Curr Cardiol Rep (2014) 16:536 DOI 10.1007/s11886-014-0536-x
PERIPHERAL VASCULAR DISEASE (MH SHISHEHBOR, SECTION EDITOR)
Diagnosis and Management of Acute Aortic Syndromes: Dissection, Intramural Hematoma, and Penetrating Aortic Ulcer Marc P. Bonaca & Patrick T. O’Gara
Published online: 26 August 2014 # Springer Science+Business Media New York 2014
Abstract Acute aortic syndromes constitute a spectrum of conditions characterized by disruptions in the integrity of the aortic wall that may lead to potentially catastrophic outcomes. They include classic aortic dissection, intramural hematoma, and penetrating aortic ulcer. Although imaging studies are sensitive and specific, timely diagnosis can be delayed because of variability in presenting symptoms and the relatively low frequency with which acute aortic syndromes are seen in the emergency setting. Traditional classification systems, such as the Stanford system, facilitate early treatment decisionmaking through recognition of the high risk of death and major complications associated with involvement of the ascending aorta (type A). These patients are treated surgically unless intractable and severe co-morbidities are present. Outcomes with dissections that do not involve the ascending aorta (type B) depend on the presence of acute complications (e.g., malperfusion, early aneurysm formation, leakage), the patency and size of the false lumen, and patient co-morbidities. Patients with uncomplicated type B dissections are initially treated medically. Endovascular techniques have emerged as an alternative to surgery for the management of complicated type B dissections when intervention is necessary. Patients with acute aortic syndromes require aggressive medical care, risk stratification for additional complications and targeted genetic assessment as well as careful long-term monitoring to assess for evolving complications. The optimal care of patients with acute aortic syndrome requires the cooperation of members of an experienced multidisciplinary team both in the acute and chronic setting. This article is part of the Topical Collection on Peripheral Vascular Disease M. P. Bonaca (*) : P. T. O’Gara Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA e-mail: [email protected]
Keywords Acute aortic syndrome . Intramural hematoma . Penetrating aortic ulcer . Aortic dissection
Introduction Acute aortic syndromes represent a spectrum of related entities which are characterized by an acute disruption of aortic integrity with an associated risk of complications including organ ischemia, rupture, and death. Although imaging for acute aortic syndromes is sensitive and specific, diagnosis and management remain a challenge as influenced by several factors, including the lower frequency with which they are encountered (3–16 cases per 100,000 person-years) relative to other acute cardiovascular conditions [1] (Fig. 1a), nonspecific symptoms at presentation that may overlap with more common entities, and the intensity of resources needed for appropriate testing and care [2, 3•, 4]. The challenge for the clinician is further complicated by the knowledge that risk of death and major complication is high early in the course of the illness and increases rapidly with time, making prompt and accurate diagnosis essential to maximize the opportunity for successful therapeutic intervention (Fig. 1b) [5, 6•]. Traditional classifications systems have provided a clear pathway for early management based on the involvement of the ascending aorta (type A) and the associated need for early surgery. Initial medical management is recommended for dissections that do not involve the ascending aorta (type B) unless complications are present [3•]. The role of thoracic endovascular aortic repair (TEVAR) in the management of patients with acute, uncomplicated type B aortic dissection is evolving. In addition, patients initially triaged to medical management may experience early complications and require intervention during their index hospitalization. The complex decision-making surrounding the acute aortic syndrome patient requires the close collaboration of
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Fig. 1 a Incidence of selected acute cardiovascular conditions [1, 6•]. b Short-term mortality by diagnosis [1, 6•, 26]
specialists in emergency medicine, vascular surgery, cardiovascular surgery, cardiovascular medicine, and vascular imaging. Systems which facilitate this interaction may improve decision-making. This article reviews the epidemiology, clinical presentation, diagnosis, and treatment of acute aortic syndromes.
Definitions and Pathogenesis Acute aortic syndromes comprise aortic dissection; intramural hematoma (IMH); and penetrating aortic ulcer (PAU), acute aneurysm expansion, and trauma [2, 3•]. Aortic dissection occurs as a consequence of an intimal tear that allows access of blood under systolic pressure into the medial layer of the aorta with propagation that is more often antegrade than retrograde [2]. The resulting flap of tissue divides the aorta into a “true” lumen, which represents the original vessel lumen, and a “false” lumen, which is the space created by the medial disruption. The intimal flap may occlude or compromise branch vessels and lead to malperfusion. The dissecting hematoma may re-enter the true lumen via one or more distal re-entry tears, which provide a mechanism for false lumen decompression. Alternatively, there may be no functioning re-entry site, causing the false lumen to act as a “wind
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sock” with increasing false lumen pressures, propagation of the dissection, aneurysm formation, compression of the true lumen or branch vessels, or rupture. Observational studies suggest that the status of flow within the false lumen in patients with type B dissection may have long-term prognostic importance [7]. Although medial disruption is a defining feature of dissection, cases of isolated intimal tears without hematoma formation have been described [8]. The related condition of intramural hematoma (IMH) occurs as a consequence of either medial hemorrhage from ruptured vasa vasorum or a microscopic intimal tear, which seals and thus does not allow communication with the true lumen after inception. IMHs comprise approximately 5– 15 % of acute aortic syndromes [9–12]. Approximately one-third of IMHs may resolve spontaneously. Two-thirds will evolve into classic dissection, aneurysm, or false aneurysm formation. Penetrating aortic ulcers (PAU) are lesions that occur in older patients with a heavy burden of atherosclerosis and have a predilection for the descending thoracic aorta. They form as a consequence of the inflammatory erosion of the internal elastic membrane and result in penetration of aortic blood beyond its true lumen, with subsequent false aneurysm formation, evolution to IMH, dissection, or rupture [13]. These three conditions are interrelated and occur along a spectrum of disease presentation and evolution. All can cause similar symptoms; however, malperfusion is more common with dissection [9, 12]. Of the three, dissection is the most common followed in order by IMH and PAU [14]. Although outcomes are best described for patients with aortic dissection, the natural history of these lesions generally depend on their location within the aorta. Management strategies are similar across the three entities [14]. Medial degeneration owing to a variety of processes predisposes to the development of acute aortic syndrome [2, 14]. This degeneration, previously described as “cystic medial necrosis,” is generally associated with age and hypertension, but can occur with several other disorders. The aortic lesions seen on histologic analysis need not be cystic in their appearance, but rather are distinguished by the disruption or loss of elastic fiber integrity. A pre-mature loss of tensile strength can occur in younger patients with a genetic predisposition, such as Marfan syndrome characterized by FBN1 mutations and elastin deficiencies, Ehlers-Danlos syndrome (COL3A1), familial thoracic aortic aneurysm disease (FTAAD), and in patients with bicuspid aortic valve disease with associated aortopathy. Aortic dissection has also been reported in Noonan’s syndrome, polycystic kidney disease, and during pregnancy, typically during the 3rd trimester or early puerperium. Many pregnant women with dissection, however, may have an underlying connective tissue abnormality predisposing to its development. In addition, trauma or inflammatory processes (Takayasu’s, Behçet’s, polychondritis, idiopathic
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aortitis) can predispose to aortic disruption in the absence of more typical risk factors [2, 3•].
