Background

The incidence of MFS is among the highest of any heritable disorder: about 1 in 3000/5000 births in most racial and ethnic groups. Mutations are generally inherited as autosomal dominant traits, but about one-fourth of patients have sporadic new mutations. More than 90% of patients clinically classified as having MFS by the “Ghent criteria” have a mutation in the gene for fibrillin-1 (FBN1). Mutations in the same gene are found in a few patients who do not meet the Ghent criteria. Also, a few MFS patients without mutations in the FBN1 gene have mutations in the gene for TGF-β receptor 2 (TGFBR2) [1].

The diagnosis of Marfan syndrome relies on a set of defined clinical criteria (the Ghent nosology) developed to facilitate accurate recognition of the syndrome and improve patient management and counselling. Based on modified Ghent’s criteria; If family/genetic history is not contributory, major criteria in at least two different organ systems and involvement of a third organ system. If a mutation known to cause Marfan syndrome is detected, one major criterion in an organ system and involvement of a second organ system [2].

Case Presentation

30 years, male, presented with complaints of exertional dyspnea, easy fatiguability and palpitations since three months. On evaluation he was diagnosed to have Mitral valve prolapse with severe Mitral regurgitation. Patient was a known case of Marfan’s syndrome, post Bentall’s procedure for ascending aorta aneurysm with 23mm SJM metallic valve conduit and Pectus Excavatum which required surgical correction 15 years back (Figure 1). Patient also elicited other features of modified Ghent’s criteria like Dural ectasia, positive wrist sign, Pes planus, retinal degeneration, recurrent pneumothorax, unexplained stria & history of inguinal hernia repair.

2D Echo revealed normally functioning Aortic valve prosthesis, severe mitral valve regurgitation caused by prolapse of both the leaflets into LA. Dilated LA (5.7cms), LV(LVEDD=62mm), normal LVEF=55% and trace TR. CT thorax was suggestive of densely adhered pericardium with the sternum.

Minimally Invasive technique was opted in view of Redo procedure and Right anterior thoracotomy incision was done in fourth intercostal space to avoid previous plate of pectus excavatum repair in third intercostal space. Peripheral cannulation was done using right femoral vessels and right internal jugular vein. St. Thomas blood cardioplegia was administered through aortic root and patient was cooled to 28 degrees centigrade. Mitral valve was replaced trans-LA and a 31/33 On-X metallic mitral valve prosthesis was implanted using Cor-knot technique (Figure 2). Total CPB time was 205 minutes and ACT was 112 minutes. Patient was weaned off bypass and was shifted to ICU on moderate inotropic support and ventilatory support.

Discussion

Marfan syndrome is the most common heritable connective tissue disorder with multisystem manifestations [3]. Cardiovascular manifestations include aneurysmal dilatation of the ascending aorta, aortic valvar regurgitation, aortic dissection, floppy mitral valve with mitral valve prolapse, mitral valvar regurgitation, and mitral anular dilatation [3]. If untreated, cardiovascular manifestations account for as high as 50% mortality during the first 4 decades of life [4]. Aortic root dilatation and aortic complications account for most of these deaths [4].

Mitral valve abnormalities have received little attention in the past, despite 80% of patients with Marfan syndrome having mitral valve dysfunction [3,5]. In the pediatric Marfan population, mitral valve dysfunction is the most common cause of mortality and morbidity [4]. On clinical examination and echocardiographic investigation, 60% to 80% of pediatric Marfan patients have mitral prolapse [3,5]. This is progressive: by the age of 30 years, 1 in 8 patients has moderate to severe mitral regurgitation [2]. Once the mitral valve is regurgitant, pathologic findings include fibromyxomatous changes of the leaflets and chordae, anular dilatation, calcium deposits, and elongation and rupture of the chordae [3].

Structural alterations of the mitral valve in patients with the Marfan syndrome include annular dilation, annular calcification, fibromyxomatous changes of leaflets and chordae, chordal rupture and elongation, and leaflet fenestration [6]. The latter finding may represent residua of endocarditis [6]. It has also been recently demonstrated that 15% of patients with the Marfan syndrome have abnormal chordal attachments whereby posterior leaflet chordae arise atypically from the posterior ventricular wall [7].

Patients with Marfan syndrome and mitral regurgitation have better survival with repair than with replacement. Survival and risk of reoperation for patients with Marfan syndrome were similar to those for patients with myxomatous mitral disease. These results support the use of mitral valve repair in patients with Marfan syndrome and moderate or more mitral regurgitation, including those having composite replacement of the aortic root [8].

Dietzman and colleagues [9] reported the first successful MVR in a patient with the Marfan syndrome in 1967. The following year, Sirak and Ressallat provided late follow-up data for two patients with the Marfan syndrome in whom they attempted mitral valve repair [10]. Using suture annuloplasty and posterior leaflet plication, they achieved temporary reduction of MR in both patients. Because MR recurred in both patients within 2 years, they concluded that the underlying tissue defect prohibited durable repair. Other authors subsequently concurred with this conclusion [11] and MVR became the accepted treatment of MR in the patient with the Marfan syndrome.

In patients without the Marfan syndrome, Carpentier and colleague reported 89% freedom from reoperation 9 years after repair and Cosgrove and associates noted a 2-year actuarial freedom from reoperation of 96.1% [12,13].

It has been demonstrated that mitral valve dysfunction is progressive in 56% of patients with the Marfan syndrome. Therefore, in the setting of aortic root replacement, mitral valve repair was attempted when MR is 2+ or greater. Mitral repair can be done quickly and safely in these patients, and it may obviate the need for further cardiac operations to correct progressive mitral dysfunction. Mitral valve repair in patients with the Marfan syndrome offers a challenge to the surgeon. Pronounced annular dilation, anterior leaflet disease, and ventricular remodelling that occurs after aortic root replacement can complicate mitral valve repair [6].

In our case, Minimally Invasive approach provided the patient with early recovery and lesser morbidity. Right anterior thoracotomy not only avoided the complications and morbidity related to redo sternotomy but also saved the manoeuvring of the previously placed pectus excavatum reconstruction plate. Use of Cor-knots also provided greater ease in implanting the prosthetic valve at mitral position.

Figure 1: Pre-operative radiograph showing sternal wires and chest reconstruction plate from previous Bentall’s procedure and chest wall reconstruction surgery.

Figure 2: Metallic mitral valve prosthesis implanted using Cor-knot technique.

References

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