What is the management approach for Marfan syndrome?

Management of Marfan Syndrome

Patients with Marfan syndrome require immediate initiation of either a beta blocker or ARB in maximally tolerated doses to slow aortic dilation, with prophylactic aortic root surgery recommended when the diameter reaches ≥5.0 cm to prevent life-threatening aortic dissection. 1

Diagnostic Approach

Early identification is critical because prophylactic surgery prevents aortic dissection and rupture. 1

• Diagnosis requires a multidisciplinary team and is primarily clinical, based on the revised Ghent nosology 1
• Cardinal features carry the most diagnostic weight: aortic root aneurysm/dissection and ectopia lentis 1
• A definite diagnosis requires major manifestation in two different organ systems plus involvement of a third system 1
• FBN1 gene mutations are identified in 90% of cases, though 10% with definite clinical diagnosis remain mutation-negative 1

Key differential diagnoses to exclude: Loeys-Dietz syndrome, familial aortic aneurysm, bicuspid aortic valve with dilation, familial ectopia lentis, MASS phenotype, and Ehlers-Danlos syndrome 1

Initial Cardiovascular Imaging

Transthoracic echocardiography (TTE) is the primary imaging modality and must include: 1

• Measurements at the aortic annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta
• Left ventricular function assessment
• Evaluation for aortic, mitral, and tricuspid valve abnormalities (regurgitation and prolapse)

Complete aortic imaging with cardiac MRI or CT is mandatory at initial evaluation to visualize the entire aorta from root to pelvis, then repeated every 3-5 years if stable 1

Medical Management Algorithm

First-Line Pharmacotherapy

Start either a beta blocker OR an ARB, titrated to maximally tolerated doses (Class I recommendation): 1, 2

• Beta blockers (e.g., propranolol, atenolol) reduce heart rate, myocardial contractility, and slow aortic root growth 1, 2
• ARBs (e.g., losartan) are equally effective at reducing aortic dilation rates 1, 2
• Randomized trials found no significant difference between beta blockers and ARBs in preventing aortic root growth or clinical events 1

Combination Therapy

Add the second agent (beta blocker + ARB together) if single-agent therapy is well-tolerated (Class IIa recommendation): 1, 2

• Multiple trials demonstrated that combination therapy reduces aortic root growth rates over 3-5 years compared to monotherapy 1, 2
• Meta-analysis confirmed slower aortic growth with combination therapy 1, 2

Blood Pressure Targets

Maintain systolic blood pressure <120 mmHg, or <110 mmHg in patients with prior aortic dissection 3

Surveillance Protocol

Echocardiographic Monitoring Frequency

The surveillance interval depends on aortic root diameter and risk factors: 1

• Aortic root <45 mm without risk factors: Annual TTE 1
• Aortic root <45 mm with risk factors: TTE every 6 months 1
• Aortic root ≥45 mm: TTE every 6-12 months 1

Cross-Sectional Imaging

Repeat cardiac MRI or CT every 3-5 years if the aorta remains stable 1

Surgical Intervention Thresholds

Absolute Indication

Aortic root replacement is mandatory when diameter reaches ≥5.0 cm (Class I recommendation) 1, 2

Earlier Surgery Considerations

Surgery is reasonable at ≥4.5 cm diameter when high-risk features are present (Class IIa recommendation): 1

• Family history of aortic dissection at small diameters
• Rapid aortic growth (>3 mm/year in adults, >5 mm/year in children)
• Severe aortic or mitral regurgitation requiring surgery
• Desire for pregnancy

Alternative threshold: Aortic root area-to-height ratio ≥10 cm²/m (Class IIa recommendation) 1

Surgical Technique

Composite valve-graft conduit with coronary artery reimplantation is the standard approach 1

Pregnancy Management

All women with Marfan syndrome require pre-conception counseling about maternal cardiovascular risks 1

Pre-Pregnancy Assessment

• Complete aortic imaging with MRI or CT is mandatory before conception 1
• Prophylactic aortic root surgery is recommended if diameter >45 mm 1
• Consider prophylactic surgery for diameters 40-45 mm 1

During Pregnancy

• Beta blocker therapy must continue throughout pregnancy 1
• Surveillance frequency is determined by aortic diameter and growth rate 1
• Women with aortic root >4.0 cm, unrepaired coarctation, or residual lesions face increased risk of aortic rupture and cerebral aneurysm rupture during third trimester and delivery 1

Delivery planning: Adequate analgesia prevents blood pressure surges; obstetric techniques to shorten second-stage labor are appropriate; cesarean section under general anesthesia may provide optimal hemodynamic control 1

Activity Restrictions

Individualize physical activity based on aortic diameter, family history of dissection, and baseline fitness 1

• Regular moderate aerobic exercise is recommended for most patients 1
• Prohibit high-intensity static (isometric) exercise and competitive contact sports 1
• Post-operative cardiac rehabilitation should be considered after aortic surgery 1

Prognosis

Untreated patients have mean survival of 40 years, with aortic dissection or rupture as the primary cause of death 1, 3

With optimal medical and surgical management, life expectancy improves substantially to 60-72 years 3, 4

Critical Pitfalls to Avoid

• Aortic dissection can occur even with mild aortic dilation (<4.5 cm), though risk increases substantially with larger diameters 1
• Patients remain at risk for distal aortic dissection even after successful aortic root replacement 1
• Long-term post-operative complications include graft infections, pseudoaneurysms, and aneurysms in distal aortic segments 1
• Medical therapy slows but does not reverse aortic dilation—surgical thresholds must still be respected 2