An often forgotten cause of chest pain

Short answer

Acute aortic syndrome.

Discussion

Acute aortic syndrome (AAS) is the term used to describe patients with “aortic pain” caused by one of three diseases: aortic dissection, penetrating aortic ulcer (PAU), and intramural haematoma (IMH). Aortic pain is the sensation of sharp, tearing, or pulsating pain in the back or chest.1 Before advances in high resolution imaging these conditions had not been differentiated and were thought to be variants of aortic dissection.2 The term AAS was first used in 1998 when it was realised that these three diseases can have a similar presentation.1 3 Its purpose was to raise awareness of PAU and IMH and to stress the clinical importance of aortic pain, which is often a precursor of aortic rupture.1 4 The incidence of AAS in the Western world is 2.6-3.5 cases per 100 000 person years.2 5 6

IMH (fig 3A⇓) was first described as a “dissection without intimal rupture.”7 Advances in imaging have proved this description to be inaccurate. The formation of IMH, unlike aortic dissection, involves rupture of the vasa vasorum and bleeding into the outer half of the aortic tunica media.4 The haematoma formed may then extend, regress, resorb, or lead to a dissection of the aorta.4 IMH can be confidently differentiated from aortic dissection only by imaging. A subtle difference in the clinical presentation of IMH includes its tendency to produce segmental symptoms, whereas aortic dissection often radiates to the lower limbs or head and neck region.4 6

Fig 3 (A) Intramural haematoma occurs when the vasa vasorum ruptures spontaneously causing haematoma to spread in the media layer of the aortic wall. It is identified on computed tomography as high attenuation and thickening of the wall of the aorta (A; white arrows). Penetrating ulcer is an ulcerated atheromatous plaque that penetrates the intima and progresses into the media (B; black arrow). Dissection occurs when blood flows through a tear separating the intima from the media and adventitia and creates a false lumen. It is identified on computed tomography as true and false lumen separated by an intimal flap (C; black arrows)

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PAU (fig 3B⇑) is an ulceration of an aortic atherosclerotic plaque that penetrates through the internal elastic lamina into the aortic tunica media.1 It accounts for 2.3-7.6% of AAS presentations.3 These ulcers are classified by the depth and breadth of their penetration through the internal elastic lamina. They can progress to cause IMH, aortic dissection, and rupture.1 One retrospective study showed an association between PAU and the development of pleural effusions in 75% of patients (fig 1⇑).8 This is one of the few useful prognostic signs in PAU and is thought to suggest marked instability.8

Aortic dissection (fig 3C⇑) is caused by tearing of the intimal layer. Blood under high pressure then passes through the tear and creates a new false channel, which dissects the media layer from the aorta.1 4 As the tear propagates in an anterograde or retrograde fashion it can affect other branching arteries and lead to organ malperfusion, pericardial tamponade, or aortic insufficiency. A dissection is thought to be “acute” if it is less than two weeks old.9

Stanford classification for aortic dissection is thought to be the most clinically relevant classification system. Stanford type A dissections involve the ascending aorta or arch irrespective of its origin.4 Type B dissections do not involve the ascending aorta (they involve the descending aorta or arch distal to the left subclavian artery).4 Type A dissections comprise 62.3% of cases, with type B dissections comprising the remaining 37.7%.10 As a result of their location, type A dissections pose a higher risk of complications, with a 24 hour mortality of 24% in the absence of acute surgical intervention.4 Type B dissections tend to be more stable and have traditionally been managed medically. When no complications arise, mortality is 10% at 30 days.10 Complications of type B dissection include visceral, renal, spinal cord, and lower limb ischaemia and contained rupture.3 4 If these arise, an aggressive surgical approach to management is usually required.

Short answer

Hypertension, old age, pregnancy, aortic instrumentation, and congenital risk factors that include various connective tissue disorders.

