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Netherlands Heart Journal logoLink to Netherlands Heart Journal
. 2008 Nov;16(11):382–386. doi: 10.1007/BF03086183

The distal aorta in the Marfan syndrome

BJM Mulder 1
PMCID: PMC2584767  PMID: 19065277

Abstract

Prolonged survival of patients with Marfan syndrome after aortic root replacement has led to an increased number of patients with aortic complications beyond the root. Elective replacement of the aortic root removes the most important predilection site for aneurysms, but the distal aorta remains at risk. Predictors for aortic growth and adverse events in the distal aorta include aortic diameter, aortic distensiblity, previous aortic root replacement, hypertension and aortic regurgitation. After aortic dissection, the initial false lumen diameter is an independent predictor for late aneurysm formation. Although there are a few reports of short-term success after endovascular stent grafting of the descending thoracic aorta, stent grafting in patients with Marfan syndrome is not recommended unless intervention is clearly indicated and the risk of conventional open surgical repair is deemed prohibitive. Optimal long-term outcome demands lifelong radiographic follow-up and medical treatment with β-blocker therapy. After aortic dissection rigorous antihypertensive medication is of utmost importance. Losartan, an angiotensin II type I receptor antagonist, might offer the first potential for primary prevention of clinical manifestations in Marfan syndrome, but the results of clinical trials have to be awaited. (Neth Heart J 2008;16:382-6.)

Keywords: Marfan syndrome, distal aorta, aortic growth, aortic aneurysm, aortic dissection therapy, intervention

The leading cause of premature death in patients with Marfan syndrome is aortic dissection due to progressive dilation of the aorta. The abnormal fibrillin protein which results from the genetic defect that causes the disease gives rise to pathology of the aortic wall, especially of the proximal aorta. Elective repair of the aortic root has greatly improved survival of patients with Marfan syndrome. It has been recommended to replace the aortic root before the aortic diameter exceeds 50 to 55 mm.1-3 Adherence to these guidelines may lead to a substantial reduction of type A dissections in Marfan syndrome.4,5 Measurement of aortic diameters have, therefore, become a strongly recommended strategy of management (figures 1 and 2). Asymmetric dilation of the aortic root may go unnoticed as in the majority of Marfan patients the largest aortic diameter (from left to right coronary cusp) might not be detected with the standard echocardiography measurements in the long-axis view (right to noncoronary cusp).6

Figure 1 .

Figure 1

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Long-axis echocardiography showing a dilated aortic root in a patient with Marfan syndrome.

Figure 2 .

Figure 2

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MR imaging of a dilated aortic root in a patient with Marfan syndrome.

Distal aortic diameters

Prolonged survival after aortic root replacement has led to an increase in the number of patients with aortic complications beyond the root.7 Pathology of the aorta distal from the root remains a cause of concern. After surgery, many patients need second operations for aneurysms or dissections distal from the aortic root (figure 3).8,9 In fact, the Marfan syndrome may affect any vessel in which elastin fibres are an important structural component of its wall. This applies to the entire aorta, although elastin is found in diminishing quantities from its proximal to its distal part.10

Figure 3 .

Figure 3

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MR angiogram showing dilation of the abdominal aorta after previous aortic root replacement in a patient with Marfan syndrome.

In a European survey of all aortic events observed during follow-up, almost one out of three occurred in the distal aorta.11 In 18% of these patients the distal aorta was the site of first complications. In a study by Finkbohner et al., the first aortic event occurred in the distal aorta in 16% of the patients.12

Elective replacement of the aortic root removes the most important predilection site for aneurysms, but the distal aorta remains at risk. In the European survey, the rate of events involving the distal aorta increased after elective aortic root surgery. Diameters of the distal aorta were greater in patients who had than in those who had not undergone aortic root surgery.11 A clarification of this finding may be that patients who undergo elective surgery are patients with a more advanced stage of the disease. Another explanation is that intervention at the level of the root has an impact on the more distal aorta, as a result of haemodynamic factors, altered wall mechanics, or because of clamping of the aorta during the operation.

Predictors for aneurismal formation

It is widely known that an increased diameter of the proximal aorta is the strongest predictor of adverse outcome. Similarly, in the distal aorta, increased diameters have been shown to be associated with a higher risk of aortic events.11 In addition, Nollen et al. have demonstrated that a reduced distensibility of the descending thoracic aorta is a predictor of progressive dilation of the descending thoracic aorta.13 A decrease of one 10-3 mmHg-1 was associated with a fourfold increase of risk independently of aortic diameter. None of the patients with a thoracic distensibility >3.10-3 mmHg-1 had progressive descending thoracic aortic dilation.

