of the flow rate (Eq. (5)) (**Figure 5**).

$$\mathbf{Q} = \Delta \mathbf{P} \pi \mathbf{r}^4 / 8 \eta \mathbf{L} \tag{5}$$

Therefore, the stenotic or occlusive arterial lesions are affecting to the decreasing of blood flow rate in the PAD of lower extremity. A severe stenosis and long length of the arterial lesions, meaning a greater decrease in blood flow and perfusion to lower limb when compare with a mild stenosis and short lesions. For the geographic pattern of stenosis. The irregular and abrupt change of arterial lumen results in more reduction of blood flow rate than a gradual tapering of the lumen (**Figure 5**) [37, 44, 45].

In addition, the blood flow rate is also affected by the anatomic distribution of a stenosis or occlusion. The inertial losses, an entry and exit of blood in a stenosis area which are resulting in the reduction of blood flow rate is important factors to the lower limb perfusion. The abrupt change of luminal stenosis of the entry site and expansion of the flow stream of the exit site has created the dissipation of kinetic energy in a zone of turbulence flow (**Figure 3**). Thus, the multiple short stenotic lesions result in more energy losses than single long stenotic lesion [37, 44, 45]. Commonly, the anatomic distribution of atherosclerosis in CLTI patients usually presents in multilevel occlusive disease [3]. The concomitant FP occlusive disease and IP arterial occlusive lesions usually occurred. The pattern of disease often presents the long occlusion or multiple severe stenosis lesions in CLTI [3, 35, 39].

In mild to moderate severity of LEAD, a stenosis vascular lesions are not influenced to lower limb perfusion at resting blood flow rates but become critical when flow rates are increased by reactive hyperemia through the vasodilatation which produce the intermittent claudication symptom during walking or exercise [12, 37, 43].

So, the revascularization strategy in patients with intermittent claudication have only increased flow rate to prevent the insufficiency perfusion during walking or exercise. In CLTI patients, the goal of lower limb revascularization is to increase the blood flow rate which is ensuring adequate straight inline to the wound or maintain resting metabolic requirement of lower limb for tissue loss and rest pain, respectively [3, 35, 43]. Therefore, the alterations of physiologic flow rate during revascularization in intermittent claudication is lower than CLTI which more extensive calcified and severe atherosclerotic stenotic or occlusive lesions. Moreover, the associated coronary and cerebrovascular disease are usually occurred and more severity in patients with extensive anatomic distribution of atherosclerotic CLTI [14, 35]. Altogether, the perioperative MACE is frequently present during revascularization in CLTI which is severe, multilevel atherosclerotic disease.

### **3.3 Type of lower limb revascularization related to MACE**

The best choice for lower limb revascularization is dependent on multiple factors which determine, by the characteristic of patients, disease, and expertise of physicians. The patient's co-morbidities, anatomic distribution and severity of disease, patient's clinical presentation or degree of tissue loss, availability of venous conduit for below the knee lesion as well as doctor's preference, and experience (doctors included vascular surgeons, interventionist, cardiologist, and angiologist) are established to the important factors to determine the type of revascularization [14, 37, 43, 46–48].

Currently, the "endovascular-first strategy" or "endovascular-first approach" for lower limb revascularization in patients with LEAD have increased significantly [46]. This minimally invasive approach is aimed to decrease the morbidity and mortality of the open vascular bypass procedure. There are a lot of publications report the ET in CLTI patients with suprainguinal disease (aortoiliac disease, AIOD) and infrainguinal disease such as FP, IP, and inframalleolar arteries segment (IM) [3, 35, 46, 47]. Complex, severe, multilevel atherosclerotic occlusive can performed revascularization by ET which is associated with amputation free survival improvement over the long-term with modest relative increased risk of reintervention [47]. CLTI patients with multiple co-morbidities, the initial surgical bypass is associated with poorer amputation-free survival compare with an endovascular-first approach due to increased severity of wounds at the time of presentation [46]. The study of CLTI in the Vascular Quality Initiative (VQI) reports the ET procedures are more offered to older and more co-morbidities patients. The patients who performed ET demonstrated the lower perioperative mortality when compare with open vascular bypass. However, the benefit of ET is not demonstrated when treating patients with few comorbidities or less advanced disease [48]. Finally, the CLTI which is the advance form of atherosclerosis of LEAD are usually involved to other vascular bed. The coexisting multiple co-morbidities due to systemic atherosclerotic disease including CAD and CVA are usually present in CLTI patients who plan for revascularization [34, 43]. Therefore, the endovascular-first strategy is still the preferred approach for the majority of CLTI patients. The open vascular bypass procedures are more likely to perform for reintervention procedures, young patients, and few comorbidities [48].

