Peripheral Arterial Disease: What’s new in the assessment and 

treatment?treatment?

Albert Chan, MD FRCPCl d lInterventional Cardiologist, RCH

Why are cardiologists involve in PAD care?

1. Pathophysiology of CAD and PAD are disease ofand PAD are disease of continuum

2. PAD represents more d d th l tiadvanced atherosclerotic process in a pt

3. Most PAD pts die from MI4. 10 and 20 prevention are 

the same in PAD and CAD5 Endovascular skills are5. Endovascular skills are 

transferrable from cardiac to peripheral interventions

Atherosclerosis is a polyvascular disease

REACH registry, 68,236 pts enrolled in 5,587 centers across 44 countries from 12/03‐12/04countries from 12/03 12/04

REACH registry.  JAMA 2007;297:1197

1‐year CV outcomes in REACH registry1 year CV outcomes in REACH registry

REACH registry.  JAMA 2007;297:1197

REACH: 4‐year event rates according to l l l dsingle vs polyvascular disease

50Si l l di

354045 Single vascular disease

Polyvascular disease

202530

%

051015

0All‐cause mortality

CV death Non‐fatal MI Non‐fatal stroke CV death, MI, stroke

CV death,MI, stroke, re‐

hospitalization

REACH investigators.  ESC 2010.

REACH: ConclusionsREACH: Conclusions

• Polyvascular disease is the most powerfulPolyvascular disease is the most powerful predictor for future events 

• Other predictors include:• Other predictors include:– Prior ischemic events < 1 yearP i i h i i– Prior ischemic event at any time

– Diabetes

REACH investigators.  ESC 2010.

Five vascular territories that are associated major morbidity and mortalitymajor morbidity and mortality

S b l i t di

Carotid artery disease

Subclavian artery disease

Aortic aneurysm

Renovascular disease

Iliofemoral disease

Screening for primary prevention?Screening for primary prevention?

Criqui et al.  Circulation 2008;118:2830

What are the criteria for screening?What are the criteria for screening?

• The disorder should be commonThe disorder should be common• There is an asymptomatic latent phase

h i h l h h ld b• The treatment in the latent phase should be more effective than in the later stage

• The screening test should be safe, precise, feasible, validated, ethically acceptable, and cost‐effective 

Current recommendationsCurrent recommendationsCost Prognostic Evidence            Recommended

ABI + +++ ++ ++

Carotid US ++ ++ + +

AAA US ++ +++ +++ +++AAA US ++ +++ +++ +++

Renal US ++ ++ + 0 

Criqui et al.  Circulation 2008;118:2830

Cerebrovascular diseaseCerebrovascular disease

• TIA/stroke/st o e– Old definition of TIA (1960’s) = symptomatic focal cerebral ischemia <24 hrs

– 30‐50% “TIA’s” associated with infarct on MRI– Current definition of TIA (2002) = focal neurological deficit typically <1 hr without sign of infarctdeficit typically <1 hr without sign of infarct

– Time is brain! Investigation and management should be carried out like ACS

– Large stroke: IV TPA if <4.5 hours– Catheter‐directed reperfusion an alternative

Zoppo et al.  Stroke 2009;40:2945‐8

Carotid ultrasound and DopplerCarotid ultrasound and Doppler• Excellent negative predictive value

• Tends to overcall severity• Characterization of plaque• Characterization of plaque morphology (soft, calcified, mixed)PSV 230 / ICA/CCA• PSV>230cm/s, ICA/CCA ratio>4.0, EDV >100cm/s indicate >80% stenosis in ICA

• Influenced by contralateralocclusion, arrhythmia, stent, techniques, equipmentq , q p

CTA• Non‐invasive assessment of cerebral vasculature

l i l ibl h• Relatively more accessible than MRA in FHR

• Heavy calcification prohibits y paccurate assessment of the severity

• Excellent assessment for CoWExcellent assessment for CoW

MPR=Multiplanar reformationMTT=Mean transit timeCBF=cerebral blood flow

MRI/MRA• More sensitive in confirming early 

stroke (<24 h), multiple emboli• Calcification not an issue• 2D/3D Time‐of‐flight, 

perfusion/diffusion mismatch to p /guide revascularization

• Assessment of extracranial and intracranial atherosclerosis, ,dissection, aneurysm, venous thrombosis, vasculitis

• Sometimes overcall ostialvertebral, common carotid disease

• Nephrogenic systemic fibrosis in p g ypatients receiving dialysis

DWI=diffusion‐weighted imagePWI=perfusion‐weighted image

MIP=maximal intensity projectionFLAIR=fluid attenuated inversion recovery

Catheter AngiographyCatheter Angiography

h ld• Remains as the gold‐standard

• Now usually reserved for catheter reperfusion or CAS

Other investigations for TIA/strokeOther investigations for TIA/stroke

• ECGECG• 24 hr Holter Monitor• Echocardiography +/‐ TEE• Echocardiography +/‐ TEE

– Rule out structural heart disease– Patent foramen ovale (PFO) an under‐diagnosed– Patent foramen ovale (PFO) an under‐diagnosed cause of TIA/stroke

