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Long Case Viva Questions on Peripheral Arterial Disease (PAD)

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SECTION 1: Introduction and Epidemiology

• PAD is atherosclerotic occlusive disease of the peripheral (predominantly lower limb) arteries, causing a spectrum from asymptomatic stenosis to limb-threatening ischemia.
• It is age-dependent, underdiagnosed, and undertreated. The PARTNERS program found PAD in 29% of primary care patients aged >70 or aged 50-69 with smoking/diabetes history.
• More than 50% of patients with PAD are entirely asymptomatic.
• Clinically significant because it is a powerful independent predictor of mortality - PAD patients have a ~4-fold higher risk of MI and 2-3x higher risk of stroke vs. non-PAD patients. Approximately 40% of patients with atherosclerotic vascular disease have disease in more than one vascular bed.
• Patients with critical limb ischemia (CLI) have an annual mortality rate of ~25%.

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• Modifiable: Cigarette smoking (single most important), diabetes mellitus, hypertension, hyperlipidaemia, obesity, sedentary lifestyle.
• Non-modifiable: Age (>50 years), male sex, family history, ethnicity (higher in Black populations).
• Emerging: Hyperhomocysteinaemia, elevated lipoprotein(a), chronic kidney disease (CKD), inflammatory markers (CRP).
• Smoking is particularly important - it roughly doubles the risk of PAD and is directly associated with claudication severity and amputation risk.

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SECTION 2: History Taking

• Claudication history:
  • Onset, site, character of pain (cramping/aching in muscle groups)
  • Claudication distance (how far before pain starts) - note this varies little day to day
  • Relieved by standing still within 5 minutes (differentiates from nerve compression, which requires sitting)
  • Pain not present on first step (unlike osteoarthritis)
  • Worsening with uphill walking, increased speed, carrying weights
• Rest pain:
  • Pain in foot/calf at rest, worse at night, worse with leg elevation
  • Patient hangs foot out of bed or sleeps in chair for relief (gravity effect)
  • Indicates more severe ischemia than claudication
• Skin changes: Non-healing ulcers, blackened tissue (gangrene)
• Cardiovascular review: Ask about chest pain, dyspnoea, palpitations, TIA/stroke, renal impairment (co-existing atherosclerosis)
• Risk factor assessment: Smoking history (pack-years), diabetes management, hypertension and medications, lipid profile, family history
• Functional impact: How has claudication affected occupation, social, and leisure activities?
• Erectile dysfunction - may indicate aortoiliac disease (Leriche syndrome)

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• Leriche syndrome results from aortoiliac occlusion.
• Classic triad: (1) Buttock and thigh claudication; (2) absence of femoral pulses bilaterally; (3) erectile dysfunction (sexual impotence) in men due to internal iliac artery insufficiency.
• The level of claudication is one anatomical level below the arterial obstruction - aortoiliac disease causes thigh and buttock claudication.

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SECTION 3: Clinical Examination

• General inspection: Pallor, cyanosis, tar-stained fingers (smoking), xanthelasma, corneal arcus
• Inspect the limbs: Skin colour (pallor, cyanosis, dependent rubor "sunset foot"), hair loss, muscle wasting, trophic skin changes, ulcers, gangrene
• Buerger's test:
  • Elevate both legs to 45 degrees for 1-2 minutes - ischaemic limb goes pale (positive)
  • Then hang legs down - ischaemic limb flushes deep red-purple (reactive hyperaemia/dependent rubor = "sunset foot" sign)
  • Buerger's angle = the angle at which the limb becomes pale; <20 degrees = severe ischemia
• Capillary refill time: Press heel/toe pulp for 5 seconds; normal 2-3 seconds; prolonged >10 sec in severe ischemia
• Pulses: Systematically palpate femoral, popliteal, posterior tibial, dorsalis pedis
  • Compare bilateral femoral pulses
  • Note: pulse distal to an arterial occlusion is usually absent; collaterals may occasionally allow palpable distal pulses even with stenosis
  • Exercise (walking to claudication) will cause a distal pulse to disappear as vasodilation occurs below the obstruction
• Auscultation: Bruit over aorta, iliac, femoral arteries (indicates turbulent flow, suggests stenosis). Note: tight stenoses/complete occlusions may be silent.
• Abdomen: Palpate for aortic aneurysm (may coexist with lower limb occlusive disease)
• Venous guttering: A chronically ischaemic leg elevated will show collapsing, guttered veins

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SECTION 4: Investigations

• ABI = highest ankle systolic pressure (dorsalis pedis, posterior tibial, or peroneal) / highest ipsilateral brachial systolic pressure.
• Measured using a hand-held Doppler probe and sphygmomanometer.
• Interpretation:
  • 0.9-1.4: Normal
  • <0.9: Hemodynamically significant arterial lesion (PAD diagnosis)
  • 0.5-0.9: Claudication range
  • <0.4: Critical limb-threatening ischemia (CLTI)

  • 1.4: Arterial calcification/incompressibility (falsely elevated - seen in diabetes, chronic renal failure)

• A drop of >20% from resting ABI after exercise is indicative of flow-limiting arterial disease (exercise ABI is useful when resting ABI is normal but symptoms suggest PAD).
• Pitfall: In diabetics with medial calcification, vessels are non-compressible. Use toe-brachial index (TBI) instead - toe (digital) arteries are rarely affected by calcification. TBI <0.6 suggests significant arterial disease.

