Background
Marfan syndrome is a disorder of connective tissue with wide variability in clinical symptoms. It affects the skeletal and cardiovascular systems, eyes, and skin. The disease is inherited mostly in autosomal dominant way, but about 25% cases are sporadic. It is caused by mutations in the fibrillin-1 gene. The most common cardiovascular complications are: aortic dilation, aortic valve insufficiency and mitral valve prolapse.
Case presentation
A 18-year-old male with Marfan syndrome was referred to hospital due to class II NYHA dyspnoe evolving over the last few months. In 2003 patient had genetic consultation, there was no previous history of genetic disorders in the family and he was described as a new mutation. Thereafter he was periodically controlled by cardiologist. In physical examination:
height – 204 cm, weight – 64kg, BSA-1.9 m2, apexian systolic murmur was audible. Abnormalities in skeletal system were observed: scoliosis, pectus excavatum, arachnodactyly, abnormal joint flexibility, flat feet, high palate, micrognathia; nearsightedness and lens subluxation had previously been detected by ophthalmologist. Initial ECG showed sinus rhythm, left posterior hemiblock, signs of left atrium and left ventricle enlargement. Echocardiogram revealed enlargement of the left ventricle (LV) and left atrium (LA): LV 80/55 mm, LA area 44 cm2, with mild systolic dysfunction of LV- ejection fraction – (LV EF) was 50%. Mitral valve prolapse (of both leaflets), mitral insufficiency with regurgitation volume 75 ml. Mitral annulus lateroseptal systolic diameter – 43 mm. Ascending aorta dilated up to 52 mm. Aortic valve tricuspid without regurgitation. An angio cardiac magnetic resonance (CMR) imaging was performed. In CMR maximum aortic bulb diameter was 53×53 mm, tubular part not extended. Mitral regurgitation (MR) volume 110 ml. Chest deformation. The minimal axial chest diameter was 22 mm.
Current guidelines
According to the 2010 Guidelines on the management and diagnostic of patients with Marfan syndrome, CMR or CT should be performed in every patient, providing imaging of the entire aorta including aortic dimensions beyond the root. Patients should undergo surgery when aortic root maximal diameter is > 50mm or 46-50 mm with familiar history of dissection or
patient has progressive dilation >2 mm/year, severe aortic regurgitation (AR) or MR or desire of pregnancy (Ic). Composite replacement of the aortic valve and ascending aorta has become a low-risk and a durable operation. In patients with anatomically normal valves, in whom the insufficiency is due to the dilated annulus or dissection, valve-sparing operations with root replacement by a Dacron prosthesis and with reimplantation of the coronary arteries into the prosthesis (David’s procedure) or remodelling of the aortic root (Yacoub’s procedure) have now become the preferred surgical procedures. AR is, however, a common complication, requiring reoperation in 20% of patients after 10 years. Long-term results of valve sparing aortic root replacement in Marfan syndrome are still unknown.
References
1.Pearson, G.D., et al. Report of the National Heart, Lung, and Blood Institute and National Marfan Foundation Working Group on Research in Marfan Syndrome and Related Disorders. Circulation 2008;118: pages 785-791.
2.Keane, M.G., Pyeritz, R.E. Medical Management of Marfan Syndrome. Circulation 2008; 117: 2802-2813.
3.ESC Guidelines for the management of grown-up congenital heart disease (new version 2010), European Heart Journal (2010) 31, 2915-2957
Expert’s comments:(Written authorization required from each expert)
1. Krzysztof Bederski MD
Marfan’s syndrome is an autosomal dominant disorder of connective tissue, which has both high penetrance and variable severity. The incidence of Marfan’s syndrome is around 2–3 per 10 000 individuals. In 25% of individuals there is no family history, which suggests that the condition has presented de novo.
Marfan’s syndrome is caused by an abnormality of fibrillin, a 350‐kD glycoprotein, which is the main structural component of microfibrils. Microfibrils provide a supporting scaffold for the deposition of elastin throughout the body. Fibrillin is present in many other tissues including lung, dura mater, skin, tendons, ciliary zonules of the lens, myocardium, heart valves and periosteum. Abnormalities in these fibrillin‐containing tissues are found in most patients with Marfan’s syndrome.
Virtually all adults with Marfan’s syndrome have an abnormal cardiovascular system. In early childhood, however, the features may be mild and easily missed. The most common cardiovascular abnormalities are dilatation of the aorta and mitral regurgitation. Most children with Marfan’s syndrome have aortic root dilatation. The reported frequency of other valve abnormalities depends to some extent on the rigour of the method of assessment. Moreover, some abnormalities (eg, mitral regurgitation and prolapse) can be intermittent and vary from mild to severe at different times in the same patient. Children with valvular complications are at increased risk of infective endocarditis. Recommendations for antibiotic prophylaxis are changing, but good dental hygiene and early treatment of skin sepsis remain vital. A dilated pulmonary artery is a minor criterion used in diagnosis, but this is of relatively little importance in the paediatric Marfan’s population[1].
