Peripheral vascular disease, Peripheral arterial disease, Peripheral Arterial occlusive disease, Chronic limb ischemia, Acute limb ischemia, Critical Limb Ischemia, Revascularization, aortoiliac disease, iliofemoral disease, antiplatelet therapy

1. Peripheral Vascular Disease
CHRONIC LIMB ISCHEMIA
Sushil Gyawali
MS Resident
MCVTC

2. Peripheral Vascular Disease (PAD)
• PAD/PAOD is a chronic progressive
atherosclerotic disease leading to partial or
total peripheral vascular occlusion.
• PAD typically affects the abdominal aorta,
iliac arteries, lower limbs, and occasionally
the upper extremities.
• PAD affects nearly 200 million people
worldwide

3. Limb Ischemia
• Acute Limb Ischemia: A sudden onset (< 2weeks) of severe pain,
paraesthesia and paralysis in a previously asymptomatic patient suggests an
acute embolic event
• Chronic Limb Ischemia: A long history (>2 weeks) of reduced walking
distance with claudication pain is suggestive of atherosclerotic disease
• Acute on Chronic Ischemia: A sudden worsening of symptoms in a
patient who has a long history of claudication may suggest thrombosis of a
critically stenosed vessel

4. Chronic Limb Ishemia
• CLI is PAD that results in a symptomatic reduced arterial supply to the limbs.
• It is typically caused by atherosclerosis (rarely vasculitis)
• commonly affect the lower limbs (upper limbs and gluteals can also be
affected).
• Around 15-20% individuals over 70yrs have PAD.
• The Framingham study demonstrated an increase in the prevalence of the
disease from 0.4 per 1000 males aged 35-45yrs to 6 per 1000 males aged
>65yrs.

5. Persons with PAD are at increased risk of
•CAD mortality (RR = 6.6),
•Cardiovascular mortality (RR = 5.9), and
• All-cause mortality (RR= 3.1).
• Nearly 75% of patients with PAD die from cardiovascular events

6. Risk Factors
progressive atherosclerotic disease resulting in the reduction blood flow and
end-organ ischemia. Some risks factors for atherosclerosis:
• Smoking (x2-5)
• Diabetes mellitus (x2-3): 1%HbA1c: 30% increase in PAD)
• Hypertension(x2-4)
• Hyperlipidaemia
• Increasing age(>55 yr: 10-25%)
• Obesity and physical inactivity
• Elevated homocysteine levels
• Family history of cardiovascular disease

7. AHA 2016 guideline

8. Pathophysiology
• Progression of atherosclerotic disease → macro and
microvascular dysfunction
• Complex inflammatory response involving various
vascular cells, thrombotic factors, and cholesterol and
inflammatory molecules.

9. • Endothelial injury → lipoprotein accumulation within the intimal layer of large arteries. → lipid oxidation and cytokine
response with the infiltration of lymphocytes and macrophages.
• Macrophages consume these oxidized lipids and form foam cells → "fatty streaks → more advanced plaques consisting of
necrotic lipid cores and smooth muscle cells (SMC).
• SMC and endothelial cells secrete cytokines and GFs → migration of SMC to the luminal side of the plaque → ECM synthesis
→ fibrous plaque →plaque rupture → platelet adhesion and aggregation → thrombosis →stenosis → ischemia

10. • As narrowing progresses , collateral circulatory
beds frequently develop to preserve distal
perfusion
• These collateral circulatory pathways are unable
to match the blood supply provided by a healthy
vessel completely.
• IC results when blood flow distal to the occlusion
is sufficiently compromised, resulting in fixed
oxygen delivery that is unable to match oxygen
demand.

11. • Patients with in-situ vascular thrombosis tend to have improved outcomes
compared to embolic causes due to the presence of extensive collateral
circulation.
• Arterial thrombosis secondary to progressive atherosclerotic disease and
thrombosis represents 40% of acute limb ischemia (ALI) cases

12. PAD: Spectrum of manifestation
• Asymptomatic (70-80%)
• Intermittent claudication
• Atypical symptoms
• Critical limb ischemia
–Rest Pain
–Ulceration
–Necrosis/Gangrene
• Acute limb ischemia
•atypical: Exertional leg pain that
– may involve areas other than the calves
– may not stop the patient from walking
– may not resolve within 10 minutes of rest

13. • Intermittent claudication is the most classic symptom of PAD
• IC: exercise-induced fatigue, discomfort, weakness, cramping, or pain of
vascular origin in the muscles of the lower extremities and consistently
relieved by rest (within 10 min). (AHA2016)
• Leriche syndrome is a form of PAD affecting the aortic bifurcation. It
specifically presents with buttock or thigh pain and associated erectile
dysfunction.

