The role of advanced echocardiography and cardiovascular magnetic resonance in the assessment of myocardial function in Marfan syndrome-An update.

Cardiovascular assessment of patients with Marfan syndrome has normally focused on the aortic root and vascular manifestations of the disease due to the high risk of aortic dissection. Although primary myocardial impairment has long been suspected in these patients, the evidence has been controversial. Advanced echocardiography and cardiovascular magnetic resonance imaging have proven to be effective, accurate, and more sensitive in the detection of subtle cardiac dysfunction. The application of these techniques to Marfan syndrome over the last 10 years has made significant progress in demonstrating the presence of primary myocardial impairment in these patients, but further work is still required to obtain confirmatory molecular, pathophysiological, and prognostic clinical data. Phenotypic expression of the disease has prognostic value, also suggesting potential effective medical therapy.

Value of two-dimensional speckle tracking and real time three-dimensional echocardiography for the identification of subclinical left ventricular dysfunction in patients referred for routine echocardiography.

BACKGROUND: While speckle tracking echocardiography (2DSTE) can be used to study longitudinal, circumferential, and radial function, real time 3D echocardiography (3DE) generates dynamic time-volume curves, offering a wide array of new parameters for characterizing mechanical and volumetric properties of the left ventricle (LV). Our aim was to investigate the merit of these new techniques to separate normal from abnormal echocardiograms as well as to identify subclinical disease in reportedly normal subjects. METHODS: Eighty-one patients (mean age 61 ± 16 years) underwent standard 2D echocardiography (2DE) enhanced by 2DSTE and 3DE. The data included LV volumes and ejection fraction (EF), velocities, strain/strain rate, and peak ejection/filling rates. The patients were divided into Group 1: normal (n = 42) and Group 2: abnormal (n = 39) on the basis of an expert interpretation of the resting 2DE. RESULTS: Global longitudinal strain (%) was 17 ± 4 in Group1 and 14 ± 4 in Group2 (P < 0.002). Strain rates (SR, 1/sec) at peak systole (1.1 ± 0.2 vs 0.9 ± 0.3, P < 0.001) and early diastole (1.3 ± 0.3 vs 0.9 ± 0.3, P < 0.001) were also higher in Group1. Three-dimensional peak ejection and filling rates (EDV/sec) were significantly higher in Group1 (-2.5 ± 0.4 vs -2.1 ± 0.7, and 1.8 ± 0.2 vs 1.5 ± 0.5, P < 0.002, P < 0.001, respectively). The best discriminatory power for predicting a normal 2DE was systolic SR with a sensitivity of 82% and a specificity of 54% using a cutoff value of 1.09. Interestingly, 19/41 (46%) of Group1 patients had systolic SR < 1.09, suggesting subclinical disease. CONCLUSIONS: 2DSTE and 3DE can discriminate between normal and abnormal echocardiograms and have the potential to detect subclinical LV dysfunction.

Assessment of aortic stiffness in marfan syndrome using two-dimensional and Doppler echocardiography.

BACKGROUND: Extracellular matrix remodeling in the aortic wall results in increased aortic stiffness (AoS) in Marfan syndrome (MFS). Pulsed-wave velocity (PWV) constitutes the best indirect AoS measurement. We aimed to assess PWV in MFS patients using two-dimensional (2D) and Doppler echocardiography. METHODS: Thirty-one MFS patients, (mean age 31 ± 14 years, 16 men) and 31 controls were examined. Blood flow was recorded in the aorta near the aortic valve and immediately after in the descending aorta with simultaneous electrocardiography. PWV was calculated by dividing the distance between the two sample volume positions (D) by the time difference (TD) between the intervals from the QRS start to the ascending and descending aortic flow onsets. B-stiffness was also measured. RESULTS: TD (described in "Methods" section) and, aortic arch length were significantly increased in MFS patients, P < 0.001. Thus, PWV values were significantly higher in patients when compared with controls, 7.20 m/s (5.12, 9.43) versus 4.64 m/s (3.37, 6.24), P < 0.001. B-stiffness was also significantly increased in MFS patients; 5.15 (3.69, 7.65) versus 2.44 (1.82, 3.66), P < 0.001. Multiple regression analysis showed a positive association with MFS diagnosis and age, (P = 0.002 and 0.009, respectively). Reproducibility of PWV measurements was <5%. CONCLUSIONS: AoS was significantly higher in MFS patients as expected. Our data demonstrated that PWV measurements can be performed, in the absence of serious musculoskeletal abnormalities in MFS adults, as part of a cardiac ultrasound scan. This technique can be helpful in diagnosis and management in MFS.

Impaired biventricular deformation in Marfan syndrome: a strain and strain rate study in adult unoperated patients.

