1.1 Chronic ischemia of the lower extremity

It is a disease in which the tissues of the lower limbs suffer from a chronic lack of oxygen and nutrients needed for its proper function, either during exercise or even when the limb is at rest. The disease is characterized by high morbidity and mortality (but mainly due to atherosclerosis of the whole cardiovascular system, such as myocardial infarction and ischemic stroke)

1.1.1 Etiology of chronic ischemia of the lower extremity

·        Occlusive atherosclerosis of arteries of the lower extremities (most common)

·        Trombangiitis obliterans (young smokers)

·        Compression syndromes (entrapment of the popliteal artery etc.)

·        Cystic degeneration of media / adventitia

·        Vasculitis (inflammation of the blood vessels)

·        Recurrent microembolization into peripheral arteries (in aortic aneurysm, popliteal aneurysm, etc.)

·        etc.     

1.1.2 Risk factors for chronic ischemia of the lower extremity (similar to the general risk factors for all cardiovascular diseases):

• gender (3x more in men)

• age

• diabetes mellitus

• smoking

• hypertension

• hyperlipidemia

• hyperhomocysteinemia

• race (higher incidence in non-europoid patients)

• CRP                 

• renal insufficiency

1.1.3 Epidemiology of chronic ischemia of the lower extremity:

About 4  % of the population is affected (200 million people worldwide)

population over 50 years: 3 – 10 %

population over 70 years: 15 – 20 %

Ratio of symptomatic and asymptomatic form - 1: 3 to 1: 4

Co-incidence of ischemic lower limb disease and:

a) ischemic heart disease: 40 – 60 %

b) cerebrovascular disease: 25 – 50 %

1.1.4 Chronic ischemia of the lower extremity according to symptomatology:

a) asymptomatic form (up to 80 % of patients, symptomatology is obscured by other diseases, such as diabetes mellitus with neuropathy, reduced performance in cardiac patients prevents longer walking with manifestations of claudication, etc.)

b) symptomatic form (20 % of patients) - 2 grades of manifestations:

a. Intermittent Claudication (IC)

b. Chronic Limb-Threatening Ischemia (CLTI) – rest pain and / or ischemic defect (ulceration or gangrene) - a severely ischemic limb

1.1.5 Classification according to the nature of the patient's difficulties

- traditional division according to Fontaine (st. I - IV), more recently according to Rutherford (st. 0 - 6)

Bellow is a comparison of the two classifications

Fontain’s classification of chronic ischemia of the lower extramity:

I – asymptomatic state

IIa – claudications (above 200 m)

IIb – claudications (below 200 m)

IIc – claudications (below 50 m)

III – ischemic rest pain

IV – ischemic ulcer

Img. 1: Rutherford’s classification

Adapted from Cronenwett, Jack L. and Johnston, K. Wayne, "Rutherford's Vascular Surgery, 2-Volume Set (8th ed.)" (2014).

1.1.6 Intermittent claudications (IC)

Symptomatology:

muscle discomfort (fatigue, pain or cramps), repeatedly induced by muscle strain (walking, exercise), which subsides at rest within 10 minutes, the location of pain is related to the level of arterial damage (pain in the calf, thigh, buttocks)

Pathophysiology:

it is a reduction of the lumen area of the artery below a critical limit (hemodynamically significant stenosis when narrowing by half the diameter or by 75% of the lumen area)

in the case of multi-level disease, stenoses add up to multiply and blood flow to the periphery is reduced much more significantly

Diagnostics - basic examination:

complete history of the patient (family, personal, pharmacotherapy, work and social, allergies, physical functions)

physical examination (including aspection, palpation of pulsations on peripheral arteries and auscultation of possible murmurs)

Note:

The maximal walking distance given by the patient may underestimate the difficulties (the patient does not estimate the distance, disimulates). In contrast, non-palpable peripheral pulsations overestimate the incidence and the grade of chronic ischemia of the lower extremity (collaterals, etc.)

