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Acute aortic syndromes
AORTIC DISEASE
Acute aortic syndromes
Acute aortic syndrome is an established term that includes aortic dissection, intramural haematoma (IMH) and symptomatic penetrating aortic ulcer (PAU), as well as traumatic aortic lacerations. First described by Morgagni more than 200 years ago,1 acute aortic dissection requires a tear in the aortic intima that is commonly preceded by medial wall degeneration or cystic medial necrosis. Although early studies2 highlighted the high mortality rate and infrequency of ante mortem diagnosis,2 knowledge regarding the incidence of aortic dissection in the general population is limited. Studies suggest an incidence of 2.6 e3.5 cases per 100,000 person/year3 and the prevalence is 0.2 e0.8% in large autopsy series. Peak incidence is in the sixth and seventh decade of life and men are affected twice as commonly as women.4 Aortic dissection in individuals under the age of 40 years is most common in those with Marfan’s syndrome and during pregnancy.
Ibrahim Akin Rachel Clough Tim C Rehders Christoph A Nienaber
Abstract Acute aortic syndromes comprise acute aortic dissection, intramural haematoma, symptomatic penetrating aortic ulcers and traumatic aortic dissection. These conditions result primarily from disruption of the outer aortic layer, and involve thinning of the aortic wall, increased wall stress, progressive dilatation, evolution of intramural haemorrhage, and possible dissection and rupture. Chronic hypertension and connective tissue disorders are often implicated. Echocardiography, contrast-enhanced CT, dynamic MRI and aortography are currently used to confirm the diagnosis. Aortic dissection is primarily classified according to anatomical characteristics; those with and without ascending aortic involvement are distinguished for prognostic and therapeutic reasons. In general, open surgery is indicated when dissection involves the ascending aorta, whereas medical management or endovascular stent-graft implantation are reserved for cases where the ascending aorta is spared. Pathology involving the aortic arch may be treated using a hybrid approach combining debranching of the head and neck vessels and interventional stent-graft implantation. Stent-graft induced remodelling of dissected aorta seems to have long-term benefits both in complicated and so-called uncomplicated distal dissection. In addition, long-term medical therapy to control hypertension is of paramount importance in all patients who have survived aortic dissection to reduce late complications, including recurrent dissection, aneurysm formation or late extension or rupture.
Pathology Aortic dissection is believed to begin with formation of a tear in the aortic intima, which exposes an underlying diseased medial layer directly to the driving force of intraluminal pulsatile blood. Penetration cleaves the diseased medial layers and progressively dissects the aortic wall. Driven by persistent intraluminal pressure, the dissection may progress antegradely (and sometimes retrogradely) along the aortic wall from the site of initial intimal tear, thereby forming a false lumen. Shear forces may lead to further tears in the intimal flap (the inner portion of the dissected aortic wall) to create additional entry or exit sites into the false lumen. Distension and systolic pressure within the false lumen may lead to dynamic compression of the true lumen and distal malperfusion. Aortic IMH is considered a precursor of dissection and originates from ruptured vasa vasorum within the medial wall layers, resulting in aortic wall infarction that may provoke a secondary tear and classic aortic dissection. IMH is usually located in the descending aorta, typically associated with hypertension, and may extend, progress or resorb.5,6 Deep penetrating aortic atherosclerotic plaques can lead to IMH, aortic dissection, or perforation. Non-invasive imaging has recently elucidated this disease process, which often further complicates IMH.
Keywords Acute aortic syndrome; aortic dissection; hybrid approach; intramural haematoma; penetrating aortic ulcer; peripheral vascular disease; stent-graft
‘Disease is very old, and nothing about it has changed. It is we who change as we learn to recognise what was formerly imperceptible’ Jean Martin Charcot
Classification The prime classification is based on the anatomical location of the intimal tear and degree of propagation of the false lumen. Intimal tears occur at points of presumed greatest haemodynamic stress; namely, the lateral wall of the ascending aorta and just distal to the ligamentum arteriosum of the descending thoracic aorta. Overall, 65% of intimal tears occur in the ascending aorta, 20% in the descending aorta, 10% in distal aortic arch and 5% at abdominal level. Two anatomical classification systems predominate (Figure 1) e in both, dissections with and without ascending aortic involvement are distinguished for prognostic and therapeutic reasons.7,8 Aortic dissection may also be classified according to the timing of diagnosis relative to the onset of symptoms: acute within 2 weeks, subacute within 2e8 weeks, or chronic beyond 8 weeks. About one-third of patients with aortic dissection fall into
Ibrahim Akin MD is a Physician at University Hospital Rostock, Germany. Competing interests: none declared. Rachel Clough MD is a Clinician-Scientist at King’s College London, Cardiovascular Imaging Department, UK. Competing interests: none declared. Tim C Rehders MD is Consultant Physician at the University Hospital Rostock, Germany. He qualified from Hamburg University and €tsklinikum Hamburg-Eppendorf, Germany. Competing Universita interests: none declared. Christoph A Nienaber MD FACC FESC is Head Cardiologist at the University Hospital Rostock, Germany. Competing interests: Professor Nienaber has received funds for research in the area of aortic diseases and fees for speaking about this topic at meetings; he has served as an expert witness in the John Ritter case in Glendale, California.
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Ó 2014 Elsevier Ltd. All rights reserved.