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• ABI with hand-held Doppler (confirms diagnosis, grades severity)
• Blood glucose, HbA1c (diabetes screening/monitoring)
• Full blood count (anaemia worsens ischemia by reducing O2 delivery)
• Lipid profile (identify and quantify dyslipidaemia)
• Renal function (coexisting renovascular disease; relevant for contrast use)
• ECG (coexisting coronary artery disease is present in ~50%)

• Duplex Doppler Ultrasonography (DUS): First-line non-invasive imaging. Localises stenosis, determines degree using peak systolic velocity ratio (PSVR). PSVR ≥2.4 = obstructive disease; PSVR ≥3.0 = functionally significant. Useful for graft/stent surveillance.
• CT Angiography (CTA): Best anatomical detail, 3D reconstruction, invaluable for pre-operative planning. Limitation: iodinated contrast (risk of nephropathy, especially in diabetics), ionising radiation. Metformin must be withheld periprocedurally.
• MR Angiography (MRA): No ionising radiation, no iodinated contrast. Uses gadolinium (caution in severe CKD - nephrogenic systemic fibrosis). Good for aortoiliac and femoropopliteal segments.
• Digital Subtraction Angiography (DSA): Gold standard for arterial anatomy. Access via Seldinger technique (usually common femoral artery). Provides dynamic flow information and can be combined with endovascular treatment. Complications: haematoma, false aneurysm, thrombosis, arterial dissection, distal embolisation, renal dysfunction, allergic reaction (~5%). Reserved for when intervention is planned.

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• A technique for gaining percutaneous arterial access.
• Steps: (1) Needle puncture of the artery (usually CFA); (2) guidewire inserted through needle; (3) needle withdrawn over wire; (4) sheath/catheter threaded over wire; (5) wire removed.
• Allows introduction of catheters, sheaths, and interventional devices without surgical cut-down.

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SECTION 5: Classification

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• CLTI (previously called critical limb ischemia/CLI) refers to patients with ischaemic rest pain and/or ischaemic ulceration/gangrene (tissue loss).
• Defines the highest-risk end of the PAD spectrum with an imminently threatened limb.
• Requires urgent vascular assessment and revascularisation to prevent major amputation.
• These patients have the lowest ABIs (<0.4) and the highest annual mortality (~25%).
• Bilateral co-morbidities (coronary, cerebral, renal) are almost universally present.

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SECTION 6: Management

• Smoking cessation - single most effective intervention; dramatically slows progression
• Supervised exercise rehabilitation - structured walking programme (30-45 min, 3x/week); increases pain-free walking distance by improving collateral flow and muscle metabolism
• Antiplatelet therapy - aspirin 75-100 mg/day or clopidogrel 75 mg/day (reduces cardiovascular events, not claudication per se)
• Statins - reduce cardiovascular events; some improvement in walking distance
• Antihypertensives - ACE inhibitors preferred (also shown to reduce cardiovascular events in HOPE trial)
• Diabetes control - tight glycaemic control
• Cilostazol (PDE-3 inhibitor) - only drug with evidence of improving claudication: increases maximal walking distance by 54% vs placebo. Contraindicated in heart failure. Approved by FDA for claudication.
• Pentoxifylline - no randomised data showing benefit over placebo; not recommended.
• Foot care - especially in diabetics to prevent ulceration

• Indications: lifestyle-limiting claudication not responding to 3-6 months of conservative treatment, rest pain, tissue loss
• Angioplasty ± stenting (PTA): First-line for short segment lesions (TASC A/B); shorter recovery, less morbidity. Risk of restenosis from neointimal hyperplasia.
• Surgical bypass: For long-segment occlusions (TASC C/D), failed endovascular procedures; e.g., aortobifemoral bypass (aortoiliac), femoro-popliteal bypass.
• Graft material: Autologous vein (long saphenous - best patency) vs. synthetic (PTFE or Dacron - acceptable above knee, poor below knee).

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• Cilostazol is a phosphodiesterase type III (PDE-3) inhibitor. It inhibits platelet aggregation and causes arterial vasodilation by preventing breakdown of cAMP.
• Approved by the FDA for treatment of intermittent claudication (1999).
• In randomised trials comparing cilostazol 100 mg twice daily vs. pentoxifylline vs. placebo, cilostazol improved maximum walking distance by 54% vs. 30% for pentoxifylline and 34% for placebo.
• Contraindication: Heart failure of any severity (increased mortality in trials with PDE inhibitors in heart failure).
• Dose: 100 mg twice daily.

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• Lifestyle-disabling intermittent claudication not improved after 3-6 months of maximal conservative therapy
• Ischaemic rest pain (Fontaine III / Rutherford 4)
• Tissue loss - non-healing ulceration (Fontaine IV / Rutherford 5)
• Gangrene with limb salvage potential (Rutherford 6)
• In CLTI, revascularisation should be performed urgently

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• TASC (Trans-Atlantic Inter-Society Consensus) classifies lesions by morphology to guide revascularisation strategy:
  • TASC A: Short single stenoses; recommended endovascular (PTA ± stenting)
  • TASC B: Multiple short stenoses or single longer stenosis; endovascular preferred
  • TASC C: Multiple long stenoses or single occlusion; surgery preferred
  • TASC D: Complete occlusions, long segment or aortoiliac involvement; surgery recommended
• Endovascular has lower short-term morbidity; surgery has better long-term patency for complex lesions.