Therefore, if the chronic limb ischemia is suspected, it is necessary to use objective methods

Objective methods for the diagnosis of chronic ischemia of the lower extremity:

a) Stress test (walking, treadmill) - confirmation of the diagnosis, determination of the claudication interval (today, however, the patient's subjective difficulties are more important for the indication of treatment of), also monitoring the success of therapy

b) ABI (Ankle / Brachial Index) - the ratio of systolic pressure above the ankle to systolic pressure on the arm (special equipment is needed for the examination - narrow cuff for measuring ankle pressure and pencil doppler), normal value is 0.9-1.4 (pressure on the lower limb is normally higher than on the arm), a value below 0.9 is pathological, reflects an increased risk of cardiovascular disease, value above 1.4 is in uncompressible arteries (patients with mediocalcinosis - diabetes mellitus, renal insufficiency with calcium in the arteries), it is recommended to add TBI (Toe / Brachial Index) - examination of systolic pressure on the digital artery of the great toe, which is not usually affected by mediocalcinosis, special narrow cuff required, TBI value below 0.7 indicates for chronic ischemia of the lower extremity, below 0.3 for CLTI

c) Duplex ultrasonography - determination of location, hemodynamic significance and nature of stenoses, long-term monitoring of patency of reconstructions, but it is a subjective examination and also difficult to examine arteries in some areas (pelvic and calf arteries), and examination in obese patients

d) CT angiography of the arteries of the lower limbs - the gold standard in imaging arteries, iodine contrast agent is administered into a vein during examination, premedication is necessary in allergic patients, metformin must be discontinued in diabetics for 2 days before examination, in case of renal insufficiency patient's hydration is necessary before the examination, or adding of nephroprotective N-acetylcysteine ​​(ACC Long), the examination is also associated with radiation exposure. Therefore, we indicate the examination only if we consider a subsequent intervention. The examination is short, the result is primary axial sections, from which 3D reconstructions and analyzes can be created by post-processing for a more accurate assessment of the severity of arterial involvement and for the indication of treatment.

e) Digital subtraction angiography (DSA) - contrast X-ray examination, it is already an invasive method, after artery puncture, arteries are injected with iodine contrast agent (it is luminography, dorsal plaque in the artery is not visible on anteroposterior projection, therefore oblique projections are performed to unmasking of plaques or artery stenosis). The examination is associated with radiation exposure and administration of iodine contrast agent. Today, this method no longer belongs primarily to diagnostics, it is performed as an introduction to the endovascular therapeutic procedure

f) angiography using magnetic resonance (MRA) techniques - not a method of first choice, images overestimate arteries, unsuitable for patients with metal implants (ferromagnetic materials), also unsuitable for claustrophobia (closed MR system), long examination, risk of nephrogenic systemic fibrosis in patients with renal insufficiency after administration gadolinium contrast agents

Therapy of patients with chronic ischemia of the lower extremity in the stage of intermittent claudication (IC):

A) conservative - the priority is not the treatment of claudication, but influencing the risk factors of atherosclerosis and thus the prevention of cardiovascular complications (myocardial infarction, ischemic stroke)

a) structured muscle training - walking into pain 3 times a week for 60 minutes, the goal is to develop collaterals, the effect is evaluated in 3-6 months, according to available studies it is possible to extend the claudication distance by 150 - 180%, but therapy encounters low patient compliance

b) modification of risk factors - no smoking, weight reduction, therapy of hyperlipidemia, compensation of hypertension and diabetes

c) pharmacotherapy - antiplatelet agents (acetylsalicylic acid, clopidogrel; combination only after interventions or in high-risk patients); vasodilators (naphthidrofuryl, cilostazol, sulodexide X effect not confirmed for pentoxifylline and prostaglandins); statins (reduction of LDL cholesterol below 2.6 mmol,  pleiomorphic effect on the ongoing inflammatory process with subsequent stabilization of plaques etc.)