14. Rest pain
• Grade IV Boyd’s classification (ABI<0.5)
•Felt in the foot (most distal parts)
•ischemia of the somatic nerves (cry of the dying
nerves)
•Worse at night; patient sits in “hen-holding”
position
•Pressure of even bed clothes worsens the pain
•Exacerbate on lying down or elevation of foot
•Lessened by hanging the foot down or sleeping
on a chair
Boyd’s classification of
claudication pain

15. Clinical stages of LEAD

16. Worsening
Claudication
16%
Natural History
Intermittent Claudication
Population (> 55 yr)
Intermittent
Claudication
5%
Peripheral Vascular
Outcomes
Other Cardiovascular
Morbidity/Total Mortality
Lower Extremity
Bypass Surgery
7%
Major
Amputation
4%
Nonfatal
Cardiovascular
Event
(MI/Stroke)
20%
5-yr
Mortality
30%
Cardiovascular
Cause
75%
Weitz JI et al. Circulation. 1996;94:3026–3049.

17. • Anatomically the level of obstruction is usually
seen one level above the area of discomfort/pain
• Aorto iliac A - buttock and hip pain
• CFA/Aortoiliac A- thigh
• SFA/popliteal A-calf
• Tibioperoneal A-foot

18. Buerger’s test
• Buerger’s test involves lying the patient
supine and raising their legs until they
go pale (blanching) in 2-3 mins and
then lowering them until
the colour returns (or even becoming
hyperaemic).
• The angle at which limb goes pale is termed Buerger’s angle; an angle of <
20⁰ indicates severe ischaemia.

19. Chronic Limb Threatening Ischaemia Or
Critical Limb ischemia
• CLTI is the advanced form of chronic limb ischaemia.
• It can be clinically defined in three ways:
1. Ischaemic rest pain for > 2 weeks duration
2. Presence of ischaemic lesions, non healing wound or ulcer, or gangrene
objectively attributable to the arterial occlusive disease
3. ABPI less than 0.5
• Common in diabetics: present in 50–70% of cases, presents mostly as
neuro-ischaemic diabetic foot ulcers.
• Fontaine stage III-IV or Rutherford Cat 4-6

20. Warning S/S of Critical Limb Ischemia
Any of the following symptoms:
•Pain or numbness in the feet
•Shiny, smooth, dry skin of the legs or feet
•Thickening of the toenails
•Absent or diminished pulse in the legs or feet
•Open sores, skin infections or ulcers that will not heal
•Dry gangrene (dry, black skin) of the legs or feet

21. Alive with 2 Limbs
45%
Natural History of Critical Limb Ischemia
Critical Limb Ischemia
(Rest Pain, Ulceration or Gangrene)
1-3%
1-Year Outcomes
Mortality
25%
Amputation
30%
Hirsh et al. JACC. 2006;47:1239-1312.
Continued CLI
20%
CLI Resolved
25%

22. Claudication Pseudoclaudication
Characteristic of
discomfort
Cramping, tightness,
aching, fatigue
Same, tingling, burning,
numbness
Location of
discomfort
Buttock, hip, thigh,
calf, foot
Same
Exercise-induced Yes Variable
Distance Consistent Variable
Occurs with standing
No Yes
Action for relief Stand Sit, change position
Time to relief Less than 10 minutes Up to 30 minutes

23. D/D
Neurological
•Spinal stenosis
•Nerve root compression
•Peripheral neuropathy
•Nerve entrapment
Musculoskeletal
•Osteoarthritis
•Muscle strain
•Baker cyst
Vascular
•Chronic venous insufficiency
•Thrombophlebitis
•Deep venous thrombosis
•Raynaud phenomenon
•Thromboangiitis obliterans
Pseudo-claudication

24. Complications
• Nonhealing ulcer
• Gangrene
• Amputation required in 1-2% ( 5% in DM)
• Deep vein thrombosis
• Erectile dysfunction
• Sepsis (secondary to infected gangrene)
• acute-on-chronic ischaemia,
• reduced mobility and quality of life.