Epidemiology and Risk Factors Acute aortic syndromes are reported to occur with a frequency of approximately 3–16 cases per 100,000 person-years. Most acute aortic syndromes occur in older patients (in the fifth and sixth decade), with a male predominance, and in those with a history of hypertension (Table 1) [5, 6•, 15, 16]. While the majority of patients (~60 %) with dissection are male, recent community-based studies suggest that at age 75 or above, the incidence is similar for men and women [6•]. A history of uncontrolled hypertension in spite of multi-agent therapy has been noted in patients with acute aortic syndromes, suggesting an increased risk in this subgroup [6•]. Patients with connective tissue disorders may present at a younger age without hypertension as can patients with vascular inflammatory diseases or trauma [5, 6•, 17•]. Therefore, the clinician should not discount the possibility of acute aortic disease in patients who are young and do not have hypertension and must think broadly when evaluating the history [3•]. Table 1 Aortic dissection: risk factors and predisposing conditions
Acute aortic disruption may also be iatrogenic or traumatic. Aortic injury has been described in the setting of percutaneous vascular procedures as well as cardiac surgery. In one series, complications involving the proximal aorta in the setting of aortic surgery occurred with a rate of approximately 0.15 % [18]. Interestingly, there was evidence of medial degeneration on histologic analysis of these cases suggesting a possible underlying predisposition rather than a purely procedural complication [18]. Cocaine ingestion is associated with abrupt increases in heart rate and blood pressure. Its use has been associated with acute type B dissection, particularly among young, urban male smokers. Aortic injury and transection can occur in the setting of chest trauma with rapid deceleration such as that occurring in motor vehicle accidents.
Classification There are two systems in clinical use for the classification of acute aortic syndromes, the DeBakey classification and the Stanford Classification [19, 20]. The DeBakey classification is based on the site of origin of the dissection, while the Stanford classification is based on the presence or absence of ascending aortic involvement (Fig. 2). Since initial management is largely
Patients without Predisposition Age Sixth and seventh decade Gender
Male predominance (~1.5:1)
Hypertension
Prevalence 68–72 %
History of smoking Prevalence ~60 % Atherosclerosis Prevalence ~30 % Predisposing Conditions Inflammatory diseases
Genetic conditions
Trauma Other
Observational data suggest women present at an older age then men Incidence by gender varies with age with data suggesting that the incidence in men and women is similar at age 75 and above Studies suggest increased prevalence of poorly controlled blood pressure in spite of multi-agent antihypertensive therapy
Giant cell arteritis Takayasu arteritis Behçet arteritis Rheumatoid arteritis Systemic lupus erythematosus Marfan syndrome Loeys-Dietz syndrome Ehlers-Danlos syndrome Familial syndrome Bicuspid aortic valve Turner syndrome Iatrogenic Deceleration injury Cocaine or stimulant use Valsalva maneuver
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Fig. 2 Classification systems for acute aortic dissection [26]. Adapted from Tsai et al. Circulation 2005
determined by the involvement of the ascending aorta (rather than site of origin), the Stanford classification is more frequently used. However, both may be useful in that site of origin may be considered in decision-making [14]. These classification schemes are also used to characterize IMH and PAU [14]. Although the existing systems provide a relatively straightforward approach to classification and therapeutic decision-making, one anatomic area which remains challenging for clinicians is the aortic arch. Both the DeBakey and Stanford systems identify involvement of the ascending aorta as a key factor in classification. Dissections isolated to or originating in the arch and extending distally (e.g., not involving the ascending aorta), therefore, are neither type A nor type B technically speaking (also called non-A, non-B dissection) [21]. The natural history of isolated arch dissection has been less well characterized [21].
Natural History Acute aortic syndromes are associated with significant morbidity and mortality. However, outcomes vary depending on the type, location, and the presence of complications [6•]. Presentation with type A dissection is more common than type B dissection. Overall 30-day mortality, inclusive of prehospital deaths, for aortic dissection of any type exceeds 50 % [5, 6•]. In one community-based cohort study, nearly 50 % of patients with dissection died before hospitalization. Thirtyday survival for those admitted alive was only 53 % [5, 6•]. The mortality rate for untreated aortic dissection is 1–2 % per hour over the first 24 h and in excess of 75 % by 2 weeks [5]. Delayed recognition is associated with poor outcomes [4]. An analysis from the International Registry of Aortic Dissection (IRAD) found a mortality rate of 0.22 % per hour during
the first 24 h and 0.77 % per hour for medically managed type A dissections [22]. Type A dissection may be complicated by tamponade, aortic regurgitation, stroke, or malperfusion, including myocardial ischemia from compromise of the coronary arteries [5, 23]. Iatrogenic dissection of the ascending aorta at the time of cardiac surgery is also associated with increased mortality risk with the highest rates for those that occur in the early (42 %) or late (32 %) post-operative periods compared to those that are discovered intraoperatively (17 % mortality) and presumably addressed as part of the index procedure [18, 24, 25]. Type B dissection is associated with a lower mortality risk than type A dissection. One study reported a 30-day mortality rate of approximately 13 % and 5-year mortality rate of 33 % for patients with type B dissection (Fig. 1b) [6•]. In IRAD, inhospital mortality for type B dissections was 13 % [16, 26]. Independent predictors of death included hypotension/shock at presentation, absence of chest or back pain, and branch vessel involvement (the deadly triad) [16]. Patients with type B aortic dissection comprise a heterogeneous group. One study observed that 21 % of patients with type B dissection developed malperfusion and 27 % required intervention for complications during the index hospitalization [16]. Another IRAD study demonstrated that nearly half of type B dissections were complicated, as defined by the development of shock, periaortic hematoma, spinal cord ischemia, mesenteric ischemia/infarction, acute renal failure, limb ischemia, recurrent or refractory pain, or refractory hypertension [26]. In-hospital mortality varied significantly as a function of such complications (20 % for complicated vs. 6.1 % for uncomplicated, p70, pre-operative limb ischemia, periaortic hematoma, and surgical management [26]. Identifying early complications in patients with type B dissection is critical for risk stratification and treatment [3•].
Clinical Presentation Presenting symptoms for aortic dissection are variable depending on both the location and extent of the disruption as well as on patient factors such as age and gender (Table 2) [2, 3•, 27]. The most common symptom is sudden and severe chest or back pain; however, patients may present with atypical symptoms or no pain. The chest pain of aortic dissection is abrupt in onset with maximal intensity at inception. Pain may be severe and occasionally may be described as “tearing” or migratory [2, 3•, 4]. Its initial location and radiation may provide clues as
to the site of origin and the extent of aortic involvement. Syncope can be a particularly ominous symptom indicating tamponade or stroke [28]. Acute neurologic symptoms may occur in the setting of aortic dissection and may be transient [3•, 29]. The lack of specificity in presenting symptoms can be challenging and lead to delay in diagnosis, particularly among patients with atypical symptoms [2, 3•, 4, 30]. Physical examination signs in patients presenting with acute aortic syndromes can also be non-specific. Hypertension is relatively frequent, but non-specific. A pulse deficit is described in approximately 30 % of patients with type A dissection and is associated with increased mortality [31]. Focal neurologic deficits are described in 17 % of patients. Signs in the acute setting may evolve rapidly as the dissection progresses and include acute aortic regurgitation, myocardial ischemia, cardiogenic shock, tamponade, neurologic deficits, and peripheral or mesenteric ischemia [3•, 23, 31, 32]. In addition, findings generally attributed to alternative diagnoses such as pleural effusion (either reactive or from hemorrhage) may occur in as many as 16 % of patients [3•, 5]. Timely diagnosis requires a high index of suspicion, particularly in the elderly where typical symptoms may be less common and comorbid diseases such as coronary artery disease further complicate initial clinical assessment [3•].
