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Ann Thorac Surg 1998;66:68-72
© 1998 The Society of Thoracic Surgeons

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Original articles: cardiovascular

Surgical management of mitral regurgitation associated with marfan’s syndrome

^a Department of Cardiovascular Surgery, Broussais Hospital, Paris, France
^b Department of Pathology, Broussais Hospital, Paris, France

Accepted for publication February 5, 1998.

Address reprint requests to Dr Fuzellier, Department of Cardiovascular Surgery, Broussais Hospital, 96 rue Didot, 75014 Paris, France

	Abstract

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Background. The surgical treatment of mitral regurgitation associated with Marfan’s syndrome remains controversial because of the underlying degenerative process.

Methods. From October 1986 to June 1996, 33 patients with Marfan’s syndrome underwent a mitral valve procedure. The mean age was 30 years (range, 2 to 55 years). Mitral regurgitation was caused by annulus dilatation in 2 patients, leaflet prolapse in 30 patients, and restricted leaflet motion in 1 patient. Mitral valve repair was performed in all patients except 1 who had mitral valve replacement.

Results. Two patients died in the perioperative period. All survivors were available for follow-up, which ranged from 1 month to 122 months (mean follow-up, 39 months). There were three late deaths, two of which were related to aortic complications. The actuarial survival rate was 78.9% at 10 years. Freedom from mitral valve reoperation was 87.1% at 10 years. Echocardiographic studies were obtained in all survivors and showed absent or mild (1+) mitral regurgitation in 21 patients and moderate (2+) mitral regurgitation in 3.

Conclusions. Mitral valve repair for mitral regurgitation in patients with Marfan’s syndrome can be performed safely in almost all instances. This technique provided stable midterm results comparable with those obtained for other degenerative mitral valve diseases.

	Introduction

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Marfan’s syndrome is an autosomal dominant heritable disorder of connective tissue involving the skeletal, ocular, and cardiovascular systems [1] caused by alteration in the synthesis of fibrillin. Patients with Marfan’s syndrome have a shortened life expectancy because of cardiovascular complications of the disease [2, 3]. Mitral valve dysfunction is present in 80% of patients with Marfan’s syndrome [4, 5] and is the most common cause of morbidity and mortality in infants with Marfan’s syndrome [6]. The optimal surgical management of mitral regurgitation in Marfan’s syndrome remains controversial, the question being whether mitral valve repair in this context is suitable or whether the underlying connective tissue defect will compromise repair durability. The aim of the present study was to examine the clinical and histologic patterns of the mitral valve in patients with Marfan’s syndrome who underwent a mitral valve procedure for mitral regurgitation and to evaluate the midterm results of the surgical operation.

	Material and methods

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From October 1986 to June 1996, 33 patients with Marfan’s syndrome had operation for mitral regurgitation in our institution. There were 15 male and 18 female patients ranging from 2 to 55 years old (mean age, 30 ± 14 years). Seven patients were younger than 20 years. All patients had criteria of Marfan’s syndrome as established by consensus at a conference in Berlin [7]. The diagnosis of Marfan’s syndrome was based on the presence of clinical manifestations as follows: involvement of at least two of three systems (ocular, cardiovascular, and skeletal) if a first-degree relative was affected or involvement of all three systems if a first-degree relative was not affected. Patients who had undergone a previous mitral valve procedure were excluded from this study.

At the time of operation, 5 patients (15.2%) were in New York Heart Association class I, 18 (54.5%) were in class II, 9 (27.3%) were in class III, and 1 patient (3%) was in class IV. The cardiothoracic ratio ranged from 0.45 to 0.8 (mean ratio, 0.55 ± 0.1). There were 7 patients (21.2%) in atrial fibrillation. Three patients had had a previous surgical procedure: aortic valve replacement in 2 and operation for aortic dissection in 1.

Preoperative Doppler echocardiographic study was used to assess the severity of the mitral regurgitation: 29 patients had grade 3+ to 4+ mitral regurgitation, and 4 patients had grade 2+. Mitral regurgitation was classified into three functional types according to the classification of Carpentier and associates [8]: type I, normal leaflet motion; type II, leaflet prolapse; and type III, restricted leaflet motion. Two patients (6.1%) had type I; 30 (90.9%) had type II (prolapse of the anterior leaflet, 7 patients [21.2%]; prolapse of the posterior leaflet, 9 [27.3%]; and prolapse of both leaflets, 14 [42.4%]); and 1 patient (3.0%) had type III. The mean left ventricular end-diastolic and end-systolic diameters were 66.9 ± 9.4 mm and 42.1 ± 9.4 mm, respectively.