However, long term patency and freedom from reintervention rate of open vascular bypass procedures are better than ET. The selection of CLTI patients to performed open vascular bypass or ET should be considered carefully. The patient's based individual approach and risk–benefit consideration including the risk of perioperative *Cardiovascular Complications Related to Lower Limb Revascularization and Drug-Delivering… DOI: http://dx.doi.org/10.5772/intechopen.107973*

MACE, MALE, quality of life, morbidity, and mortality of each procedure are very important [3, 35, 43].

#### *3.3.1 MACE related to open vascular bypass*

The open vascular bypass procedures are significant impact of the physiological changes of the cardiovascular system by decreasing afterload which is loaded to the cardiac function [41–43]. The degree of revascularization and increasing of blood flow rate of open vascular bypass procedures are determined by the level of inflow artery, quality of distal runoff and unimpaired of foot arch arteries as well as the total length of the bypass which cross to the atherosclerotic lesion. Higher or larger arterial inflow, better quality of distal runoff and foot arch arteries, longer length of bypass are more increasing of blood flow and pressure to lower limb [37, 41–43, 49]. Example: The CLTI patients with multisegmented AIOD, FP, and IP disease who performed common iliac artery to tibial artery bypass which allow inline flow to the complete foot arch artery is a higher physiologic alteration of the cardiovascular system during revascularization than the CLTI patients who performed distal superficial femoral artery to tibial artery short bypass with incomplete foot arch artery to treat the isolated IP disease [37, 41]. The in-situ anatomical bypass procedures such as aortobifemoral bypass is a higher risk of perioperative MACE than extra-anatomical bypass such as axillobifemoral bypass due to more rapid increasing of blood flow rate, third space loss from abdominal exploration of the in-situ anatomical bypass procedures. Therefore, a complexity and planning of open vascular bypass are related to risk of perioperative MACE. Comparing with ET, the open vascular bypass procedure is a higher risk of perioperative MACE because more rapid increasing of blood flow and more alteration of the cardiovascular system (**Figure 6**).

#### **Figure 6.**

*The impact of revascularization in CLTI patients with TASC-D AIOD (A) open vascular bypass by vascular bifurcate graft (B) and endovascular treatment by stent graft (C) on the blood flow of lower limb and cardiovascular system. TASC, trans-Atlantic inter-society consensus; AIOD, aortoiliac occlusive disease; CLTI, chronic limb-threatening ischemia.*

The risk of open vascular bypass also includes the risk of anesthesia which related to perioperative MACE. Most of the open bypass procedure needs to perform under general or spinal anesthesia which impact on the cardiovascular system [37]. Most anesthetic agent and muscle relaxant during anesthesia are negative impact on the cardiovascular system. The potential complications and morbidities of open vascular bypass procedures include surgical wound infection, bleeding, adjacent tissue/organ injury (such as nerve injury) due to the vessel dissection, and manipulation in open vascular bypass operation [37]. The surgical infection is usually present in CLTI with a history of wound infection, major tissue loss, diabetic foot ulcer, below the knee vascular bypass, redo-open vascular bypass in the previous surgical area [3, 13, 37]. All perioperative non-cardiovascular complication led to reintervention or the stress and inflammation which are precipitate the perioperative MACE.