OBJECTIVE: To investigate the presence of any regional myocardial deformation abnormalities in Marfan syndrome (MFS) and determine the benefits of using advanced echocardiography compared to conventional techniques. BACKGROUND: Myocardial dysfunction in MFS may be caused by extracellular matrix remodeling thus, resulting in uniform reduced functionality. However, increased aortic stiffness may cause segmental ventricular abnormalities. Strain rate imaging (SRI) constitutes a validated technique to assess regional deformation in various clinical conditions. With this in mind, we aimed to investigate biventricular function in MFS using SRI. METHODS: Forty-four MFS patients (mean age 30 ± 12 years, 26 men) and 49 controls without valvular disease were examined using SRI. Ejection fraction (EF) was calculated by the Simpson's biplane method. Biventricular deformation was assessed by measuring strain/strain rate. Strain values were divided by left ventricular (LV) end-diastolic volume to adjust LV deformation for geometry changes providing a strain index (SI). Aortic stiffness was evaluated using the ß-stiffness index. RESULTS: EF (%) was reduced in MFS patients (59 ± 5 vs 72 ± 4, P < 0.001), whereas ß-stiffness was increased (P < 0.001). LV radial and LV and right ventricular (RV) long-axis strain values (%) were reduced in the patient group (70 ± 17 vs 93 ± 10; 19 ± 2 vs 25 ± 2; 30 ± 9 vs 36 ± 8, respectively, P < 0.001). Strain rate measurements were also reduced (P < 0.001). In a multiple regression analysis, MFS diagnosis was negatively associated with LV SI (-0.262 [-0.306, -0.219], P < 0.001). ß-Stiffness was negatively associated with SI obtained from the septum, inferior and anterior walls. ROC analyses demonstrated that SRI, when compared with conventional echocardiography, had higher sensitivity and specificity in predicting biventricular dysfunction in MFS. CONCLUSIONS: Our study showed a uniform reduction in biventricular deformation in MFS. These findings suggest that assessment of myocardial function using advanced echocardiographic techniques could be more accurate in MFS patient evaluation than conventional echocardiography alone.

Biventricular and atrial diastolic function assessment using conventional echocardiography and tissue-Doppler imaging in adults with Marfan syndrome.

AIMS: Previous studies provided evidence about left ventricular systolic and diastolic dysfunction in adults with Marfan syndrome (MFS). However, in the literature, data on right ventricular and bi-atrial diastolic function are limited. We aimed to investigate whether, in the absence of significant valvular disease, diastolic dysfunction is present not only in both ventricles but also in the atrial cavities. METHODS AND RESULTS: Seventy-two adult unoperated MFS patients and 73 controls without significant differences in age, sex, and body surface area from the patient group were studied using two-dimensional, pulsed, and colour-Doppler and tissue-Doppler imaging (TDI). Biventricular early filling measurements were significantly decreased in MFS patients when compared with controls (P < 0.001). Pulsed TDI early filling measurements obtained from five mitral annular regions and over the lateral tricuspid valve corner were significantly reduced in the patient group (P < 0.001). Indices reflecting atrial function at the reservoir, conduit and contractile phases were also significantly decreased in MFS patients (P < 0.001). CONCLUSION: This study demonstrated significant biventricular diastolic and biatrial systolic and diastolic dysfunction in MFS patients. Our findings suggest that MFS affects diastolic function independently. Diastolic abnormalities could be attributed to fibrillin-1 deficiency and dysregulation of transforming growth factor-beta activity in the cardiac extracellular matrix.

Impaired right ventricular systolic function demonstrated by reduced atrioventricular plane displacement in adults with Marfan syndrome.

AIMS: The right ventricle (RV) ejects the same volume of blood at the same rate as the left ventricle (LV). Mild LV dysfunction has been demonstrated in Marfan syndrome (MFS). However, little attention has been paid to the functioning of the RV. The aim of this study was to assess RV function in unoperated adult MFS patients. METHODS AND RESULTS: In 66 unoperated (15-58 years) MFS patients and 61 controls, rate of pressure rise (dp/dt) in RV, and tricuspid annular motion (TAM) were studied using conventional echocardiography and tissue Doppler imaging (TDI). When compared with controls, MFS patients showed impaired RV systolic function as expressed by a reduced dp/dt, TAM obtained by M-mode echocardiography, and peak TDI systolic velocities at the basal lateral wall (745.36+/-37.85 vs. 1103.30+/-27.30 mmHg, P<0.001; 2.2+/-0.05 vs. 2.5+/-0.05 cm, P<0.001; and 0.13+/-0.002 vs. 0.16+/-0.002 m/s, P<0.001, respectively). CONCLUSION: This study demonstrated a primary impairment of RV systolic function in MFS. This is the first study to report RV dysfunction in MFS. Such data could prove valuable during the peri-operative and long-term medical management of MFS patients.