Operative techniques
Standard hypothermic (28°C) cardiopulmonary bypass with bicaval cannulation was performed in all patients. Cold blood cardioplegia was used for myocardial protection. The mitral valve was approached through the left atrial roof after dissection of the atrioventricular groove. The valve was analyzed systematically using functional classification and segmental analysis as described by Carpentier and coworkers [9]. Prolapse of one or both leaflets was the most frequent dysfunction. The annulus was dilated in all patients, and this dilatation was the only dysfunction in 2 patients. The lesions responsible for the mitral regurgitation were as follows: chordal elongation, 24 patients (72.7%); chordal rupture of the posterior leaflet, 8 (24.2%); chordal rupture of the anterior leaflet, 6 (18.2%); congenital malformation, 2 (6.1%); and annulus calcification, 8 (24.2%).

Thirty-two patients underwent mitral valve repair using Carpentier’s techniques [8] (Table 1). Chordal elongation was the lesion most frequently responsible for leaflet prolapse. Elongation often involved all chords and necessitated use of all the techniques of chordal shortening. When the chords of the posterior leaflet were elongated, resection of the posterior leaflet was performed. For the anterior leaflet, the abnormality could be corrected either by chordal shortening by embedding the chord into the papillary muscle or by papillary muscle shortening when all chords were elongated. Decalcification of the annulus was performed in 5 patients as previously described [10]. The mean size of the prosthetic ring for annuloplasty was large (35 mm) because of the importance of dilation of the annulus and the need to avoid systolic anterior motion, a great concern in these patients.

Associated procedures were performed in 12 patients. These operations included a Bentall procedure in 3 patients, aortic valve replacement in 3, aortic valvuloplasty in 2, tricuspid valve repair in 6, and repair of an atrial septal defect in 2. Mean cardiopulmonary bypass time was 130 ± 47 minutes, and mean cross-clamp time was 88 ± 43 minutes.

Histologic examination
Histologic examination of resected valve tissue from 18 patients was performed. Slides were stained with hematoxylin and eosin, Alcian blue for myxomatous changes, and orcein for elastic fibers.

Method of follow-up
Follow-up was accomplished through questionnaires and telephone calls to patients and referring cardiologists. Follow-up was available on all patients. The mean follow-up was 39 months (range, 1 month to 122 months).

The frequency of late deaths and reoperations was obtained actuarially by the Kaplan-Meier method. This study followed the recommendations of the Ad Hoc Liaison Committee for Standardizing Definition of Prosthetic Heart Valve Morbidity [11].

	Results

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Early results
The in-hospital mortality rate was 6.1% (2 patients). The causes of death were multiple-organ failure in 1 patient who had an associated operation for aortic dissection and sudden death in the other. Postoperative complications included chronic complete atrioventricular block in 1 patient and low cardiac output syndrome in another. No reoperations were necessary in the immediate postoperative period.

Histologic findings
In all specimens, there were alterations in the pattern of arrangement of collagen bundles, quantitative and structural abnormalities in the elastic fibers observed in leaflets and chordae tendineae, and myxomatous changes (Fig 1).

View larger version (142K): [in this window] [in a new window]   Fig 1. Histologic sections of mitral valve showing alterations in elastic fibers of leaflet. Elastic fibers are disrupted, fragmented, and granular and form amorphous clumps (arrows). (Orcein elastic stain; A, x40, and B, x250 before 3% reduction.) (A = auricularis; F = fibrosa; S = spongiosa.)

View larger version (9K): [in this window] [in a new window]   Fig 2. Actuarial survival.

View larger version (9K): [in this window] [in a new window]   Fig 3. Freedom from reoperation for mitral regurgitation.

Current status
At the time of follow-up, all patients were in New York Heart Association class I or II. Twenty-five patients (89%) were in sinus rythm and 3 (11%), in atrial fibrillation. Among the survivors, 24 patients had their native valve. All of these patients underwent echocardiography postoperatively. Twelve patients had no mitral regurgitation, 9 had mild regurgitation, and 3 had moderate regurgitation (Table 2). The mean left ventricular end-diastolic and end-systolic diameters were 58.1 ± 8 mm and 36 ± 7.5 mm, respectively. All patients had normal left ventricular function as defined by a shortening fraction greater than 0.27.

	Comment

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Pathologic involvement of the mitral valve is frequently seen in patients with Marfan’s syndrome. Echocardiographic studies in patients with this syndrome reveal mitral valve dysfunction in 60% to 80% [1, 4]. Mitral valve dysfunction often precedes aortic involvement and progresses in childhood, and 1 patient in 8 will have development of moderate or severe mitral regurgitation [1].

