Marfan Syndrome (MFS) Treatment & Management

No specific surgical procedure exists to cure Marfan syndrome (MFS); however, specific medical and surgical interventions may ameliorate certain aspects of the syndrome. System-specific treatment options are discussed below. Any evidence of aortic dilatation must be treated medically or surgically, before any spinal reconstruction is attempted for scoliosis. Any evidence of imminent cardiac compromise would preclude surgical intervention until that issue is addressed.

Many new areas of investigation into MFS exist. With regard to the skeletal system, investigators are seeking to discover new modalities by which to delay or reduce the progression of scoliosis and assess the effect of hypermobility on joint degeneration and deformity. Cardiovascular research has focused on trying to identify patients at risk for compromise as early as possible and to determine if medications other than beta blockers are useful in terms of their cardioprotective effects.

Some preliminary data based on murine studies indicated that an angiotensin II receptor antagonist (eg, losartan) or transforming growth factor (TGF)-β neutralizing antibodies may have the potential to reverse some of the primary clinical manifestations in MFS, such as aortic root dilatation, mitral valve prolapse, lung disease, and skeletal muscle dysfunction. ^[7]

Researchers are also focusing on the effects of laser surgery on the cornea and lens, as well as the correction of cataracts and the preservation of sight.

The majority of medical therapy as it relates to MFS has been targeted at preventing cardiovascular compromise, which is the most likely cause of demise in this patient population. ^{[29, 9, 15, 16]} Beta blockers and afterload-reducing agents are used to reduce stress on the aortic and mitral valves and the aortic root. ^[17]

Given that patients with MFS often have abnormal or prosthetic valves, all patients must receive routine antibiotic prophylaxis before undergoing procedures that could produce bacteremia. Researchers have demonstrated that the entire aorta, and especially the root, is stiffer than normal in patients with MFS.

Beta blockers have been used in attempts to decrease the onset and rate of aortic root dilatation and dissection. Studies have demonstrated a synergistic effect with regard to the reduction of aortic stiffness, decreased vascular resistance, and improved cardiac compliance when nitroprusside and beta blockers are used concomitantly.

Beta blockade is used because it is believed to reduce both inotropy and chronotropy and thereby reduce the stress on the aortic root. Nitroprusside reduces overall systemic vascular resistance, which serves to reduce overall afterload and stress on the heart. Further long-term data are needed to establish whether and to what extent these effects translate into decreased morbidity and mortality.

Some evidence suggests that angiotensin-receptor blockers (ARBs) may be useful in MFS. In a systematic review and meta-analysis comparing beta-blocker therapy with ARB therapy in patients with MFS (N = 1449; nine trials), Wang et al found that ARB-only therapy was not inferior to beta blockade alone and that combining the two approaches yielded superior therapeutic effects without significant adverse effects. ^[30]

Calcium-channel blockers (eg, verapamil) and angiotenson-coverting enzyme inhibitors (ACEIs) have also been investigated with respect to potential effects on cardiovascular physiology in patients with MFS. ^[29]

Scoliosis is the most common major skeletal deformity encountered in patients with MFS that necessitates intervention. No specific medicinal intervention exists to treat scoliosis. Nonoperative means of treatment (eg, bracing) may be attempted but are usually unsuccessful. Scoliosis occurs in approximately 50-70% of patients with MFS and differs from idiopathic adolescent scoliosis with regard to curve pattern, progression, and symptoms. ^[31] The double major right thoracic–left lumbar curve is the most common type among patients with MFS, whereas a single pattern is usually seen in the idiopathic type. Pelvic obliquity is uncommon in both types, however.

Unfortunately, these patients often have an earlier onset of scoliosis with severely rigid, painful, and deforming curves, as well as a high incidence of curve progression. The curve progression may average 7-10° per year after the onset of scoliosis, and the curve often progresses rapidly in the early adolescent period during maximal vertebral growth. This is also in contrast to the idiopathic type, which is typically not painful and is not as progressively deforming as the scoliosis in patients with MFS. Scoliosis, in combination with poor musculature and chest deformities, can cause significant respiratory compromise, which mandates early detection and prevention, if possible, in this patient population.