Diagnosis Current guidelines recommend performance of a focused history and exam to assess the pre-test likelihood of acute aortic syndrome [3•]. This assessment should include questions about known genetic, connective tissue, or familial conditions associated with aortic disease, history of recent aortic
Table 2 Aortic dissection: presenting signs and symptoms Symptoms/signs
Frequency
Note
Chest pain
Type A 79 % Type B 63 % Type A 47 % Type B 64 % Type A 43 % Type B 22 % Type A 36 % Type B 70 % 13 % Overall
Sudden and severe
Back pain Abdominal pain Hypertension (at presentation) Syncope
Pulse deficit Neurologic deficit No pain Aortic regurgitation murmur
Type A 19–30 % Type B 9–21 % 17 % Overall [5] 4.5 % Overall Type A 45 %
Sudden and severe Associated with higher mortality and delay in diagnosis [74] More common in type B May indicate development of a dangerous complication (e.g., tamponade) [28]. Associated with increased in-hospital mortality (34 % with syncope, 23 % without) Associated with increased in-hospital mortality May be more frequent with type A (29 %) Associated with increased mortality
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manipulation, typical pain, or high-risk signs such as pulse deficit, blood pressure differential, focal neurologic signs or symptoms, and new murmur of aortic regurgitation [3•]. In one analysis, the median time to diagnosis was 4.3 h with an intraquartile range of 1.5 to 24 h, meaning that 25 % of patients were diagnosed 24 h or later after presentation [4]. Factors associated with delayed diagnosis included atypical symptoms, hemodynamic stability, absence of pulse deficit, and presentation to a non-tertiary care hospital. Risk scores based on the AHA/ACC consensus guidelines for the diagnosis of acute coronary syndrome have been evaluated and shown to be highly sensitive [33]. The ECG is often (69 %) abnormal, but in most cases shows non-specific findings [5]. In one IRAD review, ST-T wave abnormalities suggestive of ischemia were found in 15 % of patients with type A dissection with an acute injury current in 5 % [5]. Chest x-ray is likewise abnormal in most cases (80 %), but findings may be non-specific [5]. These including widening of the mediastinum and displacement of aortic calcification (Fig. 4). Importantly, a normal chest x-ray or ECG should not delay definitive imaging in patients in whom there is clinical suspicion [3•]. Biomarkers are emerging as a diagnostic tool in patients with suspected acute aortic syndromes. D-dimer, a fibrin degradation product indicative of intravascular coagulation, has established utility in the setting of suspected pulmonary embolism and is widely available. A D-dimer >500 ng/mL has been shown to be highly sensitive for acute dissection (~97 %, negative predictive value 96 %) but relatively non-specific (56 %, positive predictive value 60 %) [34–38]. Based on this high sensitivity, D-dimer may be a potential screening tool to “rule out” acute aortic dissection [34]. One potential concern is that D-dimer levels may decline over time, reducing sensitivity in patients presenting late after symptom onset or with atypical symptoms. In one study, 18 % of patients with aortic dissection had D-dimer levels 95 %) and specificity (>95 %) (Fig. 5a–c) [14, 44–48]. CTA is the most commonly utilized modality; current consensus guidelines recommend that if a high clinical suspicion existing after initial imaging is negative, a second imaging study should be obtained [3•]. Imaging acquisition must be performed optimally in order to maximize diagnostic accuracy. Several factors, including the timing of contrast injection, ECG gating to reduce artifact from cardiac motion, and imaging the full extent of the aorta, should be considered [47, 48]. Consultation with an imaging specialist and communication of the clinical considerations are important as studies conducted for other diagnoses (e.g., evaluate for pulmonary embolism) may not have sufficient diagnostic accuracy for aortic dissection [3•, 48].
Treatment Assessment of Clinical Stability Stabilizing medical treatment should be initiated in all patients with suspected acute aortic dissection as dictated by clinical findings and targeted at controlling heart rate, blood pressure (and its rate of rise, dP/dT), and symptoms [14]. Recognition of acute complications (e.g., tamponade, aortic regurgitation, malperfusion) is critical in determining appropriate therapy and initiating definitive management. Unstable patients should undergo concomitant surgical consultation, with rapid imaging assessment to facilitate management. A recommended approach to medical therapy in stable, uncomplicated patients is discussed below. Indications for Surgery in Acute Dissection
Fig. 4 Portable chest x-ray in a patient with acute type A dissection showing a widened mediastinum and pulmonary vascular congestion
Urgent surgical consultation should be obtained in all patients with acute aortic syndromes [14]. The need for and timing of surgery are dictated by the location of aortic involvement, presence of complications, and the clinical stability of the patient.
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the extent of the tear, whether it involves critical structures such as the coronary ostia or aortic valve, and its distal extent into and beyond the arch. Surgical approaches include primary repair with an interposition graft or use of a composite valve graft conduit with re-implantation of the coronary arteries. Valve-sparing re-suspension is performed when the anatomy allows. Perfusion is most commonly established via the right axillary artery, and deep hypothermic circulatory arrest is frequently employed to complete the distal, open anastomosis &
Acute type B (descending aortic involvement) –
Fig. 5 a CT angiogram in both the axial and sagittal views showing a dissection flap originating in the ascending aorta and propagating through the descending aorta. Both lumens show contrast enhancement indicating patency of the false lumen which is larger than the true lumen. b CT noncontrast (images left) and with contrast (images right) demonstrating an intramural hematoma originating in the distal ascending aorta and arch and extending into the descending aorta. c CT angiogram of a patient with multiple penetrating aortic ulcers. Shows axial images as well as threedimensional reconstruction
&
The need for early surgery—or endovascular stent grafting—in patients with type B dissection depends on the presence of complications, including malperfusion, progression of the dissection, aortic expansion or impending rupture, dissection location within a previously aneurysmal segment, refractory pain, or refractory hypertension. Some have argued that Marfan syndrome or other types of primary connective tissue disease should prompt early surgical repair. In the absence of early complications, medical management is recommended. The routine use of endovascular stent grafting for uncomplicated type B dissection has not been adequately studied, though it has gained increasing application. When used, stent grafting is often supplemented by fenestration procedures and stenting of major, aortic side branches. A framework for managing type B dissection is shown in Fig. 6.
Aortic surgery in the chronic phase of dissection is usually dictated by the size of the aorta (≥5.5 cm ascending aorta, ≥5.5–6.0 cm descending aorta), its rate of growth over time, and the presence of associated complications such as aortic regurgitation and left ventricular dysfunction in some patients with type A disease.
Acute type A (ascending aortic involvement) –
In general, urgent surgical repair is indicated for all type A dissections. The type of repair depends on several factors including the location of the entry site,
Fig. 6 Management of type B aortic dissection
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Initial Medical Management
Table 3 Aortic dissection: signs and symptoms of complication in type B dissection
General guidance for medical therapy derives from consensus guidelines for the treatment of patients with acute aortic syndromes [14]. Medical therapy should be initiated promptly in all patients even while diagnostic studies are underway.
Symptoms
Signs
New, worsening, or refractory pain involving the chest, flank, abdomen. May be transient in the setting of dynamic obstruction Focal neurologic symptoms Anorexia or dyspepsia Limb pain
New or sudden hypotension or hypertension refractory to medical therapy
1. Beta-blocker therapy should be started with the goal to lower heart rate and blood pressure to the lowest tolerable levels. Short-acting agents such as esmolol may be used if there are concerns regarding tolerability. Agents with both alpha and beta antagonism such as labetalol may be useful. Non-dihydropyridine calcium channel blockers can be used in patients unable to tolerate beta-blockers. Caution should be exercised in the setting of hemodynamic instability or acute severe aortic regurgitation so as not to cause decompensation through blunting of compensatory tachycardia. 2. If, after control of heart rate through the use of betablockade, the blood pressure remains elevated, then a vasodilator (e.g., sodium nitroprusside, angiotensinconverting enzyme inhibitor) may be added. Vasodilators should not be added prior to beta-blockade as this may increase heart rate and the rate of LV pressure rise (dP/ dT), which would be deleterious in these circumstances. 3. Control of pain as well as other drivers of adrenergic tone (e.g., anxiety, alcohol withdrawal) is useful.
