Peripheral Vascular Disease A non-invasive perspective

AZHARI GANI

24 Januari 2009

Peripheral artery disease and cerebrovascular disease are artherosclerotic disease involving the the vascular tree of the particular organs Majority are asymptomatic Prevalence are increasing:
Ageing population Co morbidities cigarette, DM, HPT,

Hyperlipidemia Better screening

Claudication intermittent is a sensation of aching, burning, heaviness, or tightness in the muscles of the legs that usually begins after walking a certain distance, walking up a hill, or climbing stairs, and goes away after resting for a few minutes. Buttock, thigh, or calf pain with exertion (claudication) No symptomsdiagnosed by abnormal ABI test Erectile dysfunction Uncommon Pain in legs and feet at rest Sore (ulcer) on leg that does not heal Arm pain with exertion (PAD of arms) Different blood pressures in the right and left arms of more than 15 points (PAD of arms)

 painful joints (arthritis), tingling or a pinsand- needles sensation

(neuropathy), pain running down the back of the thighs due to arthritis of the spine (sciatica or spinal stenosis).

PVD prevalence

16% in men > 60 years 20% in men > 80 years 13% in women > 60 years

Incidence of 3 vessel higher in patients with PVD (63%) than those without PVD (11%)
Schroll M, J Chr Dis 1981 Sukhija R, Am J Cardiol 2003

Persons with PVD at increased risk for all cause mortality (RR 3.1), cardiovascular mortality (RR 5.9) and cardiovascular events. Marked reduction in QOL, similar to CCF and other chronic diseases

Criqui MH, NEJM 1992 Jaff M, PCR 2003

PVD is a notably underdiagnosed and undertreated health condition. Offering a screening program is an excellent approach for providing services. PVD screening programs can tap new patient markets, increase referrals and ultimately boost direct and indirect revenue Medicare contribution margin is 30% for PVD, comparable to cardiac services
Vesey J, Health Care Strategic Mx 2003

Supraaortic arteries carotids, vertebral, subclavian Renal arteries Aorta abdominal and thoracic Lower limbs iliacs, femoral, infrageniculate Others areas
Intracranial Penile Coeliac, mesenteric

Duplex USG is one of the most important techniques in evaluating PVD Combination of B mode, colour and pulsed Doppler is the way- accurate and simple Sensitivity and specificity of close to > 95% Newer tissue Doppler, harmonic imaging, contrast enhancement and 3D imaging yet to play role in daily practice CT and MRI has a role but impractical for screening

More than 80% of ischaemic events are due to arteriosclerosis affecting the extracranial arteries, mostly at the bifurcation/prox ICA Duplex examination most important Most vascular surgeons rely on USG alone prior to CEA Carotid artery stenting still limited to symptomatic patients with >50% stenosis and asymptomatic with >80% stenosis with high risk

Diagnosis of arterial occlusion usually made on basis of history and physical examination ABI plays a major role in screening Duplex scanning of arteries can identify specific segment for study with high accuracy Image however less accessible in the deeper vessels, pelvic area, adductor canal and infrageniculate arteries. Lower sensitivity for detecting second order stenosis, or stenosis distal to severe occlusions

Meluzin et al Eur J Echo 2003

Simple test to screen for arterial occlusion ABI : ratio of the leg pressure to the arm pressure (ankle blood pressure divided by arm blood pressure) ABI > 0.9 normal 0.7-0.89 mild disease 0.41-0.69 moderate < 0.4 severe Unreliable in calcified vessels, diabetics. Segmental blood pressure recordings might be measured to further pinpoint area of occlusion Plethysmography and exercise component may be added

USG proves to be useful in terms of safety, low cost and high sensitivity Several Doppler criteria from few groups: e.g. Renal aorta ratio > 3.5 signifies 60-99% stenosis, velocity >180cm/s

Neumeyer M, Hershey Med Dept

Colour and CW Doppler from inflow, graft and outflow artery Doppler signals are triphasic and changes to biphasic can be significant Graft velocity of < 45 cm/s signifies a potential graft failure Peak stenotic and prestenotic systolic velocities will estimate narrowing :
2:1 ratio 4:1 ratio > 400cm/s

