Marfan syndrome is a multisystemic connective tissue disorder associated with a mutation affecting fibrillin-1, the main component of microfibrils. Fibrillin-1 gene mutations may affect the carotid arterial wall. The aim of this study was to investigate carotid arterial mechanics using Velocity Vector Imaging (VVI) in patients with Marfan syndrome.
Forty-five patients (26 men; mean age, 39 ± 10 years) with Marfan syndrome who fulfilled the Ghent criteria and 45 gender-matched and age-matched healthy volunteers were evaluated. Transverse images of right common carotid artery proximal to the bifurcation were obtained for each subject and divided into six segments. The peak radial velocity, circumferential strain, and strain rate of the six segments were analyzed using VVI. The time to peak radial velocity ( T s ), peak circumferential strain ( T st ), and peak strain rate ( T sr ) of the six segments were calculated. Intima-media thickness was measured for each subject.
The average diameter of the common carotid artery in patients with Marfan syndrome was significantly larger than that of controls. Carotid compliance coefficients and distensibility coefficients as assessed by B-mode echocardiographic images were comparable between the two groups. In VVI analyses, averages and standard deviations of peak radial velocities, circumferential strain, and strain rates were not significantly different between the two groups. However, T s , T st , and T sr were more delayed ( P < .01), and the standard deviations of T s , T st , and T sr were significantly larger in patients with Marfan syndrome ( P = .01, P < .01, and P < .01, respectively), suggesting delayed and dyssynchronous arterial expansion during systole. The presence of Marfan syndrome was independently and significantly related to increased standard deviations of T st (β = 0.33, P < .01) and T sr (β = 0.44, P < .01), even after adjusting for age in multiple regression analysis.
In patients with Marfan syndrome, carotid arteries assessed with VVI exhibited delayed, dyssynchronous arterial expansion during systole compared with healthy controls. Arterial assessment using VVI may be useful for noninvasively quantifying vascular alterations associated with Marfan syndrome.
Marfan syndrome is an autosomal dominant, multisystemic connective tissue disorder. Mutations of the gene coding for fibrillin-1, the main component of microfibrils, account for the cardinal features of Marfan syndrome. Microfibrils are the key constituents of extracellular elastic fibers and play an important role in regulating transforming growth factor–β, which relates to extracellular degeneration. Both the structural abnormality of the extracellular matrix and the dysregulation of transforming growth factor–β are responsible for the cardiovascular manifestations of Marfan syndrome. Increased fragmentation and disarray of elastic fibers and abnormal collagen deposits result in progressive aortic dilation and dissection, which are the major causes of morbidity and mortality in Marfan syndrome. Although pathologic changes of the aortic wall have been evaluated extensively, few studies have investigated the properties of peripheral arteries in Marfan syndrome.
Because pathologic changes of the aortic wall may also occur in peripheral arteries via similar mechanisms, we hypothesized that carotid arteries may exhibit abnormal vascular characteristics in Marfan syndrome. Therefore, the purpose of our study was to investigate carotid arterial mechanics using Velocity Vector Imaging (VVI) in patients with Marfan syndrome.
Forty-five patients (26 men; mean age, 39 ± 10 years) with Marfan syndrome who fulfilled the Ghent criteria and 45 gender-matched and age-matched healthy volunteers were evaluated prospectively. Patients with arrhythmia, diabetes mellitus, hypertension, dyslipidemia, significant coronary or peripheral artery disease, renal failure (serum creatinine > 1.5 mg/dL), hepatic dysfunction (transaminase levels > 2.5 times the upper limit of normal), or systemic inflammatory disease were excluded from the study. Patients with aortic regurgitation more than grade I were also excluded. This study was approved by our institutional ethics committee and complied with the Declaration of Helsinki.
All subjects refrained from coffee, alcohol, and tobacco use for 24 hours before echocardiographic evaluation. After subjects rested for 5 min, the right carotid arteries were examined by a single sonographer, blinded to subject details, with a high-resolution, real-time, 8-MHz linear scanner (Sequoia C512; Siemens Medical Solutions USA, Inc., Mountain View, CA). Optimal longitudinal and cross-sectional B-mode images of the common carotid artery (CCA) proximal to the bifurcation were obtained and stored digitally. Carotid diameters were measured at 1 cm below the origin of the right carotid bulb. Systolic and diastolic diameters were defined as the distance between the two leading edges of the far and near wall lumen-intima interfaces. Systolic diameters were measured at the maximal diameter of the CCA and diastolic diameters were measured at the moment of QRS onset. The mean and maximum carotid intima-media thickness of the far walls of the CCA were measured 1 cm proximal to the bifurcation on the highest quality end-diastolic frame using an automated edge-detection method program on an offline workstation (Syngo US Workplace; Siemens Medical Solutions USA, Inc.).
Carotid Artery Elasticity Indices
The elastic properties of the CCA were assessed by the distensibility coefficient, compliance coefficient, and β stiffness index. Distensibility coefficient, compliance coefficient, and stiffness indices were calculated as follows :
distensibility coefficient ( mm Hg – 1 ) = ( A s − A d / A d ) / ( P s − P d ) , compliance coefficient ( mm 2 · mm Hg − 1 ) = A s − A d / ( P s − P d ) , and β stiffness index = ln ( P s / P d ) / [ ( D s − D d ) / D d ] ,