Discussion

The risk factors for the development of IMH and aortic dissection are almostthe same. Acquired risk factors contribute to aortic dissection and IMH mainly by causing aortic medial wall degeneration or cystic medial necrosis.4 This compromise in function and stability increases the risk of dissection and haematoma formation. Although risk factors for the development of PAU are similar to those for aortic dissection and IMH, the underlying pathophysiology differs, being largely based on the formation of atherosclerosis.11

Hypertension, is the most important modifiable risk factor for AAS and is reported to be present in 70% of patients.1 It can increase the risk of both aortic dissection and IMH through three primary mechanisms:

• Chronic exposure to high pressures can cause direct damage to the intima in the form of intimal thickening, fibrosis, calcification, and extracellular fatty acid deposition

• Hypertension causes increased shearing forces on the aorta, particularly where it is anatomically less mobile.11 Such sheer stress can act as a trigger for a tear to begin

• Hypertension is also a risk factor for the development of PAU. It causes the arterial wall to undergo oxidative stress and produce free radicals, which increases foam cell production and enhances the formation of atherosclerosis.12

Increasing age is another risk factor for AAS. With time cystic medial necrosis may occur, whereby the aorta’s collagen, elastin, and smooth muscle cells are broken down and replaced with cystic lesions. When subjected to sheer stress, a cystic lesion may become the point of origin of a dissection, explaining why age is a risk factor for IMH and aortic dissection.13 Furthermore, as patients age the risk of accumulation of atherosclerotic material increases, which may explain the increased frequency of PAU in older people.14

Various connective tissue disorders weaken the aortic media predisposing patients to AAS.4 15 These include:

• Marfan syndrome (cystic medial necrosis is a classical finding here)

• Ehlers-Danlos syndrome

• Annuloaortic ectasia

• Familial aortic dissection

• Adult polycystic kidney disease

• Turner’s syndrome

• Noonan syndrome

• Osteogenesis imperfecta

• Metabolic disorders (such as homocystinuria and familial hypercholesterolaemia)

• Loeys-Dietz syndrome.

Iatrogenic causes have been shown to account for 5% of cases of acute aortic dissection.16 All patients undergoing procedures that involve or predispose them to aortic intimal damage carry a risk of AAS. The following procedures pose a particularly high risk:

• Aortic and mitral valve replacement

• Coronary artery bypass surgery

• Coronary angioplasty.

Pregnancy, specifically in the third trimester and immediately postpartum, is another risk factor for aortic dissection,15 probably because of the pregnancy related increase in cardiac output and heart rate.15 Pregnant women with underlying connective tissue disorders are at greatest risk.

Rarer acquired causes of AAS include syphilitic aortitis, deceleration injuries, and cocaine use.4

Short answer

Acute and severe ripping, tearing, or pulsating chest pain that radiates to the back.

Discussion

The most common presenting problem is aortic pain—an acute and severe ripping, tearing, migrating, or pulsating pain that begins in the chest and radiates to the back.4 17 This may cause diagnostic confusion with cardiac causes of chest pain, such as myocardial infarction. It is important to suspect AAS in patients presenting with chest pain who have negative electrocardiography and troponin changes.1 4 Dissection within the proximal aorta can also affect coronary perfusion, causing myocardial ischaemia and central crushing chest pain. These patients may have the classic clinical and biochemical presentation of a myocardial infarction, which might mask the diagnosis of AAS. Such mixed presentations explain why AAS is often misdiagnosed or diagnosed incidentally.

By contrast, some patients present with minor symptoms such as mild back pain that may be attributed to musculoskeletal ailments. These findings are more common in PAU and IMH.

Furthermore, the International Registry of Acute Aortic Dissection (IRAD) found that 4.5% of patients with aortic dissection had no pain at presentation.10 This is more common in patients with connective tissue disorders or those with neurological deficits such as diabetic neuropathy.¹Syncope is a sinister sign seen in 13% of patients on the IRAD.10 It may denote the development of complications such as cardiac tamponade, obstruction of cerebral vessels, or simply the activation of cerebral baroreceptors.18 Unsurprisingly, patients presenting with syncope are more likely to die in hospital (34% v 23% without syncope).18

Hypertension (systolic blood pressure >150 mm Hg) has been shown to be a presenting sign in 39% of patients with acute aortic dissection.19 Hypertension, which often complicates the initial management of acute type B dissections, may be pre-existing or secondary to the severe aortic pain experienced by the patient.

Neurological signs of a stroke such as hemiparesis, facial weakness, and dysarthria may arise in AAS if the great vessels are involved. Paraplegia may occur as a result of type B dissections, necessitating immediate drainage of cerebrospinal fluid to alleviate the spinal cord ischaemia. Limb ischaemia is another sign that warrants prompt surgical attention. Other neurological symptoms include distal limb paraesthesia and weakness due to nerve ischaemia in the extremities. Furthermore, Horner’s syndrome and voice hoarseness can arise if the cervical ganglia or larynx are damaged by the dissection.1 4

Haemoptysis and dyspnoea are worrying symptoms caused by rupture of the aorta into the pleural cavity. These symptoms have a wide differential diagnosis and may not be immediately linked with AAS.