B) interventional treatment

The patient is limited in everyday life and conservative treatment options had insufficient effect on the state of the patient

The following should be considered:

a) clinical parameters (degree of ischemia, comorbidities, smoking)

b) anatomical parameters (location and length of stenosis / occlusion, quality of the outflow tract, number of treated arterial lesions)

We usually proceed from proximal to distal revascularisation (first it is necessary to improve blood inflow to the limb, then proceed to peripheral reconstruction)

Classification of lesions according to TASC II

- a guide to the type of revascularization according to morphology

Recommendations: Short and isolated lesions (TASC A, possibly also B) - rather endovascular treatment, extensive and complicated arterial disease of the given locality (TASC C and especially D) - rather surgical treatment

It is only a recommendation and it is necessary to assess each patient individually. Furthermore, it is necessary to take into account the experience of the workplace and the preferred procedures for dealing with arterial lesions.

A)     aorto-iliac region - TASC II

Img. 2

Adapted from Norgren L, Hiatt WR, Dormandy et al.: Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg, 2007, 45: 1, suppl. 5, p. S5A-S67A

B)     sub-inguinal region - TASC II

Img. 3

Adapted from Norgren L, Hiatt WR, Dormandy et al.: Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg, 2007, 45: 1, suppl. 5, p. S5A-S67A

Endovascular therapy of intermittent claudications

- PTA (percutaneous transluminal angioplasty), possibly with stent implantation (steel or nitinol alloy, implantation primarily, or in case of artery dissection after PTA, they are not implanted in complicated areas (groin before possible surgery, popliteal artery due to the risk of stent fracture), PTA on calf arteries is not indicated in stage of intermitent claudications - risk of arterial thrombosis and acute limb ischemia). After the procedure, low molecular weight heparin (LMWH) is administered subcutaneously, with conversion to antiplatelet therapy (after implantation of an anopyrin + thrombex dual antiplatelet stent for 1-2 months, then permanent mono-antiplatelet with acetylsalicylic acid, oral anticoagulation only if indicated by a cardiologist). The patient is monitored sonographically to rule out early or late arterial restenosis after the intervention.

Surgical therapy in intermittent claudication

a) Aorto-femoral area

 - anatomic reconstructions: aorto-femoral or aorto-bifemoral bypass (open surgery, possibly laparoscopically or robotically) with a knitted vascular prosthesis with collagen, good long-term patency, other options: iliac-femoral bypass, possibly supplemented by sub-inguinal reconstruction to the popliteal or calf artery

- extra-anatomic reconstructions: do not follow the physiological course of arteries, reinforced ePTFE prosthesis used, it has worse patency rates: axillo-femoral or axillo-bifemoral bypass, obturator bypass (from the iliac artery through the foramen obturatum to the groin), iliac-femoral or femoro-femoral cross-over bypass)

Note: in case of infected defect at the time of implantation, or in case of infection of vascular reconstruction - replacement with autologous femoral vein, cryopreserved or fresh allograft, more recently reconstruction from bovine pericardium or vascular prosthesis impregnated with silver and soaked in rifampicin

b) Femoro-popliteal region

- proximal femoro-popliteal bypass (distal anastomosis to the proximal part of the popliteal artery) or distal (to the distal popliteal artery below the knee joint), by a vascular prosthesis or rather by a saphenous vein graft, reversed routing, or non-reversed with the need to cancel the valves using a valvulotome)

- endarterectomy and patch angioplasty by vascular prosthesis or venous graft (in patients with infected wound on the limb, with a higher risk of infection reconstruction), hybrid procedures (simultaneous endovascular and angiosurgical procedures)

Note: distal reconstructions (so called crural and pedal bypasses) are not usually indicated in patients in the stage of intermittent claudication, they are reserved for critical limb threatening ischemia as an attempt to save it.

Prognosis in patients with intermittent claudication:

During a follow up of the patients for 5 years - in most patients the difficulties are similar, only in 1-3 % of cases the limb reaches the stage of critical limb threatening ischemia (CLTI) and the risk of limb amputation within 5 years is also 1-3 %.

