have been equivocal, with some patients experiencing benefit and others showing no change in their symptom complex. Cilostazol is a cellular phosphodiesterase inhibitor that is believed to improve claudication through platelet disaggregation, and recent studies again suggest modest improvements in exercise capacity among patients with mild to moderate disease. Neither medicine nor exercise substantially alter the natural progression of the disease toward occlusion. Without question, the most important risk factor intervention to try and achieve in patients with lower extremity atherosclerosis is smoking cessation, which improves symptoms, slows disease progression, and reduces amputations. Similarly aggressive control of diabetes, hypertension, and cholesterol is very important. Revascularization therapy Revascularization therapy is aimed at restoring normal flow to the affected limb, and includes transluminal angioplasty with stenting and bypass surgery. Transluminal angioplasty and stenting is less invasive than surgery and does not require general anesthesia. However, experience with the technique thus far shows that it is most effective when atherosclerosis causes significant stenoses in the larger limb vessels (for example, iliac and proximal femoral arteries); in such cases surgery has excellent long-term benefits for both large and medium caliber vessels further downstream. Surgical therapy for intermittent claudication has been most successful at improving symptoms, but does not clearly alter the rate of amputations. Association with coronary artery disease Perhaps the most important issue to be addressed among patients with lower extremity atherosclerosis is that their disease is systemic and affects other circulations. In particular, patients with lower extremity atherosclerosis have a high prevalence of coronary artery disease, which is often asymptomatic because these patients are sedentary. The mortality of patients with peripheral lower extremity atherosclerosis remains extremely high as compared with that in a general population, and an overwhelming proportion of that mortality is accounted for by coronary artery disease. Therefore, when patients with intermittent claudication present for medical attention, an evaluation for the presence of coronary artery disease is at least as important as the evaluation and relief of their presenting symptoms. 3 The relationship between lower extremity atherosclerosis and coronary artery disease is so strong that there is an inverse correlation Cardiology Core Curriculum 564 between the ankle brachial index and the risk for death from coronary events (i.e. the lower the index, the higher the risk for cardiac death). In a landmark study conducted during the mid-1970s, coronary angiography was performed in all patients who presented with peripheral atherosclerosis. It was found that, by the time the patients presented with peripheral atherosclerosis, two-thirds had evidence of coronary atherosclerosis. Within this group, approximately half had clinically significant coronary artery disease. It is not surprising, therefore, that when patients with lower extremity atherosclerosis present for peripheral vascular surgery, their chances of surviving the surgery without significant cardiovascular morbidity are substantially poorer than in patients presenting for other types of surgery. Cardiac risk stratification In recent years the perioperative risk associated with vascular surgery has been decreasing. Although the approach to identifying coronary artery disease among patients with lower extremity atherosclerosis is still controversial, more clinicians are paying attention to this issue. It has become common for patients undergoing vascular surgery to undergo a preoperative clinical evaluation by an internist or a cardiologist. Patients are often stratified with respect to their risk for coronary artery disease by several clinical criteria, including age, the presence of diabetes, the presence of symptoms suggesting angina pectoris, past history of myocardial infarction, or the presence of cardiac arrhythmias. In combination, those factors may suggest a high prevalence of coronary artery disease. Should all patients with peripheral atherosclerosis presenting for surgery receive non-invasive cardiac tests to establish the presence of coronary artery disease? This issue remains controversial because no cardiac non-invasive test is perfect. A reasonable approach is to identify those patients who are at highest risk for active coronary artery disease based on their age (for example, >70 years), and the presence of angina, myocardial infarction, cardiac arrhythmia, or diabetes. Patients who have any, or all, of these criteria are then tested with some non-invasive cardiac test to assess their risk further. Tests successfully used to identify cardiac risk among patients with lower extremity atherosclerosis include the following. Exercise treadmill testing This is a procedure that requires patients to walk on a treadmill while serial electrocardiograms are obtained. Exercise capacity, presence