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SECTION 7: Acute Limb Ischaemia (ALI) - Viva Extension

• Pain - sudden severe onset
• Pallor - white/pale limb
• Pulselessness - absent distal pulses
• Paraesthesia - pins and needles (early nerve ischaemia)
• Paralysis - motor deficit (late/severe; urgent sign)
• Perishing cold (Poikilothermia)

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• Immediate: IV heparin to prevent propagation; analgesia; urgent vascular surgical referral
• Imaging: Emergency DSA or duplex to determine level and cause
• Surgical embolectomy (Fogarty balloon catheter) - for embolic occlusion, viable limb
• Catheter-directed thrombolysis - for thrombotic occlusion or if surgical risk is high; slower, requires ICU monitoring, risk of haemorrhage
• Surgical bypass - for thrombotic occlusion with anatomical disease
• Amputation - if limb is non-viable (irreversible ischemia with fixed mottling, rigor, paralysis)
• Post-procedure: Investigate and treat the source (echocardiogram if AF/cardiac embolism; anticoagulation)

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SECTION 8: Complications and Prognosis

• Progression to rest pain and CLTI
• Amputation (major or minor) - <5% of claudicants reach amputation; much higher in CLTI
• Myocardial infarction (fourfold risk vs. non-PAD)
• Stroke (2-3x risk)
• Cardiovascular death (leading cause of death in PAD patients)
• Reduced quality of life and functional decline

• Apparent "improvement" in IC over time does NOT reflect disease improvement - it often reflects functional decline (patients walk slower/shorter distances to avoid pain).
• PAD is a progressive disorder causing significant decline in quality of life.
• ~25% of claudicants deteriorate, 25% improve (often due to functional decline), 50% stable.
• Fewer than 5% will ever require amputation.
• The dominant risk is cardiovascular mortality - not limb loss.
• The lower the ABI, the greater the cardiovascular event risk.

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SECTION 9: Special Situations

• PAD in diabetics is more distal (tibial/peroneal vessels affected preferentially), more diffuse, and often bilateral.
• Neuropathy may mask ischemic pain - patient may present with painless ulceration or gangrene without preceding claudication.
• ABI is unreliable due to medial calcification; use TBI <0.6 as threshold.
• Foot ulcers in diabetics are often of mixed ischaemic and neuropathic origin.
• Worse prognosis with higher amputation rates.
• Tight glycaemic control, meticulous foot care, podiatry referral are essential.
• Metformin must be withheld before iodinated contrast studies (CTA/DSA) due to risk of lactic acidosis.

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• A - Antiplatelet agents (aspirin or clopidogrel) + ACE inhibitors
• B - Blood pressure control (target <130/80)
• C - Cholesterol (statins - target LDL <1.8 mmol/L) + Cigarette cessation
• D - Diabetes control (HbA1c target ~7%) + Diet and exercise

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KEY IMAGES TO KNOW

• Aortoiliac bifurcation disease angiogram with collateralisation via lumbar and inferior mesenteric arteries

• Dependent rubor / "sunset foot" - elevation pallor, dependency rubor

• Dry gangrene of the toes in CLTI

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QUICK REFERENCE SUMMARY TABLE

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PG Viva Questions on Peripheral Arterial Disease

Compiled from Sabiston Textbook of Surgery, Schwartz's Principles of Surgery, Bailey & Love, Textbook of Family Medicine, Goldman-Cecil Medicine

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PART 1: BASIC SCIENCE & PATHOPHYSIOLOGY

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• Atherosclerosis is the underlying cause of PAD in >90% of cases. It begins in childhood as fatty streaks and progresses through:
  1. Endothelial injury - by smoking, hypertension, hyperlipidaemia, hyperglycaemia, shear stress
  2. Lipid deposition - LDL enters the subintima and undergoes oxidation
  3. Inflammatory recruitment - monocytes migrate into the intima, differentiate into macrophages, engulf oxidized LDL to become foam cells
  4. Foam cell accumulation forms the fatty streak
  5. Smooth muscle cell migration from media to intima; SMCs produce extracellular matrix forming a fibrous cap over the lipid core - the atheromatous plaque
  6. Plaque progression - calcification, neovascularisation, enlargement causing lumen stenosis
  7. Plaque rupture/erosion - triggers acute thrombosis, can cause acute limb ischemia
• In the lower limb, atherosclerosis preferentially affects:
  • Aortoiliac segment
  • Superficial femoral artery at the adductor canal (most common - 70%)
  • Tibial/peroneal arteries (especially in diabetics)
• The muscle group affected by claudication is characteristically one level below the arterial occlusion (because it is the most distal vascular territory that becomes ischemic under exercise demand).

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• At rest, blood flow through a stenosed vessel may be adequate because vascular resistance in the distal capillary bed is high.
• With exercise, the metabolic demands of muscle increase massively. The capillary bed vasodilates, reducing peripheral resistance. In a normal limb, this drives increased flow.
• Across a stenosis, the pressure gradient rises as flow increases (Poiseuille's Law: resistance ∝ length/radius⁴). Flow cannot keep pace with metabolic demand.
• Anaerobic metabolism occurs in the exercising muscle → lactic acid and other metabolites accumulate → nociceptive pain stimulus → claudication.
• On resting, metabolic demands fall, lactate clears within 2-5 minutes, and pain resolves. This is the basis of the classic "stop and rest" relief.
• In rest pain (critical ischemia), perfusion pressure is inadequate even without exercise. It is exacerbated by elevation (removes gravity-assisted perfusion pressure) and relieved by dependency (gravity augments pressure in the distal arteries).