Monitoring Patients diagnosed with dissection may develop complications and decompensate rapidly. Intensive monitoring should be instituted including frequent vital signs with use of an intraarterial line if necessary, evaluation of symptoms, serial exams, and laboratory measurements (Table 3). Branch vessel occlusion may be dynamic so signs or symptoms of malperfusion may be transient. Options for Complicated Type B Dissection Current guidelines reserve surgery or endovascular stent grafting of type B dissection for cases with early complications [3•]. In IRAD, 27 % of patients with type B dissection required an interventional procedure during index hospitalization [16]. A more recent IRAD review noted that 45 % of type B cases were considered complicated [26]. Open surgical repair was formerly the traditional approach for patients with complicated type B dissection [49], but newer transcatheter approaches to complicated type B dissection have become more frequently utilized and may be associated with better outcomes than surgery, although randomized trials in the acute setting are lacking [50,
Focal neurologic signs; paraplegia Gastrointestinal bleeding Pulse deficit or visible changes in limb color or perfusion Anuria or hematuria Laboratory abnormalities (increasing creatinine, metabolic acidosis, elevated lactate)
51]. Fenestration of the intimal flap, performed with a balloon or wire, decompresses the false lumen by creating a re-entry tear, thereby restoring flow to compromised branch vessels [50]. Branch vessel stenting can be also used to maintain luminal flow. Endovascular stent grafts seal the entry tear and prevent further expansion and propagation. Fenestration A single study case series described outcomes with fenestration in 40 patients presenting with acute dissection (10 type A and 30 type B) including 30 patients with renal malperfusion, 22 with limb malperfusion, and 18 with mesenteric ischemia [50]. Successful restoration of perfusion to ischemic beds was achieved in 93 % of patients with nine procedure-related complications. Mortality at 30 days was 25 %, but was largely attributed to irreversible organ damage present prior to the procedure. Of the surviving cohort, 83 % were alive at 29 months [50]. A more recent series described 35 patients with acute aortic dissection and malperfusion syndrome. Fenestration had a procedural success rate of 100 % (with 97 % angiographic success) although the majority of patients required concomitant branch vessel stenting [52]. Mortality at 30 days was 34 % and attributed to malperfusion or stroke [52]. Aortic diameter remained stable in 70 % of patients who underwent fenestration at a mean follow-up of 48 months [52].
Thoracic Endovascular Aortic Repair (TEVAR) The theory that closure of the primary entry tear may reduce the risk of propagation and further complications, as well as
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increase the likelihood of false lumen thrombosis, has led to the development and investigation of the use of covered stent grafts in selected patients with aortic dissection. An early series described outcomes in 12 patients with subacute or chronic type B dissection and indications for surgery treated with stent grafting compared to matched controls treated surgically [53]. Compared to surgery, stent grafting had higher procedural success, shorter hospital stay, and lower mortality [53]. The authors concluded that their data suggested that endovascular therapy was safe and effective for selected patients with aortic dissection for whom surgery was indicated [53]. A number of single and multicenter series describing outcomes after endovascular repair of type B aortic dissection were published and combined in a 2006 meta-analysis [54]. The authors included 39 studies comprising 609 patients who underwent endovascular stent-graft placement for type B dissection and found that overall procedural success was high (>95 %) and that rates of major complications and mortality were higher in the acute compared to the chronic setting [54]. The authors concluded that outcomes with TEVAR compared favorably to those observed after surgical intervention [54]. The IRAD investigators reported outcomes in 571 patients with acute type B dissection, and after propensity score adjustment, they found that surgical repair was associated with an increased risk of mortality when compared to TEVAR, suggesting better outcomes with endovascular intervention [55]. As additional small studies on endovascular therapies continued to appear, Zhang et al. performed another meta-analysis based on a Cochrane review and including controlled trials in which patients with acute type B dissection were assigned to TEVAR or surgery [56]. They identified five trials comprising 318 participants and found that TEVAR was associated with reduced short-term mortality compared to surgery. Due to data limitations, however, they were unable to assess long-term outcomes [56]. Noting the increasing use of endovascular repair for type B dissection across a spectrum of acuity and complications in the absence of robust randomized data, an interdisciplinary group produced an expert consensus document on the management of type B dissection in 2013 [57]. Data from 63 studies published between 2006 and 2012 including 6,729 patients were reviewed [57]. The authors recommended medical treatment for uncomplicated acute type B dissection but felt that complicated acute type B dissection should be treated with TEVAR rather than surgery, when feasible and combined with other endovascular interventions such as fenestration, noting a survival benefit with the less invasive approach [57]. Intervention for subacute and chronic type B dissection was recommended only if complications developed; in these settings as well, TEVAR was favored over surgery when feasible [57]. Non-randomized observations from IRAD also
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found that TEVAR was associated with lower 5-year mortality when compared to medical therapy, suggesting that improved techniques may be associated with better outcomes and prompting a call for further randomized trials [58]. No adequately sized randomized trials have reported outcomes with TEVAR compared to surgery for acute complicated type B dissection. Observational data suggest lower shortterm mortality with TEVAR compared with open surgery. It should also be noted that existing data largely reflect outcomes at high-volume centers with experience in TEVAR; outcomes may not be generalizable to smaller-volume centers. Centers using TEVAR should incorporate systems to insure systematic follow-up after discharge to assess for the need for reintervention.
Intervention for Uncomplicated Type B Dissection While current guidelines reserve invasive management for type B dissection for those patients who develop complications [3•], the observation that false lumen patency may be associated with outcome [7] has led to the notion that prophylactic stent grafting may improve long-term aortic-related survival and reduce complications [59]. In order to evaluate this possibility, 140 patients with stable uncomplicated type B dissection were randomized to optimal medical therapy (OMT) alone or OMT plus thoracic endovascular aortic repair (TEVAR) in the Investigation of Stent Grafts in Aortic Dissection (INSTEAD) trial [59]. Patients were randomized to treatment between 2 and 52 weeks after dissection (mean time intervals from dissection to randomization 45 days for OMT group versus 39 days for TEVAR + OMT group). The primary endpoint was all-cause death at 2 years. Secondary endpoints included aortic-related deaths, progression, and aortic remodeling. No differences between groups in either the primary or secondary endpoint were seen at 2 years [59]. A subsequent analysis of 5-year outcomes in the INSTEAD cohort, however, suggested a benefit of TEVAR for all-cause mortality, aortic-related mortality, and disease progression between 2 and 5 years after TEVAR [60•]. Further study will be needed to place the use of TEVAR for uncomplicated type B dissection into sharper focus.
Longitudinal Follow-up Although early mortality is higher for patients with type A dissection compared to those with type B dissection, longterm outcomes after hospital discharge are similar [5, 6•]. Importantly, a significant proportion of patients with type B dissection requiring intervention as the risk of subsequent complication (e.g., aneurysm formation) is sobering [61–64]. Five-year mortality rates with type B dissection range up to
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40 %. Close follow-up is essential for all patients with acute aortic syndrome, irrespective of the type of treatment they receive in the acute setting (medical, surgical, endovascular) [61, 64]. Patients lost to follow-up constitute a significant proportion of the post-discharge cohort [60]. Strict heart rate and blood pressure control is essential. A beta-blocker should form the mainstay of medical therapy, and patients should be educated about warning symptoms and instructed to refrain from strenuous exercise. Imaging of the entire aorta is advised at hospital discharge; at 1, 3, 6, and 12 months; and annually thereafter.