: >50% : >75% : > 75%

Venous Thrombo-embolisms (VTE) is serious medical problem Prevalence of VTE is high VTE usually undiagnosed Many physicians still unrecognized VTE Heart failure is one of the high risk for VTE The best treatment VTE is prophylaxis

 Deaths caused of VTE: 543,4541 Exceed combined deaths due to:

AIDS 5,8602 breast cancer 86,8312 prostate cancer 63,6362 transport accidents 53,5992

1Cohen

AT. Presented at the 5th Annual Congress of the European Federation of Internal Medicine; 2005. 2Eurostat statistics on health and safety 2001. Available from: http://epp.eurostat.cec.eu.int.

 Within 5 years of DVT, 80% of patients developed become Post Phlebotic Syndrome (varicose veins, ulceration veins) 30-70% of patients with DVT (VTE) have

Asymptomatic Pulmonal Embolisms

GRIP- VTE SURVEY

Prevalence of VTE is High

DVT prevalence in stroke patients is one of the highest in hospitalized patients (no prophylaxis)

Acute ischemic stroke

Orthopedic surgery General surgery 20

50 50

Internal medicine
0
1Geerts 2Leizorovicz

17
10 20 30
(%)

40

50

60

WH, et al. Chest. 2004;126:338S-400S. A, et al. Circulation. 2004;110(24 Suppl 1):IV13-9.

5,039 Hospitalized Patients

Inpatient VTE, %

70% of deaths due to PE occur in medical patients In 5,000 autopsies, VTE was discovered in 43% of patients PE causes 10% of hospital deaths

70% Medical

30% Surgical

Adapted from: Diebold J, Lohrs U. Pathol Res Pract. 1991;187:260-266.

VTE mostly Undiagnosed

20 %
Often goes undetected until too late

80 %
Less than half of all cases of fatal PE are detected prior to death 1

Approximately 80% of DVT are clinically silent 2,3

1. Goldhaber SZ, et al. American Journal of Medicine 1982;73:822-826. 2. Lethen H, et al. American Journal of Cardiology 1997;80:1066-1069. 3. Sandler DA, et al. J. Royal Soc. Med. 1989; 82:203-205.

The Acute illness Hospitalized medical Patients frequency of VTE in the absence of prophylaxis
General medical patients 10-26% [Cade 1982, Belch et al., 1981] Stroke 11- 75% [Nicolaides et al.,1997] Myocardial infarction (MI) 17-34% [Nicolaides et al., 1997] Spinal cord injury 6 -100% [Nicolaides et al. , 1997] Congestive heart failure 20- 40% (Anderson et al., 1950]

Medical intensive care 25- 42% [Cade, 1982, Dekker et al., 1991,

Hirsh et al., 1995]

MECHANISME VTE IN HEART FAILURE

Rudolf Ludwig Karl Virchow (1821-1902) "Father of Pathology

Hypercoagulability. (Deficiency of Protein C, Protein S, AT III)

Vascular lesion (surgical, trauma, inflammation)

Thrombogenesis

Venous stasis (Immobilization)

Chest 2002;122;1440-1456

Model for venous thrombosis

Monocytes stimulation to produce TF -Cancer -IBD -infection (TNF-) Endothelial activation Stasis (eg., RVF) -infection (TNF-) (Vessel injury) Lopez, J. A. et al. Hematology 2004;2004:439-456

Venous thrombosis:

Slow, turbulent blood flow in valve cusps result in areas of local stasis

Stasis leads to the development of a thrombus composed of red cells and fibrin
Prandoni P, et al. Haematologica 1997; 82:423428.

Venous thrombosis:

Thrombus growth results in proximal progression along the vein

Deep vein thrombosis

Damage to veins (PTS)

Pulmonary embolism
Prandoni P, et al. Haematologica 1997; 82:423428.