of symptoms to suggest myocardial ischemia, and/or electrocardiographic changes that are diagnostic for ischemia confirm the presence of active coronary artery disease. The disadvantage of this test is that often patients are unable to walk Arterial vascular disease 565 because of claudication. The presence of a normal baseline electrocardiogram is also required for accurate interpretation. Dipyridamole thallium/sestamibi imaging Dipyridamole is a coronary vasodilator that causes shunting of blood flow from coronary arteries with significant atherosclerotic stenoses to normal coronary arteries, resulting in a steal syndrome. Simultaneous radionuclide imaging can document hypoperfusion of areas of myocardium within the distribution of coronary atherosclerotic vessels. This is the most widely used cardiac test for assessing risk among patients with peripheral atherosclerosis. Although studies have suggested that this test is highly effective, it should not be used as a screening measure among all patients with peripheral atherosclerosis, but rather should be used for those at highest risk for coronary artery disease. Holter monitoring for asymptomatic ischemia Patients wear a small tape recorder that monitors two leads of the electrocardiogram continuously over a 24-hour period. Patients with peripheral atherosclerosis have a high prevalence of coronary disease and may have frequent episodes of asymptomatic ST-segment depression due to spontaneous myocardial ischemia. The absence of ST-segment depressions predicts a very low risk for coronary artery disease or adverse cardiac events after vascular surgery, whereas the presence of ischemia predicts a higher risk. Other studies These include the use of intravenous dipyridamole in conjunction with echocardiography, as well as the use of other stress agents such as dobutamine in conjunction with radionuclide imaging or echocardiography. Dobutamine stress echocardiography now has a well established track record for accurately predicting perioperative risk among vascular disease patients. Management of peripheral atherosclerosis in the presence of high cardiac risk Once a patient with peripheral atherosclerosis is identified as a high risk cardiac patient, what to do next is controversial. Conventional wisdom argues that those patients at high cardiac risk should undergo revascularization therapy (with coronary artery bypass graft surgery or coronary angioplasty/stenting). This aggressive approach should be used with caution. Patients with peripheral atherosclerosis are often poor candidates for coronary angiography and coronary bypass surgery because they tend to be older and have frequent comorbid diseases such as stroke, renal failure, or diffuse coronary atherosclerosis. This makes the techniques of revascularization risky or Cardiology Core Curriculum 566 unsuitable. Hence, the overall risk of a strategy of myocardial revascularization may outweigh the risk associated with undergoing vascular surgery alone, and should only be undertaken if it will also substantially reduce long-term risk. 4 The combined morbidity and mortality of cardiac and peripheral arterial revascularization should not exceed the risk associated with vascular surgery alone in a patient with known, clinically relevant coronary artery disease. What has become very clear is that, in high risk patients, therapy with β-blockers reduces death from cardiac causes and non-fatal myocardial infarction, both perioperatively and on long-term follow up. 5 Case studies Case 18.1 A 67-year-old woman presented to a vascular surgery clinic with severe right calf pain at rest radiating to the foot. She was found to have adult onset diabetes mellitus 8 years previously. Over the prior 5 years she developed bilateral calf pain that occurred when she walked more than 50 feet on flat ground. The pains promptly resolved with rest and she was able to continue walking. For a 1 year period she was unsuccessfully treated with pentoxifylline, with no improvement in her exercise capacity or calf pain. She stopped the medication. Over the prior 4 months her calf pains had become more severe, particularly in the right leg, and she began to experience more frequent episodes of pain with less walking capacity. For 1 month she woke in the middle of the night with severe leg cramping that was not relieved unless she dangled her right leg outside of the bed. For the preceding 72 hours her right foot had become bright red and extremely painful to the touch. She retired from her job as a school teacher at age 65 years. She was an active, 96 pack-year smoker. There was no history of prior myocardial infarction or angina. Examination. Physical examination: the patient appeared chronically ill. She was afebrile. Pulse: 78 beats/min, regular, normal sinus rhythm. Blood pressure: 150/80 mmHg. Jugular venous pulse: normal. Cardiac impulse: normal. First heart sound: normal. Second heart sound: split normally on inspiration. No murmurs or added sounds. Chest examination: normal air entry, no rales or rhonchi. Abdominal examination: soft