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• Collateral vessels are pre-existing arterioles and small arteries that expand (arteriogenesis) in response to a chronic pressure gradient across a stenosis.
• Driven by increased shear stress, growth factors (VEGF, FGF, PDGF), and monocyte infiltration.
• Collaterals develop slowly - explain why chronic occlusion is better tolerated than acute occlusion.
• Important examples:
  • Inferior mesenteric artery (IMA) and lumbar arteries collateralise around aortoiliac disease
  • Profunda femoris (deep femoral artery) is the most important collateral route around a superficial femoral artery (SFA) occlusion - hence it is called the "artery of the thigh"
  • Geniculate arteries collateralise around a popliteal occlusion
• Clinically: a patent, non-diseased profunda is the key vessel to preserve in infrainguinal surgery - inflow to the profunda should always be assessed.

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• The profunda femoris artery (PFA/deep femoral artery) is the major collateral supply to the thigh and lower leg when the SFA is occluded.
• Its branches (perforators) communicate with the geniculate arteries around the knee and tibial vessels distally.
• In SFA occlusion, the limb survival often depends on the profunda - a patient with SFA occlusion but a healthy profunda may have only mild claudication.
• Profundaplasty - endarterectomy and patch widening of the profunda ostium - can improve perfusion to the limb when the SFA is occluded, especially in patients unfit for more complex bypass surgery.
• In above-knee amputation, the profunda-geniculate collaterals supply the skin flap; this is why amputation should be above the knee (not through the distal thigh where these collaterals are absent) when the profunda is compromised.

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PART 2: CLINICAL ASSESSMENT

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• Fontaine is simpler and widely used in Europe; Rutherford is more detailed and used in research.
• Rutherford Grade III, Categories 4-6 = Chronic Limb-Threatening Ischaemia (CLTI). (Schwartz's Principles of Surgery 11e; Sabiston Textbook of Surgery)

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• Method: The patient lies supine. Both legs are elevated to 45° for 1-2 minutes. Then the patient sits up and hangs both legs down.
• Positive test (ischaemic limb):
  • On elevation: the foot becomes pale/white (blood drains away and cannot be replenished against gravity due to low perfusion pressure)
  • On dependency: the foot flushes deep red/purple (reactive hyperaemia = dependent rubor / "sunset foot" sign) - ischaemic vessels maximally dilate and fill slowly with blood on dependency
• Buerger's angle: The angle of leg elevation at which the foot goes pale. Normal = >90°. Significant ischaemia = <20°.
• A positive Buerger's test strongly suggests critical limb ischemia (CLTI).

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• Pathology: Atherosclerotic occlusion of the abdominal aorta at or just above the bifurcation into the iliac arteries, or bilateral common iliac artery stenosis/occlusion.
• Clinical Triad:
  1. Bilateral buttock and thigh claudication (sometimes calf)
  2. Absent or markedly diminished bilateral femoral pulses
  3. Erectile dysfunction/impotence in men (due to ischaemia of the internal iliac arteries supplying the corpora cavernosa)
• Other features: Atrophy of lower limb musculature, pallor of both legs, absent distal pulses bilaterally, aortoiliac bruit on auscultation
• Treatment:
  • Endovascular: aortoiliac angioplasty ± kissing stents (bilateral iliac stenting)
  • Surgery: Aortobifemoral bypass (gold standard for extensive AIOD) using Dacron/PTFE bifurcated graft. 5-year patency >85%.
  • Extraanatomic (high-risk patients): axillofemoral bypass or femoro-femoral crossover bypass.

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• Signs of hyperlipidaemia (xanthelasma, xanthomata, corneal arcus)
• Smoking history (tar staining)
• BMI, blood pressure, signs of diabetes (acanthosis nigricans)

• Colour: pallor, cyanosis, dependent rubor ("sunset foot")
• Trophic changes: loss of hair, shiny atrophic skin, muscle wasting
• Ulcers: site (tips of toes/pressure areas/trauma points = arterial; gaiter area = venous), depth, slough/necrosis, surrounding skin
• Gangrene: dry (mummified, demarcated - arterial) vs wet (infected, malodorous)
• Venous guttering (visible collapse of veins on leg elevation in severe ischaemia)

• Temperature: compare both limbs - ischaemic limb is cooler
• Capillary refill: press heel/toe pulp for 5 seconds; normal <3 sec; prolonged >10 sec = severe
• Pulses: Radial (general cardiovascular), carotid, abdominal aorta, femoral, popliteal, posterior tibial, dorsalis pedis (compare sides)
• Popliteal pulse - must be examined bimanually with knee slightly flexed; if aneurysmal pulsation - suspect popliteal aneurysm

• Bruits over: aorta, renal, iliac, femoral arteries
• Continuous "machinery" murmur = arteriovenous fistula

• Sensation (ischaemic neuropathy) - assess in digits and forefoot
• Motor power (paralysis = irreversible ischaemia in acute setting)

• Cardiac rhythm (AF = embolic source), murmurs, JVP, evidence of heart failure

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PART 3: INVESTIGATIONS

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1. Patient rests supine for 10 minutes.
2. Apply BP cuff just above the ankle.
3. Apply Doppler probe over dorsalis pedis then posterior tibial artery.
4. Inflate cuff to suprasystolic pressure, then deflate slowly until Doppler signal returns = ankle systolic pressure.
5. Record both ankle pressures and both brachial pressures.
6. ABI = highest ankle pressure (DP or PT) / highest brachial pressure (left or right).