AORTIC DISEASE
Commonly used classification systems in aortic dissection De Bakey Type I
Type II
Type III
Type A
Type A
Type B
Acuity: Acute: <2 weeks after onset Subacute: 2–8 weeks after onset Chronic: >8 weeks after onset Anatomic location: Ascending aorta: Stanford Type A, De Bakey Type II Ascending and descending aorta: Stanford Type A, De Bakey Type I Descending aorta: Stanford Type B, De Bakey Type III Pathophysiology: Class 1: Classical aortic dissection with initimal flap between true and false lumen Class 2: Aortic intramural hematoma without identifiable intimal flap Class 3: Intimal tear without hematoma (limited dissection) Class 4: Atherosclerotic plaque rupture with aortic penetrating ulcer Class 5: Iatrogenic or traumatic aortic dissection (intra-aortic catheterization, high-speed deceleration injury, blunt chest trauma) Figure 1
the latter category; both mortality and the risk of progression decrease over time, with implications for the most appropriate treatment strategy.9,10
A bicuspid aortic valve is associated with acute aortic syndrome in 7e14% of patients. Other congenital cardiovascular abnormalities may predispose to dissection, including coarctation of the aorta and giant cell arteritis. Direct trauma to the aorta may cause dissection, whereas blunt trauma tends to cause localized tears, haematomas or transection; iatrogenic trauma (e.g. during cardiac catheterization, cardiac surgery or insertion of an intra-aortic balloon pump) may induce dissection, probably as a result of direct trauma to the aortic intima.11
Aetiology and pathogenesis Any disease process that undermines the integrity of the elastic or muscular components of the media predisposes the aorta to dissection, and degeneration of this layer is the major predisposing factor in most non-traumatic aortic dissection (Table 1). Degeneration of the media as a result of enhanced apoptosis is a feature of several hereditary connective tissue defects, notably Marfan’s and EhlerseDanlos syndromes. In the absence of Marfan’s syndrome, medial degeneration is usually minor in most cases of aortic dissection but is nevertheless qualitatively and quantitatively greater than that expected as part of the ageing process, possibly as a result of increased apoptosis secondary to hypertension.
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Clinical features Diagnosis and effective clinical management of acute aortic syndromes require a high level of clinical suspicion and prompt action. The differential diagnosis in acute aortic dissection includes acute coronary syndrome, pulmonary embolism, pneumothorax, pneumonia, musculoskeletal pain, acute cholecystitis,
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AORTIC DISEASE
Natural history
Conditions associated with increased risk of aortic dissection
Despite major advances in the non-invasive diagnosis of aortic dissection and its treatment, up to 28e55% of patients die without correct diagnosis.4 Registry data demonstrate that medical management of type A dissection is associated with a mortality of nearly 24% after 1 day, 29% after 2 days, 44% after 1 week and 50% after 2 weeks. Less than 10% of untreated patients live for 1 year and almost all patients die within 10 years.4 Type B dissection has a better prognosis with survival rates of 89% at 1 month, 84% at 1 year, and 80% at 5 years.4 However, patients with complications such as renal failure, visceral ischaemia or contained rupture fare less well with a mortality of 20% at day 2 and 25e50% at 1 month, and often require urgent repair. Population-based data show a trend to higher incidences of the disease and higher mortality figures with increasing age.13
Long-standing arterial hypertension Smoking, dyslipidaemia, cocaine/crack Connective tissue disorders Hereditary fibrillinopathies Marfan’s syndrome EhlerseDanlos syndrome Hereditary vascular diseases Bicuspid aortic valve Coarctation Vascular inflammation Giant cell arteritis Takayasu’s arteritis Behc‚et’s disease Syphilis Ormond’s disease Deceleration trauma Car accident Fall from height Iatrogenic factors Cardiac catheterization Valvular/aortic surgery Side- or cross-clamping/aortotomy Graft anastomosis Patch aortoplasty Cannulation site Aortic wall fragility
Diagnosis A low threshold of clinical suspicion is vital for timely diagnosis and management of this catastrophic condition. Chest radiography is often non-specific and does not have a definitive role.14 Possible findings include widening of the aortic contour, displaced calcification, aortic kinking, and opacification of the aortopulmonary window. Transthoracic/transoesophageal echocardiography, contrast-enhanced CT, MRI and aortography (Table 2) may all be used to confirm suspected dissection. Each modality has advantages and disadvantages in terms of convenience, risk, cost and local availability. Diagnostic accuracies are similar, but all differ in their ability to detect associated complications. The ideal imaging modality should: confirm or refute the diagnosis of aortic dissection determine whether dissection involves the ascending aorta or is confined to the descending aorta or arch reveal the anatomic features of the dissection, including its extent, the site(s) of entry and re-entry, the presence of thrombus in the false lumen, and branch vessel involvement. Unfortunately, no single modality provides all of this information. In the IRAD registry, the first diagnostic step was transthoracic and transoesophageal echocardiography (TTE/ TEE) in 33%, CT in 61%, MRI in 2% and angiography in 4%. Two or three of these investigations were required in many patients.
Table 1
oesophageal spasm or rupture, acute pancreatitis and acute pericarditis. The most common initial symptom is severe migrating back or chest pain.12 Amongst 464 patients reported from the International Registry of Acute Aortic Dissection (IRAD), 95% reported pain that was of abrupt onset in 85%.4 Those without pain are usually found to have chronic dissection. The pain is typically stabbing, tearing or ripping and often described as the worst pain ever experienced e it is clearly different from the pain of myocardial infarction. The pain of aortic dissection tends to migrate from its point of origin to other sites, generally following the path of the dissection as it extends through the aorta. Such migratory pain is described by about 20% of patients and may be helpful in pinpointing the anatomical location of the dissection. Aortic dissection is a ‘clinical chameleon’. The clinical manifestations in more than one-third of the patients may be explained by impaired perfusion of key organs as a result of sidebranch obstruction.4 However, physical findings are variable and may be subtle or absent, even in the presence of extensive dissection. Aortic regurgitation with resultant congestive heart failure may occur and patients may exhibit pulse deficits and neurological manifestations, such as headache, cerebrovascular accidents (as a consequence of carotid involvement), syncope (caused by cardiac tamponade) and paraparesis/paraplegia secondary to spinal ischaemia.