Study population
In this series, the mean age was 30 years, which is comparable to that in other series of patients with Marfan’s syndrome having operation for mitral regurgitation. Mitral dysfunction without aortic disease was the primary indication for operation in 66% of patients. Seventy percent of patients were asymptomatic or mildly symptomatic. Indications in these patients were based on the importance of the regurgitation or the dilatation of the left cardiac cavities when mitral regurgitation was moderate.

Lesions and surgical techniques
There is a consensus regarding the surgical management of the aortic lesions in Marfan’s syndrome, but controversy continues to exist about the surgical management of the mitral valve dysfunction. According to Sirak and Ressallat [13], the underlying tissue and the anterior leaflet abnormalities prohibit mitral valve repair. However, this study is old, and currently, mitral valve repairs using Carpentier’s techniques have attained excellent long-term results, especially in degenerative mitral valve diseases [14–16]. Lesions responsible for mitral regurgitation in Marfan’s syndrome necessitate the use of all techniques of valve repair.

The preponderant mitral valve dysfunction found in our patients with Marfan’s syndrome was leaflet prolapse involving the anterior leaflet, the posterior leaflet, or both. Prolapse was due to chordal elongation or chordal rupture. Prolapse of the anterior leaflet, present in 64% of our patients, does not present a surgical challenge and can be repaired by simple and safe procedures [8] including chordal transposition and shortening.

Calcification of the annulus is often present in patients with Marfan’s syndrome (24% of patients in our series). The pathophysiology of mitral annulus calcification is a subject of controversy: mechanical factors through excess tension on the leaflets as a result of excess tissue and leaflet prolapse and chemical factors through proteoglycans and collagen alteration caused by the underlying degenerative tissue play a role in the genesis of these calcifications [10]. Extensive calcification of the annulus does not contraindicate reconstructive techniques [10]. Ring annuloplasty was used in all patients but 1 because of the important annulus dilatation, often associated with mitral regurgitation in Marfan’s syndrome.

Mitral valve repair can be performed in almost all these patients. However, the technique must be complete and take into consideration all the lesions of the mitral valve, even extensive calcification of the annulus. In this experience, we were able to perform valve repair in all patients except 1. The sole valve replacement was performed because of extension of calcification into the ventricular myocardium. In the John Hopkins Hospital experience [17], repair could be done in only 80% of patients because of annulus calcification or anterior leaflet abnormalities. This difference between studies could be due to the necessary learning curve in complex mitral valve repair.

Late results
The benefits of reconstructive surgical procedures versus replacement surgical procedures are well recognized. These include preservation of ventricular function, decreased risk of endocarditis and thromboembolism, and no long-term anticoagulation. These benefits are important in patients with Marfan’s syndrome, who usually comprise a young age group with a high risk of aortic dissection. Our results with a longer follow-up confirm results obtained in a preceding series [17]. The long-term outcome for mitral valve repair in Marfan’s syndrome is similar to that obtained with this technique for other degenerative mitral valve diseases. The durability was demonstrated by echocardiography. Freedom from mitral valve reoperation was 87% at 10 years, the same as for other degenerative diseases [14].

The durability of mitral repair does not seem to be affected by the underlying connective tissue defect. In the present series, we found histologic changes involving the leaflets and chordae similar to those found by others at postmortem examination of patients with Marfan’s syndrome [18]. The lesions also included myxomatous changes in the leaflets and chordae and alterations in collagen and elastic fibers. It is noteworthy that the histologic changes in our series did not seem to be specific and were similar to those seen in patients with other degenerative diseases [19]. Therefore, mitral valve lesions in patients with Marfan’s syndrome do not preclude reconstruction.

The factors affecting the prognosis in terms of mortality and morbidity depend on the aortic complications. In our series, there were two late reoperations for aortic regurgitation and two late deaths related to aortic complications. Recent data [20] suggest that increasing patient age is associated with more severe histologic abnormalities in cardiovascular tissue in Marfan’s syndrome. In our series, the older patients were not more likely to be severely affected by Marfan’s syndrome.

In conclusion, mitral valve repair for mitral regurgitation in patients with Marfan’s syndrome offers long-term results similar to those obtained in other degenerative mitral valve diseases. This technique can be performed in almost all patients despite the frequent occurrence of annulus calcification and for us, was the treatment of choice for patients with Marfan’s syndrome. Our histologic findings suggest that the mitral lesions in patients with Marfan’s syndrome are unlikely to compromise mitral valve repair. The long-term prognosis depends mainly on the aortic complications once the mitral regurgitation has been corrected.

	References

Top Abstract Introduction Material and methods Results Comment References

 

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