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Ann Thorac Surg 1997;64:1140-1144
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Cardiac Operations in Children With Marfan's Syndrome: Indications and Results

Division of Cardiac Surgery and Center for Medical Genetics, The Johns Hopkins Medical Institutions, Baltimore, Maryland

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. The development of new screening techniques for the early detection of Marfan's syndrome has prompted evaluation of the results of cardiac operations in children with this syndrome. The purpose of this study was to determine the surgical indications, operative results, and need for reoperation in children with Marfan's syndrome.

Methods. From 1980 to 1996, 245 patients underwent cardiac operations for complications of Marfan's syndrome; 26 (11%) were less than 18 years of age. The mean age at the time of operation was 10.3 ± 1 years (range, 8 months to 17 years); 18 of the patients were male. Indications for operation were aortic root dilatation (15 patients), mitral regurgitation (4 patients), aortic root dilatation and mitral regurgitation (6 patients), and aortic arch aneurysm (1 patient). Operations included aortic root replacement (15 patients), aortic root replacement and mitral repair (5 patients), aortic root replacement and mitral replacement (1 patient), mitral repair (3 patients), mitral replacement (1 patient), and arch aneurysm repair (1 patient). The mean aortic root diameter in patients undergoing aortic root replacement was 6.2 ± 0.2 cm. Only 1 patient underwent ascending aortic dissection.

Results. There were no operative deaths. At a mean follow-up of 67.1 ± 10.2 months, 8 patients required a second cardiac procedure (41% ± 17% 10-year freedom from reoperation). Indications for further operations were distal aortic pathology (3 patients), aortic root dilatation after initial mitral operation (3 patients), failed mitral repair (1 patient), and homograft degeneration (1 patient). Risk factors for a second cardiac procedure were age less than 10 years at the time of the first operation (p < 0.003) and mitral regurgitation (p < 0.04). Overall, 25 (96%) of 26 patients have undergone aortic root replacement and 11 (42%) patients have undergone a mitral procedure. There have been 4 late deaths, all of presumed cardiac origin. The 10-year survival rate is 79% ± 10%. All surviving patients are in New York Heart Association functional class I or II.

Conclusions. We conclude that (1) aortic root dilatation is the most common surgical indication in children with Marfan's syndrome, (2) mitral regurgitation is the second most common indication, (3) aortic dissection is unusual in children with Marfan's syndrome, and (4) careful follow-up is necessary, particularly in younger children, because more than half of all children with Marfan's syndrome require repeated cardiac operations within 10 years.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
See also page 1144.

Marfan's syndrome is the most common heritable disorder of connective tissue; it is characterized by cardiovascular, skeletal, and ocular abnormalities [1]. Left untreated, cardiovascular manifestations of Marfan's syndrome cause death in half of all patients within the first four decades of life [2]. Recent data demonstrate that surgical intervention significantly prolongs survival in adults with Marfan's syndrome [3, 4].

Although numerous studies document the safety and efficacy of cardiac operations in adults with Marfan's syndrome [3–5], there are few data concerning the results of such operations in children with Marfan's syndrome. The development of new screening techniques for the early detection of Marfan's syndrome will result in a higher proportion of cases being diagnosed during childhood. The purpose of this study was to determine the surgical indications, operative results, and incidence of reoperation in children with Marfan's syndrome.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Patients
More than 400 patients with Marfan's syndrome are evaluated each year in the Center for Medical Genetics of The Johns Hopkins Hospital; 90% of the patients in this series were referred from that clinic. From January 1980 to January 1996, 245 patients underwent cardiac operations for complications of Marfan's syndrome. Twenty-six (11%) of these patients were less than 18 years of age at the time of operation; they form the subject of this report. All the patients met standard diagnostic criteria for the Marfan syndrome, which include family history and characteristic cardiovascular, skeletal, and ocular manifestations [1].

There were 18 boys and 8 girls. Seven (27%) patients had a family history of Marfan's syndrome. The mean age at the time of diagnosis of Marfan's syndrome was 1.5 ± 0.6 years (range, birth to 12 years). The mean age at the time of operation was 10.3 ± 1 years (range, 8 months to 17 years). Four patients underwent operations before the age of 2 years. The mean interval between diagnosis and operation was 9 ± 1.1 years (range, 9 months to 15.8 years).

Seven patients had undergone previous thoracic operations: repair of pectus excavatum (6 patients) and ligation of a patent ductus arteriosus (1 patient). Eighteen patients were treated with ß-blocker medications before operation. Ten patients were in New York Heart Association functional class III or IV; the mean preoperative New York Heart Association functional class was 2.0 ± 0.2. All patients underwent preoperative echocardiograms, and Table 1 documents the findings of these studies.

Surgical Techniques
Standard hypothermic (28°C) cardiopulmonary bypass and crystalloid potassium cardioplegic arrest were used for all cases. Replacement of the aortic root by modified Bentall technique has been described in detail elsewhere [5, 6]. Techniques for mitral valve repair and replacement also have been described previously [7].

