Diagnosis and acute management of type A aortic dissection

Abstract

Acute type A aortic dissection is a devastating aortic disease associated with significant morbidity and mortality. Clinicians should maintain a high degree of suspicion in patients presenting with sudden-onset chest pain, although the diagnosis may be confounded by the broad spectrum of attendant symptoms and signs. Accurate and timely identification of the acute dissection is of paramount importance to ensure suitable patients are referred promptly for definitive surgical management. This review focuses on the diagnosis of acute type A aortic dissection and discusses the haematological tests, and electrocardiographic, echocardiographic and radiological investigations necessary to confirm the diagnosis and assess for associated complications. The acute medical management of patients with acute type A dissection is also reviewed.

Introduction

The acute aortic syndrome refers to a spectrum of potentially life-threatening emergencies encompassing intra-mural haematoma, penetrating aortic ulcer and acute aortic dissection, each with different pathophysiological mechanisms.¹ Of these, acute dissections comprise 85–95% of acute aortic syndrome, with an annual incidence of 3–4 per 100,000 in the UK and US.² According to the Stanford classification, type A aortic dissection (ATAD) involves the aorta proximal to the left subclavian artery origin, whereas type B dissections occur distal to this landmark. The disruption of aortic wall integrity in ATAD with proximal extension may cause tamponade from intra-pericardial aortic rupture, myocardial infarction from coronary ostial involvement or acute aortic valve regurgitation, while antegrade propagation may lead to end-organ malperfusion, including stroke, renal failure, and ischaemia of the spine, viscera and lower limbs.³ ATAD, consequently, carries a significantly worse prognosis, with an untreated mortality rate of 1% per hour in the first 48 hours after symptom onset, and necessitates urgent or emergency surgical management, whereas uncomplicated acute type B dissection is generally managed conservatively.⁴ Accurate and timely diagnosis and prompt referral for definitive specialist intervention are, therefore, essential. This review focuses on the diagnosis and peri-operative medical treatment of ATAD.

Clinical presentation and diagnosis

Patients with ATAD can demonstrate a variety of signs and symptoms (table 1),⁵ which may confound diagnosis, and the broad differential diagnosis can involve multiple organ systems (table 2).⁶ Sudden-onset, severe chest pain is the presenting symptom in more than 90% of ATAD cases, often radiating to the neck or interscapular region, although pain may be absent in 10%.^3,7 Depending on the location and extent of the dissection, malperfusion may manifest with acute stroke or paraplegia, abdominal pain, renal impairment or lower limb ischaemia.^3,4 Patients with ATAD are usually normotensive or hypotensive on presentation with associated tachycardia. Hypotension may indicate aortic rupture, cardiac tamponade, myocardial infarction or heart failure from acute aortic regurgitation.⁸ Syncope occurs in 9–15% of patients with ATAD and may be attributed to cardiac causes including aortic rupture or cardiac tamponade, or arise following cerebral vessel obstruction or central baroreceptor stimulation.^5,8 Physical examination may reveal a widened pulse pressure or murmur in aortic insufficiency,³ and pulse deficits may develop in up to 30% of patients with ATAD. Sympathetic left pleural effusions are common in ATAD, although acute haemothorax implies imminent aortic rupture.⁸

Table 1. Presenting signs and symptoms in acute type A aortic dissection⁵.

Sign/symptom	Frequency
Chest pain	80%
Back pain	40%
Aortic regurgitation	40–75%
Cardiac tamponade	<20%
Myocardial ischaemia or infarction	10–15%
Heart failure	<10%
Pleural effusion	15%
Syncope	15%
Stroke	<10%
Spinal cord injury	<1%
Mesenteric ischaemia	<5%
Acute renal failure	<20%
Lower limb ischaemia	<10%

Table 2. The differential diagnosis of acute type A aortic dissection⁶.

