Q J Med 1999; 92: 341-346
© 1999 Association of Physicians
Aortic atherosclerotic debris detected by trans-oesophageal echocardiography—a risk factor for cholesterol embolization
From the Department of Cardiology, John Radcliffe Hospital, Oxford, UK
Received 13 November 1998 and in revised form 9 April 1999
Dr W.P. Orr, Department of Cardiology, John Radcliffe Hospital, Headington, Oxford. e-mail: william.orr{at}cardiov.ox.ac.uk
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Summary |
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The clinical syndrome of cholesterol embolization is uncommon but is associated with a poor prognosis. Patients with severe atheromatous disease of the aorta appear to be at particular risk from cholesterol embolization, particularly following vascular instrumentation or surgery. Trans-oesophageal echocardiography is the investigation of choice for imaging atherosclerotic disease of the aorta, and may be useful in assessing the risk of vascular procedures, and diagnostically helpful in patients with suspected cholesterol emboli syndrome. We report five cases of athero-embolism, and illustrate the role of trans-oesophageal echocardiography in making a diagnosis of cholesterol embolization.
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Introduction |
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Cholesterol embolization usually happens within 8 weeks of arteriography, angioplasty, cardiac surgery or thrombolysis, but may occasionally occur spontaneously. It particularly affects elderly male smokers with evidence of significant peripheral vascular disease and a history of hypertension. Because cholesterol embolization is commonly asymptomatic, accurate data on the true incidence and pathophysiology are not available, but characteristic needle-shaped cholesterol clefts within the lumen of affected arterioles can be detected in up to 10% of asymptomatic patients following cardiac catheterization.1 We review five cases of cholesterol embolization which illustrate the aetiology and presentation of this condition.
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Case reports |
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Patient 1
A 53-year-old male smoker, with a 10-year history of hypertension and non-insulin-dependent diabetes, was admitted to hospital with an acute inferior myocardial infarction. He received prompt thrombolysis with streptokinase, leading to resolution of the ECG changes. Three days later, he experienced further chest pain with recurrent inferior ST elevation. Once again, treatment with streptokinase resulted in resolution of the ECG changes. Renal function, which was abnormal on admission (creatinine 220 µmol/l), subsequently deteriorated, and over the next 14 days he developed oliguric renal failure. Investigation demonstrated marked elevation of C-reactive protein (>500 mg/l), a leucocytosis with eosinophilia, a normochromic normocytic anaemia, proteinuria and microscopic haematuria. He was transferred to the Regional Renal Unit, where renal ultrasound and angiography were normal, and haemodialysis was commenced. Twenty-one days after his initial admission, he developed severe abdominal pain with radiological signs of a toxic megacolon. Laparotomy demonstrated a grossly inflamed and perforated colon, which was resected. Post-operatively, his recovery was complicated by further chest pain associated with widespread ST elevation, confusion, severe hypertension and purple discolouration of the toes with prominent sub-ungual haemorrhages. Trans-oesophageal echocardiography demonstrated marked left ventricular hypertrophy with good systolic function and severe semi-occlusive mobile atherosclerotic debris in the arch and descending thoracic aorta (Figures 1a and b
). Cholesterol embolization was diagnosed and aggressive blood pressure control and analgesia were administered. His condition stabilized but 10 days post-operatively he sustained a cardiac arrest and died. Subsequent histology of the resected colon demonstrated bi-convex needle-shaped cholesterol clefts within the lumen of colonic arterioles with widespread accompanying inflammation (Figure 2). These appearances are characteristic of cholesterol embolization.
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Patient 2
A 67-year-old man with a history of hypertension, smoking and non-insulin-dependent diabetes presented to the cardiology clinic with a history of severe limiting angina refractory to conventional medical treatment. Examination revealed a blood pressure of 190/95 mmHg in both arms, with impalpable lower limb pulses but no clinical evidence of carotid disease or abdominal aortic aneurysm. Cardiac catheterization using the right brachial approach was recommended. Early in the procedure he developed severe chest and abdominal pain accompanied by marked ischaemic changes on the ECG. Coronary angiography demonstrated a severe proximal left main stenosis, diffuse disease of the left coronary artery and occlusion of the proximal right coronary artery. At the completion of the procedure, the pain persisted despite administration of nitrate and opiate analgesia. Routine investigations including a serum amylase were normal. Because of the possibility of iatrogenic aortic dissection, a CT scan was performed, and suggested possible dissection involving the ascending and descending aorta. As the diagnosis remained uncertain, trans-oesophageal echocardiography was undertaken in the anaesthetic room and did not show any evidence of dissection, but clearly demonstrated marked intraluminal thrombus and calcified atheroma of the descending aorta and arch. The patient's chest pain persisted throughout this period, associated with 3 mm of ST depression despite maximal medical treatment, and emergency coronary artery bypass surgery was therefore performed. Although weaning from cardiopulmonary bypass was uneventful, he rapidly became severely acidotic and oliguric. Investigations revealed an amylase of >1000 IU and a rising creatinine and urea. His clinical state deteriorated and he died 24 h later. A post-mortem examination revealed acute necrotic pancreatitis with histological evidence of renal cholesterol embolization.