The wide variety of presentations of AAS highlights the necessity for clinicians to assume a high index of suspicion in any patient with aortic pain. The potential for such a diverse collection of symptoms, signs, and investigation findings may distract clinicians from this underlying life threatening disease.

Short answer

Computed tomography angiography.

Discussion

The role of imaging in AAS is not only to diagnose the disease but also to characterise it. Imaging can classify aortic dissection and IMH, assess the depth and breadth of PAU, and identify emergency complications.

Signs of aortic dissection on chest radiography, such as widened mediastinum, double aortic contour, irregular aortic contour, and aortic calcification, are all non-specific and are rarely seen in practice. In addition, IMH and PAU are impossible to diagnose on chest radiography; any patient with suspected AAS should have cross sectional imaging such as computed tomography angiography (CTA).

CTA plays a central role in the diagnosis of AAS. It has several advantages over other imaging modalities including widespread availability, speed, and the ability to identify a wide range of extravascular diseases that may be present. Spatial resolution is excellent, often achieving isovolumetric voxels as small as 0.5 mm. Disadvantages include the use of ionising radiation and the administration of iodinated contrast agents that can cause contrast induced nephropathy.

CTA for suspected AAS should be performed with electrocardiographic gating to “freeze” cardiac motion. A non-contrast scan should be performed initially because it can identify the high attenuation wall thickening that is characteristic of IMH.20 This is followed by contrast enhanced CTA of the entire aorta to improve sensitivity and enable planning of any future intervention.

CTA also helps to identify renal or visceral organ malperfusion and suitable areas to deploy stents. CTA enables radiologists to identify signs indicative of aortic dissection: 70% of scans show an intimal flap with the presence of a double lumen.21 Other CTA signs include: aortic dilatation, displacement of aortic wall calcification, and identification of embolic material with or without evidence of end organ ischaemia.22 CTA allows for a more confident identification of IMH and PAU. PAU is classically described as a mushroom shaped contrast filled protrusion into the wall of the aorta often accompanied by an enhancing aortic wall, signs of atherosclerosis, and ulceration. Unlike aortic dissection no intimal flap is present in IMH.

Magnetic resonance angiography (MRA) is useful in the diagnosis of AAS, and it has similar sensitivities and specificities to CTA. Spin echo, gradient echo, and contrast enhanced sequence techniques can evaluate aortic morphology, dissection flaps, and flow disturbances such as those related to entry and re-entry sites in dissection. Time resolved flow sensitive MRA may be used to evaluate blood flow patterns.20 No ionising radiation is needed and because the contrast agents are less nephrotoxic than those needed for CTA, MRA can be used instead of CTA in patients with poor renal function23 (although with very poor renal function there is a risk of nephrogenic systemic sclerosis).

Disadvantages include the relatively long scan times compared with CTA and relative difficulty looking after potentially unstable patients during scanning.23 In addition, MRA may be less readily available than CTA, particularly out of hours.

Transthoracic echocardiography may be used for assessing the proximal thoracic aorta but is poor at visualising the rest of the aorta. Abdominal ultrasound may be used to assess the abdominal aorta and can help diagnose intermittent occlusion of a branch vessel by demonstrating mobility of the dissection membrane during the cardiac cycle.

Transoesophageal echocardiography is probably the most useful ultrasound modality. It can assess the thoracic aorta from the aortic root to the coeliac artery except for a short segment of the ascending aorta just proximal to the brachiocephalic artery due to interposition of the trachea and right main bronchus. Advantages include its portability and ability to be performed and interpreted immediately at the patient’s bedside.24 It can produce high resolution images in real time, and with the use of colour Doppler is can provide information on flow dynamics. However, the procedure is relatively invasive and requires adequate sedation and blood pressure control (particularly in AAS). As with all ultrasound, it is highly operator dependent and the necessary expertise may be less readily available than it is for CTA.

Intravascular ultrasound, when available, may help to characterise AAS, particularly when findings from other imaging modalities are equivocal.24 However, this test is invasive and requires common femoral artery puncture.