abdomen, no tenderness, and no masses. Normal liver span. No peripheral edema. Femoral arteries: loud bruits bilaterally. Left leg: faint popliteal pulse, and absent dorsalis pedis and posterior tibial pulses. Right leg: absent popliteal, dorsalis pedis, and posterior tibial pulses. The right foot was pale with the patient supine and red when the patient sat up and dangled the Arterial vascular disease 567 foot (dependent rubor). The nail beds of both feet were yellowed and sclerotic, and there was hair loss in a stocking distribution on both legs. Carotid pulses: normal, no bruits. Optic fundi: diabetic arterial changes. Investigations. Laboratory studies: normal complete blood count and normal electrolytes, with the exception of a random serum glucose of 192 mg/dl (10·7 mmol/l). Electrocardiogram: normal sinus rhythm, normal axis, intervals, and no evidence of prior infarction or ST-T changes. A non-invasive arterial study comprising segmental pressure measurements was also obtained (see Figure 18.1): systolic pressure gradients throughout the right and left legs consistent with severe arterial occlusive disease that most affected the right leg in the distribution of the superficial femoral artery. Progress The consulting vascular surgeon recommended she undergo femoral angiography. Femoral angiography was carried out uneventfully via a left femoral arterial puncture approach and the right superficial femoral artery was found to be occluded. A cardiologist evaluated her. The interview with the cardiologist confirmed no history to suggest coronary artery disease or myocardial infarction, and physical examination failed to document any evidence of congestive heart failure. Accordingly, the cardiologist felt that her risks from general anesthesia, and femoral bypass surgery if this were required, were acceptable. The patient agreed to participate in a research study evaluating ST-segment changes on a Holter monitor 24 hours before surgery and up to 48 hours after surgery. The patient underwent femoral/popliteal bypass surgery with an intraoperative angiogram documenting good run-off (see Figure 18.2). In the 8 hours following surgery the patient’s vital signs were stable. She intermittently complained of pain in her leg throughout the night and received a total of four injections of narcotics. On the morning of her first postoperative day, the patient casually reported that she had a vague, heavy sensation in the center of her chest, which had occurred 2 hours previously and was gradually building in intensity. She was sweating. Vital signs showed a blood pressure of 160/80 mmHg, heart rate of 100 beats/min, and a respiratory rate of 20/min. Her physical examination was not substantially changed from her preoperative state except her right foot was now pink in color, warm, and with a palpable dorsalis pedis pulse. An electrocardiogram was obtained and showed new, deep T-wave inversions in leads V 1 –V 3 . She was transferred to an intensive care unit and serial cardiac enzymes revealed an abnormal rise in creatine kinase to a peak of 475 mg/dl (7·9 µkat/l), and 16% of the rise was creatine kinase-MB fraction. Cardiology Core Curriculum 568 Intravenous heparin was administered. Her symptoms resolved with intravenous nitroglycerin, but returned abruptly on the second postoperative day. Electrocardiography failed to document new changes but because of unremitting chest symptoms the cardiology consultant recommended that she undergo coronary angiography. Angiography demonstrated severe three vessel coronary artery disease, and she was found to have mild anteroseptal hypokinesis with a left ventricular ejection fraction of 55%. She again complained of a dull ache returning to her chest approximately 2 hours after her coronary angiography. Intravenous metoprolol at a dose of 5 mg every four hours was instituted until her heart rate dropped to below 70 beats/min. Aspirin 325 mg was administered. A cardiac surgeon was consulted, and coronary bypass surgery was recommended as soon as possible. The patient underwent uneventful three vessel coronary bypass grafting on the third day after her vascular surgery. She spent a total of 10 days in the hospital (7 days after cardiac surgery), slowly ambulating on her sore right leg. She had no further episodes of chest pressure, and was discharged taking aspirin, metoprolol, and glyburide. She saw her vascular surgeon 2 weeks after her discharge and his examination documented palpable pulses in her right foot. The patient remained well. One year after her discharge from the hospital she received a telephone call from the cardiac research specialist who had enrolled her in the research study. Her Holter had demonstrated three, prolonged, asymptomatic ST-segment depression episodes during 24-hour monitoring before her femoral angiography. There were also extensive episodes of ST-segment depression detected during the 24 hours after surgery, preceding her complaints of chest pressure and documentation of myocardial infarction (Figure 18.3). Comments This case illustrates that asymptomatic myocardial