• Stress test to detect IHD is indicated inStress test to detect IHD is indicated in patients with symptomatic extracranial carotid disease

ACC/AHA guidelines.  Circulation 2003;108:1278

Medical TreatmentMedical Treatment

• Antiplatelet RxAntiplatelet Rx– ClopidogrelASA + extended release dipyridamole– ASA + extended release dipyridamole

• Warfarin for atrial fibrillation• Statin• Blood pressure management

Statin in stroke reduction

Heart Protection Study.  Lancet 2002;360:7‐22

ACE inhibitor in stroke preventionRamipril 10mg od vs placebo among 9,297 patients with vascular disease or DM, normal LVEF, over mean of 5 yrs

HOPE study.  N Engl J Med 2000;342:145‐53.

Traditional guidelines for carotid revascularization

• Carotid Endarterectomy–Symptomatic: >50% ICA stenosisy p(periprocedural risk <6%)

–Asymptomatic: >80% ICA stenosis(periprocedural risk <3%) and if life‐expectancy >5 yrs

• CAS as an alternative for symptomatic carotid disease

SAPPHIRE – Primary EndpointsSAPPHIRE  Primary Endpoints

Yadav et al. NEJM 2004;351:1493

SAPPHIRE at 3 yearsSAPPHIRE at 3 years

Gurm H et al. N Engl J Med 2008;358:1572-1579

CREST: CAS is durable and meets non‐i f i it d i t h d ithinferiority endpoints when compared with 

CEA in long‐term follow‐up7,2

5,2

6,8

678

N = 2,502

5,2

4,14,5

2 3 2 3

4,8

2 4345%

0,9 1,1

0,3

2,02,3

0,7

2,3 2,4

012 CAS

CEA

0*P<0.05

CREST.  N Engl J Med Jun 14, 201010 endpoints = Death/stroke/MI at 30 days and ipsilateral stroke w/n 4 years

CAS more fit for young patients than ldolder patients in CREST

CREST.  N Engl J Med Jun 14, 2010

What a vascular surgeon never tells gyou, but you (and your patients) 

always want to knowalways want to know……

(Permanent) Cranial nerve palsy(Permanent) Cranial nerve palsy

CEA CASSAPPHIRE   5.0% 0%EVA‐3S                                      7.7%          1.1%*ICSS 5 3% 0 1%ICSS                                           5.3%          0.1%   CREST  4.8%          0.3%

* All except for 1 patient were related to conversion to CEA

Importantly, these data were achieved by the p y, ybest surgeons around the world!

Treatment preference should be driven by local/institutional experiencelocal/institutional experience

30‐day death/stroke

9,6

8 5

10,0

12,0

6,0

4,9

5,86,2

6,8

8,5

5,26,0

8,0%

3,0 3,1

,4,2

3,3 3,2

1,72,0

4,0

*

0,0

* 2 post‐OHS death & 1 peri‐CAS stroke

My opinion in management of carotid disease in 2010

• CAS is indicated in patientsld ( )– <69 year old (CREST)

• Symptomatic >50%• Asymptomatic >80%

– 69‐80 year old (SAPPHIRE, RCH experience)• Symptomatic >50%• Asymptomatic >80%

– >80 year old• Symptomatic >50%

– Severe uni‐ or bilateral carotid stenosis prior to cardiac surgery• CEA

– Is an alternative to CAS in patients with symptomatic >50% or asymptomatic >80% among patients with low‐surgical risk; esp if there isg p g ; p

– Contraindication for CAS (Heavy calcification, lack of access)• Conservative Rx for the rest

Renal artery diseasey• Indications for screening for renal artery disease:g y

1. Refractory HTN (persistent HTN on triple anti‐hypertensives that include a diuretic)

2 HTN at age <30 or >50 years2. HTN at age <30 or >50 years3. Hx of atherosclerosis and renal insufficiency4. Asymmetric kidneys on U/Sy y5. ARF after initiation of ACEi/ARB, or systemic BP lowering6. Cardiac disturbance syndrome in the absence of CAD, 

VHD or cardiomyopathyVHD, or cardiomyopathy• Atherosclerosis (>90%), fibromuscular dysplasia (involving renal, carotid, vertebral, femoral) ( g )

Caveats

• Renal ischemia = Nephropathy, but often co‐existp p y,– Their relationship is central in understanding clinical trials of renal 

artery disease and benefits of renal revascularization

• Return of renal function depends on the extent of underlying• Return of renal function depends on the extent of underlying nephropathy (inversely proportion)

• Clinical evaluation of nephropathy– Scr, urinalysis, renal ultrasound for RI, selective renal arteriography not 

predictive of outcome– Advanced nephropathy: proteinuria >1g/d, renal length <10mm, RI d a ced ep opat y: p ote u a g/d, e a e gt 0 ,

>0.8– Scr insensitive, only after >50‐75% renal mass lost

Imaging

Evaluation of Renal IschemiaEvaluation of Renal Ischemia

• Modalities to assess renal ischemia– Non‐invasive evaluation of single‐kidney GFR