Cardiac	Gastrointestinal	Musculoskeletal	Neurological	Pulmonary
Myocardial infarction	Oesophageal spasm	Rib fracture	Cerebrovascular accident	Pulmonary embolus
Pericarditis	Peptic ulcer disease	Muscular strain	Seizures	Pneumothorax
Angina	Biliary tract disease	Disc disease	Spinal cord compression	Pleuritis
Aortic aneurysm	Pancreatitis		Syncope

Clearly, these varying presenting signs and symptoms warrant a high index of clinical suspicion. To enhance diagnosis in the most vulnerable individuals, the American Heart Association (AHA) has devised a risk assessment tool to determine the probability of acute aortic syndrome, incorporating high-risk features across three categories of predisposing conditions, pain characteristics and examination findings.⁹ High-risk predisposing conditions include Marfan syndrome, recent aortic manipulation, or known thoracic aneurysm. High-risk pain features include abrupt onset of ripping, tearing or stabbing pain in the chest, back or abdomen. High-risk examination features are pulse or blood pressure discrepancy, neurological deficit, new aortic regurgitation murmur, and hypotension or shock. The presence of ≥1 high-risk feature in the absence of both electrocardiogram (ECG) changes of myocardial infarction and history or examination findings strongly suggestive of an alternative diagnosis should prompt urgent aortic imaging.

Following confirmation of a diagnosis of ATAD, the next step involves delineation of the proximal and distal extents of the dissection, and defining the involvement of the coronary arteries, aortic valve, supra-aortic vessels and other major branches of the descending aorta, to select the appropriate treatment strategy.

Haematological studies

Patients admitted to hospital with suspected ATAD should undergo baseline haematological investigations to confirm the diagnosis and analyse the severity of any associated complications.^5,9 A full blood count for haemoglobin levels is useful for assessing bleeding and pre-operative anaemia, alongside the white cell count as a marker for infection and inflammation in systemic inflammatory response syndrome (SIRS). Pro-calcitonin can help to differentiate between SIRS and sepsis where the white cell count is significantly elevated, and C-reactive protein (CRP) levels can help to gauge the inflammatory response to acute dissection. Baseline creatinine measurements can identify pre-existing or evolving renal failure and should be correlated with imaging findings where renal involvement is suspected, particularly in anticipation of prolonged durations of cardiopulmonary bypass, which may exert a deleterious effect on renal function. Similarly, liver function tests to determine aspartate transaminase and alanine aminotransferase levels can distinguish patients with liver ischaemia or pre-existing liver dysfunction, which in turn may influence liver synthetic function and induce troublesome post-operative coagulopathy. Elevated creatinine kinase may suggest reperfusion injury or rhabdomyolysis. Substantial increases in troponin I or T may reflect underlying myocardial ischaemia or infarction due to coronary ostial involvement. However, care should be taken in the interpretation of troponin levels since injudicious anticoagulation for a primary acute coronary syndrome in the setting of unrecognised ATAD will compound surgical bleeding risks. Elevated D-dimers should increase clinical suspicion of ATAD, since levels are usually very high following ATAD, although their diagnostic utility is greatest during the first hour.¹⁰ A D-dimer level >500 ng/ml has been validated as being highly sensitive for acute dissection (˜97%, negative predictive value 96%) although quite nonspecific (56%, positive predictive value 60%).^11–13 However, D-dimer is not a specific biomarker for ATAD, and may be raised in other conditions presenting with chest pain, such as myocardial infarction with mural thrombus or pulmonary embolism.¹⁴ D-dimer levels also decline with time, reducing its applicability as a screening tool in patients with delayed presentation. Furthermore, even the most sensitive D-dimer assay cannot be utilised to adequately exclude acute dissection in high-risk populations, and both the American and European guidelines do not recommend D-dimer screening across all patients with suspected ATAD.^5,9 Arterial blood gas sampling with lactate measurement can provide useful information on metabolic function and oxygenation, and is particularly valuable in detecting bowel ischaemia.