1. Medial arterial calcification (diabetes, CKD, elderly) - vessels cannot be compressed; ABI falsely elevated >1.4. Use Toe-Brachial Index (TBI) instead (toe arteries are rarely calcified). TBI <0.6 = significant arterial disease; TBI <0.15 = CLTI.
2. ABI does not localise the level of disease - use imaging for this.
3. Normal resting ABI does not exclude PAD if symptoms are present (use exercise ABI).
4. Operator-dependent skill required.
5. Proximal disease (aortoiliac) may be missed if collaterals maintain near-normal ankle pressures at rest.

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• A NVIS is a battery of non-invasive tests to assess arterial haemodynamics:
  1. Segmental limb pressures - BP cuffs at thigh (proximal/distal), calf, ankle. A drop of >20 mmHg between adjacent segments suggests occlusive disease at that level.
  2. Pulse volume recordings (PVR) - pneumatic cuffs measure volumetric pulsation. Reduced amplitude = reduced flow. Waveform analysis: triphasic (normal) → biphasic → monophasic (severe disease).
  3. ABI at rest and after exercise
  4. Toe pressures (especially useful in diabetics)
• Provides: Physiological/haemodynamic information, approximate level of disease.
• Does not provide: Precise anatomical localisation needed for intervention (duplex, CTA, or DSA required for this).
• The NVIS also includes Doppler waveform analysis: triphasic in normal vessels (forward flow, brief reversal, forward flow); monophasic in severe disease.
• A PSVR (peak systolic velocity ratio) ≥2.4 on duplex = obstructive disease; ≥3.0 = functionally significant stenosis.

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• Haematoma at access site
• False aneurysm (pseudoaneurysm)
• Arterial thrombosis/dissection
• Distal embolisation
• Contrast-induced nephropathy
• Allergic reaction to contrast
• Retroperitoneal haematoma (if high puncture above inguinal ligament)

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• FBC - anaemia worsens ischaemia (reduces O₂ delivery); polycythaemia increases viscosity and thrombosis risk
• Urea, creatinine, eGFR - CKD is common co-morbidity; limits use of contrast agents; calcification causes false ABI
• Fasting blood glucose and HbA1c - diabetes accelerates PAD; affects ABI interpretation; influences wound healing
• Fasting lipid profile - identifies dyslipidaemia; guides statin dosing
• Coagulation screen - if thrombolysis or surgery planned; screens for hypercoagulable state
• Cardiac enzymes (troponin, BNP) - co-existing CAD is present in ~50%; cardiac risk stratification pre-operatively
• ECG - atrial fibrillation (embolic source in ALI); coronary disease
• Echocardiography - if embolic source suspected (thrombus in LA/LV, valvular disease, patent foramen ovale)
• Thrombophilia screen (in younger patients, non-atherosclerotic PAD): protein C, protein S, antithrombin III, antiphospholipid antibodies, factor V Leiden, homocysteine
• Inflammatory markers (CRP, ESR) - if vasculitis or Buerger's disease suspected

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PART 4: MEDICAL MANAGEMENT

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• All symptomatic PAD patients should receive antiplatelet therapy (expert consensus despite the 2022 USPSTF guidance on primary prevention in the general population).
• Aspirin (75-325 mg/day) - COX-1 inhibitor, most widely used
• Clopidogrel (75 mg/day) - P2Y12 receptor antagonist; CAPRIE trial showed clopidogrel reduced cardiovascular events more than aspirin in PAD subgroup (3.71% vs 4.86%/year). Preferred in current smokers.
• Ticagrelor - EUCLID trial showed similar benefit to clopidogrel for MACE prevention in symptomatic PAD (HR 1.02; not superior).
• Dual antiplatelet therapy (DAPT): CHARISMA trial - clopidogrel + aspirin not significantly better than aspirin alone for MACE; increased bleeding risk.
• Low-dose rivaroxaban (2.5 mg BD) + aspirin - COMPASS trial showed reduced MACE and MALE events vs aspirin alone in PAD, at cost of increased bleeding. Now guideline-recommended for selected high-risk PAD patients.