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Management All patients in whom acute aortic dissection is strongly suspected should be managed in an acute-care setting where blood pressure, cardiac rhythm and urine output can be monitored. Initial therapeutic aims to include elimination of pain and reduction of systolic blood pressure to 120 mmHg or less (or the lowest level ensuring adequate vital organ perfusion), using intravenous bblockers (e.g. labetalol or esmolol) and vasodilators.11,12 Surgical treatment Definitive therapy for aortic dissection has evolved over the last two decades. The need for surgery should be determined whenever possible at the time of initial clinical evaluation. Surgical risk is increased by advancing age, comorbid disease (particularly coronary artery disease and emphysema), partial or
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Ó 2014 Elsevier Ltd. All rights reserved.
AORTIC DISEASE
Imaging modalities in the evaluation of suspected aortic dissection28,29 Diagnostic performance
Angiography
CT
MRI
Transoesophageal echocardiography
Sensitivity Specificity Site of intimal tear Presence of thrombus Presence of aortic regurgitation Pericardial effusion Branch vessel involvement Coronary artery involvement Advantages Readily available Quickly performed Bedside evaluation Non-invasive Intravenous contrast Cost
þþ þþþ þþ þþþ þþþ þþþ þþ
þþþ þþþ þ þþ þþ þþ
þþþ þþþ þþþ þþþ þ þþþ þþ
þþþ þþþ þþ þ þþþ þþþ þ þþ
Fairly Fairly No No Yes High
Quite Quite No Yes Yes Reasonable
Fairly Fairly No Yes No/yes Moderate
Very Very Yes Yes No Reasonable
þþþ, Excellent; þþ, good; þ, fair; , not detected.
Table 2
encouraging.19,20 Data from the IRAD registry indicate better survival rates in patients after endovascular treatment of complicated type B dissection in comparison with open surgical repair.21,22 Accepted indications for the procedure include vital organ ischaemia, intractable pain, rapid expansion of the false
complete aortic rupture, hypotension (systolic blood pressure 100 mmHg), shock/cardiac tamponade and compromise of vital organs. Limb ischaemia, new neurological deficits and congestive heart failure may further complicate the outcome.15 Preoperative mortality in acute dissection ranges from 3% in stable patients who undergo surgery without delay to 30% or more when evaluation is prolonged or the case more complex. These data reinforce the need for prompt diagnosis and surgical repair to prevent even minimal progression of the dissection with associated complications. The aim of surgery in type A dissection is prevention of rupture or the development of pericardial effusion, which may lead to cardiac tamponade and death. Similarly, the sudden onset of aortic regurgitation or obstructed coronary flow requires urgent surgery to resect the region involved with subsequent replacement using a composite or interposition graft (provided the aortic valve leaflets are intact or resuspendable).16 Resection of the entire intimal flap may not be possible if the dissection extends to the aortic arch or descending aorta, when partial or total arch replacement may be necessary. Acute type A dissection in a previously ectatic proximal aorta (usually encountered in Marfan’s syndrome) requires a different approach, entailing use of a composite graft (aortic tube graft with integrated valve) and coronary reimplantation.17 Valve-sparing operations are delicate endeavours in the emergency setting and best undertaken by expert operators in specialist centres.
Concept of interventional reconstruction of the dissected descending aorta with sealing of the proximal entries, depressurization of the false lumen and initiation of false lumen thrombosis Proximal entry Left carotid artery Left subclavian artery
Thrombus
Endovascular aortic repair Percutaneous stent-grafts (Figure 2) are an established treatment alternative in type B dissection.18 The aim of the procedure is to close entry to the false lumen using a tube-like nitinol grid covered with a Dacron shell and thereby induce thrombosis of the false lumen with subsequent healing of the aortic wall (Figure 3). Early results describing this approach are
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Perfused false lumen
Stent-graft
Figure 2
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AORTIC DISEASE
Figure 3 CT scan demonstrating a type B aortic dissection in a 48-year-old man; note dynamic obstruction of the true lumen in the acute phase. After stent-graft placement across the proximal thoracic entry site the entire true lumen of the thoracic aorta is reconstructed with complete ‘healing’ of the dissected aortic wall and shrinking of the completely thrombosed false lumen. TL, true lumen; FL, false lumen; TH, thrombus.
lumen (diameter > 55 mm), and signs of imminent rupture.3,18 Successful stent-graft treatment of the descending thoracic aorta has also been recently described;23 pre-emptive stent grafting and remodelling lead to long-term prognostic benefits and better 5-year survival than does medical management alone.24,25 The window of opportunity for best endovascular results seems to be 3 months in elective cases of type B dissection.26 Technological advances and increased operator expertise make it likely that endovascular techniques will soon become first-line therapy for most patients presenting with anatomically suitable thoracic and thoraco-abdominal aortic pathology, regardless of initial clinical symptoms.
REFERENCES 1 Leonhard JC. Thomas Bevill Peacock and the early history of dissecting aneurysm. Br Med J 1979; 2: 260e2. 2 Hirst Jr AE, Johns Jr V, Kime Jr SW. Dissecting aneurysm of the aorta: a review of 505 cases. Med Baltim 1958; 37: 217e79. 3 Clouse WD, Hallett Jr JW, Schaff HV, et al. Acute aortic dissection: population-based incidence compared with degenerative aortic aneurysm rupture. Mayo Clin Proc 2004; 79: 176e80. 4 Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA 2000; 283: 897e903. 5 Vilacosta I, San Roman JA, Ferreiros J. Natural history and serial morphology of aortic intramural hematoma: a novel variant of aortic dissection. Am Heart J 1997; 134: 495e507. 6 Evangelista A, Mukherjee D, Mehta RH, et al. International registry of aortic dissection (IRAD) investigators. Acute intramural hematoma of the aorta: a mystery in evolution. Circulation 2005; 111: 1063e70. 7 Svensson LG, Labib SB, Eisenhauer AC, et al. Intimal tear without hematoma: an important variant of aortic dissection that can elude current imaging techniques. Circulation 1999; 99: 1331e6. 8 Richartz BM, Smith DE, Cooper JV, et al. New classification of aortic dissection with improved impact on prognosis. J Am Coll Cardiol 2002; 39: A 863. 9 Booher AM, Isselbacher EM, Nienaber CA, et al. The IRAD classification system for characterizing survival after aortic dissection. Am J Med 2013; 126: 730 e 19e24. 10 Steuer J, Bjorck M, Mayer D, et al. Distinction between acute and chronic type B aortic dissection: is there a sub-acute phase? Eur J Vasc Endovasc Surg 2013; 45: 627e31.