A variety of other plasma biomarkers are currently being evaluated as a non-invasive and rapid tool to discriminate patients with ATAD. Substances released during vascular injury from the vascular endothelial or smooth muscle cells (smooth muscle myosin), the vascular interstitium (calponin, matrix metalloproteinase 8), the aortic elastic laminae (soluble elastin fragments), or during inflammation (tenascin-C) or thrombosis (D-dimers), in addition to circulating microRNAs and the novel biomarker ST2, have demonstrated promise in preliminary research.^11,15–20 However, these biomarkers have not yet emerged in routine clinical application to screen individuals with suspected ATAD, owing to their lack of prospective evaluation in large, randomised trials.

Electrocardiography

As a common investigation in the emergency department, the main utility of ECG in ATAD is to eliminate other conditions causing chest pain, principally myocardial infarction, in patients at lower risk of ATAD.²¹ Importantly, if a myocardial infarction is being considered in a patient with risk factors for ATAD, then additional diagnostic studies should be undertaken specifically to exclude ATAD before thrombolytic or anticoagulant therapy is administered. Ischaemic changes on ECG due to coronary ostial involvement are only reported to occur in around 20% of patients.³ The ECG in ATAD can yield an assortment of findings, and in the International Registry of Aortic Dissection (IRAD) analysis, ECG changes in patients with ascending aortic dissection included non-specific ST-segment and T-wave changes (42%), ischaemic changes (15%), acute myocardial infarction (5%) or was normal (31%).²² However, ECG cannot be used to exclude aortic dissection,²³ and a normal ECG should not delay crosssectional imaging in patients in whom there is a high index of suspicion for ATAD.

Chest radiography

Chest X-ray (CXR) is a commonly performed and inexpensive initial investigation, which can suggest ATAD, although a normal CXR is not sufficient to exclude ATAD and should not delay definitive imaging.²² The CXR is abnormal in 60–90% of patients with ATAD, with the classical feature being a widened mediastinum, which is observed in 50% of acute dissections,²⁴ but may be absent in 20–28%.²⁵ Additional CXR findings include cardiomegaly, pleural effusion, haemothorax, irregular aortic contour, double aortic shadow, displacement of aortic knob calcification, thickening of the aortic wall beyond intimal calcification, and apical cap.^3,23–26 Since 10–20% of patients with ATAD will have an unremarkable CXR, additional imaging should be performed in all patients. The sensitivity and specificity of CXR for acute dissection is reported at 64% and 67%, respectively, although sensitivity is lower for proximal aortic involvement, meaning that CXR has limited benefit in the diagnosis of ATAD.⁷ It is also advisable that the CXR is omitted in unstable patients to expedite treatment.²⁷

Diagnostic imaging

Computed tomography (CT), magnetic resonance imaging (MRI), trans-oesophageal echocardiography (TOE) and aortography represent the standard diagnostic imaging modalities for ATAD in the contemporary era, and generally demonstrate high sensitivity and specificity. These imaging techniques are compared in table 3.^28,29 The specific choice of imaging depends on institutional availability and radiological expertise, while considering the patient’s clinical status.³⁰ Patients with suspected ATAD require imaging of the entire aorta, while echocardiography is first line for unstable patients for whom transfer to the radiology suite is inappropriate. Contemporary CT scanning has largely superseded invasive aortography, once the gold standard for diagnosis of acute aortic syndrome, for the visualisation of thoracic and abdominal aortic side branches.

Table 3. Comparison of the imaging modalities used in the diagnosis of acute type A aortic dissection^28,29.

Imaging modality	Strengths	Weaknesses
Radiography	Frequent first-line investigation Quick Low radiation exposure	Low sensitivity and specificity Poor for evaluating extent of dissection
Echocardiography	Available at the bedside and intra-operatively Assesses cardiac and valve function	Operator dependent Requires sedation and endo-tracheal intubation Limited views of aortic arch, distal ascending aorta, and abdominal aorta
Computed tomography (CT)	Quick Excellent definition of anatomy, dissection extent, detection of complications, predictors of progression and end-organ ischaemia	Exposure to ionising radiation Exposure to contrast agents Not available at bedside
Magnetic resonance imaging (MRI)	Good definition of anatomy, dissection extent, detection of complications and end-organ ischaemia	Long scan times Not appropriate for unstable patients Limited availability
Aortography	Detects localised tears and assesses branch vessels Useful for endovascular stenting and fenestration procedures	Invasive Exposure to contrast agents