• Target <130/80 mmHg
• ACE inhibitors preferred (HOPE trial: ramipril reduced cardiovascular events in PAD patients independent of BP-lowering effect)
• Beta-blockers NOT contraindicated in PAD (historical concern unsubstantiated)

• Mandatory for all PAD patients
• Reduce MACE, slow atherosclerosis progression
• High-intensity statin (atorvastatin 40-80 mg); target LDL <1.8 mmol/L (<70 mg/dL)
• Also shown to modestly improve claudication distance

• Target HbA1c ~7% (53 mmol/mol)
• Tight control prevents microvascular complications (neuropathy, retinopathy, nephropathy) but does not clearly reduce macrovascular PAD progression

• Supervised exercise programme: 30-45 min walking, 3x per week, minimum 3 months
• More effective than pharmacotherapy or angioplasty for claudication
• Mechanism: improved collateral function, mitochondrial enzyme activity, oxygen utilisation, muscle metabolism

• Cilostazol (PDE-3 inhibitor): 100 mg BD - 54% improvement in maximal walking distance vs placebo; superior to pentoxifylline (30% improvement). Contraindicated in heart failure.
• Pentoxifylline - no RCT evidence of benefit over placebo; NOT recommended.
• Naftidrofuryl - 5-HT₂ antagonist; modest benefit in claudication (used in Europe)

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• Historical teaching held that beta-blockers caused peripheral vasoconstriction, worsening claudication.
• However, multiple RCTs and meta-analyses have shown beta-blockers do not worsen claudication in PAD patients and do not increase the risk of limb loss.
• PAD patients often have co-existing coronary artery disease (CAD in ~50%). Withholding beta-blockers in these patients would increase cardiac mortality.
• ACC/AHA guidelines: Beta-blockers are not contraindicated in PAD and should be used when there is a co-existing cardiac indication (post-MI, heart failure, angina).
• The concern was primarily theoretical - based on alpha-adrenergic unopposed vasoconstriction with non-selective beta-blockers. In practice, this is not clinically significant.

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PART 5: SURGICAL & INTERVENTIONAL MANAGEMENT

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• Lifestyle-disabling intermittent claudication not improved after 3-6 months of optimal conservative therapy
• Ischaemic rest pain (Fontaine III / Rutherford 4)
• Tissue loss / non-healing ulcers (Fontaine IV / Rutherford 5-6)
• Gangrene with potential for limb salvage

• Rutherford Grade I (viable) and Grade II (threatened) - attempt revascularisation
• Rutherford Grade III (irreversible) - primary amputation

• Non-ambulatory patients with CLTI (amputation may be preferable)
• No suitable conduit or outflow target vessel
• Severe co-morbidities making surgery prohibitive
• Irreversible ischaemia (rigor, fixed mottling)

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• TASC A/B: endovascular first (less morbidity, shorter hospital stay, quicker recovery)
• TASC C/D: surgery recommended (better long-term patency)
• Decision also depends on: patient fitness, life expectancy, conduit availability, institutional expertise

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• Aortobifemoral bypass - gold standard for extensive AIOD. Synthetic bifurcated graft (Dacron or PTFE) from aorta to bilateral CFAs. 5-year patency >85-90%.
• Aortoiliac endarterectomy - for localised disease
• Iliofemoral bypass - unilateral iliac disease

• Axillofemoral bypass - axillary artery → femoral artery (unilateral or bilateral); lower patency
• Femoro-femoral crossover bypass - for unilateral iliac disease; uses contralateral side as inflow
• Thoracofemoral bypass - when aorta cannot be used (redo surgery, infection)

• Femoro-popliteal bypass (above knee or below knee) - most common
• Femoro-tibial/peroneal bypass - for CLTI with distal disease
• Profundaplasty - endarterectomy and patch widening of profunda femoris ostium

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1. Percutaneous Transluminal Angioplasty (PTA) - balloon catheter inflated at stenosis/occlusion to expand the lumen. Introduced by Charles Dotter (1964).
2. Balloon-expandable or self-expanding stents - metallic scaffolds deployed to maintain patency after PTA (prevent elastic recoil and dissection).
3. Drug-eluting balloons (DCB) - balloons coated with paclitaxel or limus analogues; drug released on contact with vessel wall reduces neointimal hyperplasia (restenosis). Used in SFA disease.
4. Drug-eluting stents (DES) - similarly coated stents.
5. Stent grafts - covered stents (ePTFE-lined); used for aortic/iliac lesions, especially aneurysmal disease.
6. Atherectomy - mechanical debulking of plaque:
   • Directional atherectomy (SilverHawk)
   • Rotational atherectomy (Jetstream, Rotablator)
   • Laser atherectomy
   • Useful for calcified lesions or in-stent restenosis
7. Catheter-directed thrombolysis (CDT) - infusion of thrombolytic (alteplase/urokinase) through catheter embedded in thrombus; for acute/subacute thrombotic occlusion.
8. Mechanical thrombectomy - aspiration or fragmentation of thrombus.
9. Hybrid procedures - combination of open and endovascular (e.g., fem-pop bypass + iliac stenting).

• Primary patency - patency maintained without any reintervention
• Primary assisted patency - intervention on stenotic (but patent) lesion
• Secondary patency - patency restored after occlusion with reintervention

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• Restenosis = re-narrowing of a vessel after angioplasty/stenting, most commonly from neointimal hyperplasia.
• Occurs in 30-50% of plain balloon angioplasties at 6-12 months.