Prognosis Although patients with types A and B dissections have significantly different early mortality rates, longer-term outcomes for patients who survive to hospital discharge are similar (5-year survival 85.7 % for type A; 83.3 % for type B, Fig. 7) [6•]. In the acute setting, perioperative mortality in type A dissection appears to be reduced by rapid initiation of treatment [65]. Risk factors for mortality in the perioperative setting include fluid extravasation on TEE pre-operatively and an open false lumen with high communication. Thrombus formation within the false lumen appears to be a good prognostic sign [65]. In an IRAD analysis, patients with type A dissection who were treated surgically and survived to hospital discharge had 1- and 3-year survival rates of 96.1 and 90.5 %, while those treated medically had lower rates of survival (88.6 % at 1 year, 68.7 % at 3 years). Late mortality in both groups after hospital discharge appeared to be driven primarily by pre-existing comorbidities such as atherosclerosis [66]. Outcomes after type B dissection vary. Some studies suggest that 30 % or more of patients with type B dissection treated medically and followed for approximately 5 years may need surgery and up to 28 % may develop aneurysms [61, 63]. Patients with large false lumen diameter (≥22 mm) in the
Fig. 7 Survival after hospital discharge stratified by syndrome type. (With permission from 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; 127:2031–2037) [6•]
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upper descending thoracic aorta have a markedly greater risk of late aneurysm formation (42 vs. 5 %, p
PERIPHERAL VASCULAR DISEASE (MH SHISHEHBOR, SECTION EDITOR)
Diagnosis and Management of Acute Aortic Syndromes: Dissection, Intramural Hematoma, and Penetrating Aortic Ulcer Marc P. Bonaca & Patrick T. O’Gara
Published online: 26 August 2014 # Springer Science+Business Media New York 2014
Abstract Acute aortic syndromes constitute a spectrum of conditions characterized by disruptions in the integrity of the aortic wall that may lead to potentially catastrophic outcomes. They include classic aortic dissection, intramural hematoma, and penetrating aortic ulcer. Although imaging studies are sensitive and specific, timely diagnosis can be delayed because of variability in presenting symptoms and the relatively low frequency with which acute aortic syndromes are seen in the emergency setting. Traditional classification systems, such as the Stanford system, facilitate early treatment decisionmaking through recognition of the high risk of death and major complications associated with involvement of the ascending aorta (type A). These patients are treated surgically unless intractable and severe co-morbidities are present. Outcomes with dissections that do not involve the ascending aorta (type B) depend on the presence of acute complications (e.g., malperfusion, early aneurysm formation, leakage), the patency and size of the false lumen, and patient co-morbidities. Patients with uncomplicated type B dissections are initially treated medically. Endovascular techniques have emerged as an alternative to surgery for the management of complicated type B dissections when intervention is necessary. Patients with acute aortic syndromes require aggressive medical care, risk stratification for additional complications and targeted genetic assessment as well as careful long-term monitoring to assess for evolving complications. The optimal care of patients with acute aortic syndrome requires the cooperation of members of an experienced multidisciplinary team both in the acute and chronic setting. This article is part of the Topical Collection on Peripheral Vascular Disease M. P. Bonaca (*) : P. T. O’Gara Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA e-mail: [email protected]
Keywords Acute aortic syndrome . Intramural hematoma . Penetrating aortic ulcer . Aortic dissection
Introduction Acute aortic syndromes represent a spectrum of related entities which are characterized by an acute disruption of aortic integrity with an associated risk of complications including organ ischemia, rupture, and death. Although imaging for acute aortic syndromes is sensitive and specific, diagnosis and management remain a challenge as influenced by several factors, including the lower frequency with which they are encountered (3–16 cases per 100,000 person-years) relative to other acute cardiovascular conditions [1] (Fig. 1a), nonspecific symptoms at presentation that may overlap with more common entities, and the intensity of resources needed for appropriate testing and care [2, 3•, 4]. The challenge for the clinician is further complicated by the knowledge that risk of death and major complication is high early in the course of the illness and increases rapidly with time, making prompt and accurate diagnosis essential to maximize the opportunity for successful therapeutic intervention (Fig. 1b) [5, 6•]. Traditional classifications systems have provided a clear pathway for early management based on the involvement of the ascending aorta (type A) and the associated need for early surgery. Initial medical management is recommended for dissections that do not involve the ascending aorta (type B) unless complications are present [3•]. The role of thoracic endovascular aortic repair (TEVAR) in the management of patients with acute, uncomplicated type B aortic dissection is evolving. In addition, patients initially triaged to medical management may experience early complications and require intervention during their index hospitalization. The complex decision-making surrounding the acute aortic syndrome patient requires the close collaboration of
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Fig. 1 a Incidence of selected acute cardiovascular conditions [1, 6•]. b Short-term mortality by diagnosis [1, 6•, 26]
specialists in emergency medicine, vascular surgery, cardiovascular surgery, cardiovascular medicine, and vascular imaging. Systems which facilitate this interaction may improve decision-making. This article reviews the epidemiology, clinical presentation, diagnosis, and treatment of acute aortic syndromes.
Definitions and Pathogenesis Acute aortic syndromes comprise aortic dissection; intramural hematoma (IMH); and penetrating aortic ulcer (PAU), acute aneurysm expansion, and trauma [2, 3•]. Aortic dissection occurs as a consequence of an intimal tear that allows access of blood under systolic pressure into the medial layer of the aorta with propagation that is more often antegrade than retrograde [2]. The resulting flap of tissue divides the aorta into a “true” lumen, which represents the original vessel lumen, and a “false” lumen, which is the space created by the medial disruption. The intimal flap may occlude or compromise branch vessels and lead to malperfusion. The dissecting hematoma may re-enter the true lumen via one or more distal re-entry tears, which provide a mechanism for false lumen decompression. Alternatively, there may be no functioning re-entry site, causing the false lumen to act as a “wind
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sock” with increasing false lumen pressures, propagation of the dissection, aneurysm formation, compression of the true lumen or branch vessels, or rupture. Observational studies suggest that the status of flow within the false lumen in patients with type B dissection may have long-term prognostic importance [7]. Although medial disruption is a defining feature of dissection, cases of isolated intimal tears without hematoma formation have been described [8]. The related condition of intramural hematoma (IMH) occurs as a consequence of either medial hemorrhage from ruptured vasa vasorum or a microscopic intimal tear, which seals and thus does not allow communication with the true lumen after inception. IMHs comprise approximately 5– 15 % of acute aortic syndromes [9–12]. Approximately one-third of IMHs may resolve spontaneously. Two-thirds will evolve into classic dissection, aneurysm, or false aneurysm formation. Penetrating aortic ulcers (PAU) are lesions that occur in older patients with a heavy burden of atherosclerosis and have a predilection for the descending thoracic aorta. They form as a consequence of the inflammatory erosion of the internal elastic membrane and result in penetration of aortic blood beyond its true lumen, with subsequent false aneurysm formation, evolution to IMH, dissection, or rupture [13]. These three conditions are interrelated and occur along a spectrum of disease presentation and evolution. All can cause similar symptoms; however, malperfusion is more common with dissection [9, 12]. Of the three, dissection is the most common followed in order by IMH and PAU [14]. Although outcomes are best described for patients with aortic dissection, the natural history of these lesions generally depend on their location within the aorta. Management strategies are similar across the three entities [14]. Medial degeneration owing to a variety of processes predisposes to the development of acute aortic syndrome [2, 14]. This degeneration, previously described as “cystic medial necrosis,” is generally associated with age and hypertension, but can occur with several other disorders. The aortic lesions seen on histologic analysis need not be cystic in their appearance, but rather are distinguished by the disruption or loss of elastic fiber integrity. A pre-mature loss of tensile strength can occur in younger patients with a genetic predisposition, such as Marfan syndrome characterized by FBN1 mutations and elastin deficiencies, Ehlers-Danlos syndrome (COL3A1), familial thoracic aortic aneurysm disease (FTAAD), and in patients with bicuspid aortic valve disease with associated aortopathy. Aortic dissection has also been reported in Noonan’s syndrome, polycystic kidney disease, and during pregnancy, typically during the 3rd trimester or early puerperium. Many pregnant women with dissection, however, may have an underlying connective tissue abnormality predisposing to its development. In addition, trauma or inflammatory processes (Takayasu’s, Behçet’s, polychondritis, idiopathic
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aortitis) can predispose to aortic disruption in the absence of more typical risk factors [2, 3•].
Epidemiology and Risk Factors Acute aortic syndromes are reported to occur with a frequency of approximately 3–16 cases per 100,000 person-years. Most acute aortic syndromes occur in older patients (in the fifth and sixth decade), with a male predominance, and in those with a history of hypertension (Table 1) [5, 6•, 15, 16]. While the majority of patients (~60 %) with dissection are male, recent community-based studies suggest that at age 75 or above, the incidence is similar for men and women [6•]. A history of uncontrolled hypertension in spite of multi-agent therapy has been noted in patients with acute aortic syndromes, suggesting an increased risk in this subgroup [6•]. Patients with connective tissue disorders may present at a younger age without hypertension as can patients with vascular inflammatory diseases or trauma [5, 6•, 17•]. Therefore, the clinician should not discount the possibility of acute aortic disease in patients who are young and do not have hypertension and must think broadly when evaluating the history [3•]. Table 1 Aortic dissection: risk factors and predisposing conditions
Acute aortic disruption may also be iatrogenic or traumatic. Aortic injury has been described in the setting of percutaneous vascular procedures as well as cardiac surgery. In one series, complications involving the proximal aorta in the setting of aortic surgery occurred with a rate of approximately 0.15 % [18]. Interestingly, there was evidence of medial degeneration on histologic analysis of these cases suggesting a possible underlying predisposition rather than a purely procedural complication [18]. Cocaine ingestion is associated with abrupt increases in heart rate and blood pressure. Its use has been associated with acute type B dissection, particularly among young, urban male smokers. Aortic injury and transection can occur in the setting of chest trauma with rapid deceleration such as that occurring in motor vehicle accidents.