The ideal imaging modality in ATAD should first, confirm or disprove the presence of acute dissection, second, determine whether the dissection involves the ascending aorta in isolation or extends to the aortic arch and descending aorta, and third, demonstrate the extent of the dissection, the site(s) of the entry and re-entry tears, presence of false lumen thrombus and aortic branch vessel involvement.^27,31

Computed tomography

Multi-detector CT angiography is recommended in European guidelines as a primary investigation in patients with suspected ATAD,²⁷ and is the most common initial diagnostic imaging worldwide for acute dissection.³² CT possesses an average sensitivity of 95% and specificity 87–100%.³³ The diagnosis of ATAD with CT is based upon evidence of an intimal flap separating the true and false lumens,³³ while indirect CT signs of aortic dissection include true lumen compression by the false lumen, displacement of intimal calcification, and widening of the aortic lumen.³⁴ Besides establishing the presence of dissection, CT scanning permits open surgical or endovascular planning by accurately delineating the proximal and distal extents of the dissection, demonstrating malperfusion, determining involvement of aortic side branches and the sizes of the true and false lumens, and prognostication by assessment of aortic dimensions.^3,4,30 CT can additionally reveal thrombus volume, aortic calcification patterns, and peri-aortic, pericardial and pleural fluid collections.³⁵ CT scanning in the emergency setting of acute dissection confers particular advantages, since it is readily available at most institutions, is performed with shorter image acquisition and processing times to facilitate triage decisions, and is familiar to physicians and surgeons. Recent ‘triple rule-out’ CT protocols can differentiate between acute aortic syndrome, pulmonary embolism and coronary artery disease in patients presenting with acute chest pain to the emergency department.^36,37 However, CT is limited by the use of iodinated contrast agents, which can provoke allergic reactions or exacerbate renal dysfunction in the peri-operative period, exposure to ionising radiation, particularly in younger patients, and inability to characterise aortic valve function.⁴ Another drawback of CT in ATAD is that the intimal tear is recognised in <75% of cases, while the entry site is rarely identified.³⁸ An important consideration is that CT angiography should be performed with ECG-gated protocols to improve temporal resolution and, thereby, avoid aortic root and ascending aortic pulsation artefacts, which hinder precise evaluation of the dissected aorta and, especially, the coronary ostia.^35,39 These often generate diagnostic uncertainties that translate into delays in patient care. CT scanning in patients with ATAD should include examination of both the thoracic and abdominal aorta down to the iliac arteries because of the likelihood of distal extension, to plan subsequent endovascular procedures and to gauge vessel diameter for peripheral cannulation for cardiopulmonary bypass.^24,28,40

Magnetic resonance imaging

MRI achieves the greatest sensitivity and specificity in the characterisation of ATAD of all the imaging modalities.^3,26 The modality affords comprehensive structural evaluation of the dissected aorta, while providing valuable information on cardiac and aortic valve function, and quantifying flow patterns in the true and false lumens.³ Sophisticated black blood and bright blood techniques, combined with gadolinium-contrast aortography, provide high-resolution detail from which the location of the intimal tear, presence of aortic wall thrombus and branch vessel involvement can be determined.²⁶ In the IRAD database, only 0.7% of ATAD were diagnosed with MRI.²² MRI is rarely utilised as the initial imaging modality in ATAD since it is not readily available, particularly out-of-hours, and compatibility issues exist in patients with implanted metal devices. Additionally, the extended scan durations and space restrictions within the MRI suite pose difficulties with patient monitoring, and mean that MRI cannot be applied in haemodynamically unstable patients, or may be poorly tolerated in awake patients with uncontrolled pain or claustrophobia.³ In contrast, MRI may be of greater benefit in the longer-term surveillance of patients following dissection surgery, since the gadolinium-based contrast agents used are less nephrotoxic than those used in CT scanning, and also because the risks of ionising radiation are eliminated.⁴