25. Complications
• Over a 5 year period, of those patients with intermittent claudication: Most will
have stable claudication
• 10-20% develop worsening symptoms
• 5-10% develop critical limb ischaemia
• Two years following a BKA for chronic limb ischaemia,
15% require a further AKA,
30% have died, and
only 40% have full mobility.
• The 5 year mortality rate in chronic limb ischaemia is around 50%.

26. Evaluation of CLI
 History
 Physical exam:
• shiny skin with coolness to palpation,
• reduced or absent pulses,
• abnormal capillary refill time,
• pallor with leg elevation,
• dependent rubor, and
• auscultation of bruits in major vessels including the femoral and popliteal
arteries.
 Advanced disease may manifest as nonhealing ulcers or gangrene.

27. Investigation
• The diagnosis of chronic limb ischaemia is clinical.
 The ankle-brachial pressure index (resting ABPI) is used to confirm the
diagnosis and quantify severity of chronic limb ischaemia
 Cardiovascular risk assessment
• Blood glucose, HbA1c, lipid profile, ECG, ECHO)
• thrombophilia screen and homocysteine levels checked.
 Functional testing: Treadmill Exercise testing (Exercise ABI)

28. ABI
• cost-effective noninvasive objective measure for PAD diagnosis.
• ABI: systolic ankle pressure <0.9
systolic brachial pressure
• Its sensitivity is poorer in patients with noncompressible vessels in diabetes
or end-stage CKD because of medial calcification.
• Alternative tests such as toe pressure, toebrachial index (TBI) or Doppler
waveform analysis of ankle arteries are useful.

29. Calculating ABI
≥0.9 — Normal
0.81-0.90 — Mild Obstruction
0.51-0.80 — Moderate Obstruction
≤0.50 — Severe Obstruction
Right Arm
Pressure:
Left Arm
Pressure:
Pressure:
PT
DP
Right ABI
Higher Right Ankle Pressure mm Hg
Higher Arm Pressure mm Hg
= =
Left ABI
Higher Left Ankle Pressure mm Hg
Higher Arm Pressure mm Hg
Pressure:
PT
DP

30. AHA Guidelines
ABI for Diagnosis of PAD
• Use resting ABI to establish diagnosis in those with suspected PAD, with 1
or more of the following:
exertional leg symptoms,
nonhealing wounds,
age ≥65 years, or ≥50 years with a history of smoking or diabetes.
• Use ABI to confirm and diagnosis and establish a baseline in all new
patients with PAD, regardless of severity
• Use toe-brachial index to establish a diagnosis of PAD in those with non-
compressible vessels
• Segmental pressure measurements are useful to when anatomic
localization of PAD is required to create a therapeutic plan

31. Duplex ultrasonography
• Initially evaluated with Doppler
ultrasound, to assess the severity and
anatomical location of any occlusion.
• Gold standard inv
• Safe and cost-effective method of
determining PAD location, stenosis
severity, and length of stenosis or
occlusion, hemodynamic severity, and
plaque characteristics.
• 85–90% sensitivity and >95% specificity
to detect stenosis >50%.

32. Duplex ultrasonography continue..
• A normal DUS at rest should be completed by a post-exercise test when iliac
stenosis is suspected, because of lower sensitivity.
• Another imaging technique is usually required when revascularization is
considered.
• DUS is also important to address vein quality for bypass substitutes.
• It is the method of choice for routine follow-up after revascularization.

33. MR angiography
• MRA / CTA both provide excellent high-quality vascular imaging.
• MRA has 90% sensitivity and 97% specificity in identifying hemodynamically
significant lesions.
• Advantages : ability to identify small runoff vessels that sometimes may not
be seen with DSA.
• Drawback: MRA tends to overestimate the degree of stenosis. It cannot
visualize arterial calcifications, useful for the estimation of stenosis severity in
highly calcified lesions.

34. CT ANGIO
• Advantages: visualization of calcifications, clips,
stents, bypasses and concomitant aneurysms.
• Limitations: general (radiation, nephrotoxicity and
allergies), severe calcifications (impeding
the appreciation of stenosis, mostly in distal arteries)
• CTA has similar diagnostic accuracy to MRA with
both imaging techniques useful for determining
candidacy for bypass surgery versus angioplasty.

