Peripheral arterial disease

Peripheral arterial disease (PAD) is defined as chronic occlusive disease of the lower extremities

Pathophysiology

Chronic manifestation of systemic atherosclerosis in the arteries of the lower extremities
Think of the disease as a progression from asymptomatic PAD, to intermittent claudication (IC), to chronic limb-threatening ischaemia (CLTI)

Risk factors:

Age - rare in <40yo, may affect 25% of >80yo
Smoking (OR 2-4)
Diabetes (OR 2-4)
- Association modified by age and duration of diabetes
HTN
Dyslipidaemia
- Both elevated total cholesterol and reduced HDL levels
Obesity
Inflammation
Socioeconomic status

Anatomical distribution

Smokers - aortoiliac and fempop
Diabetes - tibiopedal or fempop
Claudication is usually a manifestation of a single segment of disease
CLTI usually means multiple levels of stenosis

History

Claudication (see separate topic)
- May not be present, as other comorbidities may limit exercise tolerance before claudication sets in
Ischaemic rest pain
- Typically occurs in forefoot
- Onset with flat or elevated limb
- Resolves with limb in dependent position (gravity facilitates perfusion)
- Classically occurs at night
- Seen with dependent rubor, pallor on elevation
- May have associated non-healing ulcers
- Represents a significant decrease in circulation
- Conditions mimicking rest pain:
  - Diabetic neuropathy - burning, hyperaesthesia, pins and needles. Constant, unrelieved by dependency.
  - Complex regional pain syndrome - generally originates in soft tissue or nerve injury - frequently burning.

Examination

In cases where there is a mismatch between history and physical exam, you might need to repeat the exam after exercise
Calf atrophy
Loss of hair growth over leg and foot
Thickening of nails
More advanced:
- Atrophy of skin
- Decrease in subcutaneous tissue
- Skin assumes fragile, shiny appearance
Severe ischaemia:
- Dependent rubor, which is replaced by pallor with elevation
- Distal part of leg, foot and digits may be reddish
Ischaemic ulcers:
- Small and circular
- Pale, grayish granulation tissue in the base
- Generally seen on toes, heels or fingertips (if seen more proximally, usually secondary to trauma). Can sometimes be pre-tibial.
- Usually painful, can progress to tissue necrosis and gangrene
- Absent surrounding inflammation
- Minimal bleeding with probing/debriding
- Always examine between the toes

Investigation:

ABI
- <0.9 is highly sensitive and specific
USS Doppler to locate lesions

Classification of PAD:

Note that Rutherford 6 has been defined as non-salvageable foot or necrosis extending anywhere proximal to the forefoot

Mild claudication = 300m

Moderate claudication = 200m

Severe claudication <100m

Asymptomatic disease:

May be asymptomatic because of mild disease, or adequate collateral supply, or limited activity for other reasons
Risk of progression not well-defined, but about 7% deteriorate to IC over a 5-year period
Manage by treating comorbidities and counselling risks

Claudication:

Clinical syndrome - reproducible leg pain brought on by exercise and relieved by rest
Muscular impairment due to exercise-induced ischaemia, aka effort discomfort.
- Most frequent presentation of lower extremity PAD
- Marker of systemic atherosclerosis
- Cramping/burning/aching muscular calf, thigh or buttock pain
  - Occurs with walking
  - Resolves with rest (complete relief within 5-10 minutes), but not necessary to sit
  - Reproduced at same exertion level/distance
  - Can be associated with numbness, fatigue
- Can also occur in upper limb:
  - Secondary to stenosis of subclavian or axillary arteries
  - Differentiate from thoracic outlet syndrome
- Distribution is reflective of affected vessels:
  - Aortoiliac - buttock/thigh
  - Femoropopliteal - thigh
  - Tibial - calf
- Signs that claudication is not due to arterial pathology:
  - Pain does not limit exertion
  - Pain does not involve calves or other major muscles in the leg
  - Pain does not resolve within 10 minutes of rest
Management:

Prognosis:
- 21% of IC patients experience deterioration of limb status over 5 years
- Especially if comorbidities are not controlled and continue smoking

Chronic limb-threatening ischaemia (sometimes called severe limb ischaemia or chronic limb ischaemia)