Long-term therapy and follow-up Continued follow-up is essential for medically treated patients and those who have undergone open surgery or endovascular aortic repair. The primary aim of long-term surveillance is maintenance of blood pressure control and early detection of changes or unstable aortic lesions that require subsequent open surgery or endovascular intervention (e.g. rapid expansion of a new or existing aneurysm, progression or recurrence of dissection, aortic regurgitation, peripheral vascular compromise). CT angiography and/or dynamic MRI are non-invasive and the preferred techniques for monitoring these patients e MRI also avoids repeated radiation exposure and provides excellent anatomical detail that may be helpful in evaluating serial changes.27 Patients are at greatest risk immediately following hospital discharge and during the first 2 years thereafter, so early follow-up is warranted; for example, patients may be seen at 3 and 6 months initially, then every 6 months for 2 years, after which the follow-up interval will be determined by individual patient risk. A MEDICINE 42:9
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11 Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: executive summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Catheter Cardiovasc Interv 2010; 76: E43e86. 12 Nienaber CA, Powell T. Management of acute aortic syndromes. Eur Heart J 2012; 33: 26e35. 13 Howard DP, Banerjee A, Fairhead JF, et al. Population-based study of incidence and outcome of acute aortic dissection and premorbid risk factor control: 10-year results from the Oxford Vascular Study. Circulation 2013; 127: 2031e7. 14 von Kodolitsch Y, Nienaber CA, Dieckmann C, et al. Chest radiography for the diagnosis of acute aortic syndrome. Am J Med 2004; 116: 73e7. 15 Trimarchi S, Nienaber CA, Rampoldi V, et al. Contemporary results of surgery in acute type A aortic dissection: the International Registry of Acute Aortic Dissection experience. J Thorac Cardiovasc Surg 2005; 129: 112e22. 16 David TE, Feindel CM. An aortic valve-sparing operation for patients with aortic incompetence and aneurysm of the ascending aorta. J Thorac Cardiovasc Surg 1992; 103: 617e21. 17 Milewicz DM, Dietz HC, Miller DC. Treatment of aortic disease in patients with Marfan syndrome. Circulation 2005; 111: e150e157. 18 Nienaber CA, Fattori R, Lund G, et al. Nonsurgical reconstruction of thoracic aortic dissection by stent-graft placement. N Engl J Med 1999; 340: 1539e45. 19 Clough RE, Mani K, Lyons OT, et al. Endovascular treatment of acute aortic syndrome. J Vasc Surg 2011; 54: 1580e7. 20 Eggebrecht H, Nienaber CA, Neuhauser M, et al. Endovascular stentgraft placement in aortic dissection: a meta-analysis. Eur Heart J 2005; 4: 489e98. 21 Fattori R, Montgomery D, Lovato L, et al. Survival after endovascular therapy in patients with type B aortic dissection: a report from the International Registry of Acute Aortic Dissection (IRAD). JACC Cardiovasc Interv 2013; 6: 876e82. 22 Fattori R, Tsai TT, Myrmel T, et al. Complicated acute type B dissection: is surgery still the best option. A report from the International Registry of Acute Aortic Dissection. J Am Coll Cardiol 2008; 1: 395e402.
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23 Nienaber CA, Rousseau H, Eggebrecht H, et al. Randomized comparison of strategies for type B aortic dissection e the Investigation of Stent-grafts in Aortic Dissection (INSTEAD) trial. Circulation 2009; 120: 2519e28. 24 Nienaber CA, Kische S, Rousseau H, et al. Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial. Circ Cardiovasc Interv 2013; 6: 407e16. 25 Patterson B, Holt P, Nienaber C, et al. Aortic pathology determines midterm outcome after endovascular repair of the thoracic aorta: report from the Medtronic Thoracic Endovascular Registry (MOTHER) database. Circulation 2013; 127: 24e32. 26 Akin I, Kische S, Ince H, et al. Indication, timing and results of endovascular treatment of type B dissection. Eur J Vasc Endovascular Surg 2009; 1e8. 27 Clough RE, Hussain T, Uribe S, et al. A new method for quantification of false lumen thrombosis in aortic dissection using magnetic resonance imaging and a blood pool contrast agent. J Vasc Surg 2011; 1 e14. 28 Tsai TT, Nienaber CA, Eagle KA. Acute aortic syndromes. Circulation 2005; 112: 3802e13. 29 Cigarroa JE, Isselbacher EM, DeSanctis RW, et al. Diagnostic imaging in the evaluation of suspected aortic dissection. Old standards and new directions. N Engl J Med 1993; 328: 35e43. FURTHER READING Harris KM, Strauss CE, Eagle KA, et al. Correlates of delayed recognition and treatment of acute type A aortic dissection: the International Registry of Acute Aortic Dissection (IRAD). Circulation 2011; 124: 1911 e8. Isselbacher EM. Diseases of the aorta. In: Libby P, Bonow RO, Mann D, Zipes, eds. Braunwald’s heart disease. 8th edn. Philadelphia: Saunders, 2007; 1457e91. Ranasinghe AM, Bonser RS. Biomarkers in acute aortic dissection and other aortic syndromes. J Am Coll Cardiol 2010; 56: 1535e41. Suzuki T, Isselbacher EM, Nienaber CA, et al. Type-selective benefits of medications in treatment of acute aortic dissection (from the International Registry of Acute Aortic Dissection [IRAD]). Am J Cardiol 2012; 109: 122e7. Svensson LG, Kouchoukous NT, Miller DC, et al. Expert consensus document on the treatment of descending thoracic aortic disease using endovascular stent-grafts. Ann Thorac Surg 2008; 85: S1e45.