Classification There are two systems in clinical use for the classification of acute aortic syndromes, the DeBakey classification and the Stanford Classification [19, 20]. The DeBakey classification is based on the site of origin of the dissection, while the Stanford classification is based on the presence or absence of ascending aortic involvement (Fig. 2). Since initial management is largely
Patients without Predisposition Age Sixth and seventh decade Gender
Male predominance (~1.5:1)
Hypertension
Prevalence 68–72 %
History of smoking Prevalence ~60 % Atherosclerosis Prevalence ~30 % Predisposing Conditions Inflammatory diseases
Genetic conditions
Trauma Other
Observational data suggest women present at an older age then men Incidence by gender varies with age with data suggesting that the incidence in men and women is similar at age 75 and above Studies suggest increased prevalence of poorly controlled blood pressure in spite of multi-agent antihypertensive therapy
Giant cell arteritis Takayasu arteritis Behçet arteritis Rheumatoid arteritis Systemic lupus erythematosus Marfan syndrome Loeys-Dietz syndrome Ehlers-Danlos syndrome Familial syndrome Bicuspid aortic valve Turner syndrome Iatrogenic Deceleration injury Cocaine or stimulant use Valsalva maneuver
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Fig. 2 Classification systems for acute aortic dissection [26]. Adapted from Tsai et al. Circulation 2005
determined by the involvement of the ascending aorta (rather than site of origin), the Stanford classification is more frequently used. However, both may be useful in that site of origin may be considered in decision-making [14]. These classification schemes are also used to characterize IMH and PAU [14]. Although the existing systems provide a relatively straightforward approach to classification and therapeutic decision-making, one anatomic area which remains challenging for clinicians is the aortic arch. Both the DeBakey and Stanford systems identify involvement of the ascending aorta as a key factor in classification. Dissections isolated to or originating in the arch and extending distally (e.g., not involving the ascending aorta), therefore, are neither type A nor type B technically speaking (also called non-A, non-B dissection) [21]. The natural history of isolated arch dissection has been less well characterized [21].
Natural History Acute aortic syndromes are associated with significant morbidity and mortality. However, outcomes vary depending on the type, location, and the presence of complications [6•]. Presentation with type A dissection is more common than type B dissection. Overall 30-day mortality, inclusive of prehospital deaths, for aortic dissection of any type exceeds 50 % [5, 6•]. In one community-based cohort study, nearly 50 % of patients with dissection died before hospitalization. Thirtyday survival for those admitted alive was only 53 % [5, 6•]. The mortality rate for untreated aortic dissection is 1–2 % per hour over the first 24 h and in excess of 75 % by 2 weeks [5]. Delayed recognition is associated with poor outcomes [4]. An analysis from the International Registry of Aortic Dissection (IRAD) found a mortality rate of 0.22 % per hour during
the first 24 h and 0.77 % per hour for medically managed type A dissections [22]. Type A dissection may be complicated by tamponade, aortic regurgitation, stroke, or malperfusion, including myocardial ischemia from compromise of the coronary arteries [5, 23]. Iatrogenic dissection of the ascending aorta at the time of cardiac surgery is also associated with increased mortality risk with the highest rates for those that occur in the early (42 %) or late (32 %) post-operative periods compared to those that are discovered intraoperatively (17 % mortality) and presumably addressed as part of the index procedure [18, 24, 25]. Type B dissection is associated with a lower mortality risk than type A dissection. One study reported a 30-day mortality rate of approximately 13 % and 5-year mortality rate of 33 % for patients with type B dissection (Fig. 1b) [6•]. In IRAD, inhospital mortality for type B dissections was 13 % [16, 26]. Independent predictors of death included hypotension/shock at presentation, absence of chest or back pain, and branch vessel involvement (the deadly triad) [16]. Patients with type B aortic dissection comprise a heterogeneous group. One study observed that 21 % of patients with type B dissection developed malperfusion and 27 % required intervention for complications during the index hospitalization [16]. Another IRAD study demonstrated that nearly half of type B dissections were complicated, as defined by the development of shock, periaortic hematoma, spinal cord ischemia, mesenteric ischemia/infarction, acute renal failure, limb ischemia, recurrent or refractory pain, or refractory hypertension [26]. In-hospital mortality varied significantly as a function of such complications (20 % for complicated vs. 6.1 % for uncomplicated, p70, pre-operative limb ischemia, periaortic hematoma, and surgical management [26]. Identifying early complications in patients with type B dissection is critical for risk stratification and treatment [3•].
Clinical Presentation Presenting symptoms for aortic dissection are variable depending on both the location and extent of the disruption as well as on patient factors such as age and gender (Table 2) [2, 3•, 27]. The most common symptom is sudden and severe chest or back pain; however, patients may present with atypical symptoms or no pain. The chest pain of aortic dissection is abrupt in onset with maximal intensity at inception. Pain may be severe and occasionally may be described as “tearing” or migratory [2, 3•, 4]. Its initial location and radiation may provide clues as
to the site of origin and the extent of aortic involvement. Syncope can be a particularly ominous symptom indicating tamponade or stroke [28]. Acute neurologic symptoms may occur in the setting of aortic dissection and may be transient [3•, 29]. The lack of specificity in presenting symptoms can be challenging and lead to delay in diagnosis, particularly among patients with atypical symptoms [2, 3•, 4, 30]. Physical examination signs in patients presenting with acute aortic syndromes can also be non-specific. Hypertension is relatively frequent, but non-specific. A pulse deficit is described in approximately 30 % of patients with type A dissection and is associated with increased mortality [31]. Focal neurologic deficits are described in 17 % of patients. Signs in the acute setting may evolve rapidly as the dissection progresses and include acute aortic regurgitation, myocardial ischemia, cardiogenic shock, tamponade, neurologic deficits, and peripheral or mesenteric ischemia [3•, 23, 31, 32]. In addition, findings generally attributed to alternative diagnoses such as pleural effusion (either reactive or from hemorrhage) may occur in as many as 16 % of patients [3•, 5]. Timely diagnosis requires a high index of suspicion, particularly in the elderly where typical symptoms may be less common and comorbid diseases such as coronary artery disease further complicate initial clinical assessment [3•].