ischemia and adverse cardiac events are most common in the 24–48 hour period after surgery (see Figure 18.3), a time period of heightened pain perception, increased adrenergic tone, higher average heart rates, and a hyperthrombotic state. Antiplatelet and β-adrenergic blocker therapies have established records for the control of myocardial ischemia via their effects on adrenergic tone and thrombosis, and could be easily concentrated during the high risk postoperative period. However, the use of antiplatelet and β-blocker therapy in patients with peripheral atherosclerosis, even when it is known that at least two-thirds of them have coronary artery disease, is remarkably low. β-Blocker therapy is often thought to be contraindicated in patients Arterial vascular disease 569 with intermittent claudication because β-receptor antagonism in the peripheral circulation causes paradoxic vasoconstriction. Although this is theoretically plausible, a careful look at the medical literature reveals that the vast majority of patients with intermittent claudication can take β-blockers safely and with little change in their exercise capacity. Thromboembolism Arterial embolism from the heart is a complication of cardiovascular disease. There are three common clinical settings that make cardiac embolism a serious possibility in a differential diagnosis, namely recent myocardial infarction, atrial arrhythmia (more specifically, atrial fibrillation and/or flutter), and valvular heart Cardiology Core Curriculum 570 Figure 18.3 Relationship between postoperative myocardial ischemia and postoperative myocardial infarction in a patient undergoing femoral bypass surgery. The patient has a normal baseline electrocardiogram (ECG). On several occasions during the first 24 hours after surgery, the patient has episodes of asymptomatic ischemia manifest by ST-segment depression. All these episodes occur at a time when pain perception and average heart rates are at their highest, and precede the clinical event, a myocardial infarction (MI), by minutes to hours. Subsequent angiography demonstrates three vessel coronary artery disease. CK, creatine kinase; Post op, postoperative Post op-ambulatory monitoring of ECG ECG Post op MI CK475(MB16%) 12 : 45pm 3 : 47 pm 10 : 44 am 11 : 00 am 11 : 15 am Mary M. 67y female (femoral) Left coronary artery Right coronary artery disease. Arterial embolization from a cardiac source may affect any organ system, but common sites of embolization include the lower extremities, and the cerebral and visceral vessels. The potential for embolization should be considered particularly in the setting of a recent anterior myocardial infarction associated with a significant regional wall abnormality and/or left ventricular aneurysm. This can predispose to the formation of mural thrombus and arterial embolization. Similarly, atrial fibrillation causes abnormal asynchronous, atrial wall motion, creating areas of reduced blood flow that are highly susceptible to thrombus formation. This may be exacerbated by enlargement of the left atrial chamber. Finally, valvular disease in general, and mitral valvular disease in particular, predispose the heart to the formation of thrombus via left atrial enlargement and reduction in blood velocities. In the setting of an anterior wall myocardial infarction or atrial fibrillation, the prevalence of thromboembolic disease is so high and the associated morbidity so troublesome that prophylactic anticoagulation is in order unless a specific contraindication exists. Numerous clinical trials have documented that the risk for stroke, death, or myocardial infarction due to thromboembolic disease is significantly reduced with anticoagulation in the setting of anterior infarction or atrial fibrillation (Table 18.1). 6,7 Although thromboembolism originating from the left ventricle or atrium can involve any organ system or limb, one of the most common clinical syndromes caused by thromboembolism is cerebrovascular accidents with emboli to either the anterior circulation (carotid arteries) or the posterior circulation (vertebral arteries). The degree of deficit encountered with thromboembolic cerebrovascular disease largely depends on the abruptness of the Arterial vascular disease 571 Table 18.1 Incidence of stroke, death, or myocardial infarction among patients on or off warfarin in the setting of prior myocardial infarction or atrial fibrillation Risk reduction History On warfarin Placebo with warfarin History of atrial fibrillation ( n = 420) 6 Incidence of stroke 1% 6% 86% Incidence of death 5% 12% 62% Prior myocardial infarction ( n = 1214) 7 Incidence of stroke 3% 7% 55% Incidence of death 15% 20% 24% Incidence of reinfarction 14% 20% 34% Presented is a summary of two studies 6,7 event, the size of the embolus (and hence the size of the vessel being occluded), and the presence of adequate collateral circulation from other vessels. A large embolism that occludes a major cerebral vessel suddenly will usually cause a large stroke. By contrast, a small embolism affecting a branch vessel in the setting of excellent