Echocardiography

TOE represents a high sensitivity (almost 100%) and specificity (95%) adjunct in the diagnosis of ATAD,³⁴ often at the bedside in unstable patients unfit for transfer for cross-sectional imaging. The echocardiographic diagnosis of ATAD is confirmed by identification of a mobile echogenic membrane separating the true and false aortic lumens,³ with the true lumen demonstrating systolic expansion and diastolic collapse. TOE provides rapid, real-time functional data on aortic valve and ventricular function, and accurately evaluates coronary ostial involvement in ATAD.³ Although perhaps less available than CT, operator-dependent and necessitating sedation, TOE is portable and can be used intra-operatively to guide endovascular interventions within the desired aortic lumen, but cannot visualise the sub-diaphragmatic aorta.³⁵ Oesophageal disease is a relative contraindication. Acoustic blind spots at the distal ascending aorta and arch restrict TOE evaluation of these aortic segments.^26,28 Trans-thoracic echocardiography (TTE) can immediately provide essential information on aortic valve structure and function, biventricular function and even proximal aortic dissection, necessary to guide surgical decision-making in time-critical scenarios.⁴¹ Although TTE can also detect complications of ATAD, including aortic regurgitation, pericardial effusion, cardiac tamponade and regional wall motion abnormalities, its low accuracy implies that a negative study does not exclude ATAD.⁴²

Aortography

Retrograde aortography was historically the modality of choice in the diagnosis of ATAD, with 86–88% sensitivity and 75–94% specificity,^24,26,33 but has been largely succeeded by CT, MRI and TOE. It can evaluate aortic valve competence, ventricular function, coronary artery dissection, native coronary disease, the location of the dissection and arch vessel involvement.^3,26,34 Diagnosis of ATAD is based on the appearance of two aortic lumens or the presence of an intimal flap.³⁴ Features on aortography consistent with ATAD include splitting or distortion of the contrast column, flow alterations, stasis and non-filling of major vessels.²⁴ The major disadvantages associated with aortography are its invasive nature, expense, the use of contrast agents, the risk of aortic injury from manipulation of stiff catheters within a potentially dissected aorta, time delays in organising a team for the procedure, and the availability of skilled personnel to perform and interpret the study.³ Aortography is, however, still used concomitant to endovascular intervention for malperfusion or coronary angiography in selected cases suspected to have significant coronary artery disease.⁵

Initial medical management of ATAD

Once the diagnosis of ATAD has been confirmed, medical management is directed at limiting extension of the dissection and propagation of the false lumen, controlling pain, managing hypotension and determining which patients are surgical candidates.^3,5,9 A multi-disciplinary team approach, involving skilled nursing care, emergency care physicians, cardiologists, cardiac and vascular surgeons, interventional radiologists and intensivists, is of paramount importance. A proposed algorithm for the management of suspected acute aortic dissection is shown in figure 1.⁴³

Figure 1. Proposed algorithm for management of suspected acute aortic dissection⁴³.

Key: BP = blood pressure; ECG = ecectrocardiogram

Patients with confirmed ATAD require adequate oxygenation and ventilation, and monitoring of respiratory, cardiovascular and neurological function. Within the emergency department, two large-bore intravenous lines should be placed for intravascular volume resuscitation and monitoring of heart rate and rhythm with ECG, invasive blood pressure monitoring via arterial line and urine output should be instituted. This usually mandates escalation to coronary care, high dependency or intensive care settings. Close attention should be paid to the avoidance of hypertension and tachycardia alongside maintenance of end-organ perfusion, as indicated by urine output, peripheral vascular condition and neurological state.⁴