Nonoperative intervention for the scoliosis typically involves observation followed by the use of a thoracolumbosacral orthosis (TLSO) if the curve is mild and reveals signs of progression. Bracing is controversial; many surgeons believe that the bulk of curves in patients with MFS progress regardless of bracing and thus require operative intervention to prevent worsening deformity.

For patients with curves less than 25°, observation and serial radiographs every 3-4 months is the recommended management. When the curve is in the range of 25-40°, Milwaukee bracing or an underarm TLSO is used. This may be a bridge to future surgical intervention. Bracing is only used in patients with mild curves (ie, 25-40°) and no sagittal plane deformity (ie, thoracic lordosis or lumbar kyphosis). Bracing is not indicated for curves that are rigid, large, or have associated sagittal deformities.

Mitral valve regurgitation may become so severe that medical therapy must be replaced with surgical intervention. The mitral valve is often found to have a dilated anulus, redundant and flaccid cusps, and ruptured chordae tendineae. Mitral valve repair is undertaken if possible, to delay the eventual mitral valve replacement; this is done because these patients often present at a young age and may require further reconstructive surgery later. Surgical repair also preserves papillary muscle function and obviates chronic anticoagulation, unlike artificial valve replacement.

The ascending aorta (aortic root) or the incompetent aortic valve may also require repair. Either a composite graft or a valve-sparing technique ^[32] is performed. ^[33] The valve-sparing technique is usually performed in patients whose aorta has dilated to approximately 50 mm. Patients with widely dilated aortic roots or significantly attenuated aortic cusps typically undergo a composite graft repair. This is also the procedure of choice in the case of an acute aortic root dissection. Some surgeons advocate prophylactic composite grafting in patients who have a history of increasing aortic dilatation and a family history of sudden cardiovascular death.

The most important aspect in the preoperative evaluation of patients with MFS is to rule out any imminent cardiac compromise. A complete cardiac workup, including electrocardiography (ECG) followed by echocardiography, is mandatory. It is well known that aortic dilatation and subsequent rupture can develop throughout these patients' childhood and adult life; thus, one must be diligent to exclude these entities before any surgical undertaking. Any evidence of aortic dilatation must be treated medically or surgically before any spinal reconstruction is attempted.

The major indication for surgery for the musculoskeletal system involves progression of moderate-to-severe scoliosis. Chest-wall deformities may also be so severe that they impact cardiopulmonary mechanics; these can be surgically corrected as well. In the past, patients with MFS did not have these chest-wall deformities addressed, and most died at an early age due to intrinsic cardiovascular disease. The advent of successful aortic root surgery as well as aortic and mitral valve replacement has changed the overall long-term outlook for patients with the disease.

Adequate treatment should be provided for those with scoliosis to reduce pain, to improve overall cosmetic appearance, and, most important, to improve pulmonary mechanics through reduction of spinal and chest-wall deformities.

It must be kept in mind that surgery for MFS differs from surgery for adolescent idiopathic scoliosis. These differences must be taken into account in surgical planning. ^[31]

As previously described, bracing can be considered in patients with mild curves (see Medical Therapy). However, most patients with MFS will have significant curve progression that eventually warrants surgical intervention. Patients with curves greater than 40-50º or with associated abnormal sagittal curvature deformities require surgery.

Posterior spinal fusion and segmental spinal instrumentation, along with autogenous bone grafting, are the mainstays of treatment. Most authors agree that scoliosis can be corrected with this approach; however, the overall incidence of complications varies in different series. Pseudoarthrosis and loss of correction can occur and are problematic; the incidence figures range from 12% to 40%.

Most authors recommend aggressive bone grafting, rigid internal fixation, and adequate patient surveillance postoperatively to diagnose complications early in the clinical course. Sagittal malalignment (kyphotic deformity) may require an anterior fusion (excision of disks) followed by posterior spinal fusion and segmental spinal instrumentation to achieve satisfactory correction of the sagittal alignment.

Complications of scoliosis surgery for MFS have been well reviewed by Levy et al. ^[34]