collateral flow from other cerebral vessels may cause minimal damage and be asymptomatic. In the same manner, thromboembolism to the extremities can result in substantial ischemia versus no symptoms at all. In the more extreme spectrum, the junction of the distal aorta with the common iliac arteries is a frequent site of thromboembolism (the so-called “saddle embolism” of the aortoiliac junction). In the vast majority of such cases the presentation is dramatic, with severe pain, paresthesia, cyanosis from the waist down, and eventually paralysis of both extremities. More distal emboli are also common, frequently presenting with pain and paresthesia at a level roughly delineating the site of the occlusive embolus. Intestinal ischemia can result from cardiac thromboembolism, which affects the superior mesenteric artery more commonly than the celiac axis or the inferior mesenteric artery. The onset of symptoms can be abrupt and dramatic but clinical examination of the abdomen may not be dramatic initially. The hallmark of acute intestinal ischemia is a paucity of physical signs in the setting of dramatic symptoms. Intestinal ischemia must be suspected, therefore, by the setting and clinical history. Specifically, risk factors for cardiac thromboembolic disease, such as a history of recent infarction, atrial fibrillation, or valvular disease, is most often present. Often, there is an associated low cardiac output state (as with anterior myocardial infarction) contributing to a slow flow state in the mesenteric vessels. Laboratory findings are generally non-specific in the presence of thromboembolic disease. There is often a mild elevation in white blood cell count. In limb or visceral embolism, lactic acidosis may ensue from the anaerobic metabolism resulting from significant tissue ischemia or necrosis. This is manifest by a drop in the total carbon dioxide content in blood, a widened anion gap, and a drop in pH. In the case of cerebrovascular ischemia, radiographic findings are generally consistent with multiple infarctions, suggesting a shower of emboli, and this is often optimally demonstrated by computed tomography. In limb ischemia, angiography remains the gold standard for demonstrating the level of occlusion of the thromboembolism. Often the degree of ischemia is so dramatic (as, for example, with saddle embolus to the aortoiliac junction) and the site of the embolism so obvious based on the clinical findings that angiography is not needed before proceeding to definitive therapy. In the case of Cardiology Core Curriculum 572 intestinal ischemia, standard or computed tomography angiography is almost always required and remains the gold standard for diagnosis. Identifying which of the three intestinal vessels is involved is of crucial importance to surgical intervention. In addition, angiography can often identify the presence or absence of collateral supply, which greatly affects the timing of surgery. Surgical intervention is rarely, if ever, required in the case of cerebrovascular thromboembolism. Anticoagulation remains the mainstay of therapy both acutely and chronically. Surgery is often required in the case of limb ischemia, where anticoagulation is adjunctive or preparatory therapy. In only the most severely ill patients, in whom general anesthesia is felt to be too hazardous, is surgery deferred. Surgery often requires only thrombectomy at the site of thromboembolism and occasionally requires bypass surgery at the site. In the case of intestinal ischemia, surgery is almost always required. Even a minor delay in surgical intervention can result in intestinal necrosis and gangrene, a syndrome that carries with it an 80% mortality rate. Survivors of severe intestinal necrosis often have severe malabsorption syndromes because of major loss of their gastrointestinal absorptive area. Acute intestinal thromboembolism is clinically distinct from intestinal vessel occlusion due to local atherosclerosis and/or thrombosis. An acute embolism to the mesenteric vessels is abrupt in onset and causes dramatic symptoms, making it relatively easy to diagnose. However, in situ occlusion/thrombosis of a mesenteric vessel, often in the setting of local atherosclerotic disease, can be a very subtle and difficult diagnosis. As with acute thromboembolism, presentation is often heralded by symptoms with no significant physical findings. Patients at risk for intestinal vessel occlusion from thrombosis are often the same as those at risk for thromboembolic disease; that is, patients with low cardiac output, recent myocardial infarction, atrial fibrillation, valvular disease, and those receiving digoxin therapy. The pain syndrome is different from acute thromboembolism in that it is quite insidious and vague in nature. There is sometimes a history of postprandial abdominal pain suggesting ischemia on a chronic basis due to fixed atherosclerotic narrowing of the mesenteric vessels. In contrast with embolic disease, in which the acute occlusion of one mesenteric vessel can cause ischemic bowel, a single vessel in situ occlusion/thrombosis occurs more slowly and rarely causes significant intestinal ischemia unless there is concomitant disease in the mesenteric vessels. Hence, the typical angiogram of patients with in situ occlusion/thrombosis and chronic ischemia is one of diffuse atherosclerotic disease of the celiac, superior mesenteric, and inferior mesenteric vessels together, with one or more vessels occluded. 