Patient 3
A 67-year-old man with a history of hypercholesterolaemia, hypertension, chronic renal impairment and severe peripheral vascular disease was admitted for cardiac catheterization because of limiting angina. He was anticoagulated with warfarin having suffered a pulmonary embolus 3 months earlier after the amputation of two ischaemic toes. Coronary angiography, performed via the right brachial artery, revealed mild left ventricular impairment with two-vessel coronary artery disease. Towards the end of the procedure, he complained of sudden severe central abdominal pain and nausea. Examination revealed a blood pressure markedly elevated at 220/130 and diffuse abdominal tenderness with reduced bowel sounds. He was anticoagulated with heparin, and an emergency laparotomy revealed five localized areas of dusky small bowel but no clearly ischaemic segments. Laparotomy was repeated electively the following day, and a short segment of non-viable jejunum was resected, the histology showing the typical changes of ischaemic mucosal ulceration. He subsequently made a full recovery. Trans-oesophageal echocardiography at a later date visualized mobile and protruding atheromatous debris in the thoracic aorta.
Patient 4
A 67-year-old man with a long history of hypertension presented with recurrent episodes of pulmonary oedema. Renal function was abnormal (creatinine 215 µmol/l), ECG showed left bundle branch block and transthoracic echocardiography demonstrated marked left ventricular hypertrophy with moderate impairment of systolic function. Diagnostic cardiac catheterization revealed diffuse minor coronary irregularity. An abdominal aortogram excluded renal artery stenosis but revealed a 4 cm fusiform abdominal aortic aneurysm and diffuse irregularity of the thoraco-abdominal aorta (Figure 3). No primary cause for hypertension was identified, and 7 days after catheterization, a renal biopsy was performed. There had been no deterioration in renal function in the interim period. The renal biopsy showed evidence of cholesterol embolization but was otherwise normal. He was treated with low-dose ACE inhibitors and diuretics, and made an uneventful recovery.
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Patient 5
A 76-year-old woman with longstanding hypertension presented to hospital with a painful blue great toe. She had been admitted 3 weeks earlier with an acute myocardial infarction for which she received thrombolysis, but had continued to experience chest pain and had proceeded to coronary angiography and stenting 1 week later. On examination she was mildly disorientated, hypertensive and dehydrated with splinter haemorrhages and well-demarcated ischaemia of the toes on both feet (Figure 4
) but intact peripheral pulses. Urinalysis revealed large amounts of blood and protein, and the plasma creatinine had risen from 250 to 559 µmol/l over the preceding 7 days. She was rehydrated but creatinine continued to rise. Renal ultrasound was normal. Blood film showed a marked eosinophilia. Trans-oesophageal echocardiography demonstrated left ventricular hypertrophy but was otherwise normal except for a heavily diseased descending aorta with large amounts of protruding and mobile atheroma and calcified thrombus. A clinical diagnosis of cholesterol embolization was made. Her confusion settled over the following 2 weeks, but she remained dialysis-dependent.
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Discussion |
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The clinical syndrome of cholesterol embolization is rare, typical features including livedo reticularis and focal digital ischaemia (the purple-toe syndrome), retinal embolization, renal failure (usually with baseline impairment), labile blood pressure and abdominal symptoms (depending on specific organ involvement). Non-specific findings of an acute-phase response (elevated C reactive protein, normochromic normocytic anaemia and leucocytosis), with a transient eosinophilia, thrombocytopoenia, reduced complement levels, proteinuria and haematuria are common. In post-mortem studies, the kidney (75%) and pancreas (52%) are the visceral organs most commonly affected,2 but lower-limb muscle biopsy is the optimum site for making a tissue diagnosis, with sensitivities of up to 100% reported.2–4
Diagnosing cholesterol embolization therefore requires a high index of clinical suspicion as, other than tissue biopsy, there is no single diagnostic investigation and differentiation from a systemic vasculitis can be difficult.5,6 A diagnosis of cholesterol embolization should be considered in any patient at risk in whom unexplained symptoms or changes in renal function are noted.
The published data on asymptomatic cholesterol embolization suggests a relatively benign clinical course,1 in contrast with the clinical syndrome which has a very poor prognosis, particularly when there is evidence of visceral and renal involvement, with mortality rates approaching 70%.2 Conventional treatment is supportive, with aggressive blood pressure control and renal replacement therapy when necessary. Corticosteroids2,7 have not been clearly shown to be beneficial and anticoagulation8 may indeed worsen outcome. Some centres have advocated aortic surgery when severe atherosclerotic disease is present, but there are no randomized comparisons with medical treatment in the cholesterol emboli syndrome and, in these patients with extensive vascular disease who are gravely ill with multi-organ involvement, any proposed surgical intervention inevitably carries an extremely high risk.
