How to assess a patient with a maternal history of cardiac aneurysms?

Assessment of Patients with Maternal History of Cardiac Aneurysms

All patients with a maternal history of cardiac aneurysms require immediate transthoracic echocardiography (TTE) to screen for asymptomatic aortic and cardiac abnormalities, as thoracic aortic disease typically remains silent until catastrophic events occur, and first-degree relatives of affected individuals have up to 50% risk of inheriting autosomal dominant aortopathies. 1, 2

Immediate Imaging Assessment

• Perform transthoracic echocardiography (TTE) as the first-line imaging modality to evaluate the aortic root, ascending aorta, aortic valve morphology, and cardiac chambers for structural abnormalities. 1, 2

• If TTE cannot adequately visualize the aortic root or ascending aorta, proceed immediately to cardiovascular magnetic resonance (CMR) or CT angiography (CTA) with ECG-gating to evaluate the entire thoracic aorta from root to descending segments. 1, 2, 3

• Do not rely on physical examination, ECG, or absence of symptoms to exclude disease—aortic complications often present catastrophically without warning, and physical findings are typically absent until advanced disease develops. 2

Family History and Clinical Evaluation

• Obtain a detailed three-generation pedigree documenting all cases of aortic aneurysms, dissections, sudden cardiac death, valve abnormalities, and syndromic features in the family. 1

• Examine specifically for clinical features of inherited connective tissue disorders including:

  • Marfan syndrome: tall stature, arachnodactyly, pectus deformities, lens dislocation, high-arched palate 1
  • Loeys-Dietz syndrome: hypertelorism, bifid uvula, cleft palate, arterial tortuosity 2
  • Vascular Ehlers-Danlos syndrome: thin translucent skin, easy bruising, characteristic facial features (triangular face, large eyes, thin nose), joint hypermobility 1
  • Turner syndrome features in female patients 1

• Document any history of bicuspid aortic valve in the family, as 9% of patients with bicuspid aortic valve have affected family members, and 20% develop concurrent ascending aortic aneurysms requiring surgical repair. 2

Genetic Testing Strategy

• Refer to medical genetics for formal consultation and testing if the family history suggests inherited arteriopathy (multiple affected relatives across generations) or if clinical features suggest a connective tissue disorder. 1

• Ideally, the affected mother should undergo genetic testing first to identify the specific pathogenic variant, then cascade testing can confirm or exclude the mutation in the offspring. 2

• Genetic testing should focus on established aortopathy genes: FBN1 (Marfan syndrome), TGFBR1 and TGFBR2 (Loeys-Dietz syndrome), COL3A1 (vascular Ehlers-Danlos syndrome), ACTA2 and MYH11 (familial thoracic aortic aneurysm and dissection). 1, 2

• ACTA2 gene sequencing is particularly reasonable given a family history pattern of thoracic aortic aneurysms/dissections (Class IIa recommendation). 1, 2

• Genetic counseling is paramount before mutation screening due to complex financial, insurance, familial, and social implications. 1

Critical Risk Stratification Considerations

• Certain genetic mutations (TGFBR1, TGFBR2) predispose to dissection at smaller aortic diameters (<5.0 cm) or even normal diameters, making early detection and lower surgical thresholds critical. 2

• Pregnancy represents a particularly high-risk period for women with underlying aortopathy due to hemodynamic and hormonal changes that increase susceptibility to dissection, with 50% of dissections occurring in the third trimester and 33% in the early postpartum period. 1

• Women with aortic root diameter >4.0 cm have a 10% risk of dissection during pregnancy, while those with normal aortic dimensions have approximately 1% risk. 1

Surveillance Protocol Based on Initial Findings

If Initial Imaging is Normal:

• Repeat echocardiography every 3-5 years initially, with more frequent surveillance as the patient ages into the typical risk period (30s-40s), as familial thoracic aortic aneurysms can present at younger ages than sporadic cases. 2

• Even with normal aortic diameter, the patient cannot be considered free of genetic risk, especially at young ages, as disease may manifest later. 2

If Aortic Dilatation is Detected:

• Annual echocardiograms for small aortic dimensions with slow rate of dilation (<0.5 cm/year). 2

• Every 6 months if aortic root exceeds 4.5 cm, growth rate exceeds 0.5 cm/year, or significant aortic regurgitation develops. 2

• Initiate β-blocker therapy for aortic root dilation to reduce hemodynamic stress on the aortic wall. 2

If Bicuspid Aortic Valve is Identified:

• Evaluate both the aortic root and ascending thoracic aorta for evidence of aortic dilatation, as family members can have thoracic aortic aneurysms even without bicuspid aortic valves. 2

• Screen all first-degree relatives with echocardiography, as 15% of patients with acute aortic dissection have bicuspid aortic valves. 2

Surgical Thresholds and Intervention Planning

• Standard surgical threshold for ascending aortic aneurysm is 5.0-5.5 cm, but this may be lowered to 4.2-4.6 cm for specific genetic syndromes like Loeys-Dietz syndrome. 2

• If a pathogenic mutation is identified, surgical timing may need to be earlier than standard thresholds, particularly for TGFBR1/TGFBR2 mutations. 2

• Pre-pregnancy aortic root replacement should be considered when aortic diameter exceeds 4.5 cm in women contemplating pregnancy, as pregnancy should be discouraged with diameters >4.5 cm. 1

Radiation Exposure Considerations

• Use radiation dose-reduction strategies for all imaging requiring ionizing radiation (invasive angiography, CCTA), particularly in young patients and women of childbearing age. 1

• Consider alternative imaging methods that avoid ionizing radiation (MRA, duplex ultrasonography) for longitudinal follow-up once systemic arteriopathy is diagnosed. 1

• Defer non-emergency imaging in pregnant or lactating patients, and use MRI rather than CT when imaging is essential during pregnancy. 1

Family Screening Implications

• All first-degree relatives of the affected mother should undergo aortic imaging regardless of genetic testing results, as the yield from screening is substantial given the familial clustering. 1, 2

• If genetic testing identifies a pathogenic variant, only relatives carrying the mutation require ongoing surveillance, which can spare unaffected family members from unnecessary repeated imaging. 1, 2

• Second-degree relatives should be screened if multiple first-degree relatives are affected, which applies when both the maternal grandmother and mother have documented aneurysms. 1, 2

Common Pitfalls to Avoid

• Do not wait for symptoms to develop before initiating screening—most hereditary aortopathies are asymptomatic until dissection or rupture occurs. 2

• Do not assume normal physical examination excludes significant disease—vascular Ehlers-Danlos syndrome may have unrevealing history and physical examination, lowering the threshold for COL3A1 mutation testing. 1

• Do not perform routine whole-genome or exome sequencing in the absence of confirmed heritable arteriopathy—focus on established gene panels for inherited arteriopathies. 1

• Do not limit imaging to the aortic root alone—the entire thoracic aorta must be evaluated, as aneurysms can occur in the ascending aorta, arch, or descending segments. 1