Pharmacological management

Pharmacological therapy aims to reduce aortic wall stress by aggressively moderating systolic blood pressure, and decreasing shear stress on the dissected aortic segments with antiimpulse therapy to reduce the rate of left ventricular pressure development (dP/ dT), thereby lowering the risk of aortic rupture.^{3,5,9,26,35,44,45} Beta blockers may be commenced to achieve a target heart rate of 60–80 bpm and a systolic blood pressure of approximately 100–120 mmHg, while ensuring sufficient coronary, cerebral and renal perfusion.^{4,5,9,26,33,44,45} A first-line agent is intravenous labetalol offering combined alpha- and beta-blockade with resultant control of blood pressure and heart rate. In patients with asthma, chronic obstructive pulmonary disease or congestive cardiac failure in whom beta-blockade is contraindicated, a trial of esmolol may be reasonable, owing to its short half-life.^9,33 Non-dihydropyridine calcium-channel blockers, such as verapamil and diltiazem, are alternative antihypertensives that may be employed in patients with beta blocker intolerance.^33,41 Multiple antihypertensive agents, and vasodilators, such as sodium nitroprusside, alongside beta blockers, may be necessary to rapidly achieve adequate blood pressure control.³⁵ Isolated vasodilator use is not recommended because they may cause reflex tachycardia, and their augmentation of left ventricular ejection force translates into increased aortic wall stress.³³ Effective pain management is another important aspect of peri-operative care in patients with ATAD, to counteract pain-related sympathetic stimulation, which can lead to surges in blood pressure and heart rate.⁹ Intravenous opiate analgesia and anxiolytics may be beneficial.

Management of hypotension

Clinicians should be attentive towards normo- or hypotensive patients on admission, in whom intravascular volume loss from bleeding into the false lumen, pericardium, mediastinum or pleura must be investigated. Other mechanisms for hypotension in ATAD include severe aortic regurgitation, true lumen compression by an expanding false lumen and acute myocardial infarction. Indeed, there is only a limited scope for medical management in dissection-related hypotension, since these conditions require immediate operative intervention. Initially, fluid resuscitation titrated to the blood pressure response should be observed. The introduction of vasopressors or inotropic agents may temporise the situation by maintaining perfusion pressures, but may contribute to false lumen enlargement and aortic wall shear stress, respectively.⁹ Preoperative pericardiocentesis to treat cardiac tamponade may be detrimental, since it may reduce intra-pericardial pressure and, thus, accelerate bleeding,⁴⁶ although guidelines advise that limited pericardiocentesis to maintain acceptable perfusion pressure is appropriate in patients with cardiac tamponade who cannot survive until surgery.⁹ Patients admitted with, or developing, haemodynamic instability require prompt intubation and mechanical ventilation, and confirmatory imaging to determine the underlying dissection-related mechanism.

Transfer for surgical management

ATAD can be a rapidly fatal disease. Concurrent with medical stabilisation, consultation with cardiac surgery should, therefore, be initiated from the onset of diagnosis of ATAD to minimise delays in transfer to an aortic centre for definitive operative management. Surgical indications and optimal timing require careful consideration of the patient’s pre-operative comorbidities and risk profile, the location and severity of aortic involvement in ATAD, the presence of complications, and the patient’s current clinical condition.⁴⁷

Conclusion

ATAD is a complex surgical emergency presenting with a diverse range of signs and symptoms. The broad differential diagnosis combined with its potentially lifethreatening nature warrants a high index of clinical suspicion. Prompt diagnosis is essential to determine the location and extent of the dissection, the presence of complications, and to inform decision-making for patient selection for definitive surgery. Once the diagnosis is established, medical management entails close monitoring, conscientious haemodynamic management with anti-impulse therapy and preparation for surgical intervention where appropriate.

Key messages

• Acute type A dissection (ATAD) is a potentially life-threatening condition with high mortality necessitating prompt and accurate diagnosis

• ATAD should be suspected in patients presenting with sudden-onset, severe chest pain

• Diagnosis is based mainly on radiological and echocardiographic investigations, although other electrocardiography and haematological tests play a role

• Acute medical management of ATAD includes cardiovascular monitoring, pharmacological anti-impulse therapy to reduce systolic blood pressure and aortic wall shear stress, management of pain and hypotension, and preparation for surgical intervention

Funding Statement

Funding None.