Aortic Root Aneurysm

An aortic root aneurysm is dilatation of the aortic sinuses of Valsalva and often the sinotubular junction. In adults the root is dilated at over 40 mm (about 36 mm in women), and it is called an aneurysm when it is 1.5 times the expected size or 45 mm or more.

Most patients are asymptomatic. The root is usually found on echocardiography or CT, or after a complication.

Causes are Marfan syndrome (FBN1; about 1 in 5,000), Loeys-Dietz syndrome (TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3), vascular Ehlers-Danlos syndrome (COL3A1), familial thoracic aortic disease (ACTA2, MYH11 and others), bicuspid aortic valve with a root phenotype, Turner syndrome, hypertension and degeneration.

Infection (syphilis, tuberculosis), aortitis, trauma and a ruptured sinus of Valsalva aneurysm are rarer causes. Growth is usually about 1 mm each year, and faster in genetic disease.

Pathophysiology. Loss of elastic fibres and smooth muscle with medial degeneration, often from altered TGF-beta signalling, weakens the wall. Wall stress rises with diameter and blood pressure, so dissection, rupture and aortic regurgitation follow.

Annual risk of dissection or rupture rises steeply with size, and is roughly 2% at 5.0 to 5.9 cm and 7% or more at 6.0 cm or over in older series. Dissection also occurs at smaller sizes in Loeys-Dietz and vascular Ehlers-Danlos syndromes.

• Usually asymptomatic. Chest discomfort, dyspnoea from aortic regurgitation, palpitations, and heart failure.
• Early diastolic murmur of aortic regurgitation with a wide pulse pressure.
• Marfan syndrome: tall stature, arm span over height, arachnodactyly, pectus deformity, scoliosis, ectopia lentis, striae, dural ectasia, mitral valve prolapse.
• Loeys-Dietz syndrome: hypertelorism, bifid or broad uvula, cleft palate, arterial tortuosity, craniosynostosis. Vascular Ehlers-Danlos syndrome: thin translucent skin, easy bruising, characteristic facies, arterial and bowel rupture.
• Family history of aneurysm, dissection or sudden death.

Red flags.

• Sudden severe tearing chest or back pain, syncope or neurological deficit (acute dissection)
• New or progressive aortic regurgitation
• Growth of 3 mm or more each year
• Root of 50 mm or more, or smaller in connective tissue disease
• Planned or current pregnancy

• Echocardiography. Measure the sinuses (leading edge to leading edge in end diastole), sinotubular junction, ascending aorta and valve. Report absolute diameter and Z score, and use the same method each time.
• ECG-gated CT or MR angiography. The whole aorta, with measurements perpendicular to the flow axis. Baseline imaging of the whole aorta in genetic disease.
• Risk indices. Aortic size index (diameter in cm divided by body surface area in m2), and cross-sectional area (cm2) divided by height (m); a value over 10 is a high risk marker.
• Genetic evaluation. Marfan syndrome is diagnosed with a root Z score of 2 or more plus ectopia lentis or an FBN1 variant, or by a systemic score of 7 or more. Panel testing for TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, COL3A1, ACTA2 and MYH11. Ophthalmology review for the lens.
• Cascade screening of first degree relatives by echocardiography and genetic testing.
• Laboratory. Creatinine, lipids, glucose, and syphilis serology when infection is possible.

Differential diagnosis.

• Normal variation in tall people and athletes (index to size)
• Ascending aortic aneurysm without root involvement
• Sinus of Valsalva aneurysm
• Aortic dissection, intramural haematoma and aortic pseudoaneurysm
• Aortitis (Takayasu, giant cell, IgG4-related, syphilitic)
• Aortic regurgitation from valve disease with secondary dilatation
• Periaortic abscess

Medical.