Perhaps the most important decision is the timing of aortic root surgery. The ideal time to replace the root is “one or two months before it dissects”[2].Although aortic dissection is rare in childhood, the success of elective replacement (>95% survival) is much lower than if emergency surgery is needed. In adults, it is usually recommended that the root be replaced when the sinus of Valsalva measures 5 cm, although this figure is reduced if there are additional risk factors such as a strong family history of dissection[3],[4]. In older children, most authors recommend root replacement at 5 cm, when enlargement is >1 cm/year or if there is progressive aortic regurgitation[5].
References
1. Stuart Ag, Williams A: Marfan’s syndrome and the heart. Arch Dis Child.2007 April;92(4): 351–356.
2. Treasure T. Cardiovascular surgery for Marfan syndrome.Heart2000.84674–678.678.[PMC free article][PubMed].
3. Judge D P, Dietz H C. Marfan’s syndrome.Lancet2005.3661965–1976.1976.[PMC free article][PubMed].
4. Lemaire S A, Carter S A, Volguina I V.et al Spectrum of aortic operations in 300 patients with confirmed or suspected Marfan syndrome. Ann Thorac Surg2006. 812063–2078.2078.
5. Cattaneo S M, Bethea B T, Alejo D E. et al Surgery for aortic root aneurysm in children: a 21‐year experience in 50 patients. Ann Thorac Surg 2004. 77168–176.176.[PubMed].
1. Jakub Podolec, MD
Aortic aneurysm and complications of this disease are the main cause of death in patients with Marfan syndrome [1]. Both procedures, Bental de Bono with aortic valve replacement and aortic valve sparing surgery are an option in this patient and tend to be equally safe [2]. Reoperations in patients with Marfan syndrome are common, up to 50% of patients, but reoperative risk remains low. Patients with elective procedures have better outcomes than those undergoing emergency surgery. Elective aortic root replacement should be considered in any Marfan patient with significant root dilatation (as mentioned in the ESC guidelines) when aortic root maximal diameter is > 50mm or 46-50 mm with familiar history of dissection or if the patient has progressive dilation > 2 mm/year, severe aortic regurgitation (AR) or MR or desire of pregnancy [3, 4]. Therefore in this patient with complex disease including ascending aorta dilatation up to 52 mm, the aortic bulb of 53 mm and mitral regurgitation an elective surgical procedure should be preferred and both valves should be treated. Bental de Bono with aortic valve replacement and mitral valve repair procedure should be recommended. Unfortunately, failure of endovascular treatment of aortic aneurysms in Marfan syndrome remains common. For the abovementioned reason this kind of procedure should not be recommended in this patient. It may be considered in some selected patients [5]. Surgical correction of pectus excavatum should be considered.
References
1. Cañadas V. et al Marfan syndrome. Part 2: treatment and management of patients. Nat Rev Cardiol. 2010 May;7(5):266-76. doi: 10.1038/nrcardio.2010.31.
2. Schmidtke C et al. Mid-term results of different aortic valve-sparing procedures in Marfan syndrome. J Heart Valve Dis. 2012 Mar;21(2):195-201; discussion 202.
3. Geisbuesch S et al. Frequency of reoperations in patients with Marfan syndrome. Ann Thorac Surg. 2012 May;93(5):1496-501. doi: 10.1016/j.athoracsur.2011.12.068.
4. Baumgartner H, ESC Guidelines for the management of grown-up congenital heart disease (new version 2010). Eur Heart J. 2010 Dec;31(23):2915-57.
5. Waterman AL et al. Endovascular treatment of acute and chronic aortic pathology in patients with Marfan syndrome. J Vasc Surg. 2012 May;55(5):1234-40; discussion 1240-1. doi: 10.1016/j.jvs.2011.11.089.
Expert’s conclusions:
This 18-year-old female with Marfan’s Syndrome requires Bentall De Bono operation: replacement of aortic valve ( mechanical valve) and ascending aorta involving composite graft as well as mitral valve repair. Thoracosurgery consultation should be performed because of pectus excavatum. Surgical correction should be consider.
Authors:
Małgorzata Konieczynska MD, PhD1, Ewa Wicher-Muniak MD, PhD1, Magdalena Urbanczyk-Zawadzka MD1, Agnieszka Pająk MD1
Experts:
Krzysztof Bederski MD2, Jakub Podolec MD3
1One-Day Diagnostic Department, John Paul II Hospital, Krakow
2Department of Thoracic Surgery in John Paul II Hospital, Krakow
3Department of Hemodynamics and Angiocardiography, Cardiology Institute, Collegium Medicum, Jagiellonian University, Krakow, Poland; Center for Interventional Cardiac and Vascular Diseases, John Paul II Hospital, Kraków, Poland