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Acute aortic syndromes
Acute aortic syndrome is an established term that includes aortic dissection, intramural haematoma (IMH) and symptomatic penetrating aortic ulcer (PAU), as well as traumatic aortic lacerations. First described by Morgagni more than 200 years ago,1 acute aortic dissection requires a tear in the aortic intima that is commonly preceded by medial wall degeneration or cystic medial necrosis. Although early studies2 highlighted the high mortality rate and infrequency of ante mortem diagnosis,2 knowledge regarding the incidence of aortic dissection in the general population is limited. Studies suggest an incidence of 2.6 e3.5 cases per 100,000 person/year3 and the prevalence is 0.2 e0.8% in large autopsy series. Peak incidence is in the sixth and seventh decade of life and men are affected twice as commonly as women.4 Aortic dissection in individuals under the age of 40 years is most common in those with Marfan’s syndrome and during pregnancy.
Ibrahim Akin Rachel Clough Tim C Rehders Christoph A Nienaber
Abstract Acute aortic syndromes comprise acute aortic dissection, intramural haematoma, symptomatic penetrating aortic ulcers and traumatic aortic dissection. These conditions result primarily from disruption of the outer aortic layer, and involve thinning of the aortic wall, increased wall stress, progressive dilatation, evolution of intramural haemorrhage, and possible dissection and rupture. Chronic hypertension and connective tissue disorders are often implicated. Echocardiography, contrast-enhanced CT, dynamic MRI and aortography are currently used to confirm the diagnosis. Aortic dissection is primarily classified according to anatomical characteristics; those with and without ascending aortic involvement are distinguished for prognostic and therapeutic reasons. In general, open surgery is indicated when dissection involves the ascending aorta, whereas medical management or endovascular stent-graft implantation are reserved for cases where the ascending aorta is spared. Pathology involving the aortic arch may be treated using a hybrid approach combining debranching of the head and neck vessels and interventional stent-graft implantation. Stent-graft induced remodelling of dissected aorta seems to have long-term benefits both in complicated and so-called uncomplicated distal dissection. In addition, long-term medical therapy to control hypertension is of paramount importance in all patients who have survived aortic dissection to reduce late complications, including recurrent dissection, aneurysm formation or late extension or rupture.
Pathology Aortic dissection is believed to begin with formation of a tear in the aortic intima, which exposes an underlying diseased medial layer directly to the driving force of intraluminal pulsatile blood. Penetration cleaves the diseased medial layers and progressively dissects the aortic wall. Driven by persistent intraluminal pressure, the dissection may progress antegradely (and sometimes retrogradely) along the aortic wall from the site of initial intimal tear, thereby forming a false lumen. Shear forces may lead to further tears in the intimal flap (the inner portion of the dissected aortic wall) to create additional entry or exit sites into the false lumen. Distension and systolic pressure within the false lumen may lead to dynamic compression of the true lumen and distal malperfusion. Aortic IMH is considered a precursor of dissection and originates from ruptured vasa vasorum within the medial wall layers, resulting in aortic wall infarction that may provoke a secondary tear and classic aortic dissection. IMH is usually located in the descending aorta, typically associated with hypertension, and may extend, progress or resorb.5,6 Deep penetrating aortic atherosclerotic plaques can lead to IMH, aortic dissection, or perforation. Non-invasive imaging has recently elucidated this disease process, which often further complicates IMH.
Keywords Acute aortic syndrome; aortic dissection; hybrid approach; intramural haematoma; penetrating aortic ulcer; peripheral vascular disease; stent-graft
‘Disease is very old, and nothing about it has changed. It is we who change as we learn to recognise what was formerly imperceptible’ Jean Martin Charcot
Classification The prime classification is based on the anatomical location of the intimal tear and degree of propagation of the false lumen. Intimal tears occur at points of presumed greatest haemodynamic stress; namely, the lateral wall of the ascending aorta and just distal to the ligamentum arteriosum of the descending thoracic aorta. Overall, 65% of intimal tears occur in the ascending aorta, 20% in the descending aorta, 10% in distal aortic arch and 5% at abdominal level. Two anatomical classification systems predominate (Figure 1) e in both, dissections with and without ascending aortic involvement are distinguished for prognostic and therapeutic reasons.7,8 Aortic dissection may also be classified according to the timing of diagnosis relative to the onset of symptoms: acute within 2 weeks, subacute within 2e8 weeks, or chronic beyond 8 weeks. About one-third of patients with aortic dissection fall into
Ibrahim Akin MD is a Physician at University Hospital Rostock, Germany. Competing interests: none declared. Rachel Clough MD is a Clinician-Scientist at King’s College London, Cardiovascular Imaging Department, UK. Competing interests: none declared. Tim C Rehders MD is Consultant Physician at the University Hospital Rostock, Germany. He qualified from Hamburg University and €tsklinikum Hamburg-Eppendorf, Germany. Competing Universita interests: none declared. Christoph A Nienaber MD FACC FESC is Head Cardiologist at the University Hospital Rostock, Germany. Competing interests: Professor Nienaber has received funds for research in the area of aortic diseases and fees for speaking about this topic at meetings; he has served as an expert witness in the John Ritter case in Glendale, California.
MEDICINE 42:9
532
Ó 2014 Elsevier Ltd. All rights reserved.