The risk of bleeding and perianastomotic pseudoaneurysm or hematoma are a significant increase in patient who take multiple antiplatelets or anticoagulants [35]. Most of perianastomotic pseudoaneurysm requires the surgical treatment which increases the perioperative MACE due to anesthesia and bleeding during the redo operation. The CLTI patients with coexisting ACS or CVD usually take dual antiplatelet such as aspirin and clopidogrel especially in CAD patients with recent percutaneous coronary intervention (PCI) with stent [35, 37]. The cardiac arrhythmic patients need to take the oral anticoagulants to prevent intracardiac clot formation. The patients who had a history of CVD usually take an anticoagulant or antiplatelet to prevent recurrent stroke. So, the open vascular bypass procedures in CLTI patients with coexisting CAD and CVD are higher risk of bleeding and wound complications than ET. On the other hand, the discontinuation of antiplatelets or anticoagulants in highrisk MACE patients preoperatively are prohibited and increasing of the incidence of recurrent MACE during lower limb revascularization [14, 35, 37]. The appropriate post-operative care of CLTI patients who underwent open vascular bypass including wound care, ambulation training, rehabilitation, and atherosclerotic risk factors modification are decreased risk of perioperative complications, perioperative MACE, and long-term MACE [37, 42, 50].

#### *3.3.2 MACE related to endovascular treatment*

The ET can decrease the risk of perioperative MACE through the two main mechanisms. (1) The risk of anesthesia, proper anesthesia is allowing safe, less complication, comfortable, and well operated of the interventions. Most of CLTI patients are classified in class III and class IV of the American Society of Anesthesiologists (ASA) physical status due to severe systemic disease such as poorly controlled DM, hypertension, HF, history of ACS or CVD, chronic kidney disease, etc. High ASA physical status is associated with perioperative morbidity and mortality, namely, perioperative MACE [37]. Most of the ET procedures are preferred under local anesthesia with adequate sedation or analgesia which decreased the risk of general and spinal anesthesia. Anesthetic agents in general and spinal anesthesia usually impacts on the cardiovascular system [37]. (2) The risk of the operation, ET procedures reported less bleeding, less surgical wound complications, and less adjacent tissue/organ injury when compare with open vascular bypass procedures. The incidence of the surgical infection such as groin wound infection, vascular graft infection is very low in CLTI patients who underwent ET. In addition, less post-operative pain due to minimally invasive procedure allow early ambulation in patients with CLTI when compare with open vascular bypass. Thus, the risk of post-operative complications due to

*Cardiovascular Complications Related to Lower Limb Revascularization and Drug-Delivering… DOI: http://dx.doi.org/10.5772/intechopen.107973*

non-ambulatory status including deep vein thrombosis (DVT), lung atelectasis, aspiration pneumonia, urinary tract infection, and bowel ileus are decreased [37, 42, 50]. Especially in suprainguinal lesion or AIOD, the in-situ open vascular bypass procedure is needed for abdominal exploration which is significantly higher morbidity and mortality when compare with ET or hybrid operation. Because of the development of a new generation of aortoiliac stent and endograft, ET was associated with high initial technical success with equal short- to mid-term patency rate and fewer in-hospital systemic complications when compare with open vascular bypass for simple and complex AIOD [35, 37, 49].

To avoid the major operation of open vascular bypass procedures, the advance age and multiple co-morbidities usually undergo revascularized procedure by ET [48]. So, the risk of perioperative MACE during ET due to revascularization process are still present in the real-world practice because of poor cardiac reserve and multiple comorbidities such as CAD, HF and CVD. The burden to cardiovascular system depends on the degree of physiologic changes after ET because of the increasing of blood flow to the lower extremity after successful revascularization [41, 42, 48]. The high level of occlusion (such as suprainguinal disease) and single stage multisegmented revascularization are high risk of perioperative MACE due to rapidly decreasing of afterload and rapid increasing of blood flow to lower limbs (**Figure 6**) [41, 42]. In addition, the new technology of the antiproliferative agent embeds endovascular device which has increased the patency of the target arterial lesion are increasing to use in CLTI patients who undergo ET [21–26]. Some cohort study and meta-analysis report the high incidence of MACE in CLTI patients after revascularization by DCB and DES. The complication such as aneurysmal degeneration in patients with ET are reported [27–31]. Therefore, the MACE related to DCB, and DES is still debatable [30, 32]. The mechanism of drug-delivering technology and pathophysiology of MACE which may precipitated by DCB and DES, and latest evidence of the relationship between drug-delivering technology and MACE and potential complications are described under the Section 4 of this Chapter.