1. Elastic recoil - immediate (within minutes): vessel returns to original shape after balloon deflation (addressed by stenting)
2. Negative remodelling - vessel shrinks inward over weeks
3. Neointimal hyperplasia - migration and proliferation of smooth muscle cells into the intima in response to vascular injury; occurs over 3-6 months (main cause of late restenosis)

• Stenting - prevents elastic recoil and negative remodelling (but does not prevent neointimal hyperplasia)
• Drug-coated balloons (DCB) with paclitaxel - anti-proliferative agent inhibits SMC proliferation; reduces restenosis rates significantly
• Drug-eluting stents (DES) - combine mechanical support with local drug delivery
• Antiplatelet therapy post-procedure (DAPT for 1-3 months post-stenting is common practice)
• Cutting balloons - create small controlled incisions in plaque to reduce injury response

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PART 6: ACUTE LIMB ISCHAEMIA (ALI)

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• ALI = arterial occlusion with symptoms present for <2 weeks, causing acute threat to limb viability.
• Causes: embolism, acute in-situ thrombosis (on background of chronic PAD), trauma, iatrogenic (post-catheterisation), aortic dissection, popliteal artery aneurysm thrombosis.

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• Introduced by Thomas Fogarty in 1963 - revolutionised treatment of embolic acute limb ischaemia.
• Principle: A balloon-tipped catheter passed distally through the clot, balloon inflated, and catheter withdrawn, dragging the clot out.

1. General or regional/local anaesthesia.
2. Groin incision - expose common, superficial, and deep femoral arteries.
3. Transverse or longitudinal arteriotomy in the CFA.
4. Heparin administered IV (5000 units).
5. Fogarty catheter (appropriate size - 3F for tibial, 4F for popliteal, 5F for femoral/iliac) passed distally beyond the clot.
6. Balloon inflated with saline; catheter withdrawn - clot extracted.
7. Process repeated until backflow from distal vessels is established.
8. Proximal clot removed by allowing inflow (unfolding of inflated balloon + suction).
9. On-table angiogram to confirm clearance and assess residual disease.
10. Arteriotomy closed with patch angioplasty (vein or PTFE) if vessel is small.
11. If residual disease is found - proceed to definitive bypass/stenting.
12. Four-compartment fasciotomy of the calf considered (especially if ischaemia >6 hours).

• Arterial intimal injury (dissection)
• Incomplete embolectomy
• Distal embolisation
• Reperfusion injury / compartment syndrome
• Reocclusion

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• CDT - infusion of thrombolytic agent (recombinant tPA/alteplase or urokinase) directly into the thrombus through a multi-sidehole catheter embedded within the clot under fluoroscopic guidance.
• Dissolves thrombus over 12-48 hours.
• Advantage: reveals underlying stenosis/plaque that caused the thrombosis - can be treated immediately by angioplasty/stenting.

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• Reperfusion injury occurs when blood flow is restored to an ischaemic limb after a period of ischaemia (usually >4-6 hours).

1. During ischaemia: ATP → hypoxanthine accumulates; neutrophils infiltrate
2. On reperfusion: xanthine oxidase converts hypoxanthine + O₂ → reactive oxygen species (ROS) / free radicals
3. ROS cause:
   • Cell membrane lipid peroxidation → cell death
   • Increased capillary permeability → massive interstitial oedema
   • Neutrophil activation → local and systemic inflammatory cascade
4. Oedema within the closed fascial compartments → raised compartment pressure → further ischaemia of muscle and nerves

• Normal compartment pressure: 0-9 mmHg
• Fasciotomy indicated when pressure >25 mmHg (or within 30 mmHg of diastolic pressure)
• Four-compartment leg fasciotomy (anterior, lateral, superficial posterior, deep posterior)
• Failure to perform fasciotomy after revascularisation is the most common preventable cause of limb loss
• Must always be considered after ischaemia >6 hours

• Hyperkalaemia (from ischaemic muscle) - can cause fatal arrhythmias
• Myoglobinuria/rhabdomyolysis - can cause acute kidney injury (pigment nephropathy)
• Metabolic acidosis (lactic acid release)
• SIRS/sepsis - systemic inflammatory response syndrome
• Multi-organ failure - can be fatal

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PART 7: SPECIAL TOPICS

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• Buerger's disease = non-atherosclerotic, inflammatory, segmental thrombosing vasculitis affecting small and medium arteries (and veins) of the distal extremities.
• Pathology: inflammatory cellular thrombus occluding the vessel lumen; the vessel wall architecture is relatively preserved (unlike atherosclerosis which destroys the media).

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• The popliteal artery is the most common site of peripheral artery aneurysm (>70% of peripheral aneurysms).
• Often bilateral (50% of cases) and associated with abdominal aortic aneurysm (AAA) in 30-50%.
• Defined as diameter >2 cm (or >150% of normal).

• Most commonly presents with acute limb ischaemia due to:
  • Thrombosis of the aneurysm sac
  • Distal embolisation from the thrombus within the aneurysm
• Rupture is rare (unlike AAA).
• Clinically: prominent pulsatile popliteal pulse on examination. Suspect if popliteal pulse feels "too full."
• Complication: Tibial artery occlusion from repeated embolisation, resulting in poor distal runoff - amputations rates 15-70% with thrombosed PAA (very high).