AORTIC DISEASE
Commonly used classification systems in aortic dissection De Bakey Type I
Type II
Type III
Type A
Type A
Type B
Acuity: Acute: <2 weeks after onset Subacute: 2–8 weeks after onset Chronic: >8 weeks after onset Anatomic location: Ascending aorta: Stanford Type A, De Bakey Type II Ascending and descending aorta: Stanford Type A, De Bakey Type I Descending aorta: Stanford Type B, De Bakey Type III Pathophysiology: Class 1: Classical aortic dissection with initimal flap between true and false lumen Class 2: Aortic intramural hematoma without identifiable intimal flap Class 3: Intimal tear without hematoma (limited dissection) Class 4: Atherosclerotic plaque rupture with aortic penetrating ulcer Class 5: Iatrogenic or traumatic aortic dissection (intra-aortic catheterization, high-speed deceleration injury, blunt chest trauma) Figure 1
the latter category; both mortality and the risk of progression decrease over time, with implications for the most appropriate treatment strategy.9,10
A bicuspid aortic valve is associated with acute aortic syndrome in 7e14% of patients. Other congenital cardiovascular abnormalities may predispose to dissection, including coarctation of the aorta and giant cell arteritis. Direct trauma to the aorta may cause dissection, whereas blunt trauma tends to cause localized tears, haematomas or transection; iatrogenic trauma (e.g. during cardiac catheterization, cardiac surgery or insertion of an intra-aortic balloon pump) may induce dissection, probably as a result of direct trauma to the aortic intima.11
Aetiology and pathogenesis Any disease process that undermines the integrity of the elastic or muscular components of the media predisposes the aorta to dissection, and degeneration of this layer is the major predisposing factor in most non-traumatic aortic dissection (Table 1). Degeneration of the media as a result of enhanced apoptosis is a feature of several hereditary connective tissue defects, notably Marfan’s and EhlerseDanlos syndromes. In the absence of Marfan’s syndrome, medial degeneration is usually minor in most cases of aortic dissection but is nevertheless qualitatively and quantitatively greater than that expected as part of the ageing process, possibly as a result of increased apoptosis secondary to hypertension.
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Clinical features Diagnosis and effective clinical management of acute aortic syndromes require a high level of clinical suspicion and prompt action. The differential diagnosis in acute aortic dissection includes acute coronary syndrome, pulmonary embolism, pneumothorax, pneumonia, musculoskeletal pain, acute cholecystitis,
533
Ó 2014 Elsevier Ltd. All rights reserved.
AORTIC DISEASE
Natural history
Conditions associated with increased risk of aortic dissection
Despite major advances in the non-invasive diagnosis of aortic dissection and its treatment, up to 28e55% of patients die without correct diagnosis.4 Registry data demonstrate that medical management of type A dissection is associated with a mortality of nearly 24% after 1 day, 29% after 2 days, 44% after 1 week and 50% after 2 weeks. Less than 10% of untreated patients live for 1 year and almost all patients die within 10 years.4 Type B dissection has a better prognosis with survival rates of 89% at 1 month, 84% at 1 year, and 80% at 5 years.4 However, patients with complications such as renal failure, visceral ischaemia or contained rupture fare less well with a mortality of 20% at day 2 and 25e50% at 1 month, and often require urgent repair. Population-based data show a trend to higher incidences of the disease and higher mortality figures with increasing age.13
Long-standing arterial hypertension Smoking, dyslipidaemia, cocaine/crack Connective tissue disorders Hereditary fibrillinopathies Marfan’s syndrome EhlerseDanlos syndrome Hereditary vascular diseases Bicuspid aortic valve Coarctation Vascular inflammation Giant cell arteritis Takayasu’s arteritis Behc‚et’s disease Syphilis Ormond’s disease Deceleration trauma Car accident Fall from height Iatrogenic factors Cardiac catheterization Valvular/aortic surgery Side- or cross-clamping/aortotomy Graft anastomosis Patch aortoplasty Cannulation site Aortic wall fragility
Diagnosis A low threshold of clinical suspicion is vital for timely diagnosis and management of this catastrophic condition. Chest radiography is often non-specific and does not have a definitive role.14 Possible findings include widening of the aortic contour, displaced calcification, aortic kinking, and opacification of the aortopulmonary window. Transthoracic/transoesophageal echocardiography, contrast-enhanced CT, MRI and aortography (Table 2) may all be used to confirm suspected dissection. Each modality has advantages and disadvantages in terms of convenience, risk, cost and local availability. Diagnostic accuracies are similar, but all differ in their ability to detect associated complications. The ideal imaging modality should: confirm or refute the diagnosis of aortic dissection determine whether dissection involves the ascending aorta or is confined to the descending aorta or arch reveal the anatomic features of the dissection, including its extent, the site(s) of entry and re-entry, the presence of thrombus in the false lumen, and branch vessel involvement. Unfortunately, no single modality provides all of this information. In the IRAD registry, the first diagnostic step was transthoracic and transoesophageal echocardiography (TTE/ TEE) in 33%, CT in 61%, MRI in 2% and angiography in 4%. Two or three of these investigations were required in many patients.
Table 1
oesophageal spasm or rupture, acute pancreatitis and acute pericarditis. The most common initial symptom is severe migrating back or chest pain.12 Amongst 464 patients reported from the International Registry of Acute Aortic Dissection (IRAD), 95% reported pain that was of abrupt onset in 85%.4 Those without pain are usually found to have chronic dissection. The pain is typically stabbing, tearing or ripping and often described as the worst pain ever experienced e it is clearly different from the pain of myocardial infarction. The pain of aortic dissection tends to migrate from its point of origin to other sites, generally following the path of the dissection as it extends through the aorta. Such migratory pain is described by about 20% of patients and may be helpful in pinpointing the anatomical location of the dissection. Aortic dissection is a ‘clinical chameleon’. The clinical manifestations in more than one-third of the patients may be explained by impaired perfusion of key organs as a result of sidebranch obstruction.4 However, physical findings are variable and may be subtle or absent, even in the presence of extensive dissection. Aortic regurgitation with resultant congestive heart failure may occur and patients may exhibit pulse deficits and neurological manifestations, such as headache, cerebrovascular accidents (as a consequence of carotid involvement), syncope (caused by cardiac tamponade) and paraparesis/paraplegia secondary to spinal ischaemia.
