Peripheral Vascular Disease J B Handler M D

Peripheral Vascular Disease J. B. Handler, M. D. Physician Assistant Program University of New England 1

Abbreviations n n n n n LDL-low density lipoprotein HDL- high density lipoprotein CAD- coronary artery disease HTN- hypertension MI- myocardial infarction BID- two times daily CVA- cerebrovascular accident C-AMP- cyclic adenosine monophosphate CHF- congestive heart failure PTA- percutaneous transluminal angioplasty n n n n n t. PA- tissue specific plasminogen activator DVT- deep vein thrombophlebitis Rx- treatment LMW- low molecular weight Abd- abbdomen AAA- abdominal aortic aneurysm PPD- pack per day CHD- coronary heart disease CHD= CAD PAD- peripheral arterial disease 2

Atherosclerosis Leading cause of cardiovascular disability and death in the U. S. n Gradual process involving the aorta, coronary, carotid, extremity arteries (legs) and other large or medium sized arteries and their branches: focal involvement is common. n Gradual reduction of arterial lumen resulting in ischemia due to reduced O 2/blood supply. n 3

Risk Factors for Atherosclerosis Dyslipidemia (aka hyperlipidemia): Total Cholesterol, LDL, HDL and triglycerides n Hypertension n Cigarette smoking n Diabetes Mellitus- CHD risk equivalent n + Family history for atherosclerosis, especially CHD: 1 st degree relative n 4

Risk Factors for Atherosclerosis Male gender (primarily for CHD/CAD) n Hypoestrogenemia n Physical inactivity n Elevated plasma homocysteine levels n Elevation of C-reactive protein (CRP): marker of inflammation n – Inflammation plays role in atherosclerosis 5

Case 1 A 62 -y/o man has been experiencing recurrent episodes of aching in his right calf while walking. The ache resolves with rest. He has HTN (controlled on meds) and continues to smoke > 1 ppd (since age 22). n What is your clinical diagnosis? Differential? n Which area of the PE is most likely to be abnormal? n 6

Peripheral Arterial Disease n n n Atherosclerosis of the extremities- leading cause of occlusive arterial disease in patients over 40. 8 -12 million in U. S. ; ½ asymptomatic Risk factors: HTN, Dyslipidemia, Diabetes Mellitus, Smoking, +F. H. et. al. – DM and smoking risk for PAD n n Compared to CHD, risk for woman equals the risk for men. Pathology: Segmental involvement of artery(ies), often at branch points. 7

Sites of Involvement Aorta n Iliac artery: Common and external iliacs n Femoral n Popliteal n Tibial n Sites of involvement and pattern vary depending on age, sex, and risk factors. n 8

Peripheral Vascular Disease Images. google. com

Clinical Evaluation n n Claudication: Most common symptom: Pain, ache, cramp, numbness or fatigue of muscles. Occurs during exercise, relieved at rest; reproducible. Site of claudication is distal to the stenosis: – buttock, hip and thigh pain indicates aorto-iliac disease. – calf claudication: femoral-popliteal disease. n n With severe disease: Rest pain, numbness/paresthesias and other signs of ischemia including ulceration, necrosis and gangrene. Other symptoms: erectile dysfunction. 10

Physical Exam n Absent or diminished pulse distal to the obstruction: Femoral, popliteal, dorsalis pedis and posterior tibialis pulses. – Hand held doppler ultrasound probe improves detection n Bruits in arteries indicates atherosclerosis. When severe: hair loss; shiny, smooth skin; reduced skin temp, pallor, cyanosis, ulcers and gangrene. With elevation of involved extremity - pallor of soles; rubor develops with legs in the dependent position. 11

Skin Findings

Vascular Testing n n n Ankle/brachial index (ABI) see below. Duplex ultrasonography- echo imaging plus pulse wave doppler: screening tool for obstructive disease. Contrast angiography – definitive; performed prior to endovascular or surgical revascularization. Invasive with risks of contrast reaction/nephropathy, bleeding, thrombosis or infection. – Alternative: Gadolinium enhanced MRA- less invasive n Cardiac stress testing - functional impairment; detection of CHD if present. 13

