What is the management approach for Marfan syndrome?

Management of Marfan Syndrome

All patients with Marfan syndrome require lifelong medical therapy with either a beta blocker or ARB in maximally tolerated doses to slow aortic dilation, combined with regular cardiovascular surveillance and prophylactic aortic root surgery when the diameter reaches ≥5.0 cm. 1

Diagnostic Approach

Early identification is critical because prophylactic surgery prevents aortic dissection and rupture, which are the leading causes of death. 1

Clinical Diagnosis

• Diagnosis requires a multidisciplinary team and is primarily based on clinical manifestations using the revised Ghent nosology 1
• Two cardinal features carry the most diagnostic weight: aortic root aneurysm/dissection and ectopia lentis 1
• The traditional Ghent criteria require a major manifestation in two different organ systems plus involvement of a third system 1
• FBN1 gene mutations are identified in 90% of cases, though genetic testing is not always required for diagnosis 1, 2

Differential Diagnosis Considerations

• Exclude mimicking conditions including Loeys-Dietz syndrome, familial aortic aneurysm, bicuspid aortic valve with aortic dilation, familial ectopia lentis, MASS phenotype, and Ehlers-Danlos syndrome 1

Initial Cardiovascular Evaluation

Baseline Imaging Protocol

• Transthoracic echocardiography (TTE) measuring aortic annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta 1
• Assess left ventricular function, aortic valve morphology, and evaluate for mitral/tricuspid valve prolapse or regurgitation 1
• Complete imaging of the entire aorta from head to pelvis using cardiac MRI or CT at initial evaluation 1
• Repeat comprehensive aortic imaging every 3-5 years if stable 1

Medical Management

First-Line Pharmacotherapy

Beta blockers or ARBs in maximally tolerated doses are Class I recommendations to reduce the rate of aortic dilation. 1, 3

Beta Blocker Therapy

• Propranolol or atenolol titrated to maximum tolerated dose reduces aortic root growth rate and clinical events 1, 3
• Mechanism: reduces heart rate, myocardial contractility, and slows aortic root growth 1, 3
• Long-term data (>10 years) demonstrates reduced aortic root growth and fewer cardiovascular complications 1

ARB Therapy

• Losartan or other ARBs are equally effective as beta blockers in randomized trials 1, 3
• Losartan prevents aneurysm formation in animal models and dramatically slowed aortic root growth in pediatric studies 1, 3
• Randomized trials found no significant difference between ARBs and beta blockers for aortic root growth or clinical events 1

Combination Therapy

• Adding an ARB to beta blocker therapy is reasonable (Class 2a) and leads to slower aortic growth rates over 3-5 years 1, 3
• Meta-analysis confirms superior efficacy of combination therapy compared to monotherapy 1, 3

Blood Pressure Targets

• Target systolic blood pressure <120 mmHg in all patients 1
• Target <110 mmHg in patients with prior aortic dissection 1

Surveillance Strategy

Echocardiographic Monitoring Frequency

• Annually if aortic root diameter <45 mm without additional risk factors 1
• Every 6 months if aortic root diameter <45 mm with additional risk factors 1
• Every 6-12 months if aortic root diameter ≥45 mm 1

Comprehensive Aortic Imaging

• Cardiac MRI or CT every 3-5 years for the entire aorta if stable and no prior surgery 1
• More frequent imaging if progressive dilation is documented 1

Surgical Intervention

Indications for Aortic Root Replacement

Surgery to replace the aortic root and ascending aorta is a Class I recommendation when the aortic diameter reaches ≥5.0 cm. 1

Lower Threshold Surgery (Class 2a)

• Aortic root diameter ≥4.5 cm with additional risk factors for dissection 1
• Risk factors include: family history of aortic dissection, rapid aortic growth (>3 mm/year), significant aortic or mitral regurgitation, or desire for pregnancy 1
• Aortic root area (cm²) to patient height (m) ratio ≥10 1

Surgical Technique

• Composite valve-graft conduit with reimplantation of coronary arteries is the standard approach 1
• Must be performed by experienced surgeons in a Multidisciplinary Aortic Team 1

Post-Surgical Considerations

• Patients remain at increased risk for aortic dissection distal to the graft even after successful repair 1
• Long-term complications include graft infections, pseudoaneurysms, and distal aortic aneurysms 1
• Continue lifelong medical therapy and surveillance 1

Special Populations

Pregnancy Management

• All women with Marfan syndrome require pre-conception evaluation and counseling against pregnancy due to rupture/dissection risk 1
• Prophylactic aortic root surgery is recommended if aortic diameter >45 mm before conception 1
• Consider prophylactic surgery for diameters 40-45 mm before pregnancy 1
• Beta blockers must be continued throughout pregnancy 1
• Aortic rupture or dissection most likely occurs during third trimester or delivery 1
• If aortic root enlargement >4.0 cm is first detected during pregnancy, some authorities recommend termination with prompt aortic repair, though this is controversial 1
• Imaging of entire aorta by MRI/CT is required prior to pregnancy 1
• Follow-up frequency during pregnancy determined by aortic diameter and growth rate 1
• Caesarean section with general anesthesia may allow optimal hemodynamic control 1

Pediatric Considerations

• Beta blocker treatment in children reduces aortic growth rate by approximately 0.2 mm/year 3
• The Ghent nosology must be used with caution in children due to age-dependent penetrance of features 4

Lifestyle Modifications

Exercise Recommendations

• Individualize physical activity based on aortic diameter, family history of dissection, and pre-existing fitness 1
• Regular moderate aerobic exercise is recommended for most patients 1
• Avoid high-intensity static/isometric exercises and competitive sports 1
• Post-operative cardiac rehabilitation should be considered after aortic surgery 1

Prognosis

Natural History

• Mean survival of untreated patients is 40 years, with aortic dissection or rupture as the predominant cause of death 1
• With optimal medical and surgical management, life expectancy has improved to 60-72 years 5, 6
• Aortic root dilation occurs in 60-80% of patients 1
• Dissection can occasionally occur even with mild aortic dilation, though risk clearly increases with increasing diameter 1

Critical Pitfalls to Avoid

• Never assume a normal aortic root dimension guarantees protection against dissection—it can occur at any size 1
• Do not delay genetic counseling for couples where a partner has or is at risk of Marfan syndrome 1
• Do not use recommendations for aortic valve replacement based on left ventricular size in pregnant patients—different criteria apply 1
• Ensure adequate analgesia during labor to prevent wide surges in blood pressure and dP/dt 1
• Do not discontinue medical therapy after successful surgical repair—lifelong treatment is required 1