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Management All patients in whom acute aortic dissection is strongly suspected should be managed in an acute-care setting where blood pressure, cardiac rhythm and urine output can be monitored. Initial therapeutic aims to include elimination of pain and reduction of systolic blood pressure to 120 mmHg or less (or the lowest level ensuring adequate vital organ perfusion), using intravenous bblockers (e.g. labetalol or esmolol) and vasodilators.11,12 Surgical treatment Definitive therapy for aortic dissection has evolved over the last two decades. The need for surgery should be determined whenever possible at the time of initial clinical evaluation. Surgical risk is increased by advancing age, comorbid disease (particularly coronary artery disease and emphysema), partial or
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Imaging modalities in the evaluation of suspected aortic dissection28,29 Diagnostic performance
Angiography
CT
MRI
Transoesophageal echocardiography
Sensitivity Specificity Site of intimal tear Presence of thrombus Presence of aortic regurgitation Pericardial effusion Branch vessel involvement Coronary artery involvement Advantages Readily available Quickly performed Bedside evaluation Non-invasive Intravenous contrast Cost
þþ þþþ þþ þþþ þþþ þþþ þþ
þþþ þþþ þ þþ þþ þþ
þþþ þþþ þþþ þþþ þ þþþ þþ
þþþ þþþ þþ þ þþþ þþþ þ þþ
Fairly Fairly No No Yes High
Quite Quite No Yes Yes Reasonable
Fairly Fairly No Yes No/yes Moderate
Very Very Yes Yes No Reasonable
þþþ, Excellent; þþ, good; þ, fair; , not detected.
Table 2
encouraging.19,20 Data from the IRAD registry indicate better survival rates in patients after endovascular treatment of complicated type B dissection in comparison with open surgical repair.21,22 Accepted indications for the procedure include vital organ ischaemia, intractable pain, rapid expansion of the false
complete aortic rupture, hypotension (systolic blood pressure 100 mmHg), shock/cardiac tamponade and compromise of vital organs. Limb ischaemia, new neurological deficits and congestive heart failure may further complicate the outcome.15 Preoperative mortality in acute dissection ranges from 3% in stable patients who undergo surgery without delay to 30% or more when evaluation is prolonged or the case more complex. These data reinforce the need for prompt diagnosis and surgical repair to prevent even minimal progression of the dissection with associated complications. The aim of surgery in type A dissection is prevention of rupture or the development of pericardial effusion, which may lead to cardiac tamponade and death. Similarly, the sudden onset of aortic regurgitation or obstructed coronary flow requires urgent surgery to resect the region involved with subsequent replacement using a composite or interposition graft (provided the aortic valve leaflets are intact or resuspendable).16 Resection of the entire intimal flap may not be possible if the dissection extends to the aortic arch or descending aorta, when partial or total arch replacement may be necessary. Acute type A dissection in a previously ectatic proximal aorta (usually encountered in Marfan’s syndrome) requires a different approach, entailing use of a composite graft (aortic tube graft with integrated valve) and coronary reimplantation.17 Valve-sparing operations are delicate endeavours in the emergency setting and best undertaken by expert operators in specialist centres.
Concept of interventional reconstruction of the dissected descending aorta with sealing of the proximal entries, depressurization of the false lumen and initiation of false lumen thrombosis Proximal entry Left carotid artery Left subclavian artery
Thrombus
Endovascular aortic repair Percutaneous stent-grafts (Figure 2) are an established treatment alternative in type B dissection.18 The aim of the procedure is to close entry to the false lumen using a tube-like nitinol grid covered with a Dacron shell and thereby induce thrombosis of the false lumen with subsequent healing of the aortic wall (Figure 3). Early results describing this approach are
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Perfused false lumen
Stent-graft
Figure 2
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Figure 3 CT scan demonstrating a type B aortic dissection in a 48-year-old man; note dynamic obstruction of the true lumen in the acute phase. After stent-graft placement across the proximal thoracic entry site the entire true lumen of the thoracic aorta is reconstructed with complete ‘healing’ of the dissected aortic wall and shrinking of the completely thrombosed false lumen. TL, true lumen; FL, false lumen; TH, thrombus.
lumen (diameter > 55 mm), and signs of imminent rupture.3,18 Successful stent-graft treatment of the descending thoracic aorta has also been recently described;23 pre-emptive stent grafting and remodelling lead to long-term prognostic benefits and better 5-year survival than does medical management alone.24,25 The window of opportunity for best endovascular results seems to be 3 months in elective cases of type B dissection.26 Technological advances and increased operator expertise make it likely that endovascular techniques will soon become first-line therapy for most patients presenting with anatomically suitable thoracic and thoraco-abdominal aortic pathology, regardless of initial clinical symptoms.
REFERENCES 1 Leonhard JC. Thomas Bevill Peacock and the early history of dissecting aneurysm. Br Med J 1979; 2: 260e2. 2 Hirst Jr AE, Johns Jr V, Kime Jr SW. Dissecting aneurysm of the aorta: a review of 505 cases. Med Baltim 1958; 37: 217e79. 3 Clouse WD, Hallett Jr JW, Schaff HV, et al. Acute aortic dissection: population-based incidence compared with degenerative aortic aneurysm rupture. Mayo Clin Proc 2004; 79: 176e80. 4 Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA 2000; 283: 897e903. 5 Vilacosta I, San Roman JA, Ferreiros J. Natural history and serial morphology of aortic intramural hematoma: a novel variant of aortic dissection. Am Heart J 1997; 134: 495e507. 6 Evangelista A, Mukherjee D, Mehta RH, et al. International registry of aortic dissection (IRAD) investigators. Acute intramural hematoma of the aorta: a mystery in evolution. Circulation 2005; 111: 1063e70. 7 Svensson LG, Labib SB, Eisenhauer AC, et al. Intimal tear without hematoma: an important variant of aortic dissection that can elude current imaging techniques. Circulation 1999; 99: 1331e6. 8 Richartz BM, Smith DE, Cooper JV, et al. New classification of aortic dissection with improved impact on prognosis. J Am Coll Cardiol 2002; 39: A 863. 9 Booher AM, Isselbacher EM, Nienaber CA, et al. The IRAD classification system for characterizing survival after aortic dissection. Am J Med 2013; 126: 730 e 19e24. 10 Steuer J, Bjorck M, Mayer D, et al. Distinction between acute and chronic type B aortic dissection: is there a sub-acute phase? Eur J Vasc Endovasc Surg 2013; 45: 627e31.