• 125I‐Iothalamate GFR99M99M•• 99M99MTc‐DTPA 

– Invasive:• Visual estimation or quantitative angiographyVisual estimation or quantitative angiography• Translesional pressure gradient >20mmHg• FFR <0.8IVUS• IVUS

• Renal frame counts• Renal blush score

ASTRAL Trial(Angioplasty and Stent for Renal Artery Lesions)

• Enrollment criteria: “ Uncertainty on theEnrollment criteria:  ….Uncertainty on the part of the clinician whether revascularization is needed”is needed

• 806 pts randomizedA 2 diff i li (7 4%• At 2 yrs, no difference in mortality (7.4% vs8.2%), CHF, creatinine changes, BP control, or 1 t l1st renal event

ASTRAL trial.  N Engl J Med 2009;361:1953

CORAL TrialCORAL Trial(Cardiovascular Outcomes in Renal Atherosclerotic Lesions)

• 5‐year NIH‐funded RCT of 1080 pts comparing revascularization vs med Rxrevascularization vs med Rx

• Broad inclusion – Including severe disease in solitary kidney– Decreased EF

• CV or renal death, MI, CHF, stroke, doubling of Scr, renal replacement 

Algorithm for evaluation, treatment, and follow‐up of patients with RAS

Clinical Indications for evaluation of RAS

Yes No

Screening tests to evaluate RAS

Yes No RAS

Establishment of RAS with vital‐organ injury

E l i f l h l di

Yes None

Evaluation of renal parenchymal disease

Revascularization

Minimal parenchymal disease Significant

Revascularization

Assess causes of post‐procedural renal failureMedical Therapy

Arrangement of longterm F/USafian, Madder.  J Am Coll Cardiol Intv 2009;2:161

Summary of Revascularization of RASSummary of Revascularization of RAS

1. Majority of ARAS do not have renovascular HTN1. Majority of ARAS do not have renovascular HTN2. All pts need to be treated with EB‐guided Rx (ASA, 

statin, ACEi/ARB), / )3. Identification of the subset of ARAS that benefits 

from revascularization is paramountp– Await for clinical trial data (eg. CORAL)– Until then, candidates with renal ischemia without 

significant nephropathy seems to benefit most

Indications for renal artery lrevascularization

• Refractory Hypertension (despite the use of triple• Refractory Hypertension (despite the use of triple antihypertensives including a diuretic)

• Cardiac Instability syndrome (CHF in the absence of CAD, severe VHD CMP)severe VHD, CMP)

• Renal function salvage– Severe stenosis in solitary kidney– Severe bilateral renal artery stenosis– Decremental renal size ipsilateral to RAS– Preocclusive unilateral RAS

• Best results would be one with vital organ injury, renal ischemia, but no nephropathy; however, these are not common

Iliofemoral artery diseaseIliofemoral artery disease• Symptom status

h f d l f– Rutherford Classification I‐VI• I ‐Mild• II – Moderate• III – Severe

IV R t l di ti• IV – Rest claudication• V – Minor tissue loss (non‐healing ulcer, gangrene)• VI Major tissue loss (above metatarsal level)

• ExaminationR ABI– Rest ABI

– Exercise ABI– Segmental limb pressure

• Non‐invasive angiographyNon invasive angiography– CTA– MRA

• Catheter angiography

Imaging for PADImaging for PAD

CHARISMA sub‐studyIncidence of CV death, MI, stroke within 2.5 years among patients with 

history of CAD, stroke, PAD

CHARISMA investigators.  J Am Coll Cardiol 2007;49:198210 endpoints = CV death, MI, stroke

Statin in PAD

Heart Protection Study.  Lancet 2002;360:7‐22

Other medical therapy for CLIOther medical therapy for CLI

Pentoxifylline (Trental) 400mg tidPentoxifylline (Trental) 400mg tid• PDE‐4 inhibitor

i l i i 6 i lki di• Marginal increase in 6 min walking distance

Treatment of lower extremity PADTreatment of lower extremity PAD• CLI with life‐style limiting claudication

– Treat inflow disease• Non‐healing ulcer, critical limb ischemia, gangrene

– Treat inflow disease firstTreat inflow disease first– Treat outflow disease if problem persists

• Aortoiliac diseaseS t it l h i ifi t bidit ll t– Surgery: retroperitoneal approach, significant morbidity, excellent patency rate

– Endovasuclar: same day discharge, excellent patencyIli f l di• Iliofemoral disease– Femoral‐popliteal bypass– Endovascular approach +/‐ stent

AHA/ACC guidleines for the management of patients with PAD.  Circulation 2006;113:1474‐1547

Management of acute limbof acute limb 

ischemia

Gray et al.  Circulation 2008;118:2864

Treatment algorithm of symptomatic aortoiliac arterial disease

Gray et al.  Circulation 2008;118:2864

Treatment algorithm of symptomatic infrainguinal arterial disease

Gray et al.  Circulation 2008;118:2864

More in‐depth discussion will be held in the case‐based workshop