• Asymptomatic PAA >2 cm: elective repair (bypass + exclusion of aneurysm or endovascular stent graft)
• Symptomatic PAA (ALI): thromboembolectomy + bypass; CDT to restore runoff first, then elective repair
• Always screen for bilateral PAA and AAA

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• WIFI = Wound, Ischaemia, Foot Infection classification - developed by the Society for Vascular Surgery (SVS).
• Three components, each scored 0-3:
  • W (Wound): 0 = no ulcer; 1 = small superficial ulcer; 2 = deep ulcer exposing tendon/bone; 3 = gangrene
  • I (Ischaemia): 0 = ABI >0.8; 1 = ABI 0.6-0.79; 2 = ABI 0.4-0.59; 3 = ABI <0.4
  • FI (Foot Infection): 0 = none; 1 = mild (skin/subcutaneous); 2 = moderate (deep/extensive); 3 = severe (SIRS/sepsis)
• Higher WIFI scores correlate with risk of major amputation.
• Guides decision-making: both wound care AND revascularisation AND infection control are required in CLTI management - one without the other gives inferior results.
• More comprehensive than simple Rutherford/Fontaine for CLTI management planning.

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• DAPT (aspirin + clopidogrel) for 1-3 months post-procedure - then single antiplatelet long-term
• Evidence for DAPT duration after peripheral stenting is extrapolated from coronary literature

• Prosthetic graft (above knee): aspirin or DAPT; anticoagulation (warfarin) sometimes used
• Vein graft (below knee): aspirin; some evidence for warfarin if vein graft at risk (small vein, poor outflow)

• Cardiovascular Outcomes for People using Anticoagulation Strategies
• Compared: rivaroxaban 2.5 mg BD + aspirin 100 mg OD vs aspirin alone vs rivaroxaban 5 mg BD alone in patients with stable atherosclerotic disease (including PAD subgroup)
• PAD subgroup result:
  • Rivaroxaban + aspirin significantly reduced MACE and MALE (major adverse limb events = acute limb ischaemia, amputation, peripheral vascular intervention) vs aspirin alone
  • At cost of increased major bleeding (but not intracranial haemorrhage)
• Current guideline recommendation: Low-dose rivaroxaban (2.5 mg BD) + aspirin may be offered to selected PAD patients at high ischaemic risk and low bleeding risk.

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• Graft occlusion (acute thrombosis)
• Bleeding - anastomotic haemorrhage
• Distal embolisation (trash foot/blue toe syndrome)
• Wound infection
• Myocardial infarction (most common cause of 30-day mortality ~2-5%)
• Renal impairment - suprarenal clamp time, contrast use, blood loss
• Bowel ischaemia - if IMA sacrificed without adequate collaterals; presents as bloody diarrhoea post-op; can be fatal
• Spinal cord ischaemia - rare; from intercostal/lumbar artery sacrifice
• Lymphocele - disruption of lymphatics at groin

• Graft thrombosis - most common late complication; treat with thrombolysis, surgical thrombectomy, or redo bypass
• Anastomotic false aneurysm (pseudoaneurysm) - at groin anastomosis; infection, suture line breakdown
• Aortoenteric fistula - graft erodes into 3rd/4th part of duodenum; presents with GI haemorrhage (herald bleed then massive haemorrhage); ~50% mortality; requires urgent graft excision and extra-anatomic bypass
• Graft infection - dreaded complication; requires graft excision and reconstruction through clean field
• Sexual dysfunction - retrograde ejaculation (injury to autonomic nerves at aortic bifurcation during dissection)
• Limb oedema - disruption of lymphatics

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• Technical error - poor anastomosis, kinking, twisting of conduit
• Conduit thrombosis - poor choice of conduit (small vein, diseased vein)
• Poor inflow - missed inflow disease
• Poor outflow - inadequate run-off

• Neointimal hyperplasia - at anastomoses or valve sites in in-situ vein grafts; most common cause of intermediate failure
• Retained valve leaflets in in-situ vein bypass (causing stenosis)
• Missed arteriovenous fistula in in-situ technique

• Progressive atherosclerosis in inflow/outflow vessels
• Graft degeneration - especially synthetic grafts (Dacron, PTFE)
• Aneurysmal degeneration of vein graft (rare)

• Duplex ultrasonography at regular intervals (6 weeks, 3 months, 6 months, then annually)
• Identify:
  • Velocity changes across graft (PSVR >3.5 = >75% stenosis)
  • Low graft velocity (<45 cm/s = risk of thrombosis)
  • Aneurysmal dilatation
• ABI at each visit - a drop ≥0.15 suggests graft deterioration
• Benefit of surveillance: Stenotic lesions can be corrected before thrombosis by angioplasty or surgical patch - maintains "secondary patency" and avoids more complex redo surgery.

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QUICK-REFERENCE FACTS FOR VIVA

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Structure Overview

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PG-Level High-Yield Points to Remember

• Fogarty catheter (1963) - Thomas Fogarty; first fem-pop bypass (1948) - Jean Kunlin; Seldinger technique (1953) - Sven-Ivar Seldinger
• Reperfusion injury >6 hrs = mandatory four-compartment fasciotomy consideration; compartment pressure >25 mmHg = fasciotomy
• COMPASS trial: Rivaroxaban 2.5 mg BD + aspirin reduces MALE + MACE in PAD
• CAPRIE trial: Clopidogrel > aspirin for secondary prevention in PAD
• Neointimal hyperplasia = predominant cause of intermediate graft/stent failure (1-24 months)
• Aortoenteric fistula = most dangerous late graft complication (herald bleed → exsanguination)
• WIFI score governs CLTI management (wound + ischaemia + foot infection must all be addressed)
• TBI <0.6 = significant arterial disease in diabetics when ABI is unreliable