Statistical Analyses
Unless otherwise indicated, all values are expressed as means ± standard errors of the mean. Risk factors for reoperation were assessed using ² analysis. The Kaplan-Meier method was used to calculate the actuarial probability of survival and freedom from reoperation.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Indications for operation were aortic root dilatation (15 patients), mitral regurgitation (4 patients), aortic root dilatation and mitral regurgitation (6 patients), and aortic arch aneurysm (1 patient). The mean aortic root diameter among those with aortic root dilatation was 6.2 ± 0.2 cm (range, 5 to 10 cm). Nine of 21 patients with aortic root dilatation had 2+ or greater aortic insufficiency; however, only 3 patients had 3+ or 4+ aortic insufficiency. One patient had ascending aortic dissection; this was not suspected before operation and was identified at operation. The 4 patients who had mitral regurgitation as the sole indication for operation all were severely affected by Marfan's syndrome, and they were the only patients who required operation before the age of 2 years.

All operations were performed electively. Table 2 lists the operations performed. Prostheses chosen for aortic root replacement were composite grafts in 15 patients (12 St. Jude Medical [St. Paul, MN] and 3 Björk-Shiley [Irvine, CA]) and homografts in 6 patients. The diameters of the aortic prostheses ranged from 19 to 27 mm. When possible, mitral regurgitation was treated by mitral valve repair rather than mitral valve replacement. Associated procedures included repair of an atrial septal defect (2 patients), ligation of a patent ductus arteriosus (2 patients), repair of pectus carinatum (2 patients), repair of the tricuspid valve (1 patient), and bypass grafting of the coronary arteries (1 patient). There were no operative deaths. Operative complications included heart block necessitating a permanent pacemaker (2 patients), low cardiac output (2 patients), pericardial effusion requiring drainage (1 patient), failed mitral valve repair (1 patient), and injury to the left anterior descending coronary artery during aortic root replacement necessitating a saphenous vein bypass graft (1 patient).

View larger version (13K): [in this window] [in a new window]   Fig 1. . Kaplan-Meier curve of late survival after cardiac operations in children with Marfan's syndrome. Error bars indicate 70% confidence intervals. The number of patients entering each time interval is indicated beneath each point.

View larger version (14K): [in this window] [in a new window]   Fig 2. . Kaplan-Meier curve of freedom from reoperation after cardiac operations in children with Marfan's syndrome. Error bars indicate 70% confidence intervals. The number of patients entering each time interval is indicated beneath each point.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Marfan's syndrome is a heritable disorder of the connective tissue caused by a mutation in the fibrillin gene on chromosome 15 [8]. The connective tissue defect affects approximately 1 in 10,000 individuals and results in characteristic cardiovascular, ocular, and skeletal abnormalities [1, 8]. Murdoch and associates [2] demonstrated that early mortality in patients with Marfan's syndrome is attributable to cardiovascular features of the disease. In their review, aortic dilatation and its complications (eg, dissection, valvular insufficiency) accounted for 80% of premature deaths [2]. Since Murdoch's 1972 publication, advances in cardiac surgery have increased the life expectancy of patients with Marfan's syndrome [3, 4]. Numerous studies demonstrate that aortic root replacement can be accomplished with low operative mortality and good long-term survival [3–5]. The median survival for patients with Marfan's syndrome currently is 72 years, whereas it was 48 years in 1972 [3].

Most published reports concern the evaluation and treatment of adults with Marfan's syndrome, but Antoine Marfan's index case reported in 1896 was a 5-year-old child [9]. Recent advances in screening for Marfan's syndrome have refocused attention on children with the syndrome. Improvements in echocardiography and identification of the gene responsible for Marfan's syndrome allow diagnosis in some cases before all the phenotypic manifestations become evident [10–12]. In selected cases, prenatal diagnosis of Marfan's syndrome is possible [11].

Manifestations of Marfan's syndrome in childhood are variable. Mitral valve prolapse is present in nearly 100% of affected children, and aortic root dilatation is found in more than 80% [12, 13]. Aortic root dilatation and mitral valve dysfunction tend to progress with time [13]. Children with no family history of Marfan's syndrome and those in whom the condition is diagnosed before 10 years of age tend to have more severe cardiovascular manifestations [12, 14]. In severely affected infants, mitral regurgitation tends to be the predominant cause of morbidity and mortality [12–14]. Although they have been reported, aortic rupture and aortic dissection are unusual in children less than 10 years of age [14, 15].

At most surgical centers, adults comprise the majority of patients undergoing cardiac operations for complications of Marfan's syndrome. Whereas surgical indications for adults are well established [5–7], few data are available concerning surgical indications for children with Marfan's syndrome. The indications that we have used are similar to those for adults and include severe mitral regurgitation (3 to 4+), severe aortic regurgitation (3 to 4+), and ascending aortic aneurysm. The decision to replace the aortic root in a child must be individualized, taking into account the size of the aortic root, the size of the patient, the rate of dilatation of the aorta on serial studies, and aortic valve function. Type A aortic dissection is a common surgical indication in adults, but we have not recognized ascending aortic dissection before operation in any child with Marfan's syndrome.