MANY PHYSICIANS UNREGCONIZED VTE

Symptoms : pain, redness and swelling of the leg, usually unilateral Within 5 years of DVT, 80% of patients develop post phlebitic syndrome, which manifest in chronic leg discomfort and swelling, varicose veins, skin discoloration and ulceration in severe cases. DOPPLER USG, VENOGRAPHY REMEMBER : 80-90% DVT ARE ASYMPTOMATIC (CLINACALLY SILENT)

C H F
SYMPTOMATIC

ASYMPTOMATIC

V T E 80-90%

V T E 10-20%

PULMONARY EMBOLISMS

Practice guidelines
ACCP 2008 - LDUH* or LMWH recommended in general medical patients with clinical risk factors for VTE (including cancer, bed rest, CHF, severe lung disease) (Grade 1A)

International Consensus Statement 2001 - LMWH OD recommended for hospitalized patients with chronic respiratory disease or CHF (Grade A)
*LDUH: UFH 5,000 U SC BID or TID
1. Albers GW, et al. Chest. 2008;133:71-109 2. Nicolaides AN. Int Angiol, 2001; 20: 1-37

LMWH vs UFH
Trial PRIME1
P < 0.001 for equivalence

RRR 86%

ThromboprophylaxisPatients with VTE (%) UFH 5000 IU tid Enoxaparin 40 mg od

1.4 0.2

THE-PRINCE2
P = 0.015 for equivalence

19%

UFH 5000 IU tid Enoxaparin 40 mg od 8.4

10.4

Hillbom, et al3
P = 0.044

43%

UFH 5000 IU tid Enoxaparin 40 mg od

1Lechler
2Kleber

34.7 19.7

tid = three times daily.

E, et al. Haemostasis. 1996;26 Suppl 2:49-56. FX, et al. Am Heart J. 2003;145:614-21. 3Hillbom M, et al. Acta Neurol Scand. 2002;106:84-92.

Safety end point

Enoxaparin (n= 332), n (%)
Patients w ith bleeding complications With minor bleeding With major bleeding Patients w ith injection site hematoma* Death Patients w ith Aes With possible/ probable drug relation With w ithdraw al due to Aes Patients w ith raised levels of ALAT Patients w ith raised levels of ASAT 5 (1.5) 4 (1.2) 1 (0.3) 24 (7.2) 9 (2.7) 152 (45.8) 7 (2.1) 12 (3.6) 75 (22.6) 46 (13.9)

UFH (n= 333), n (%)

12 (3.6) 11 (3.3) 1 (0.3) 42 (12.6) 15 (4.5) 179 (53.8) 30 (9.0) 24 (7.2) 111 (33.3) 70 (21.0)

Fisher's exact test (2-tailed) P value

NS NS NS 0.02686 NS 0.04382 0.00013 NS 0.00245 0.01851

Aes = adverse event; ALAT=Alanine aminotransferase; ASAT= aspartate aminotransferase *>5 cm diameter at injection site

CONSENSUS RECOMMENDATIONS IN ACUTE HEART FAILURE

Consensus body Recommendation Subcutaneous UFH LMWH+ Subcutaneous UFH High dose LMWH+ Recommendation grade** 1A A

ACCP Consensus Statement5

International Union of Angiology*

*Recommendations are for medical patients with disease-related and/or additional patient-related risk factors +Enoxaparin (40 mg once-daily) is the only low molecular weight heparin licensed for the prevention of venous thromboembolism in hospitalised, acutely ill patients with heart failure NYHA Class III/IV **Grade of recommendation based on scientifically sound clinical trials in which the results are clear cut

VTE risk and ACCP prophylaxis use in medical patients with 6 key diagnoses
120

At risk of VTE

At risk of VTE and receiving ACCP prophylaxis

100
100

100

100

Medical patients (%)

80

68 53 41 45 40 22 25 13 34

60

40

20

0 Acute heart failure Acute noninfectious respiratory disease Respiratory infection Infection (nonrespiratory) Ischaemic stroke Active Malignancy

Bergmann J-F, et al. XXIII World Congress of the IUA. June 2008;Athens, Greece.

Non invasive service in PVD is essential in screening and ensuring the livelihood of the peripheral intervention team Adequate training of personnel is available and accredited Good relationship with the vascular surgeons, interventional radiologists, cardiologist to ensure a healthy practice which benefits the patient Patients immobilized with critically ill condition including congestive heart failure (30%) are at risk of venous thrombo-embolism.