Duplex Ultrasound Images. google. com

Ankle-Brachial Index (ABI) n n n n Non invasive tool for diagnosis of PAD. BP cuff wrapped above ankle. Cuff inflated to above systolic BP. Hand held doppler device used to detect systolic BP in the DP and PT arteries. Measurement compared with doppler detected systolic pressure in the brachial artery. Normal ABI is 1 or ABI<. 9 is diagnostic of peripheral arterial disease. ABI with claudication: 0. 5 - 0. 8; rest pain: <0. 4 Prognostic value, too; ABI<. 5= 63% 5 yr survival. 15

Angiogram Images. google. com

Prognosis in the Presence of PAD n n Influenced by extent of co-existing Coronary and Cerebrovascular Disease. >50% patients with PAD have significant CHD – 70% 5 yr. survival – 50% 10 yr. survival from MI or sudden death. n n n Majority of patients with claudication stabilize or improve with lifestyle modification or medication. 25% progress to rest pain or skin ulceration 5 -10% progress to amputation. 17

Case 1 (continued) Diagnosis: Significant stenosis of the right femoral artery. n How will you manage this patient? n – What are his options? 18

Treatment of PAD Risk factor modification: smoking cessation crucial- significant improvement in exercise tolerance; Rx HTN, hypercholesterolemia and DM - goal is to prevent progression. n Exercise n Pharmacologic Rx. n Revascularization - tx to improve blood supply n 19

Supervised Walking Program n Goal: Improve symptoms; best tool – Improve oxygen utilization – Increases muscle anaerobic metabolism – Shifts energy of walking to muscles with higher O 2 delivery – Recruits collateral blood flow Exercise 30”, 4 x/wk : Goal is to walk on flat ground until claudication; rest and resume. n Can increase pain free walking by up to 150%. n 20

Platelet Aggregation Inhibitors Secondary prevention; decrease incidence of MI, stroke and death in patients with PAD. n Aspirin: All patients unless contraindicated; risk is bleeding. Rx for life. n Clopidogrel (Plavix): Used as an alternative to ASA in patients with ASA intolerance/allergy and for some high risk sub-groups. n 21

Cilostozol (Pletal) Released in 1999 - Phosphodiesterase inhibitor – increases c. AMP levels and inhibits platelet aggregation; improves local flow via vasodilation. n 8 large randomized studies showed clinical improvement in claudication- walking distance increased by 35%. n Contraindicated in patients with CHF. n Major side effect: dizzyness. n 22

Revascularization Indications: Improve quality of life in patients with disabling claudication already on maximal medical therapy. n Relieve rest pain and preserve limb viability. n – Non healing skin ulcers Angioplasty and stenting: Endovascular revascularization. n Surgery to bypass obstruction(s). n 23

Endovascular Revascularization n n Angioplasty, often combined with stent placement. Ideal lesion: discrete, <5 cm long, concentric lesion. Advantages over surgery: Decreased complications; rapid recovery. May replace or delay need for surgery. Drawback: Restenosis, thrombotic occlusion. Common iliac stenosis: 70 -80% 3 -yr patency rate when combined with stent. Distal disease (ext. iliac, femorals, popliteal): 55 -60% 3 yr patency rate. 24

Angioplasty and Stenting

Surgery for PAD Major surgery with 8% morbidity, 2 -5% mortality (from MI) depending on location. n Morbidity/mortality usually due to underlying CHD or stroke. n Pre-op eval often includes assessment of coronary reserve (stress testing) and carotid circulation. n – Operative risk can be quantified on basis of history, PE and testing. 26

Surgical Procedures for PAD (Interest Only) n Bilateral iliac obstruction: – Aortobifemoral bypass surgery: Uses dacron or polytetrafluroethylene grafts. Graft anastomosed to aorta proximally and femoral arteries distally. » 5 and 10 year patency: 91 and 87%. – Axillobifemoral bypass: For high risk patients with critical ischemia; utilizes synthetic grafts. » 5 yr patency 50 -60%. 27