• Blood pressure under 130/80 mm Hg. Resting heart rate 60 to 70/min where tolerated.
• Bisoprolol 2.5 mg orally once daily, increased to 5 to 10 mg once daily, maximum 20 mg daily (do not exceed 10 mg daily at creatinine clearance under 20 mL/min or in severe liver impairment). Contraindicated in severe asthma, sinus node disease and high grade atrioventricular block without a pacemaker. Lengthened diastole increases regurgitant time in severe aortic regurgitation, so monitor with echocardiography.
• Losartan 25 to 50 mg orally once daily, increased every 2 to 4 weeks to 100 mg once daily, maximum 100 mg daily, in Marfan and Loeys-Dietz syndromes, and for hypertension. Check potassium and creatinine 1 to 2 weeks after each change. Contraindicated in pregnancy and bilateral renal artery stenosis.
• Atorvastatin 20 to 40 mg orally once daily when atherosclerotic risk is present, with liver enzymes at baseline and 3 months. Avoid in pregnancy.
• Stop smoking. Avoid fluoroquinolones, stimulants and heavy isometric exertion (weightlifting, contact sport). Moderate aerobic exercise is encouraged.

Indications for surgery.

Symptoms, severe aortic regurgitation and acute dissection are indications at any size.

Operations.

• Valve sparing root replacement (reimplantation or remodelling) when the valve is suitable. After valve sparing repair give aspirin 75 to 100 mg orally once daily (usual maximum 325 mg daily) and no anticoagulation.
• Composite valve graft root replacement (mechanical or biological). Mechanical valve: warfarin 5 mg orally once daily at the start (2 to 3 mg in older adults, liver impairment or interacting drugs), adjusted to an INR of 2.5 (2.0 to 3.0) for a bileaflet valve without risk factors, or 3.0 (2.5 to 3.5) with risk factors, no fixed maximum, with INR every 2 to 3 days at the start, weekly until stable, then every 4 to 12 weeks. Biological valve: warfarin to an INR of 2.5 (2.0 to 3.0) for 3 months, then aspirin 75 to 100 mg once daily.
• Elective operative mortality is about 1 to 3% in experienced centres. Complications are bleeding, stroke, coronary ostial problems, and pseudoaneurysm.
• Endocarditis prophylaxis only with a prosthetic valve or material, or previous endocarditis.

Acute aortic syndrome (emergency).

• Analgesia with morphine 2.5 to 5 mg intravenously, titrated.
• Esmolol 500 microgram/kg intravenously over 1 minute, then infusion 50 microgram/kg/min, repeating the bolus and increasing the infusion by 50 microgram/kg/min every 4 to 5 minutes, maximum 200 microgram/kg/min, to a heart rate near 60/min and systolic pressure of 100 to 120 mm Hg. Give beta blockade before any vasodilator. If the systolic pressure stays over 120 mm Hg, add sodium nitroprusside 0.3 microgram/kg/min intravenously, increased every 3 to 5 minutes to a usual 0.5 to 3 microgram/kg/min, maximum 10 microgram/kg/min (for no more than 10 minutes at the maximum rate).
• Immediate CT angiography. Involvement of the ascending aorta needs emergency surgery. Mortality without surgery rises by 1 to 2% for each hour in the first 48 hours.

Special groups.

• Pregnancy in Marfan syndrome: a root of 45 mm or more is a contraindication, and 40 to 44 mm carries a raised risk. Repair before conception when the size reaches the surgical threshold. Continue a beta blocker with metoprolol tartrate 25 to 100 mg orally twice daily, maximum 200 mg daily in this setting. Stop losartan and statins before conception. Plan delivery by caesarean section when the root is over 45 mm.
• Children: use Z scores, and treat with beta blocker or losartan by weight under paediatric supervision.
• Region: syphilis and tuberculosis are important causes in sub-Saharan Africa and Asia, so test for both.

Monitoring. Imaging at 6 months after diagnosis to measure growth, then yearly if stable, and every 6 months at 45 mm or more or with rapid growth. Use the same modality each time. After surgery, CT or MRI at 1 year, then every 2 to 3 years. Blood pressure at each visit.

Referral and escalation. Refer to a cardiology service with a thoracic aortic programme and a genetics service. Emergency for suspected dissection.