• 2007 Revised Endocarditis Prophylaxis Guidelines, NMF Professional Advisory Board Statement
• Adult Nomogram
• Pediatric Nomogram
• Aortic Root Dilatation Nomogram
• Overview of Emergency Diagnosis and Treatment of Aortic Dissection
• Emergency Medicine Campaign Kit  

• Enhanced awareness with early diagnosis
  Diligent long-term surveillance of the aortic root diameter
• Surveillance of the entire aorta (descending thoracic and abdominal aorta) by the appropriate imaging modality 1,2
• Prophylactic surgery to replace the aortic root or other dilated aortic segments before dissection occurs is absolutely critical for survival.

CARDIAC MANIFESTATIONS   

Major Diagnostic Criteria include(3):

• Dilation of the ascending aorta, with or without aortic regurgitation, and involving at least the sinuses of Valsalva
• Dissection of the ascending aorta.
• For cardiovascular system to be involved, a major criterion must be present

Minor Diagnostic Criteria include(3):

• Mitral valve prolapse with or without mitral regurgitation.
• Dilation of the main pulmonary artery in the absence of valvular or peripheral pulmonic stenosis, or any other obvious cause, before age 40.
• Calcification of the mitral annulus before age 40.
• Primary dilation and/or dissection of the descending or abdominal aorta before the age of 50.  (Seen in approximately 10% of the Marfan population.)

Other Cardiac Manifestations may include:

• Tricuspid valve prolapse
• Cardiac arrhythmias related to heart valve disease and with cardiomyopathy/CHF
• MVP and mitral regurgitation with congestive heart failure in pediatric patients is a leading indication for cardiovascular surgery in very young age group.

IMAGING STUDIES

• Standard chest radiograph is inadequate to detect aortic root enlargement(3)
• Initial evaluation should include two-dimensional echocardiogram with 6-12 month follow-up to determine rate of aortic enlargement. Aortic diameter should be measured at the sinuses of Valsalva and related to normal values based on age and body surface area.(1,4)
• Two-dimensional echocardiograms should be performed regularly with a suggested interval of approximately one year between exams. 
  • As rate of change  (> 0.5 cm per yr) or absolute size of aorta increases (>4.5 cm) or with significant aortic valvular regurgitation, more frequent studies are necessary.
• Technical advances gated in imaging techniques now make magnetic resonance angiography (MRA) and multi-detector row CTA (MDCT) useful for evaluation of diseases of the aortic root and the entire thoracic and abdominal aorta.(2,5)
• Transesophageal echocardiography useful for evaluation of aortic root, descending aorta and mitral valve.
  • Serial TEE imaging not indicated because procedure is invasive, and requires sedation
• Routine CTA or MRA imaging of the entire aorta is recommended if: (1)
  • The descending thoracic aorta or arch or abdominal aorta are enlarged.
  • The aorta has dissected
• After aortic root surgery
  • At least annual imaging of the thoracic aorta is recommended.
  • More frequent imaging if rate of dilation of descending aorta or arch is rapid or if aorta >4.5 cm, unless documented to be stable at that size.
• Accurate measurements of the aortic diameter, perpendicular to its walls, with comparison to prior studies of aortic dimension and body surface area are critical

MEDICAL MANAGEMENT OF AORTIC DILATION

• Asymptomatic patients with mild to moderate aortic root enlargement require medical therapy and serial imaging
  • Aggressive blood pressure control
    • Beta-blocker therapy preferred(4).  In older children and adults, goal is to keep resting heart rate less than 70 and heart rate after submaximal exercise less than 100(1).  Use of long-acting medications (optimal for compliance) or divided doses helps maximize benefit and minimize symptoms at peak blood level.
    • Use other antihypertensive agents including calcium antagonists and angiotensin-converting enzyme inhibitors, or angiotensin receptor blockage (ARBs) if beta blockade medically contra-indicated, poorly tolerated, or additional blood pressure control required (1).
  • Serial imaging recommended every six months until stability of aortic size is documented, with annual imaging thereafter.
• Persons with an established descending or abdominal aortic dilation or dissection:
  • Aggressive blood pressure control
  • Frequent imaging to document stability/instability of aorta (See above recommendations under imaging studies.)