35. EU 2017 AHA 2016

36. History and Physical Exam
Resting ABI
Normal or
Indeterminant
Abnormal
(<0.90)
Treadmill
Testing
Non-Invasive Testing
•Pulse Volume Recording
•Doppler Waveform Analysis
•Duplex Imaging DUS
Normal Abnormal
Evaluate Other
Etiologies
Diagnosis Confirmed
•Assess Severity
•Initiate Therapy
Normal
Evaluation for Intermittent Claudication

37. Management
Management is divided into two broad categories
• aimed at decreasing cardiovascular events and
• improving symptoms.

38. Medical Management
Most patients require cardiovascular risk factor modification:
•Lifestyle advice (smoking cessation, regular exercise,
weight reduction)
•Pharmacotherapy
• Diabetes control

39. Medical management: Prevent Ischemic Events
Risk factor modification
• Smoking cessation
• Goal: complete cessation
• Lipid management/statins
• Target LDL < 100 mg/dL
• Blood pressure control
• Goal <140/90 mm Hg
<130/80 in DM/Renal ds
• Diabetic:Blood sugar control
• Goal: HbA1c <7%
Antiplatelet therapies
Aspirin / Clopidogrel
• Goal: reduction in risk of MI, stroke,
and vascular death in symptomatic
PAD
• Aspirin75 to 325 mg, is
recommended as safe and effective
antiplatelet therapy.
• Clopidogrel (75 mg/day) a safe and
effective alternative antiplatelet
therapy to aspirin

40. Pharmacotherapy:
guideline
The combination of aspirin and
clopidogrel may be considered to reduce
the risk of cardiovascular events in
symptomatic PAD, not at increased risk of
bleeding and at high perceived
cardiovascular risk

41. Pharmacotherapy:continue
• Offered to patients who have not benefited from exercise therapy and risk factor modification.
• Cilostazol (100 mgBD)
– Can improve symptoms & increase walking distance
– PDE3 inhibitor -inhibit platelet aggregation
– also causes vasodilation
– approved for the treatment of intermittent claudication
– Contraindicated in patients with heart failure
• Pentoxifylline (400 mg TDS)
– alternative to cilostazol
– xanthine derivative, nonselective PDE inhibitor
– Effectiveness of pentoxifylline is marginal and not well established
• Naftidrofuryl
 is a 5-HT-2-receptor antagonist, inhibits glucose uptake and increases ATP levels.
 It has fewer side effects than cilostazol and should be considered where available

42. Smoking Cessation
To reduce smoking and improve
cardiovascular outcomes
•Patient education,
•Behavioral therapy,
•Nicotine replacement therapy, or
Pharmacological therapy
(varenicline, bupropion)

43. HTN: BP control
• In subjects with hypertension,
• Calcium antagonists or ACEIs/ARBs preferred because
of their potential in peripheral arterial dilatation.

44. Exercise therapy
• Local supervised exercise programme has been shown to improve walking distance and
claudication distance
• First line therapy in any patient without critical limb ischaemia
• Effective and improves symptoms and QOL
• Supervised / Unsupervised
• Exercise did not improve ABI.
• No improvement in mortality with exercise therapy programs
• Whether ExTherapy reduces CV events and improves life expectancy is still unclear.
• Alternative exercise modes (e.g. cycling, strength training and upper-arm ergometry) may be
useful when walking exercise is not an option for patients, as these have also been shown to
be effective
However,

45. Supervised exercise program
• Structured exercise program :in hospital or outpatient facility
• Intermittent walking exercise is used as the treatment modality.
• Superervised by qualified healthcare provider(s).
• Patients may not initially achieve these targets, and a treatment goal is to
progress to these levels over time.
• 30- to 45-minute length sessions
• conducted 4 to 5 times a week (minimum total 3 hour a week)
• over the course of 12 weeks.