Surgical Procedures for PAD (Interest Only) n Unilateral iliac obstruction: – Femoral-femoral bypass: synthetic graft; 60 -80% 5 -yr patency. n Femoral and more distal obstruction: – Femoral (above the obstruction)– popliteal (below); femoral post-tibial bypass: uses saphenous vein segments as bypass conduit; 60 -80% 5 -yr patency. 28

Vascular Bypass Grafts

Acute Arterial Occlusion Etiologies: Embolism; Thrombosis in situ. n Heart- most common source of emboli: atrial fibrillation, ventricular aneurysms, anterior MI, cardiomyopathies, prosthetic valves. n Thrombosis in situ- thrombosis at the site of stenosis or aneurysm. n 30

Atrial Thrombus Images. google. com

Clinical Features n n n Depends of site, duration and severity. Rapid onset pain, paresthesia, numbness and coldness of involved extremity. P. E: Loss of pulse distal to the occulsion. Treatment: Anticoagulation with IV/SC heparin to prevent propagation of the thrombus For severe ischemia reperfusion: – surgical or catheter embolectomy – infusion of Streptokinase, Urokinase or t. PA. 32

Venous Thrombosis Def: The presence or thrombus within a superficial or deep vein, and the accompanying inflammation is termed venous thrombosis or thrombophlebitis. Risk Factors for DVT: n Stasis: n – Immobilization, regardless if underlying disease, is major predisposing factor; includes prolonged hospitalization. – Post trauma: fracture of hip, pelvis, femur. – Post orthopedic surgery involving knee or hip. – Post open abdominal and thoracic surgery. 33

DVT: Risk Factors n Hypercoagulability: – Neoplasms- high incidence DVT with certain cancers (stomach, pancreas, lung). – Clotting disorders: e. g. Factor V Leiden, others. – Estrogen use n 3 rd trimester of pregnancy and post-partum. 34

Consequences of DVT Pulmonary emboli- most important consequencelife threatening. n Chronic venous insufficiency: can occur as a consequence of both DVT as well as superficial venous insufficiency. Veins become functionally inadequate due to damage of valves resulting in bi -directional flow. n 35

Symptoms and Signs n n n 50% of patients with DVT are asymptomatic. When present, dull ache/tightness or pain in involved extremity, often worse with walking. Location - Iliac, Femoral, Popliteal or calf veins. Exam: unilateral leg swelling, warmth and tenderness along involved veins; a cord might be palpable. – Homan’s sign: pain in the calf with passive dorsiflexion of foot; of limited usefulness clinically. n Physical findings may be absent. 36

Diagnostic Eval. n n n Plasma D-dimer: (>300 -500 ng/ml) a degradation product of cross-linked fibrin- usually elevated in presence of thrombus (97% sensitivity), but not specific (45%). See below for application. Duplex venous ultrasonography- 2 d echo imaging + pulse wave doppler-very accurate in detecting proximal vein involvement (95% sensitivity); less accurate for calf veins (70% sensitivity). Venography with contrast- very accurate, more invasive. 37

Simplified Clinical Model for Assessment of Deep Vein Thrombosis* Wells, P. S. et al. JAMA 2006; 295: 199 -207. Copyright restrictions may apply.

Suggested Method for Diagnosing DVT: D-Dimer + Clinical Risk If D-dimer test is negative and low or moderate risk via Wells score: DVT ruled out- no further eval needed. n If D-dimer negative but clinical risk is high: proceed to ultrasound of involved extremity. n If D-dimer is positive: proceed to ultrasound regardless of clinical risk. n Positive Ultrasound: Treat for DVT. n 39

Treatment of DVT n n Anticoagulants- Goal: Prevent propagation of thrombus; prevent new thrombus; prevent pulmonary emboli. IV unfractionated Heparin: unpredictable response; need to follow activated Partial Thromboplastin Time (PTT) – goal: 2 x control. Loading dose: Bolus 100 U/kg; continuous infusion 10 u/kg/hr, adjusted to goal; treat for 5 -7 days; initiate oral warfarin Rx while on IV heparin and continue for up to 6 mos (see below). 40