SURGICAL MANAGEMENT OF AORTIC DILATION

• Prophylactic resection of dilated ascending aorta when certain “size threshold” is reached. (7,8)
• Determination of “size threshold” in Marfan syndrome.  (Elements need to be considered all together, for example a patient with a family history of dissection may need surgery when dilation is 4.5 to 5 cm):
  • One cannot predict the natural history of an individual’s aortic disease in the Marfan syndrome.  The larger the aortic root, the higher the risk of aortic dissection.  In general, when the aortic dimension is greater than or equal to 5 cm, prophylactic aortic root replacement is recommended.
  • Consider surgery when aorta is 4.5-5 cm. especially if valve-sparing procedure is to be an option.  (This remains controversial.)
  • Other factors which may significantly influence timing of aortic surgery include:
    • Rate of growth greater than 0.5 cm per year
    • Presence of significant aortic regurgitation (AR), or worsening AR over time.
    • Family history of dissection, especially if dissection occurred at aortic dimension less than or equal to 5 cm.
• Prophylactic aortic root replacement carries a risk of 1 to 2% operative mortality. (9)
• Surgical options include composite valve graft, valve-sparing procedure and bio-prosthetic/tissue valve. (9,10,11)
  • Composite valve graft has excellent durability but carries the risks of anticoagulation, thromboembolism, and endocarditis.
  • Valve-sparing procedures are available for most patients if the aortic valve is functioning normally.  Risk of possible re-operation in future, as long-term durability of repair is not known.
• Beta-blocker should be continued after surgery indefinitely.
• After repair of ascending aorta, one must follow the distal aortic segments over time for late-onset aneurysm formation.
• Post-operative patients require endocarditis prophylaxis (see Guidelines on Endocarditis Prophylaxis.)

 SURGICAL INDICATIONS FOR DESCENDING/ABDOMINAL AORTIC REPAIR INCLUDE (1):

• Change in size is sudden exceeding 0.5 cm in a year
• When aorta exceeds 5.0 – 6.0cm, or twice diameter of contiguous normal aorta

ENDOVASCULAR STENT-GRAFTING OF THE AORTA (1)

• Data on stent-grafts in patients with MFS or other related connective tissue diseases (RCTDs) is very limited.  Therefore, there is insufficient information available to guide decisions regarding its safety and efficacy in these conditions.
• MFS and RCTDs remain a contraindication for stent-graft repair in all investigational device exemption protocols.
• Read the NMF Professional Advisory Board Statement on Endovascular Repair in Marfan Syndrome Patients

MANAGEMENT OF AORTIC DILATION IN CHILDREN (1)

• Beta-blockers are prescribed either at time of diagnosis or upon documentation of aortic enlargement.
• In children less than 5 years of age the goal is to keep resting heart rate less than 80 and heart rate after exercise less than 110.
• Careful monitoring of dose necessary during rapid body growth.
• Reduced or divided dosing or substitution with a calcium channel blocker, ARB or ACE-I can be considered when complications due to aggravation of asthma or lethargy-induced interference with learning are associated with beta-blockers.

SURGICAL MANAGEMENT FOR CHILDREN  (1)

• Both composite graft repair and the valve-sparing procedure have shown good results.(12)
• Rapid rate of growth of the ascending aorta (>1 cm per year) is widely used as an indication for surgical intervention in the pediatric population.
• Other indicators include new aortic regurgitation or the need for mitral valve surgery in an individual with substantial aortic enlargement.
• Adolescents should use adult criteria when assessing need for surgery.

MANAGEMENT OF PREGNANT WOMEN

• All pregnancies should be considered high risk and multi-disciplinary evaluation is required (cardiologist and high risk obstetrician)
• Risk of dissection is lower if the aortic root diameter is less than 4.0 cm (13)
• Beta-blockers should be continued during pregnancy and continued after delivery because of heightened risk of dissection post-partum.
• Echocardiograms are recommended during each trimester of pregnancy and once during the two months following pregnancy.
• If possible, surgical repair of significant aortic root dilation should be done pre-partum.
• For more detailed information, see Obstetric Issues.