Digital subtraction angiography is an invasive technique that has been superseded by cross sectional imaging modalities such as CTA in the diagnosis of AAS. It is generally performed only during treatment of AAS, such as stent graft deployment.

Short answer

Prompt reduction of blood pressure in a critical care unit is crucial in patients who also have hypertension, followed by continuing medical therapy or surgery, depending on the disease site and risk of progression. Regular imaging surveillance and lifestyle modification are required thereafter.

Discussion

In haemodynamically stable patients aggressive reduction of blood pressure and heart rate in an intensive care setting is vital to prevent dissection and to encourage aortic wall stability. Intra-arterial catheter insertion and administration of an intravenous vasoactive agent is necessary to maintain a target systolic blood pressure of 100-120 mm Hg and target heart rate of 60 beats/min.4 β blockers should be used in preference to other antihypertensive agents because of their negative inotropic and chronotropic effect.17

Opiate analgesia should be administered regularly in patients with pain to prevent the associated catecholamine response and rise in mean arterial pressure.17

The general consensus is that acute aortic diseases of the ascending thoracic aorta are surgical emergencies that require open surgery to reduce the risk of complications including aortic rupture, stroke, cardiac tamponade, and circulatory failure. The process involves excision of the intimal tear with obliteration of entry into the false lumen and stabilisation with a synthetic graft. If the aortic valve is affected it can be replaced at the same time.17

Intervention, usually thoracic endovascular aortic repair (TEVAR), is indicated for complicated Stanford type B dissections—for example, those with organ, limb, or spinal cord ischaemia; aneurysm expansion or risk of rupture; peri-aortic blood collection; and intractable pain and uncontrolled hypertension despite best medical agent treatment and adequate pain relief.4 TEVAR is a minimally invasive surgical technique in which an endovascular stent graft is used to cover the aortic disease, excluding it from the circulation. Uncomplicated disease confined to the descending aorta tends to be treated by medical management alone—blood pressure control, adequate analgesia, and monitoring for end organ ischaemia.4

The future of TEVAR seems promising,25 26 27 but long term clinical outcomes and independent predictors of long term complications are still lacking. As a result, we cannot yet distinguish between patients who may benefit from early TEVAR and those who would be better managed by medical treatment alone.

The management of PAU varies. Asymptomatic patients with an incidental finding of PAU or stable patients with small ulcers can generally be treated medically by the vascular multidisciplinary team. If effective analgesia is achieved and no deterioration is seen on CTA, the patient may need close clinical and imaging follow-up only. A more aggressive surgical or interventional approach is advocated in symptomatic high risk patients with aortic pain on admission. An ulcer with a depth or diameter of greater than 20 mm is usually considered for surgery or other intervention.28 Although PAU is often managed medically, because of the segmental nature of this condition, treatment with TEVAR has had positive results so far.29

AAS is a systemic aortic disease state where dissection, aneurysm, or rupture of diseased arteries is likely to reoccur in the same or a different vessel and progression is difficult to predict on the basis of symptoms or clinical findings alone. Serial computed tomography is crucial in the acute inpatient and outpatient settings. Imaging is also recommended at one, three, six, nine, and 12 months after discharge.30 The frequency of imaging thereafter should be guided by the presence of risk factors for progression. These include old age, hypertension, patent false lumen, and increased aortic size.31 MRA may be a valuable alternative to CTA in the surveillance of patients with poor renal function. The follow-up protocols for imaging surveillance are organised by the vascular radiology and surgical team on a case-by-case basis. If the disease is stable on imaging and there are no complications the patient and GP will be informed of the findings but routine clinic attendance will not usually be required.

Although data on how much exercise is safe or beneficial for patients with thoracic aortic disease are scarce, research in patients with cardiovascular disease suggests that regular aerobic exercise is beneficial to patients’ physical and mental health.32 Aerobic exercise confers a modest situational increase in mean arterial pressure, but isometric exercise (such as heavy weight lifting) has been associated with a sudden dramatic increase in systemic arterial pressure.33 Such extreme hypertension generated by the Valsalva manoeuvre may increase the risk of rupture in predisposed patients with pre-existing aortic dilation.33 Further lifestyle adaptations such as adherence to antihypertensive drugs, smoking cessation, and the adoption of a balanced diet should be encouraged. Patients may be left severely disabled by an aggressive lowering of blood pressure, so individual management review is important.