**2.5. Diagnosis of the aortic affectation in the MFS**

440 Aneurysm

the aneurysms.

limited.

aneurysms.

*Molecular biomarkers* 

*Biomarkers in plasma and serum* 

killer. It has been demonstrated in studies the presence of population of natural killer lymphocytes in greater number in patients with abdominal aortic aneurysm compared with healthy subjects. The CD 28 T-lymphocytes appear in diverse inflammatory disorders, and express in a more frequent form with the age. It has been observed in patients with aneurysms greater quantity of this cellular type in peripheral blood compared to healthy controls. In addition, on a contradictory way, highest rates are found in patients with smaller aneurysms in comparison with patients with big aneurysms, appearing the hypothesis about the intervention of Cd 28 T-lymphocytes in the genesis of

Several circulating biomarkers have been identified with the aneurysms, in relation to their appearance, diameter or expansion. These can be classify in inflammation biomarkers, indicators of tissue turnover, and others as homocysteine, serum amyloid A, osteopontin,

Inflammation biomarkers have been the more widely studied. At present, the formation of the aortic aneurysm is understood as an inflammatory process. Many studies relate diverse inflammatory cytokines (interleukin-1, interleukin-6, tumor necrosis factor-α, interferon γ and cold-reactive proteins) to the formation, expansion or rupture of the aneurysm. Its disadvantage is the lack of specificity, being able to rise their concentrations in other inflammatory processes, reason why their clinical utility as aortic aneurysm biomarker is

Special mention is deserved to the matrix metallooproteinases (MMPs). Their main function is the degradation of the extracelular matrix. The MMPs are active in many pathological processes, either in trivial ones as periodontitis or others more serious as heart failure. In experimental models with animals, there has been demonstrated that MMP's inhibition, by genetic deletion directed or by pharmacological intervention, determines a minor progression of the abdominal aortic aneurysms. In patients with abdominal aortic aneurysm, the circulating concentrations of MMP-9 presented a direct correlation with the concentrations of MMP-9 in the aortic wall. It has been observed an increase in the concentration of MMP-1 and MMP-9 in the thoracic aortic walls with aneurysms or dissections in comparison with healthy controls. It has also been observed an increase of the quotient MMP-9/TIMP-1 (tissue inhibitor of metalloproteinases-1), favoring the proteolysis of the aortic wall. Other studies have documented a correlation of MMP's activity, especially MMP-9, with the genesis and evolution of the thoracic aortic

It has been studied the RNA of circulating leukocytes and there have been identified characteristics of expression that relate to the appearance of thoracic aneurysms, with an accuracy up to 78%. In the same line, there has been identified a hyperexpression of certain

osteoprotegerin and the concentrations of plasmin / antiplasmin complex.

In a summarized form, the management of the aortic pathology in the MFS is based on the clinical study and imaging techniques to detect and to quantify the progression of the aortic expansion [7].

The initial clinical evaluation of every patient with MFS's suspicion must include anamnesis and a complete clinical examination. The diagnosis of certainty can be reached in almost 90% of the cases through the Ghent´s nosology, being able to be completed by the genetic study as we have described before. To complete the information about diagnostic criteria (table 1) we will carry out an imaging test that allows to evaluate the ascending aorta and the cardiac valves.

The transthoracic echocardiogram (TTE) represents the main technique for the diagnosis of the cardiovascular affectation in the initial evaluation of patients with MFS, allowing to explore the aortic root, the proximal ascending aorta and the aortic arch. The maximum diameters of the aortic annulus, Valsalva sinus, sinotubular junction and of the ascending aorta must be measured perpendicularly to the longitudinal axis of the aorta. The obtained information will be compared in nomogramas with the expected values according to the age, the sex and the corporal surface. The severity of the aortic affectation relates to the degree and the extension of the dilatation, being most important when it spreads from the root over the ascending aorta up to the aortic arch. The second TTE will be carried out at 6 months of the diagnosis to determine the speed of growth. If the diameter remains stable, the ultrasonic study can be realized anually, but if accelerated expansion is detected or when it comes closer to 45mm, the evaluation will have to be more frequent (table 7).

In spite of the fact that the transthoracic echocardiogram is the most used technique to monitor the size of the aortic root, its precision depends on the operator. The computerized tomography (CT) or the magnetic resonance (MRI) are more precise and must be used if the echocardiogram does not give a suitable image of the aorta. It is advisable to know that the echocardiographic measures, being realized between internal edges, can be up to 4mm lower than the obtained ones with MRI or CT, in which the thickness of the wall joins.

**Anamnesis, physical examination, echocardiogram: At the beginning and at the 6 monthsa Later: every year, if the growth rate is stable and without complicationsa**

#### **CT or MRI:**

If there is aortic dilatation or dissection.

After the surgery, before the discharge, at 6 months, and then anually.

The evaluation will be more frequent as the aortic root approaches 45mm or if it is registered an accelerated rate of growth (> 5 mm / year)

a Class I recommendation, level of evidence C.

b It is consider of utility to correct the aortic diameters in accordance with the age and the corporal size (class IIa, level of evidence C).

**Table 7.** Cardiovascular follow-up in Marfan's syndrome