8 Arterial vascular disease 573 [...]... means, obviating the need for cardiac catheterization in the majority of cases Increasingly, non-invasive imaging techniques such as sonography, computed tomography angiography, and magnetic resonance imaging are providing viable alternatives to angiography and should be considered where available When angiography or cardiac catheterization is needed and abdominal aortic plaque is identified by non-invasive... This case illustrates an example of peripheral manifestations of atheroemboli in a very common setting – as an aftermath of cardiac catheterization and/or angiography Although atheroemboli from complex plaques within the vascular system can occur spontaneously, a large proportion of reported cases follow instrumentation with endovascular catheters and wires such as after angiography or cardiac catheterization,... International Normalized Ratio Cerebrovascular disease Atherosclerotic cerebrovascular disease remains the major cause of cerebrovascular accidents, accounting for significant mortality, and often devastating morbidity The common carotid artery and its branches are a common site for atherosclerosis In particular, the proximal internal carotid artery just after its take off at the carotid bulb is a very... mid-left subclavian artery with poststenotic dilatation in a young woman with fever and malaise, consistent with Takayasu’s arteritis After a 4 day course of heparin, the patient was taken to the operating room where a Dacron graft was used to bypass her occluded brachiocephalic trunk to the right common carotid artery The right vertebral artery was anastomosed to the limb of the graft, and a separate... mg/day, Mylanta 30 cm3 twice daily, and enteric coated aspirin once daily Pathologic examination of the native brachiocephalic artery specimen showed diffuse mononuclear cell infiltrates of the vessel intima and media with extensive fibrosis consistent with a diagnosis of Takayasu’s arteritis 593 Cardiology Core Curriculum Comments Takayasu’s arteritis is a rare inflammatory disease but an important cause... to complain of severe upper abdominal pain Intravenous nitroglycerin was instituted and an electrocardiogram showed new onset atrial fibrillation Baseline laboratory examination including an arterial blood gas was obtained A surgical consult was requested The surgery resident who evaluated the patient documented similar examination findings Laboratory examinations were notable for a mild elevation in... aortic insufficiency Angina and myocardial infarction are rare because coronary involvement in the disease is uncommon, but atrial and ventricular tachyarrhythmias are common Without medical or surgical intervention, Takayasu’s arteritis is an aggressive, fulminant disease that leads to stroke and congestive heart 594 Arterial vascular disease failure (the number one cause of death) However, even without... and a new anterior myocardial infarction with persistent ST-segment elevation in the anteroseptal leads Echocardiography: moderately enlarged left ventricular chamber with inferior and anterior akinesis, and an overall ejection fraction of 30% There was mild left atrial enlargement There was no aneurysm or significant valvular abnormalities, and normal right sided chambers Progress The patient was admitted.. .Cardiology Core Curriculum Case studies Case 18.2 An 80-year-old man was transferred to a university hospital after having sustained his second myocardial infarction His history began 5 years prior to this admission when he had his first onset of vague substernal chest pressure and diaphoresis while vacationing at a seaside resort He was admitted to the local hospital 10 hours after the onset... of renal or lower extremity branches Percutaneous transluminal angioplasty and stenting, particularly of the subclavian and lower abdominal vessels, may be effective in restoring flow via a less invasive manner Because congestive heart failure remains the 595 Cardiology Core Curriculum most common cause of death among patients with Takayasu’s arteritis, careful attention to systolic ventricular function . >70 years), and the presence of angina, myocardial infarction, cardiac arrhythmia, or diabetes. Patients who have any, or all, of these criteria are then tested with some non-invasive cardiac test. changes that are diagnostic for ischemia confirm the presence of active coronary artery disease. The disadvantage of this test is that often patients are unable to walk Arterial vascular disease 565 because. was transferred to an intensive care unit and serial cardiac enzymes revealed an abnormal rise in creatine kinase to a peak of 475 mg/dl (7·9 µkat/l), and 16% of the rise was creatine kinase-MB