Either pain at rest or tissue loss (gangrene or non-healing ulceration). Typically, symptoms must be present for at least two weeks and be associated with an ankle pressure <50mmHg or a toe pressure <30mmHg to meet criteria.
- European consensus document defines CLI as:
  - Persistent recurring ischaemic rest pain requiring opiates for at least two weeks and ankle systolic <50mm Hg OR toe systolic <30mm Hg; or
  - Ulceration or gangrene of the foot or toes and ankle systolic <50mm Hg OR toe systolic <30mm Hg OR absent pedal pulses in diabetics
- Wolfe and Wyatt divided it into:
  - Subcritical ischaemia - rest pain and ankle pressure >40mm Hg
  - Critical ischaemia - rest pain and tissue loss or ankle pressure <40mm Hg
  - At one year, 27% of patients with subcritical ischaemia achieved limb survival without revascularisation, in contrast with only 5% in the critical ischaemia group. So, certain high-risk patients with subcritical ischaemia might be managed non-operatively, but anyone expected to live longer than 1-2 years will need either revascularisation or major limb amputation.
Severe impairment of limb perfusion, insufficient to maintain baseline tissue requirements
High all-cause mortality due mostly to cardiac risks
Multiple scoring systems available to define risk - use WIFi calculator to define one-year amputation risk (see below)

Management:

For all stages of PAD:
- Risk factor modification
  - Quit smoking - reduce CV mortality and slow overall disease progress
  - Treat dyslipidaemia
  - Treat HTN
  - Treat diabetes
  - Aspirin
Decision-making factors for PAD intervention:
- Underlying pathology and natural history
- Anatomic defect
  - TASC classification - see charts in each anatomical section
- Degree of ischaemia
- Availability of conduit
  - If no GSV available, endovascular becomes more attractive
- Comorbid conditions
  - Ability to tolerate an open procedure$
- Functional status
- Ambulation potential
- Suitability of anatomy for successful revascularisation
  - Runoff score - calculated based on the degree of occlusion and the relative contribution to outflow of each vessel. This formula translates into a description of the resistance in the outflow bed.
For claudication:
- Exercise therapy
  - Clearly-demonstrated improvements in pain-free ambulation and overall walking performance with structured exercise training
  - Essentially, walking 30-45 minutes, 3 to 4 times per week, for at least 12 weeks
  - Walk until the limit of claudication pain tolerance is reached, followed by a short period of rest until relief is obtained, then return to exercise
  - 1/3 of patients can't do it due to comorbidities, and another 1/3 won't do it
- Pharmacological management of claudication symptoms
  - Cilostazol (phosphodiesterase inhibitor)
    - Has the most data supporting its use, out of all the potential drugs for claudication
    - Smooth muscle relaxant, vasodilator
    - Increases pain-free and maximum walking distances
    - Does not reduce all-cause mortality or cardiovascular events or increase QoL
    - Contraindicated in heart failure, severe CKD/hepatic impairment
    - Aes headache, diarrhoea, dizziness, palpitations
    - Start with 50mg/day for 1 week, then 50mg BD for a week, then 100mg BD in week 3, which is the standard dose
  - Pentoxifylline
- Revascularization for intermittent claudication
  - 30% of claudication patients now undergo endovascular procedures
    - Should only be offered to patients that have optimised their risk factors and failed to show improvement
    - Should have work or lifestyle-limiting lesions
    - Should not have other comorbidities that will stop them from walking anyway
    - Should have decent GA risk profiles
    - Endovascular treatment is generally preferred to open surgery. The risk/benefit ratio doesn't really stack up for surgery, given the indication is not that strong in the first place.
For CLTI:
- Treatment options:
  - Medical only
    - Approximately 40% of limbs progress to amputation within 6 months
  - Revascularize (almost always preferred)
    - Endovascular
      - Low morbidity/mortality
      - Less durable
      - Might make future bypass harder
      - Concept of situational perfusion enhancement - just need to boost perfusion while an ulcer heals, then it doesn't matter. Therefore if it's an isolated ulcer with good prospect of healing, support endovascular treatment.
    - Open surgery
      - Favour when recurrent ulceration and persistent ischaemic symptoms are expected to exceed six months, and life expectancy > 2 years
  - Amputate
    - Can be an excellent option, sometimes offering expedient return to reasonable QoL
    - Indications:
      - Unreconstructable vascular disease
      - Failed revascularisation (due to disease progression, recurrent ischaemia, persistent infection/necrosis despite patent revascularisation)
      - Patient that is too sick, comorbid or debilitated to realise the functional benefits of revascularisation

Screening

Can be done, but only in high-risk patients
- ABI testing in asymptomatic patients:
  - Age >65
  - Age 50-64 with risk factors or family history
  - Anyone with established atherosclerosis

Surveillance

Unclear if any need to
Educate on warning signs of progression
Monitor more closely if they've undergone revascularisation
- Annual visit - foot check, symptoms, lifestyle/medication compliance, functional performance