In this study, we report the results of operations in 26 children with Marfan's syndrome. Four severely affected patients who were less than 2 years old at the time of operation had mitral regurgitation as their primary surgical indication. Three of these children have required subsequent aortic root replacement, and 2 have died of cardiac causes. This confirms previous reports documenting the unfavorable prognosis in severely affected infants with mitral valve disease [13]. All other patients had aortic pathology as the main indication for operation; in most of these children, operation was not necessary until the age of 10 years or older. Recent studies have demonstrated that increasing age is associated with more pronounced fibrillin abnormalities in the aortic root of patients with Marfan's syndrome [16]. This may explain why operations for aortic root dilatation usually are not necessary within the first 10 years of life. Still, with the exception of severely affected infants with mitral valve disease, aortic root dilatation remains the most common indication for cardiac operations in children with Marfan's syndrome, as reported by Tsang and associates [15].

Operative strategies for the treatment of aortic root dilatation may differ in children and adults with Marfan's syndrome. In adults, a composite graft usually is the aortic root prosthesis of choice [15, 16]. Although composite grafts were used in most children in this series, we also offer homografts to young children who require aortic root replacement to avoid the need for anticoagulation. In contrast, significant mitral valve disease in both adults and children has been treated by mitral valve repair when possible. This generally is successful, and the intermediate results of mitral valve repair in patients with Marfan's syndrome are good [7]. We do not delay mitral valve operations to perform concomitant aortic and mitral valve operations if the aortic root is dilated mildly to moderately.

The results of cardiac operations in children with Marfan's syndrome compare favorably with those in adults. The Kaplan-Meier estimate of 10-year survival for children is 79% ± 10%. Most contemporary series report 70% to 80% 10-year survival rates in adults undergoing cardiac operations for complications of Marfan's syndrome [5, 17]. The 4 late deaths in this series all have been of cardiac origin, demonstrating that cardiac operations cannot eliminate all cardiovascular morbidity and mortality associated with Marfan's syndrome. The primary morbidity has been the need for reoperation. The incidence of reoperation in children is higher than that in adults undergoing cardiac operations for complications of Marfan's syndrome [3, 5, 17]. In adults, aortic dissection is associated with an increased incidence of late reoperation [4]. Aortic dissection is uncommon in children with Marfan's syndrome. The most common indications for a second cardiac procedure in children were distal aortic pathology and aortic root dilatation after initial mitral valve operation.

Risk factors for a second cardiac procedure were younger age at the time of the first operation and mitral regurgitation. Children clearly have a higher incidence of significant mitral valve dysfunction than adults, and this almost certainly is one reason for the higher rate of reoperation [7, 12]. Of note, 2 of the 3 children who required a second operation for distal aortic pathology were not treated with ß-blockers after the first operation. It is possible that ß-blocker therapy might reduce the rate of aortic dilatation and eliminate the need for further operations in some patients [18]. All children with Marfan's syndrome require annual imaging of the cardiac valves and aorta.

In conclusion, operations for cardiovascular complications of Marfan's syndrome can be performed in children with low operative morbidity and mortality. The primary surgical indication in severely affected young children is mitral regurgitation, whereas that in older patients is aortic root dilatation. Ascending aortic dissection and rupture are rare during the first 10 years of life, but children with Marfan's syndrome who have undergone operation require careful follow-up, because more than half will require a second cardiac procedure within 10 years of the first operation.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Presented at the Thirty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Feb 3–5, 1997.

Address reprint requests to Dr Cameron, The Johns Hopkins Hospital, 600 N Wolfe St, Blalock 618, Baltimore, MD 21287.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

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7. Gillinov AM, Hulyalkar A, Cameron DE, et al. Mitral valve operation in patients with the Marfan syndrome. J Thorac Cardiovasc Surg 1994;107:724–31.[Abstract/Free Full Text]
8. Tsipouras P, Del Mastro R, Sarfarazi M, et al. Genetic linkage of the Marfan syndrome, ectopia lentis, and congenital contractural arachnodactyly to the fibrillin genes on chromosomes 15 and 5. N Engl J Med 1992;326:905–9.[Medline]
9. Marfan AB. Un cas de deformation congenitale des quatres membres, plus pronouncée aux extremitiés, caracterisée pour l'allongement des os avec un certain degree d'amincussement. Bul Sox Chir Paris 1896;13:220–5.
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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): A. Marc Gillinov Kenton J. Zehr Vincent L. Gott Bruce A. Reitz John C. Laschinger Duke E. Cameron Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gillinov, A. M. Articles by Cameron, D. E. Search for Related Content PubMed PubMed Citation Articles by Gillinov, A. M. Articles by Cameron, D. E. Related Collections Related Article