Assessment of carotid compliance using real time vascular ultrasound image analysis in Marfan syndrome.

BACKGROUND: Fibrillin-1 deficiency, dysregulated cytokine transforming growth factor-beta, and increased collagen deposition related to fibrillin-1 gene mutations could predispose to impaired carotid compliance (CC) in Marfan syndrome (MFS). We sought to detect any alterations in CC using the vascular image analysis system (VIA). METHODS AND RESULTS: Thirty-two MFS patients, 20 men and 12 women (mean age 34.2 +/- 12.05 years), and 29 controls matched for age, sex, and body surface area (BSA) were recruited. The entire length of each carotid system was initially scanned longitudinally using a 14 MHz linear transducer. Then, a stereotactic clamp held the transducer in contact with the carotid artery. Arterial diameter changes during the cardiac cycle were recorded for 1 minute from both right (RCCA) and left common carotid arteries (LCCA) separately using the VIA system. RCCA and LCCA compliance and distensibility measurements were significantly reduced in MFS patients when compared to controls, P < 0.05. RCCA and LCCA intima-media thickness did not differ between patients and controls, P > 0.05. MFS diagnosis and age were associated with reduced CC in both carotid arteries after adjusting for variables such as, sex, BSA, heart rate, beta-blockade, intima-media thickness, and aortic root size. CONCLUSIONS: Our findings showed a reduction in CC in adult patients with MFS. This could be attributed to fibrillin-1 deficiency resulting in structural abnormalities in the carotid arterial wall.

Early impairment of left ventricular long-axis systolic function demonstrated by reduced atrioventricular plane displacement in patients with Marfan syndrome.

AIMS: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene. It has been observed that FBN1 deficient mice have reduced left ventricular (LV) systolic function which is correlated to increased transforming growth factor-beta activity. This study aimed to ascertain LV functional abnormalities in MFS patients using M-mode and tissue Doppler imaging (TDI). METHODS AND RESULTS: In 66 (15-58 years) MFS patients and 61 normal controls, ejection fraction (EF) was evaluated by Simpson's biplane method. Atrioventricular plane displacement (AVPD) obtained from five mitral annular regions was also assessed using M-mode and TDI techniques. To overcome limitations associated with conventional M-mode echocardiography, anatomical and colour anatomical M-mode were also utilized. Ejection fraction was significantly reduced in MFS patients when compared to controls (66.3 +/- 0.74 vs. 71.9 +/- 0.56, P < 0.001), although it was within the normal range. M-mode and TDI AVPD measurements obtained from lateral, septal, inferior, anterior and posterior mitral annular regions were also significantly reduced in MFS patients in comparison to controls (P <0.001, for all measurements). CONCLUSION: Left ventricular long-axis systolic function is significantly reduced in MFS patients. This data suggests that LV function should be monitored in MFS and appropriate treatment applied if necessary.

Effect of aortic stiffness on left ventricular long-axis systolic function in adults with Marfan syndrome.

INTRODUCTION: several studies have documented increased aortic stiffness in patients with Marfan syndrome (MFS) using echocardiography and magnetic resonance imaging. Recent studies have also shown primary myocardial impairment in MFS. We investigated whether left ventricular (LV) function could be further impaired when acting against a stiff vascular system. METHODS: twenty-six MFS patients (mean age 30 ± 2 years, 17 males) and 30 normal controls were examined. Mitral annular displacement, as a surrogate for LV systolic function, was evaluated from septal, anterolateral, anterior and inferior regions using M-mode and tissue Doppler imaging. Septal/anterolateral and anterior/inferior M-mode displacement measurements were normalised by dividing them by the longitudinal inner distance obtained at end diastole from the 4- and 2-chamber views, respectively. Carotid-femoral and carotid-radial (CF and CR) pulse wave velocities (PWV) were determined using an automated applanation tonometry device. Central aortic pressure was assessed by recording radial waveforms with the tonometer and central waveforms were reconstructed using a generalised transfer function. RESULTS: CF- and CR-PWV were significantly increased in the patient group (p<0.001), whilst mitral annular displacement measurements were significantly reduced (p<0.001, all regions). Regression analysis demonstrated that the disease status and CF-PWV were strongly associated with reduced LV systolic function (p<0.001, p=0.002, respectively). CONCLUSIONS: our study showed reduced LV systolic function and increased aortic stiffness in MFS patients. The efficiency of a fibrillin-1 deficient heart may be further reduced by ejection into a stiff vascular system. Care should be taken to ensure that any treatment regime addresses both increased aortic stiffness and myocardial dysfunction in MFS.