Long-term therapy and follow-up Continued follow-up is essential for medically treated patients and those who have undergone open surgery or endovascular aortic repair. The primary aim of long-term surveillance is maintenance of blood pressure control and early detection of changes or unstable aortic lesions that require subsequent open surgery or endovascular intervention (e.g. rapid expansion of a new or existing aneurysm, progression or recurrence of dissection, aortic regurgitation, peripheral vascular compromise). CT angiography and/or dynamic MRI are non-invasive and the preferred techniques for monitoring these patients e MRI also avoids repeated radiation exposure and provides excellent anatomical detail that may be helpful in evaluating serial changes.27 Patients are at greatest risk immediately following hospital discharge and during the first 2 years thereafter, so early follow-up is warranted; for example, patients may be seen at 3 and 6 months initially, then every 6 months for 2 years, after which the follow-up interval will be determined by individual patient risk. A MEDICINE 42:9
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11 Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: executive summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Catheter Cardiovasc Interv 2010; 76: E43e86. 12 Nienaber CA, Powell T. Management of acute aortic syndromes. Eur Heart J 2012; 33: 26e35. 13 Howard DP, Banerjee A, Fairhead JF, et al. Population-based study of incidence and outcome of acute aortic dissection and premorbid risk factor control: 10-year results from the Oxford Vascular Study. Circulation 2013; 127: 2031e7. 14 von Kodolitsch Y, Nienaber CA, Dieckmann C, et al. Chest radiography for the diagnosis of acute aortic syndrome. Am J Med 2004; 116: 73e7. 15 Trimarchi S, Nienaber CA, Rampoldi V, et al. Contemporary results of surgery in acute type A aortic dissection: the International Registry of Acute Aortic Dissection experience. J Thorac Cardiovasc Surg 2005; 129: 112e22. 16 David TE, Feindel CM. An aortic valve-sparing operation for patients with aortic incompetence and aneurysm of the ascending aorta. J Thorac Cardiovasc Surg 1992; 103: 617e21. 17 Milewicz DM, Dietz HC, Miller DC. Treatment of aortic disease in patients with Marfan syndrome. Circulation 2005; 111: e150e157. 18 Nienaber CA, Fattori R, Lund G, et al. Nonsurgical reconstruction of thoracic aortic dissection by stent-graft placement. N Engl J Med 1999; 340: 1539e45. 19 Clough RE, Mani K, Lyons OT, et al. Endovascular treatment of acute aortic syndrome. J Vasc Surg 2011; 54: 1580e7. 20 Eggebrecht H, Nienaber CA, Neuhauser M, et al. Endovascular stentgraft placement in aortic dissection: a meta-analysis. Eur Heart J 2005; 4: 489e98. 21 Fattori R, Montgomery D, Lovato L, et al. Survival after endovascular therapy in patients with type B aortic dissection: a report from the International Registry of Acute Aortic Dissection (IRAD). JACC Cardiovasc Interv 2013; 6: 876e82. 22 Fattori R, Tsai TT, Myrmel T, et al. Complicated acute type B dissection: is surgery still the best option. A report from the International Registry of Acute Aortic Dissection. J Am Coll Cardiol 2008; 1: 395e402.
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23 Nienaber CA, Rousseau H, Eggebrecht H, et al. Randomized comparison of strategies for type B aortic dissection e the Investigation of Stent-grafts in Aortic Dissection (INSTEAD) trial. Circulation 2009; 120: 2519e28. 24 Nienaber CA, Kische S, Rousseau H, et al. Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial. Circ Cardiovasc Interv 2013; 6: 407e16. 25 Patterson B, Holt P, Nienaber C, et al. Aortic pathology determines midterm outcome after endovascular repair of the thoracic aorta: report from the Medtronic Thoracic Endovascular Registry (MOTHER) database. Circulation 2013; 127: 24e32. 26 Akin I, Kische S, Ince H, et al. Indication, timing and results of endovascular treatment of type B dissection. Eur J Vasc Endovascular Surg 2009; 1e8. 27 Clough RE, Hussain T, Uribe S, et al. A new method for quantification of false lumen thrombosis in aortic dissection using magnetic resonance imaging and a blood pool contrast agent. J Vasc Surg 2011; 1 e14. 28 Tsai TT, Nienaber CA, Eagle KA. Acute aortic syndromes. Circulation 2005; 112: 3802e13. 29 Cigarroa JE, Isselbacher EM, DeSanctis RW, et al. Diagnostic imaging in the evaluation of suspected aortic dissection. Old standards and new directions. N Engl J Med 1993; 328: 35e43. FURTHER READING Harris KM, Strauss CE, Eagle KA, et al. Correlates of delayed recognition and treatment of acute type A aortic dissection: the International Registry of Acute Aortic Dissection (IRAD). Circulation 2011; 124: 1911 e8. Isselbacher EM. Diseases of the aorta. In: Libby P, Bonow RO, Mann D, Zipes, eds. Braunwald’s heart disease. 8th edn. Philadelphia: Saunders, 2007; 1457e91. Ranasinghe AM, Bonser RS. Biomarkers in acute aortic dissection and other aortic syndromes. J Am Coll Cardiol 2010; 56: 1535e41. Suzuki T, Isselbacher EM, Nienaber CA, et al. Type-selective benefits of medications in treatment of acute aortic dissection (from the International Registry of Acute Aortic Dissection [IRAD]). Am J Cardiol 2012; 109: 122e7. Svensson LG, Kouchoukous NT, Miller DC, et al. Expert consensus document on the treatment of descending thoracic aortic disease using endovascular stent-grafts. Ann Thorac Surg 2008; 85: S1e45.
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