Diagnosis Current guidelines recommend performance of a focused history and exam to assess the pre-test likelihood of acute aortic syndrome [3•]. This assessment should include questions about known genetic, connective tissue, or familial conditions associated with aortic disease, history of recent aortic
Table 2 Aortic dissection: presenting signs and symptoms Symptoms/signs
Frequency
Note
Chest pain
Type A 79 % Type B 63 % Type A 47 % Type B 64 % Type A 43 % Type B 22 % Type A 36 % Type B 70 % 13 % Overall
Sudden and severe
Back pain Abdominal pain Hypertension (at presentation) Syncope
Pulse deficit Neurologic deficit No pain Aortic regurgitation murmur
Type A 19–30 % Type B 9–21 % 17 % Overall [5] 4.5 % Overall Type A 45 %
Sudden and severe Associated with higher mortality and delay in diagnosis [74] More common in type B May indicate development of a dangerous complication (e.g., tamponade) [28]. Associated with increased in-hospital mortality (34 % with syncope, 23 % without) Associated with increased in-hospital mortality May be more frequent with type A (29 %) Associated with increased mortality
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manipulation, typical pain, or high-risk signs such as pulse deficit, blood pressure differential, focal neurologic signs or symptoms, and new murmur of aortic regurgitation [3•]. In one analysis, the median time to diagnosis was 4.3 h with an intraquartile range of 1.5 to 24 h, meaning that 25 % of patients were diagnosed 24 h or later after presentation [4]. Factors associated with delayed diagnosis included atypical symptoms, hemodynamic stability, absence of pulse deficit, and presentation to a non-tertiary care hospital. Risk scores based on the AHA/ACC consensus guidelines for the diagnosis of acute coronary syndrome have been evaluated and shown to be highly sensitive [33]. The ECG is often (69 %) abnormal, but in most cases shows non-specific findings [5]. In one IRAD review, ST-T wave abnormalities suggestive of ischemia were found in 15 % of patients with type A dissection with an acute injury current in 5 % [5]. Chest x-ray is likewise abnormal in most cases (80 %), but findings may be non-specific [5]. These including widening of the mediastinum and displacement of aortic calcification (Fig. 4). Importantly, a normal chest x-ray or ECG should not delay definitive imaging in patients in whom there is clinical suspicion [3•]. Biomarkers are emerging as a diagnostic tool in patients with suspected acute aortic syndromes. D-dimer, a fibrin degradation product indicative of intravascular coagulation, has established utility in the setting of suspected pulmonary embolism and is widely available. A D-dimer >500 ng/mL has been shown to be highly sensitive for acute dissection (~97 %, negative predictive value 96 %) but relatively non-specific (56 %, positive predictive value 60 %) [34–38]. Based on this high sensitivity, D-dimer may be a potential screening tool to “rule out” acute aortic dissection [34]. One potential concern is that D-dimer levels may decline over time, reducing sensitivity in patients presenting late after symptom onset or with atypical symptoms. In one study, 18 % of patients with aortic dissection had D-dimer levels 95 %) and specificity (>95 %) (Fig. 5a–c) [14, 44–48]. CTA is the most commonly utilized modality; current consensus guidelines recommend that if a high clinical suspicion existing after initial imaging is negative, a second imaging study should be obtained [3•]. Imaging acquisition must be performed optimally in order to maximize diagnostic accuracy. Several factors, including the timing of contrast injection, ECG gating to reduce artifact from cardiac motion, and imaging the full extent of the aorta, should be considered [47, 48]. Consultation with an imaging specialist and communication of the clinical considerations are important as studies conducted for other diagnoses (e.g., evaluate for pulmonary embolism) may not have sufficient diagnostic accuracy for aortic dissection [3•, 48].
Treatment Assessment of Clinical Stability Stabilizing medical treatment should be initiated in all patients with suspected acute aortic dissection as dictated by clinical findings and targeted at controlling heart rate, blood pressure (and its rate of rise, dP/dT), and symptoms [14]. Recognition of acute complications (e.g., tamponade, aortic regurgitation, malperfusion) is critical in determining appropriate therapy and initiating definitive management. Unstable patients should undergo concomitant surgical consultation, with rapid imaging assessment to facilitate management. A recommended approach to medical therapy in stable, uncomplicated patients is discussed below. Indications for Surgery in Acute Dissection
Fig. 4 Portable chest x-ray in a patient with acute type A dissection showing a widened mediastinum and pulmonary vascular congestion
Urgent surgical consultation should be obtained in all patients with acute aortic syndromes [14]. The need for and timing of surgery are dictated by the location of aortic involvement, presence of complications, and the clinical stability of the patient.
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the extent of the tear, whether it involves critical structures such as the coronary ostia or aortic valve, and its distal extent into and beyond the arch. Surgical approaches include primary repair with an interposition graft or use of a composite valve graft conduit with re-implantation of the coronary arteries. Valve-sparing re-suspension is performed when the anatomy allows. Perfusion is most commonly established via the right axillary artery, and deep hypothermic circulatory arrest is frequently employed to complete the distal, open anastomosis &
Acute type B (descending aortic involvement) –
Fig. 5 a CT angiogram in both the axial and sagittal views showing a dissection flap originating in the ascending aorta and propagating through the descending aorta. Both lumens show contrast enhancement indicating patency of the false lumen which is larger than the true lumen. b CT noncontrast (images left) and with contrast (images right) demonstrating an intramural hematoma originating in the distal ascending aorta and arch and extending into the descending aorta. c CT angiogram of a patient with multiple penetrating aortic ulcers. Shows axial images as well as threedimensional reconstruction
&
The need for early surgery—or endovascular stent grafting—in patients with type B dissection depends on the presence of complications, including malperfusion, progression of the dissection, aortic expansion or impending rupture, dissection location within a previously aneurysmal segment, refractory pain, or refractory hypertension. Some have argued that Marfan syndrome or other types of primary connective tissue disease should prompt early surgical repair. In the absence of early complications, medical management is recommended. The routine use of endovascular stent grafting for uncomplicated type B dissection has not been adequately studied, though it has gained increasing application. When used, stent grafting is often supplemented by fenestration procedures and stenting of major, aortic side branches. A framework for managing type B dissection is shown in Fig. 6.
Aortic surgery in the chronic phase of dissection is usually dictated by the size of the aorta (≥5.5 cm ascending aorta, ≥5.5–6.0 cm descending aorta), its rate of growth over time, and the presence of associated complications such as aortic regurgitation and left ventricular dysfunction in some patients with type A disease.
Acute type A (ascending aortic involvement) –
In general, urgent surgical repair is indicated for all type A dissections. The type of repair depends on several factors including the location of the entry site,
Fig. 6 Management of type B aortic dissection
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Initial Medical Management
Table 3 Aortic dissection: signs and symptoms of complication in type B dissection
General guidance for medical therapy derives from consensus guidelines for the treatment of patients with acute aortic syndromes [14]. Medical therapy should be initiated promptly in all patients even while diagnostic studies are underway.
Symptoms
Signs
New, worsening, or refractory pain involving the chest, flank, abdomen. May be transient in the setting of dynamic obstruction Focal neurologic symptoms Anorexia or dyspepsia Limb pain
New or sudden hypotension or hypertension refractory to medical therapy
1. Beta-blocker therapy should be started with the goal to lower heart rate and blood pressure to the lowest tolerable levels. Short-acting agents such as esmolol may be used if there are concerns regarding tolerability. Agents with both alpha and beta antagonism such as labetalol may be useful. Non-dihydropyridine calcium channel blockers can be used in patients unable to tolerate beta-blockers. Caution should be exercised in the setting of hemodynamic instability or acute severe aortic regurgitation so as not to cause decompensation through blunting of compensatory tachycardia. 2. If, after control of heart rate through the use of betablockade, the blood pressure remains elevated, then a vasodilator (e.g., sodium nitroprusside, angiotensinconverting enzyme inhibitor) may be added. Vasodilators should not be added prior to beta-blockade as this may increase heart rate and the rate of LV pressure rise (dP/ dT), which would be deleterious in these circumstances. 3. Control of pain as well as other drivers of adrenergic tone (e.g., anxiety, alcohol withdrawal) is useful.
