Summary
Aim
To evaluate the evolution of surgical management in a large population of patients with Marfan syndrome.
Methods
This is a retrospective study of patients fulfilling the Ghent criteria for Marfan syndrome, who visited the Centre de référence national pour le syndrome de Marfan et apparentés and underwent a surgical event before or during follow-up in the centre.
Results
One thousand and ninety-seven patients with Marfan syndrome, according to international criteria, came to the clinic between 1996 and 2010. Aortic surgery was performed in 249 patients (22.7%; 20 children and 229 adults), including the Bentall procedure in 140 patients (56%) and valve-sparing surgery in 88 patients (35%); a supracoronary graft was performed in 19 patients (7.6%), usually for aortic dissection. During the past 20 years, the predominant reason for aortic surgery has switched from aortic dissection to aortic dilatation, while age at surgery has tended to increase (from 32.4 ± 11.9 years to 35.2 ± 12.4 years; P = 0.075). Mitral valve surgery was performed in 61 patients (5.6%; six children and 55 adults), including 37 valvuloplasties (60.6%) and 18 mitral valve replacements (29.5%). No significant difference was observed when comparing mitral valve surgery before and after 2000.
Conclusion
Surgery performed in patients with Marfan syndrome has switched from emergency surgery for aortic dissection to elective surgery for aortic dilatation; this is associated with surgery performed at an older age despite the indication for surgery having decreased from 60 mm to 50 mm. No significant evolution was observed for mitral valve surgery.
Résumé
But
Apprécier l’évolution de la prise en charge chirurgicale des patients présentant un syndrome de Marfan.
Méthodes
Étude rétrospective portant sur les patients qui ont été vu au Centre national de référence pour le syndrome de Marfan et apparentés, remplissant les critères de Ghent et ayant subi une intervention chirurgicale avant ou pendant leur suivi dans le centre.
Résultats
Mille quatre-vingt dix-sept patients présentant un syndrome de Marfan selon les critères internationaux ont été vus entre 1996 et 2010. La chirurgie aortique a été pratiquée chez 249 (22,7 % ; 20 enfants et 229 adultes), soit une intervention de Bentall ( n = 140, 56 %), soit une intervention préservant la valve aortique ( n = 88, 35 %). Chez les 19 derniers patients (7,6 %), un tube sus-coronaire a été mis en place, en règle pour dissection aortique. Au cours des 20 dernières années, l’indication principale de la chirurgie a changé de dissection aortique à dilatation aortique, ce alors que l’âge de la chirurgie avait tendance à augmenter (32,4 ± 11,9 ans vs 35,2 ± 12,4 ans, avant et après 2000 ; p = 0,075). La chirurgie valvulaire mitrale a été pratiquée chez 61 patients (5,6 % ; six enfants et 55 adultes), à type de plastie chez 37 (60,6 %) et de remplacement valvulaire chez 18 (29,5 %). Les chiffres restent similaires avant et après l’année 2000.
Conclusion
La chirurgie réalisée chez les patients présentant un syndrome de Marfan et autrefois principalement une chirurgie d’urgence pour dissection est maintenant surtout une chirurgie programmée pour dilatation aortique. Cela alors que les patients sont opérés plus tard alors que le seuil chirurgical a baissé de 60 à 50 mm. Les indications et le type de chirurgie mitrale n’ont pas évolué.
Background
Marfan syndrome (MFS) is a connective tissue disorder with dominant autosomal inheritance and a prevalence of around 1/5000, mostly related to mutations in the gene coding for fibrillin 1 . The cardinal features of MFS involve the ocular, cardiovascular and skeletal systems , but aortic enlargement and dissection, mostly of the ascending aorta, was the primary cause of early death before 1970 . Much progress has been made in the understanding of this disease, with the recognition of the role of fibrillin 1 , the description of new pathologies related to mutations in transforming growth factor-beta (TGF-β) receptors , the implication of the TGF-β pathway in aneurismal aortic diseases, etc. . Advances have also been made in the global care of MFS patients, with the installation of “Centres de référence” and “Centres de competence”, through the “Plan maladies rares”. In parallel, the life expectancy of MFS patients has improved by 30 years over the past 30 years , probably as a result of better recognition of the disease, diffusion of medical therapy (including beta-blockers) and monitoring of the aortic root diameter, allowing for preventive aortic root replacement . However, the modification of patient care during this period is not documented other than by surgical series, i.e. reflecting the evolution of care in specific high-volume centres. Besides, because the populations studied were usually not completely characterized according to international criteria, the series mostly comprise aortic aneurysm patients rather than MFS patients.