No differences in the elasticity of the distal aorta were found between patients with and without previous elective aortic root surgery.14

Natural aortic growth rate and aneurismal formation have been studied in both children and adults with Marfan syndrome.15-20 Rapid aortic growth may occur in a small subset of patients and has been shown to be a risk factor for aortic dissection. Initial aortic diameter, a distensibility <3.10–3 mmHg-1 in the thoracic descending aorta, previous aortic root replacement, hypertension and aortic regurgitation have all been identified as predictors for rapid aortic growth.21,22 In a study of 23 female patients with Marfan syndrome and 33 pregnancies, pregnancy appeared to have a small but significant influence on long-term aortic growth in women with an aortic root diameter ≥4.0 cm.23

Aortic dissection

Patients who survive an acute aortic dissection remain at lifelong risk for aortic aneurysm formation, aortic rupture extension or recurrence of aortic dissection (figure 4). This applies both for patients with unrepaired type B dissection and for patients with repaired type A dissection. After successful repair of acute type A dissection, patients often have persistent dissection of the distal aortic segments, anatomically equivalent to a type B dissection.

Figure 4 .

Figure 4

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MR imaging of a type B dissection.

After aortic dissection, patients with Marfan syndrome are at increased risk for the development of late aneurysms compared with patients without Marfan syndrome.24

Late survival and the rate of distal aortic dilation after discharge from the hospital have been shown to be similar for patients with all types of aortic dissection and modes of therapy.25 A similar rate of aortic dilation among various types of surgery can be at least partly explained by the fact that the false lumen remains commonly patent after ascending aortic surgery for type A dissection.

In a study of 168 survivors of type A dissection, aortic diameter, elevated systolic blood pressure and presence of a patent false lumen were independent risk factors for aortic growth.26 Song et al. found the initial false lumen diameter at the upper thoracic aortic to be the most powerful independent predictor of late aneurismal change in patients with type A or type B dissections.24 A large false lumen probably reflects high false lumen pressure, which may play a critical role in dilating the false lumen itself and generating an aortic aneurysm.

Intervention: surgery or stenting?

The onset of aortic enlargement after aortic dissection is unpredictable. Therefore, careful monitoring and regular imaging of the entire aorta is essential for optimal timing of surgery or percutaneous intervention. During the last decades, remarkable advances have been made in endovascular stent-grafting repair. However, in patients with Marfan syndrome, there is limited information regarding the impact of persistent radial forces of a stent graft in the abnormal and weak aorta. Although there are few reports of short-term success after endovascular stent grafting of the descending thoracic aorta, stent grafting in patients with Marfan syndrome is not recommended unless intervention is clearly indicated and the risk of conventional open surgical repair is deemed prohibitive.27 To date, presence of Marfan syndrome has been a strict exclusion criterion in all thoracic aortic stent-graft trials. Furthermore, these patients are usually young, and because the current long-term durability of available stent grafts is unknown, stent grafting is not prudent and should be avoided. In experienced centres, open thoraco-abdominal aortic replacement can be achieved safely in such patients, with low morbidity and mortality.28 The optimal timing of surgery for a thoracic aortic aneurysm in patients with Marfan syndrome is uncertain. Indications for surgery include rapid aneurysm expansion and an aortic diameter greater than 50 mm.

Medical treatment

Current available data indicate that modification of surgical techniques cannot improve most factors associated with the degree of aortic enlargement. Thus, optimal long-term outcome demands lifelong radio-graphic follow-up. Moreover, the importance of rigorous antihypertensive medical treatment, aiming at a systolic blood pressure less than 120 mmHg, has been stressed by several experts.26 Beta-blocker therapy may be protective, independent of its effects on blood pressure, by reducing the impulse of left ventricular ejection.29,30

There are indicators that losartan, an angiotensin II type 1 receptor antagonist and a drug widely used to treat arterial hypertension in humans, offers the first potential for primary prevention of clinical manifestations in Marfan syndrome. It was originally believed that Marfan syndrome results exclusively from the production of abnormal fibrillin-1 that leads to structurally weaker connective tissue when incorporated into the extracellular matrix. This effect seemed to explain many of the clinical features of Marfan syndrome, including aortic root dilatation and acute aortic dissection. Recent molecular studies, mostly based on genetically defined mouse models of Marfan syndrome, have challenged this paradigm.31 These studies established the critical contribution of fibrillin-1 haploinsufficiency and dysregulated transforming growth factor-beta signalling to disease progression. It seems that many manifestations of Marfan syndrome are less related to a primary structural deficiency of the tissues than to altered morphogenetic and homeostatic programmes that are induced by altered transforming growth factor-beta signalling. Most important, transforming growth factor-beta antagonism, through transforming growth factor-beta neutralising antibodies or losartan, has been shown to prevent and possibly reverse aortic root dilatation, mitral valve prolapse, lung disease, and skeletal muscle dysfunction in a mouse model of Marfan syndrome.32

In the Netherlands, a large nationwide randomised study has recently been started to investigate the effect of losartan on aortic growth (www.comparestudy.nl).

Lifelong follow-up

Because of the advances in medical and surgical therapy, the life expectancy of patients with Marfan syndrome has improved substantially. Patients surviving multiple and complex re-operations have become a real challenge for cardiologists and surgeons and for aortic imaging with CMRor CT studies (figures 5 and 6).33-35 Lifelong and regular follow-up of these patients requires involvement of trained specialists with ample expertise in a tertiary referral centre.

Figure 5 .

Figure 5

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MR angiogram of a patientwith entire aortic replacement.

Figure 6 .

Figure 6

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MR angiogram showing aneurismal dilation of reimplanted islands in the descending aortic graft.

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