Patterns, pearls and practical medicine

Peripheral arterial disease

This section mostly covers lower-extremity atherosclerotic arterial disease. Aortic disease and cerebrovascular disease are covered elsewhere.
Early diagnosis useful, even if asymptomatic, as presence of PAD correlates to an increase in CV risk

Risk factors

The standard CV risk factors apply, though some genetic predispositions especially in regards to thoracic aortic dissection
People with PAD are 3 x more likely to die of CV disease than someone without PAD
Not all people with acute ischemia have risk factors
DM and smoking increase risk of PAD by about 3-fold
60% of those with chronic limb threatening ischemia have DM (and patients less likely to be symptomatic due to peripheral neuropathy)
DM actually reduces the risk of aortic aneurysm and dissection
Generally speaking PAD is a bit more common in women

Vascular examination

Assess for bruits (femoral, aortic, carotid) and pulses
- - Check carotid (a bruit doubles the risk of CV death), heart, abdomen, femorals, legs and feet (popliteal, dorsalis pedis, TP)
  - Can check BP in both arms
Legs
- - Ulcers
  - Temperature disparity between legs
  - Muscle atrophy
  - Skin changes (thin, shiny, discoloured, heel tissue loss, hair loss)
  - Capillary Refill Time (although not reliable)
Functional status

Chronic limb ischaemia – symptoms and aetiology

Causes
- - Mainly caused by atherosclerosis
  - Occasionally caused by vasculitis, fibromuscular dysplasia, thromboembolism, Buerger’s disease, trauma, dissection, entrapment syndromes, cystic adventitial disease
Asymptomatic peripheral arterial disease
- - Might be picked up by clinical exam, or imaging for other reasons
  - May have masked effort-related symptoms due to reduced walking capacity (for reasons other than PAD), or reduced pain sensitivity
Symptomatic peripheral arterial disease
- - Chronic lower limb wounds
  - Intermittent claudication
    - - Pain in legs on walking – often cramp-like in the calf (most often)/thigh/buttock at a predictable distance, relieved by rest.
      - Often remains stable, 15% worsen over 5 years, 5% develop critical ischaemia.
      - Amputation eventually required in 1-2%
      - Differentials include nerve root compression, spinal stenosis (bilateral pain, worse on standing, better on flexing lumbar spine), arthritis (eg hip, foot, ankle)
  - Chronic limb threatening ischaemia (CLTI) is the more severe end of the spectrum
    - - Defined as any of: ischaemic rest pain, gangrene or non-healing chronic wound (>2 weeks) and critical limb perfusion (ankle pressure <50mmHg, toe pressure <30mmHg)
      - Rest pain can be worse at night, people may sleep with leg hanging out of bed
      - Tissue loss (ulcers, gangrene, infections)
      - Poor prognosis without intervention
      - Risk of limb loss – even greater if co-existent wound infection or DM
      - 70% get revascularized. Some have amputations.
      - 5-year all-cause mortality 50% (worse than some cancers)
      - Can be confused with other causes of foot pain (planatar fasciitis gout, arthritis)
      - If wounds present, can assess risk of amputation

Investigations in suspected chronic PAD

Bloods – HbA1c, lipids, TFTs, LFTs, CRP
ABPI (ankle brachial pressure index)
- - Check when supine
  - Put BP cuff on upper arm and use doppler to check signal – inflate until it stops. Repeat on the ankle checking signal in Tibialis Posterior and Dorsalis Pedis pulses. Do both arms and both legs.
  - Divide highest ankle systolic pressure by highest brachial systolic pressure
  - Normal 1-1.4 (or 0.8-1.3, depends on the guideline)
  - >1.4 suggests non-compressible vessels /arterial calcification eg DM, severe CKD, advanced age, RA, vasculitis
  - <0.9 suggests PAD and <0.5 suggests severe PAD
  - 5-0.8 – PAD, or mixed arterial/venous disease
  - However if ABPI normal – doesn’t exclude PAD
  - Sensitivity for PAD is around 75% and specificity around 90%
  - If symptoms suggestive but ABPI >0.9, can repeat it after exercising, which can help diagnose stenoses (a decrease of >20% can suggest PAD)
  - If value very high (>1.4) – consider checking TBI, TcPO2, distal doppler waveforms.
Duplex USS
- - Best first line imaging test for PAD screening and diagnosis
  - Sensitivity of 88% and specificity of 95% for >50% stenosis detection. Can also diagnose non-atherosclerotic lesions
CT angio / MR angio
- - For revascularisation planning
  - CTA generally better than MRA (but can overestimate stenosis due to blooming effect)
Echo
- - Worth screening for co-existent HF as 25% of patients with PAD have LV dysfunction (mostly due to CAD).
  - Aortic stenosis is also commonly associated with PAD