Here we take advantage of a large MFS population followed in a multidisciplinary medical clinic caring for MFS patients throughout the territory according to modern standards, to study the evolution of surgical care over the years.
Methods
Population
All patients who came to the Centre de référence pour le syndrome de Marfan et apparentés between 1996 and 2010 were considered for this retrospective study, which was performed using the patient files. Diagnosis of MFS was based upon the Ghent criteria, which were evaluated systematically in all patients, except for mutation screening and dural ectasia detection, which were performed only when considered necessary for diagnosis or optimal patient or family care. To be included in this study, patients had to have a confirmed diagnosis of MFS and to have undergone a surgical event (either aortic or mitral). This is therefore a series of consecutive patients seen in our outpatient clinic who had been operated on because of MFS.
Surgery could have been performed either before the patients came to the Centre de référence or during follow-up, in different places, although usually in France.
Surgery
Aortic surgery
Only surgery of the ascending aorta was considered in this study. Aortic surgery was divided into supracoronary grafting versus replacement of the sinuses of Valsalva. Within surgery including replacement of the sinuses of Valsalva, valve-sparing surgery was distinguished from the Bentall procedure using either a bioprosthesis or a mechanical aortic valve. The reason for surgery was also evaluated (aortic dissection or aortic dilatation). Because aortic valve regurgitation is secondary to aortic dilatation in this population and requires surgery for an aortic diameter above our surgical threshold (50 mm), aortic surgery was considered to be performed for aortic dilatation even if in a few patients aortic regurgitation may have been the revealing factor.
Mitral valve surgery
Mitral valve replacement was distinguished from mitral valve preservation.
Data presentation and statistics
Descriptive data are presented as mean value ± standard deviation or frequency and percentage, as appropriate. The Chi 2 test was used to compare percentages and the Wilcoxon rank-sum test was used to compare age at surgery before and after 2000.
Results
A total of 4218 patients were screened for MFS in our clinic between 1996 to 2010; 57% lived in Paris or a close suburb, while the remainder came from all over the French territory. Of these, 1097 fulfilled the Ghent criteria for MFS (540 men and 557 women); 356 were first seen as children (i.e. aged < 18 years) and 741 were first seen as adults; the mean age at last consultation was 32.2 ± 16.7 years.
Surgery of the ascending aorta was performed in 249 patients, i.e. 22.7% of the whole population, comprising 20 children (5.6% of the children) and 229 adults (30.9% of the adult population). Aortic surgery included aortic valve replacement in 140 patients and aortic valve sparing in 88 patients (two unknown). In the remaining 19 patients (7.6%), a supracoronary graft was performed, i.e. in 92.4% of the patients, the sinuses of Valsalva were replaced. The reason for surgery was aortic dilatation in 67% of patients and aortic dissection in the remaining 33%. A supracoronary graft was performed mainly when aortic dissection was the reason for surgery (14/19 patients).
Surgery of the mitral valve was performed in 61 patients (5.6%), comprising six children (1.7% of the children; five valvuloplasties and one mitral valve replacement) and 55 adults (4.8% of the adults; 37 valvuloplasties and 18 mitral valve replacements).
During the past 20 years, important changes in surgical practice have occurred ( Fig. 1 ): The main reason for aortic surgery has changed from aortic dissection to aortic dilatation (which represented 54% of aortic valve surgery before 2000 vs 77% after 2000; P < 0.0001). The type of aortic surgery has switched from aortic valve replacement to aortic valve-sparing surgery (18% before 2000 vs 59% after 2000; P < 0.0001). However, these changes were not due to earlier aortic surgery as the patients who had operations on the ascending aorta before 2000 tended to be slightly younger than patients operated on during or after 2000 (32.4 ± 11.9 years vs 35.2 ± 12.4 years; P = 0.076; Fig. 2 ).