 ACTIVITY/LIFESTYLE MODIFICATIONS

• Competitive and collision contact sports are contraindicated(14)
• Static (isometric) exercise contraindicated (avoid weight lifting, gymnastics and pull-ups)
• Certain dynamic (isokinetic) exercise at decreased level of intensity is permitted with individualized heart rate limits used to determine acceptable intensity.
• Exercise should be individually determined with particular attention to variation in intensity, even in the same type of activity, among different people.
• Endocarditis prophylaxis is required for patients with valvular heart disease.

RELATED CONDITIONS ASSOCIATED WITH AORTIC ROOT ANEURYSM AND DISSECTION

• Bicuspid aortic valve(15,16,17)
  • Present in 1% of the population with significant proportion having aortic dilation
• Familial Thoracic Aortic aneurysm and dissection.(18,19)
• Loeys-Dietz syndrome(20)

EVALUATION OF FIRST DEGREE-RELATIVES

• Screening of all first-degree relatives of people with Marfan syndrome, bicuspid aortic valve or familial thoracic aortic aneurysm and dissections is warranted because of genetic predilection for aortic root aneurysm.

Sources

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2. Boyer JK, Guitierrez F, and Braverman AC.  Approach to the dilated aortic root.   Curr Opin Cardiol  2004, 19:563-569.
3. von Kodolitsch Y, Nienaber CA, Dieckmann C, et al.  Chest radiograph for the diagnosis of acute aortic syndrome [see comment]. Am J Med 2004, 116:73-77.
4. Roman MJ, Devereux RB, Kramer-Fox R, O’Loughlin J.  Two-dimensional echocardiographic aortic root dimensions in normal children and adults.  Am J Cardiol 1989 64:507-512.
5. Macura KJ, Szarf G, Fishman EK, Bluemke DA.  Role of computed tomography and magnetic resonance imaging in assessment of acute aortic syndromes Semin Ultrasound CT MR 2003, 24:232-254.
6. Shores J, Berger KR, Murphy EA and Pyeritz RE.  Progression of aortic dilation and the benefit of long-term beta-adrenergic blockage in Marfan’s syndrome. N Engl J Med  1994,  330:1335-1341.
7. Braverman AC.  Timing of aortic surgery in the Marfan syndrome.  Curr Opin Cardiol  2004, 19:549-550.
8. Davis RR, Goldstein LI, Coady MA et al.  Yearly rupture or dissection rates for thoracic aortic aneurysms.  Simple prediction based on size.  Ann Thorac Surg 2002, 73:17-28.
9. Gott VL, Greene PS, Alejo DE et al:  Replacement of the aortic root in patients with Marfan syndrome.  N Engl J Med 1999, 340:1307-1313.
10. de Olivera NC, David TE, Ivanov J, et al., Results of surgery for aortic root aneurysm in patients with Marfan syndrome.  J Thorac Cardiovasc Surg 2003, 125:789-796.
11. Miller DC.  Valve-sparing aortic root replacement in patients with Marfan syndrome.  J Thorac Cardiovasc Surg 2003, 125:773-778.
12. Cattaneo SM, Bethea BT, Alejo DE et al.  Surgery for aortic root aneurysm in children: a 21-year experience in 50 patients.  Ann Thorac Sur.  2004, 77:168-176.
13. Lind J, Wallenburg HC.   The Marfan syndrome and pregnancy: a retrospective study in a Dutch Population.  Eur J Obstet Gynecol Reprod Biol.  2001,  98:28-35.
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15. Braverman AC, Guven H, Beardslee M, Kates A, Moon M.  The Bicuspid Aortic Valve.  Curr Problems in Cardiol 2005,  30:470-522.
16. Fedak PW, de SAMP, Verma S, et al.  Vascular matrix remodeling in patients with bicuspid aortic valve malformations: Implications for aortic dilatation.  J Thorac Cardiovasc Surg 2003, 126:797-806. 
17. Nataatmadja M, West M, West J et al.  Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm. Circulation 2003, 108:11329-11334.
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