Monitoring Patients diagnosed with dissection may develop complications and decompensate rapidly. Intensive monitoring should be instituted including frequent vital signs with use of an intraarterial line if necessary, evaluation of symptoms, serial exams, and laboratory measurements (Table 3). Branch vessel occlusion may be dynamic so signs or symptoms of malperfusion may be transient. Options for Complicated Type B Dissection Current guidelines reserve surgery or endovascular stent grafting of type B dissection for cases with early complications [3•]. In IRAD, 27 % of patients with type B dissection required an interventional procedure during index hospitalization [16]. A more recent IRAD review noted that 45 % of type B cases were considered complicated [26]. Open surgical repair was formerly the traditional approach for patients with complicated type B dissection [49], but newer transcatheter approaches to complicated type B dissection have become more frequently utilized and may be associated with better outcomes than surgery, although randomized trials in the acute setting are lacking [50,
Focal neurologic signs; paraplegia Gastrointestinal bleeding Pulse deficit or visible changes in limb color or perfusion Anuria or hematuria Laboratory abnormalities (increasing creatinine, metabolic acidosis, elevated lactate)
51]. Fenestration of the intimal flap, performed with a balloon or wire, decompresses the false lumen by creating a re-entry tear, thereby restoring flow to compromised branch vessels [50]. Branch vessel stenting can be also used to maintain luminal flow. Endovascular stent grafts seal the entry tear and prevent further expansion and propagation. Fenestration A single study case series described outcomes with fenestration in 40 patients presenting with acute dissection (10 type A and 30 type B) including 30 patients with renal malperfusion, 22 with limb malperfusion, and 18 with mesenteric ischemia [50]. Successful restoration of perfusion to ischemic beds was achieved in 93 % of patients with nine procedure-related complications. Mortality at 30 days was 25 %, but was largely attributed to irreversible organ damage present prior to the procedure. Of the surviving cohort, 83 % were alive at 29 months [50]. A more recent series described 35 patients with acute aortic dissection and malperfusion syndrome. Fenestration had a procedural success rate of 100 % (with 97 % angiographic success) although the majority of patients required concomitant branch vessel stenting [52]. Mortality at 30 days was 34 % and attributed to malperfusion or stroke [52]. Aortic diameter remained stable in 70 % of patients who underwent fenestration at a mean follow-up of 48 months [52].
Thoracic Endovascular Aortic Repair (TEVAR) The theory that closure of the primary entry tear may reduce the risk of propagation and further complications, as well as
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increase the likelihood of false lumen thrombosis, has led to the development and investigation of the use of covered stent grafts in selected patients with aortic dissection. An early series described outcomes in 12 patients with subacute or chronic type B dissection and indications for surgery treated with stent grafting compared to matched controls treated surgically [53]. Compared to surgery, stent grafting had higher procedural success, shorter hospital stay, and lower mortality [53]. The authors concluded that their data suggested that endovascular therapy was safe and effective for selected patients with aortic dissection for whom surgery was indicated [53]. A number of single and multicenter series describing outcomes after endovascular repair of type B aortic dissection were published and combined in a 2006 meta-analysis [54]. The authors included 39 studies comprising 609 patients who underwent endovascular stent-graft placement for type B dissection and found that overall procedural success was high (>95 %) and that rates of major complications and mortality were higher in the acute compared to the chronic setting [54]. The authors concluded that outcomes with TEVAR compared favorably to those observed after surgical intervention [54]. The IRAD investigators reported outcomes in 571 patients with acute type B dissection, and after propensity score adjustment, they found that surgical repair was associated with an increased risk of mortality when compared to TEVAR, suggesting better outcomes with endovascular intervention [55]. As additional small studies on endovascular therapies continued to appear, Zhang et al. performed another meta-analysis based on a Cochrane review and including controlled trials in which patients with acute type B dissection were assigned to TEVAR or surgery [56]. They identified five trials comprising 318 participants and found that TEVAR was associated with reduced short-term mortality compared to surgery. Due to data limitations, however, they were unable to assess long-term outcomes [56]. Noting the increasing use of endovascular repair for type B dissection across a spectrum of acuity and complications in the absence of robust randomized data, an interdisciplinary group produced an expert consensus document on the management of type B dissection in 2013 [57]. Data from 63 studies published between 2006 and 2012 including 6,729 patients were reviewed [57]. The authors recommended medical treatment for uncomplicated acute type B dissection but felt that complicated acute type B dissection should be treated with TEVAR rather than surgery, when feasible and combined with other endovascular interventions such as fenestration, noting a survival benefit with the less invasive approach [57]. Intervention for subacute and chronic type B dissection was recommended only if complications developed; in these settings as well, TEVAR was favored over surgery when feasible [57]. Non-randomized observations from IRAD also
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found that TEVAR was associated with lower 5-year mortality when compared to medical therapy, suggesting that improved techniques may be associated with better outcomes and prompting a call for further randomized trials [58]. No adequately sized randomized trials have reported outcomes with TEVAR compared to surgery for acute complicated type B dissection. Observational data suggest lower shortterm mortality with TEVAR compared with open surgery. It should also be noted that existing data largely reflect outcomes at high-volume centers with experience in TEVAR; outcomes may not be generalizable to smaller-volume centers. Centers using TEVAR should incorporate systems to insure systematic follow-up after discharge to assess for the need for reintervention.
Intervention for Uncomplicated Type B Dissection While current guidelines reserve invasive management for type B dissection for those patients who develop complications [3•], the observation that false lumen patency may be associated with outcome [7] has led to the notion that prophylactic stent grafting may improve long-term aortic-related survival and reduce complications [59]. In order to evaluate this possibility, 140 patients with stable uncomplicated type B dissection were randomized to optimal medical therapy (OMT) alone or OMT plus thoracic endovascular aortic repair (TEVAR) in the Investigation of Stent Grafts in Aortic Dissection (INSTEAD) trial [59]. Patients were randomized to treatment between 2 and 52 weeks after dissection (mean time intervals from dissection to randomization 45 days for OMT group versus 39 days for TEVAR + OMT group). The primary endpoint was all-cause death at 2 years. Secondary endpoints included aortic-related deaths, progression, and aortic remodeling. No differences between groups in either the primary or secondary endpoint were seen at 2 years [59]. A subsequent analysis of 5-year outcomes in the INSTEAD cohort, however, suggested a benefit of TEVAR for all-cause mortality, aortic-related mortality, and disease progression between 2 and 5 years after TEVAR [60•]. Further study will be needed to place the use of TEVAR for uncomplicated type B dissection into sharper focus.
Longitudinal Follow-up Although early mortality is higher for patients with type A dissection compared to those with type B dissection, longterm outcomes after hospital discharge are similar [5, 6•]. Importantly, a significant proportion of patients with type B dissection requiring intervention as the risk of subsequent complication (e.g., aneurysm formation) is sobering [61–64]. Five-year mortality rates with type B dissection range up to
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40 %. Close follow-up is essential for all patients with acute aortic syndrome, irrespective of the type of treatment they receive in the acute setting (medical, surgical, endovascular) [61, 64]. Patients lost to follow-up constitute a significant proportion of the post-discharge cohort [60]. Strict heart rate and blood pressure control is essential. A beta-blocker should form the mainstay of medical therapy, and patients should be educated about warning symptoms and instructed to refrain from strenuous exercise. Imaging of the entire aorta is advised at hospital discharge; at 1, 3, 6, and 12 months; and annually thereafter.
Prognosis Although patients with types A and B dissections have significantly different early mortality rates, longer-term outcomes for patients who survive to hospital discharge are similar (5-year survival 85.7 % for type A; 83.3 % for type B, Fig. 7) [6•]. In the acute setting, perioperative mortality in type A dissection appears to be reduced by rapid initiation of treatment [65]. Risk factors for mortality in the perioperative setting include fluid extravasation on TEE pre-operatively and an open false lumen with high communication. Thrombus formation within the false lumen appears to be a good prognostic sign [65]. In an IRAD analysis, patients with type A dissection who were treated surgically and survived to hospital discharge had 1- and 3-year survival rates of 96.1 and 90.5 %, while those treated medically had lower rates of survival (88.6 % at 1 year, 68.7 % at 3 years). Late mortality in both groups after hospital discharge appeared to be driven primarily by pre-existing comorbidities such as atherosclerosis [66]. Outcomes after type B dissection vary. Some studies suggest that 30 % or more of patients with type B dissection treated medically and followed for approximately 5 years may need surgery and up to 28 % may develop aneurysms [61, 63]. Patients with large false lumen diameter (≥22 mm) in the
Fig. 7 Survival after hospital discharge stratified by syndrome type. (With permission from 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; 127:2031–2037) [6•]
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upper descending thoracic aorta have a markedly greater risk of late aneurysm formation (42 vs. 5 %, p
