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Re: Role of beta-adrenergic blocker therapy in children with Marfan syndrome and aortic root dilatation

The article by van Karnebeek et al[1] presented the natural history of cardiovascular manifestations in children with Marfan syndrome, and showed the importance of aortic involvement in deciding the prognosis and outcome. I would like to highlight the role of beta-adrenergic blocker therapy in retarding the progress of the aortic dilatation.

The effectiveness of negative inotropic agents in the treatment of dissection of the aorta has been documented as early as 1965.[2] Since then reports from large centres[3][4] have indicated a beneficial impact of therapy with beta-adrenergic blockers on the rate of aortic dilatation in patients with Marfan syndrome and some of these studies had included children also.[4-6] A recent study of 53 children and adolescents with Marfan syndrome[7] has served to reaffirm the effectiveness of beta-blocker therapy in slowing aortic growth rate in children and adolescents. Untoward effects were minimum and furthermore those who were intolerant to beta-blockers could be managed successfully with calcium channel blockers.

The benefit of beta-blockers derives from their negative inotropic and chronotropic effects.[2] Aortic stiffness and mean blood pressure are both reduced in patients receiving treatment.[8] Acute administration of beta-blockers may reduce excessively the arterial compliance in some children, however such patients may benefit from use of calcium channel blockers.

P Venugopalan, FRCPCH
Consultant Paediatric Cardiologist
Sultan Qaboos University Hospital
Muscat, Sultanate of Oman

References
(1) van Karnebeek CDM, Naeff MSJ, Mulder BJM, Hennekam RCM, Offringa M. Natural history of cardiovascular manifestations in Marfan syndrome. Arch Dis Child 2001;84:129-37.

(2) Wheat MW, Palmer RF, Bartley TD, Seelan RC. Treatment of dissecting aneurysm of the aorta without surgery. J Thorac Cardiovasc Surg 1965;50:364-73.

(3) Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome. N Engl J Med 1994;330:1335-41.

(4) Salim MA, Alpert BS, Ward JC, Pyeritz RE. Effect of beta-adrenergic blockade on aortic root rate of dilatation in the Marfan syndrome. Am J Cardiol 1994;74:629-33.

(5) Tahernia AC. Cardiovascular anomalies in Marfan's syndrome: the role of echocardiography and beta-blockers. South Med J 1993;86:305-10.

(6) Ose L, McKusick VA. Prophylactic use of propranolol in the Marfan syndrome to prevent aortic dissection. Birth Defects Orig Artic Ser 1977;13:163-9.

(7) Rossi-Foulkes R, Roman MJ, Rosen SE, Kramer-Fox R, Ehlers KH, O'Loughlin JE, Davis JG, Devereux RB. Phenotypic features and impact of beta blocker or calcium antagonist therapy on aortic lumen size in the Marfan syndrome. Am J Cardiol 1999;83:1364-8.

Send letter to journal:
Re: Role of beta-adrenergic blocker in Marfan syndrome with aortic root dilatation - Authors' response

In a reaction to our article,[1] in which the natural history of cardiovascular manifestations in 52 children and adolescents with Marfan syndrome is described, Dr Venugopalan highlights the role of beta-adrenergic blocker therapy in retarding the progress of aortic dilatation.[2] As stated on page 135 of the Discussion in our article, the use and effectiveness of this prophylactic pharmacotherapy was well-known to us.[3] However, as no valid studies proving the effectiveness of this medication in children were available during our study period (1981-1997) and as there were worries regarding possible adverse side-effects, very few children or adolescents managed by the Marfan Clinics of our hospital were prescribed beta-blockers.

The study of Rossi-Foulkes et al,[4] reporting positive effects of beta-blockade in a cohort of children and adolescents with Marfan syndrome was published only after submission of our paper. Along with the good results of similar treatment strategies in adult Marfan patients in our hospital, this lead us to prescribe beta-blocker therapy also in paediatric and adolescent patients.

As most Marfan clinics will probably have adjusted their treatment protocols in children in a similar manner, future gathering of information on the natural history of cardiovascular manifestations in children will hardly (if at all) be possible. Therefore, our study offers a tool allowing future comparison of aortic growth and complications in untreated children with Marfan syndrome ('natural history') to those who were treated with beta-blockers.

References
(1) van Karnebeek CDM, Naeff MSJ, Mulder BJM, Hennekam RCM, Offringa M. Natural history of cardiovascular manifestations in Marfan syndrome. Arch Dis Child 2001;84:129-37.

(2) Venugopalan P. Role of beta-adrenergic blockade therapy in children with Marfan syndrome and aortic root dilatation [eLetter]. Arch Dis Child 23 February 2001. http://adc.bmjjournals.com/cgi/eletters/archdischild;84/2/129#EL2

(3) Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome. N Engl J Med 1994;330:1335-41.

(4) Rossi-Foulkes R, Roman MJ, Rosen SE, Kramer-Fox R, Ehlers KH, O'Loughlin JE, Davis JG, Devereux RB. Phenotypic features and impact of beta blocker or calcium antagonist therapy on aortic lumen size in the Marfan syndrome. Am J Cardiol 1999;83:1364-8.