Thoracic aortic aneurysm and dissection

• Most patients with aortic aneurysm are asymptomatic; however, chest or back pain in the setting of a known aortic aneurysm is a cause for concern and should be investigated.
• Rarely, large aneurysms might compress thoracic structures and cause, for example, dysphagia, hoarseness or dyspnoea.
• Patients with aortic valve regurgitation secondary to root dilatation may have an audible diastolic murmur.
• Aortic dissection is the most serious complication of thoracic aortic disease. It involves a tear in the intima (the inner layer of the aortic wall), which allows blood to track into and disrupt the media, predisposing to aortic rupture, malperfusion of organs and pericardial tamponade. All of these can be life-threatening.
• Typical symptoms of acute aortic dissection include the sudden onset of severe (often described as a ‘tearing’ or ‘ripping’) pain in the chest, neck, back and/or abdomen, or presentation with collapse or stroke.

• There are currently 33 genes included on the NHS Genomic Medicine Service Signed Off Panels Resource’s familial thoracic aortic aneurysm and dissection panel.
• The genes associated with familial forms of aortic aneurysm and dissection can be divided into those causing syndromic conditions and those causing non-syndromic conditions.
• Syndromic conditions include Marfan syndrome, Loeys-Dietz syndrome and the vascular form of Ehlers-Danlos syndrome, all of which affect the connective tissue.
  • The FBN1 gene, variants in which cause Marfan syndrome, was the first of the associated genes to be recognised.
  • Loeys-Dietz syndrome, which has some phenotypic overlap with Marfan syndrome, is associated with variants in TGFBR1, TGFBR2, SMAD2, SMAD4, TGFB2 and TGFB3.
• Non-syndromic familial aneurysm patients – those who do not have connective tissue syndromes – are often identified through imaging investigation for other issues or, unfortunately too often, when they present with aortic dissection.
  • Non-syndromic causes of thoracic aortic aneurysm and dissection include variants in genes that encode the contractile apparatus of smooth muscle cells, such as ACTA2 and MYH11.
• Genomic testing of affected individuals is important not only to determine the need for family member screening, but increasingly to inform clinical decision-making. For example, the presence of a pathogenic or likely pathogenic variant in certain genes is known to cause a more aggressive aortopathy, and current recommendations for prophylactic aortic surgery vary accordingly.

A genetic cause of thoracic aortic aneurysm and dissection is more likely if:

• there is a positive family history;
• there is a connective tissue phenotype; and/or
• the patient presents at a young age (<60 years) without other underlying risk factors.

Most of the pathogenic genetic variants that cause familial aortic aneurysm and dissection are inherited in an autosomal dominant pattern. This means that individuals with a disease-causing variant have a 50% chance of passing the condition on to each of their children. However, the penetrance of variants even within the same family is typically variable, with some individuals being mildly affected or not affected at all, while others have an aggressive phenotype.

When a pathogenic or likely pathogenic variant is detected in an affected individual, it will usually have been inherited from one or both parents. However, for some genetic causes of thoracic aortic aneurysm there is a notable de novo rate. For example, in 25% of cases of Marfan syndrome the variant will have arisen for the first time in the affected individual, with no evidence of it in any previous generations.

Medical management strategies for thoracic aortic aneurysm and dissection are outlined below.

• Medications such as beta blockers and angiotensin II receptor blockers are prescribed in patients with aortopathy. They have been shown to work on some of the genetically mediated pathways in the aortic media homeostasis and are also beneficial in controlling hypertension, which is a known risk factor for progressive aortic dilatation and dissection.
• Lifestyle modification (smoking cessation and moderate-intensity cardiovascular exercise) and medical management of the cardiovascular risk factors diabetes mellitus and dyslipidaemia are indicated.
• Affected patients will also often need psychological support (particularly post-aortic dissection), as well as advice regarding lifestyle (for example, travel, driving and exercise recommendations).

Surgical management strategies for thoracic aortic aneurysm and dissection are outlined below.

• Currently, indications for aortic surgery are predominantly dictated by aortic diameter; however, a genetic diagnosis and family history are also taken into account.
• The location of the aneurysm, rate of aortic growth and fitness for surgery are also considered. Decisions should be made by multidisciplinary aortic teams.

For clinicians

• European Society of Cardiology: Aortic diseases guidelines
• NHS England: National Genomic Test Directory
• NHS Genomic Medicine Service Signed Off Panels Resource: Thoracic aortic aneurysm or dissection

References:

• Isselbacher EM, Preventza O, Hamilton Black J and others. ‘2022 ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines‘. Circulation 2022: volume 146, issue 24, pages 334–482. DOI: 10.1161/CIR.0000000000001106

For patients

• British Heart Foundation: Thoracic aortic aneurysm
• Cleveland Clinic: Thoracic aortic aneurysm
• Johns Hopkins Medicine: Thoracic aortic aneurysm