Anticoagulation for DVT n n Complications of IV heparin: bleeding; thrombocytopenia (<5% incidence). Low Molecular Wt. heparin: (1999)- administered sub-cut; as effective or better than conventional, unfractionated heparin; more predictable anticoagulant response; more expensive. Treat for 5 -7 days while starting warfarin. – Enoxaparin (Lovenox) 1 mg/kg 2 x/d. Does not require monitoring of PTT, less bleeding and FDA approved for out-patient treatment. Other LMW heparins are similar. 41

Anticoagulation for DVT n n n Warfarin (Coumadin) initiated within first three days of heparin; dose adjusted to maintain International Normalized Ratio (INR) 2 - 3. Full anticoagulation always indicated for proximal DVT - iliac, femoral, popliteal. Risk of Pulmonary Emboli is 50% if untreated. Isolated calf vein DVT- risk of P. Emboli is 10%anticoagulation usually indicated; proximal propagation, venous insufficiency. Note: 20+% of calf DVT extends proximally into deep veins of thigh. 42

Treatment of DVT Proximal DVT - Rx warfarin for 3 to 6 mos; calf DVT- Rx warfarin for 6 weeks; recurrent DVT or recurrent PE: Rx warfarin for LIFE. n DVT with factor V Leiden- warfarin for life. n IF anticoagulation is contraindicated (bleeding, etc. ): blood flow through the inferior vena cava can be interrupted by percutaneous placement of a filter or umbrella device. n 43

DVT Prophylaxis Used in clinical situations where risk of DVT is high (i. e. orthopedic procedures, surgeries and illnesses associated with prolonged bed rest, etc. ) n Goal: prevent DVT and pumonary emboli. n Low doses of heparin (SC), LMW heparin (SC), and warfarin all useful for prophylaxis. n 44

Chronic Venous Insufficiency n n n Progressive edema of the leg with secondary changes of the skin. Etiologies: most common is post DVT; othersvaricose veins, trauma, neoplastic obstruction. Skin shiny, discolored, atrophic and cyanotic. Stasis ulcers common- often painless. Prevention: aggressive Rx of DVT, intermittent leg elevation, compression stockings. Ulcers- debridement; special medicated boots; bioengineered living cell grafts (Apligraf, others). 45

Venous Insufficiency Images. google. com

Aortic Aneurysms Def: Pathologic dilatation of a segment of blood vessel: fusiform, saccular. n Pathology: atherosclerosis; cystic medial necrosis. Classification: abdominal, thoracic. n Presentation - often asymptomatic; as they expand, pain. n Abdominal aneurysm’s: 75% below renal arteries. n 47

Aortic Aneurysm Images. google. com

Diagnosis and Detection: AAA P. E. : Abdominal aneurysms often palpablepulsatile, non-tender mass. n Abdominal Ultrasound: can accurately measure dimensions of AA’s, and useful for serial follow up of small AA’s. n CT with contrast or MRI are also excellent in detection and quantifying both abdominal and thoracic aneurysms. n 49

Prognosis and Treatment n n n Prognosis related to size of the aneurysm and presence of concomitant CAD. Risk of rupture: < 5 cm. - 1 -2% over 5 yrs; > 5 cm - 20 -40% over 5 yrs. Treatment: Operative excision with graft replacement for rapidly expanding AA’s or those with symptoms; 3 -8% op mortality. New: placement of devices with stents reduce risk of rupture. If Asx: surgery always if > 6. 5 cm Probable surgery if > 5 cm. 50

Vasomotor Disorders n n n Raynaud’s disease and phenomenon Spasm of the digital arteries to a variety of stimuli, particularly cold exposure. Paroxysmal palor and cyanosis of the involved digits followed by flushing, rubor and discoloration. Raynaud’s disease: progressive, symmetric, and woman>men. Rx: Ca channel blockers. Raynaud’s Phenomenon: Associated with a variety of auto immune diseases; CREST, etc. 51