Mobile and protruding atheromatous debris in the aorta is a marker of severe and widespread atheromatous disease, and is an independent risk factor for first ischaemic stroke in the elderly,9,10 and for the recurrence of stroke or peripheral embolic events.11 Risk factors for this pattern of atherosclerosis include male sex, age, peripheral vascular and coronary arterial disease, hypertension, smoking and hypercholesterolaemia. Patients with evidence of aortic atheroma are at risk of developing tissue ischaemia when atheromatous debris, especially cholesterol crystals, dislodges from central atheromatous plaques and occludes smaller and more peripheral arteries. Contrast aortography has been the traditional `gold standard' investigation for this condition, but itself carries a very significant risk of causing embolization and worsening outcome. Computerized tomography (CT) can image severe atheromatous change, but the findings are commonly non-specific, and differentiation from aortic dissection can be difficult.12 Magnetic resonance imaging (MRI) is more specific but requires good patient co-operation, and its availability is limited. Multi-plane trans-oesophageal echocardiography (TOE) images most of the ascending aorta, some of the arch and the entire descending aorta, and has become the investigation of choice for the visualisation of atheromatous disease of the thoracic aorta. It is quick and easy to perform at the bedside, and histological studies have suggested sensitivity and specificity in excess of 90% for the detection of complex atheroma and mural thrombus in the thoracic aorta.13 High-grade confluent atheroma is detected by TOE in up to 95% of patients with a clinical syndrome of cholesterol embolization, but less than 20% of age-and risk-factor-matched controls.7
When high-grade aortic atheroma is detected, a strategy of attempting plaque stabilization with potent lipid-lowering agents may be appropriate, especially when elective vascular instrumentation or surgery is planned. Currently, there are only anecdotal reports of the use of statins in the treatment of cholesterol embolization,14,15 and the time has come for a properly constructed randomized controlled trial. In asymptomatic patients, strategies may also be used to reduce the risk of embolization such as avoiding cross-clamping of the aorta during coronary artery bypass graft surgery and performing cardiac catheterization via the brachial artery.
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Conclusion |
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Severe atheromatous disease of the aorta is common, and associated with a significant risk of potentially fatal embolization, with or without cardiac catheterization or surgery. Patients at high risk of developing aortic atheroma can be easily identified, and TOE is the optimal mode of assessing the extent of disease prior to embarking on invasive procedures. Detection of mobile protruding atheroma by TOE in patients presenting with a suspected cholesterol emboli syndrome may be diagnostically helpful, thereby guiding further management. Optimal management of the cholesterol embolization syndrome has yet to be defined.
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References |
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1. Blankenship JC, Butler M, Garbes A. Prospective assessment of cholesterol embolization in patients with acute myocardial infarction treated with thrombolytic vs conservative therapy. Chest 1995; 107:662–8.
2. Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: a review of 221 cases in the English literature. Angiology 1987; 38:769–84.
3. Maurizi CP, Barker AE, Trueheart RE. Atheromatous emboli. A postmortem study with special reference to the lower extremities. Arch Pathol 1968; 86:528–34.[Web of Science][Medline]
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9. Davila Roman VG, Barzilai B, Wareing TH, Murphy SF, Schechtman KB, Kouchoukos NT. Atherosclerosis of the ascending aorta. Prevalence and role as an independent predictor of cerebrovascular events in cardiac patients. Stroke 1994; 25:2010–16.[Abstract]
10. Jones EF, Kalman JM, Calafiore P, Tonkin AM, Donnan GA. Proximal aortic atheroma. An independent risk factor for cerebral ischemia. Stroke 1995; 26:218–24.
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Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke. The French Study of Aortic Plaques in Stroke Group. N Engl J Med 1996; 334:1216–21.
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Banning AP, Masani ND, Ikram S, Fraser AG, Hall RJ. Transoesophageal echocardiography as the sole diagnostic investigation in patients with suspected thoracic aortic dissection. Br Heart J 1994; 72:461–5.
13. Vaduganathan P, Ewton A, Nagueh SF, Weilbaecher DG, Safi HJ, Zoghbi WA. Pathologic correlates of aortic plaques, thrombi and mobile `aortic debris' imaged in vivo with transesophageal echocardiography. J Am Coll Cardiol 1997; 30:357–63.[Abstract]
14. Cabili S, Hochman I, Goor Y. Reversal of gangrenous lesions in the blue toe syndrome with lovastatin—a case report. Angiology 1993; 44:821–5.
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