Management of chronic PAD

General measures – reduce CV risk, foot care/podiatry, exercise programme for intermittent claudication
For asymptomatic PAD – medical treatment and vascular team assessment
For symptomatic PAD without wounds – medical treatment, home-based or supervised exercise training (unless chronic limb threatening ischaemia), vascular team assessment and consider intervention
For PAD with wounds – wound care and healing before exercise regime
Choice of intervention depends on the cause, site and feasibility
Vascular interventions include catheter directed thrombolysis, endarterectomy, bypass surgery, angioplasty / stenting, amputation
Revascularisation might be fem-pop, or aorto-iliac or below the knee
Amputation usually best option for gangrene, or when revascularisation fails
Below the knee amputation allows for better mobility / use of a prothesis, and above the knee often best if patient bedbound
Exercise training
- - Walking best
  - May be limited by pain, but some patients may benefit to exercising though pain if can tolerate
  - Should be at least 3 x week, >30 mins per session
Medications
- - Analgesia
  - Treat hypertension
    - - ACE-I or ARBs probably 1^st line, and advised in unilateral RAS
      - Can use betablockers despite commonly held belief they are contraindicated
  - Statin
  - Single anti-platelet
    - - Aspirin has not been shown to reduce rates of amputation or revascularisation, but data lacking
      - Improves CV prognosis nonetheless
      - Clopidogrel may be slightly better than aspirin if symptomatic
  - Dual antiplatelets – only generally used after endovascular therapy for 1-3 months. Long term treatment not recommended.
  - Treat DM and aim HbA1c <53. Both SGLT2i and GLP-1RAs but particularly useful
  - Naftidrofuryl oxalate for intermittent claudication if exercise hasn’t helped and not surgical candidate
  - DOAC
    - - Indicated alongside aspirin in high-risk limb presentation eg CLTI, previous amputation or revascularisation, or high-risk comorbidities (DM, HF, poly-vascular disease) without high bleeding risk
      - Also used after revascularisation
      - Use ‘vascular dose’ of 2.5mg rivaroxaban BD
      - Not used alone in PAD – should be with an antiplatelet
Spinal cord stimulation – an option for CLTI and no revascularisation options. Reduces pain and amputation rate, but no effect on ulcer healing

Acute lower limb ischaemia

Causes
- - Usually due to rupture of an atherosclerotic plaque and subsequent thrombosis (80%).
  - Occasionally caused by cardiac embolization, aortic dissection, graft thrombosis, thrombosis of popliteal aneurysm, trauma, hypercoagulable states, iatrogenic, phlegmasia cerulea dolens, ergotism
Clinical features
- - Sudden decrease in limb perfusion (< 2 weeks).
  - Leg pain / sudden deterioration in claudication
  - Loss of pulses, pallor, coldness, cyanosis, loss of sensation (or the 6 Ps – pain, pulseless, pallor, power loss, paraesthesia, perishingly cold)
  - Onset very acute if due to embolisation, with white limb, and more gradual if due to thrombosis due to collaterals
  - Can be complicated by compartment syndrome and reperfusion injury (rhabdo, arrythmias, AKI, MOF, DIC once blood flow restored)
  - Often misdiagnosed – as peripheral neuropathy, DVT, chronic ischaemia with low cardiac output
  - Higher rates of amputation the longer the delay to revascularisation
Assessment
- - Symptom duration is key
  - Neurology is also key – sensory and motor (these are important signs of limb threat and require emergency imaging and revascularization). Paralysis suggest limb may not be salvageable
  - Graded 1, 2A, 2B or 3
    - - 1 has best prognosis. Both arterial and venous signal on doppler
      - 2A involves no sensory loss, or just in toes. No motor deficit. Loss of arterial doppler signal.
      - 2B sensory loss in more than toes, and mild/mod motor deficit
      - 3 involves profound sensory loss, paralysis, elevated biomarkers, no cap refill, no venous or arterial signal on doppler
  - Urgent imaging – consider duplex, CTA, MRA (but imaging should not delay treatment)
  - Check CK (once elevated, it’s a late sign)
  - Later may require Holter, echo and aortic imaging as embolism a common cause. Also consider thrombophilia screening.
Treatment
- - Analgesia
  - Anticoagulate – usually with unfractionated heparin infusion
  - IV fluids
  - Treat acidosis and hyperkalamia if required
  - Urgent vascular review to consider intervention

Upper limb PAD

Upper limb digital ischaemia is most frequently caused by non-atherosclerotic aetiologies, including thrombo-embolism, systemic sclerosis, idiopathic, thromboangiitis obliterans, iatrogenic, or cancer
Atherosclerotic upper-limb artery disease is most frequently located in the subclavian artery
- - Inter-arm BP difference can suggest subclavian stenosis
  - Can lead to strokes, subclavian steal or severe ishcaemia
Subclavian steal syndrome
- - Can cause visual disturbances, syncope, ataxia, vertigo, dysphasia, dysarthria, and facial sensory deficits during arm movements
  - Diagnose with duplex US. Often needs CTA too.
  - Percutaneous angioplasty for subclavian arterial stenosis is often used with stenting

Other arterial disease

Renal artery stenosis
- - Hypertension at a young age, severe hypertension associated with CKD or HF, rapid worsening of previously controlled BP, or resistant hypertension
  - Abdominal bruit
  - Worsening renal function after starting ACEi
  - Unexplained atrophic kidney or discrepancy in kidney size
  - Flash pulmonary oedema
  - Diagnose by duplex US (often 1^st line), MRA or CTA
  - May need catheter-based angiography if considering intervention
  - Decision to intervene is based on viability of kidney, risk and imaging findings
Acute mesenteric ischaemia
- - Can be due to arterial emboli, thrombosis in situ, superior mesenteric artery construction, venous thrombosis
  - May present with intense sudden abdo pain, vomiting and diarrhoea
  - May be minimal clinical findings
  - Might be a history of AF
  - Do CTA
  - Most patients require immediate revascularization to survive (either open surgery or endovascular)
Chronic mesenteric artery disease
- - Symptoms typically manifest when at least two mesenteric vessels are involved due to extensive collaterals
  - May be post-prandial abdominal pain, weight loss, diarrhoea or constipation.
  - Patients may develop food aversion to avoid pain, but their appetite remains unaffected, unlike cancer
  - Bloods often normal
  - Do CTA and consider intervention (again surgery vs endovascular, the former has better long-term results, the latter lower complications)