X

But 20 % of patients suffer from myocardial infarction or ischemic stroke and 10-15 % of patients die from cardiovascular causes

1.1.7 Chronic Limb-Threatening Ischemia (CLTI)

Definition: rest pain in the affected limb and / or even an ischemic defect or gangrene of the limb

Prognosis of CLTI: significantly worse than in intermittent claudication (IC)

Dilemmas:

• whether to treat conservatively or interventionally

• whether to amputate or revascularize

• whether to perform endovascular or open surgery

Diagnostics:

the basic diagnostic tests are identical with patients with intermittent claudication

in addition, there are other options: tcpO2 (transcutaneous oxygen tension in the tissues, to assess the potential to heal ischemic defects conservatively, pressure above 20-30 mmHg is required), response to local therapy etc.

Therapy of patients in the CLTI stage:

It is an attempt to save a severely ischemic limb

The principle of IRA is applied (management of Infection, subsequent revascularization, then low amputation of part of the limb with gangrene)

Angiosome is considered when planning revascularization (reconstruction should focus on the location of the defect and the artery that directly supplies this area with blood), but due to the possibility of collateral filling of other arteries, revascularization with the outflow to any unaffected distal artery can be performed

Options for the revascularization in CLTI

a) endovascular therapy - PTA and stents, simultaneous treatment on several levels, including calf and pedal arteries

b) surgical therapy

- crural/tibial bypass (from the common femoral artery, superficial femoral artery or popliteal artery to the calf artery - anterior or posterior tibial artery, also difficult bypasses to the fibular artery; the operation always begins with surgical revision of the outflow shin artery, whether the reconstruction is technically possible, and revision of the saphenous vein as a venous graft for revascularization

- pedal bypass - revascularization from the femoral or popliteal artery to the dorsalis pedis or to the plantaris communis artery (continuation of the posterior tibialis below the level of the talus) or its branches, patent soft artery and good quality venous graft are necessary

Other treatment options - examples (these are not routine procedures, but a kind of extreme therapy in an effort to save a severely ischemic lower limb):

a) alternative venous grafts - vena saphena parva, venous graft from the contralateral extremity limb (cannot be used in case of concurrent ischemia on the other limb), superficial veins from upper limbs (as a spliced graft from several parts of the veins), venous allograft from a donor

b) stem cells - collection of vascular precursors and their application directly to the site of critical limb ischemia to induce collateral flow formation

c) hyperbaric oxygen therapy - therapy with increased oxygen tension leads to healing or improvement of the ischemic ulcer in selected patients

d) distal venous revascularization - rarely

 Prognosis in patients with CLTI:

As early as 1 year after diagnosis, 25 % of patients die of cardiovascular causes, 45 % of patients live with both limbs, 30 % survive after limb amputation

After successful distal revascularization, the ischemic defect (or wound after low amputation) often heals, and even in the case of subsequent closure of the reconstruction, the condition of the limb often remains stable for many years, but with further progression of ischemia, the possibilities of revascularization are often exhausted.

1.2. Chronic upper limb ischemia

General description of the disease:

Etiology - the most common causes are atherosclerosis, mediocalcinosis, arteriitis obliterans (Bürger), Takayasu arteriitis, post-radiation arteritis, TOS (Thoracic Outlet Syndrome), idiopathic Raynaud's disease and Raynaud's phenomenon in collagenosis, consequences of trauma, etc.

Epidemiology - less common than in the lower limbs

Diagnosis - clinic, physical examination, ultrasound, in some unclear cases CT of the arteries

Therapy - thromboembolectomy with a Fogarty catheter, event. bypass revascularization

Subclavian steal syndrome

Etiology: most often atherosclerotic stenosis of the subclavian artery, there is a reversal blood flow in the ipsilateral vertebral artery, especially during upper limb exertion, with manifestations of ischemia in the posterior cerebral circulation (dizziness, falls, etc.)

Diagnosis: physical examination, pressure difference on both upper limbs by more than 20-30mmHg, ultrasound of arteries (neurosonological examination, examination of blood flow in arteries and its direction), CT of arteries of the aortic arch

Therapy: PTA and stent insertion into the subclavian artery, access from the femoral artery, in case of failure retrograde approach from the ipsilateral brachial artery, or open surgery – carotic-subclavian bypass, reconstruction with aortic arc involvement (after sternotomy, cardiac surgeon).