46. IC management 2017

47. Surgical Management /Revascularization
Surgical intervention if risk factor modification has been discussed;
and
 supervised exercise has failed to improve symptoms.
 critical limb ischaemia
•There are two main surgical options available:
1.Angioplasty with or without stenting
2.Bypass grafting : diffuse disease or in younger patients
3.A combination such as surgery to clean a specific lesion allowing
access for angioplasty to another region

48. ACC/AHA Guidelines
Endovascular
therapies
Surgery
• Only indicated for patients with
– Prior failure of exercise or pharmacological therapy; and,
– Favorable risk-benefit ratio
– Reasonable likelihood of symptomatic improvement;
– estimated life expectancy of <2 years
• Not indicated as a prophylactic treatment
• Preferred method for revascularization of TASC type A iliac and femoropopliteal arterial
lesions
• Indicated for patients
– With significant functional disability from symptoms
– Who are unresponsive to exercise or pharmacotherapy
– Who have a reasonable likelihood of symptomatic improvement
– estimated life expectancy of >2 years,
• Surgical intervention is not indicated to prevent progression to limb-threatening
ischemia
Surgical Vs Percutaneous intervention depend on patient functional status and surgical risk, skills of the operator,
anatomic location and extent of disease, presence of multifocal vascular lesions, and patient preference.

49. Revascularization: Aorto-iliac lesions
• Isolated aorto-iliac lesions are a common cause of claudication.
• Short stenosis/occlusion (<5 cm) of iliac arteries: endovascular therapy
gives good long-term patency (>_90% over 5 years) with a low risk of
complications.
• Ilio-femoral lesions, a hybrid procedure is indicated, usually endarterectomy
or bypass at the femoral level combined with endovascular therapy of iliac
arteries, even with long occlusions.
• If the occlusion extends to the infrarenal aorta, covered endovascular
reconstruction of an aortic bifurcation can be considered
• If the occlusion comprises the aorta up to the renal arteries and iliac
arteries, aorto-bifemoral bypass surgery is indicated in fit patients with
severe life-limiting claudication.

51. Revascularization: Femoro-popliteal lesions
• If the circulation to the profunda femoral artery is normal, there is a good
possibility that the claudication will be relieved with ExT and intervention is
mostly unnecessary.
• If revascularization is needed, endovascular therapy is the first choice for
stenosis/occlusions <25 cm.
• If the occlusion/ stenosis is > 25 cm, endovascular recanalization is still
possible, but better long-term patency is achieved with surgical bypass,
especially when using GSV.

53. Amputation
•if unsuitable for revascularisation with
ischaemia causing incurable symptoms or
• gangrene leading to sepsis.
 Assessment for risk of amputation: WIFI
classification

54. CLTI severity and risk stratification:
WlFI classification
primary factors that constitute and contribute to the risk of limb threat
are wound (W), ischaemia (I) and foot infection (fi).
•the target population for this system includes any patient with
1.ischaemic rest pain, typically in the forefoot
2.diabetic foot ulcer,
3. non-healing lower limb or foot ulceration >_2 weeks duration or gangrene
involving any portion of the foot or lower limb.

57. Multidisciplinary
approach for
PAD

58. Summary:
Management
of Claudication

60. Conclusion
• PAD is common and has a significant impact uponcardiovascular
outcomes
• Treatment of PAD, even asymptomatic, should focus on risk
factor modification/risk reduction
• Treatment of IC should include exercise therapy, drug therapy
and selective use of revascularization
• Treatment for CLI warrants aggressive efforts at
revascularization, including surgery, to reduce the risk of
amputation

61. References:
•2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease
•2017 ESC Clinical Practice Guidelines: Peripheral Arterial Diseases (Diagnosis and Treatment of)
Guidelines
•Sabiston Text book of Surgery 20e

62. THANK YOU

63. Acute limb ischemia
• Acute (<2 wk), severe hypoperfusion of the limb characterized by these features : pain,
pallor, pulselessness, poikilothermia (cold), paresthesias, and paralysis. (6P)
• Potential causes are
1. artery disease progression,
2. cardiac embolization,
3. aortic dissection or embolization,
4. graft thrombosis,
5. thrombosis of a popliteal aneurysm or cyst,
6. popliteal artery entrapment syndrome,
7. trauma,
8. phlegmasia cerulea dolens,
9. hypercoagulable states and
10. iatrogenic complications related to vascular procedures.
• Limb viability is threatened and prompt management is needed for limb salvage.

68. Assess severity of claudication
Treatment Approach to Intermittent Claudication
Mild to moderate claudication
Exercise
& drug therapy
Symptoms
debilitating
Symptoms
improve
Localize lesion
Consider
percutaneous
intervention
Severe claudication
Popliteal-tibial dz
Continue present therapy
Aortoiliac or
femoral dz
Exercise & drug
therapy unless
debilitating