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.

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.

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.

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.

New approach for modelling ultrasound blood backscatter signal.

The ultrasound (US) scattered signal from blood has been treated as a random signal by many investigators. However, the degree of randomness of a medium is a relative term that can change considerably with the resolution of the sensor. In this study, the backscattered signal from blood has been looked at as a chaotic signal. By this treatment, according to Taken's theorem, a single variable (e.g., amplitude of the blood-backscattered signal) can be used to reconstruct the nonlinear dynamics of the blood-scattered signal. Multilayer perceptron neural network architecture, with error back-propagation, has been formulated and used as a basis for building and testing the chaotic model of the backscattered signal. This chaotic model is used successfully as a short-term predictor of the backscattered signal from blood-mimicking fluid (BMF) flowing in a vascular flow phantom under pulsatile flow. This modelling approach can be useful, for example, in detecting blood-borne emboli.

Microemboli detection using ultrasound backscatter.

Microemboli detection and characterisation have recently received great attention due to its clinical importance in the management of cerebrovascular disease. The new method presented in this paper is directly based on the idea that the ultrasound (US) backscattered signal from flowing blood is chaotic (El-Brawany and Nassiri 2002). The detection technique involves building a nonlinear model of the deterministic characteristics of the chaotic backscatter signal from blood, and the use of this model to look at the prediction error as a primary decision-making criterion for the microemboli detector. A complementary feature to the prediction error, namely, the degree of coherence between the US excitation pulse and the prediction error signal is used to enhance the detection process. The detector has been built using a feed-forward neural network with error back-propagation. The detection technique is tested successfully using a vascular flow phantom with solid spheres and bubbles of known sizes introduced in the flow circuit to mimic solid and gaseous emboli. Receiver operating characteristic (ROC) curve is used to assess the performance of the detection process. The total classification rate ranges from 88% to 96%.

The automated assessment of ultrasound scanner lateral and slice thickness resolution: use of the step response.

The imaging performance assessment of ultrasound scanners based on traditional phantoms is limited by repeatability, subjectivity and systematic errors giving low confidence in results. A new approach to the automated measurement of scanner resolution is described. The method utilises a step change in backscatter to derive resolution from the imaging system line spread function and has been used to calculate resolution in two dimensions as a continuous function of depth. Resolution data was used to calculate resolution integrals for both lateral and slice thickness independently. For resolution integral repeatability, analysis of variance showed no significant difference between operators (p=0.05) with intra and inter-operator repeatability (+/-1 standard deviation) of 1.5% and 1.5% for lateral resolution, respectively, and 2.6% and 3.3% for slice thickness, respectively. Low contrast penetration was also calculated automatically and the worst case operator repeatability was 1.3%. The acoustic properties of the phantom were validated. The possibility of extending the technique to axial resolution is discussed.

Development of a thermal test object for the measurement of ultrasound intracavity transducer self-heating.

The elevated surface temperature of diagnostic ultrasound transducers imposes an important limitation to their safe use in clinical situations. Moreover, particular care should be taken if transvaginal transducers are to be used during routine scans in the first few weeks of pregnancy as the transducer surface can be very close to embryonic/fetal tissues. Published results have shown that the heating of tissue due to transducer self-heating can equal and often exceed the acoustic heating contribution. In this article, we report the development of a portable self contained thermal test object (TTO) capable of assessing the self-heating of intracavity diagnostic ultrasound transducers. The thermal conductivity and volumetric heat capacity of the tissue mimicking material (TMM) used in the TTO were measured, yielding values of (0.56 +/- 0.01) W m(-1) K(-1) and (3.5 +/- 0.8) MJ m(-3) K(-1). The speed of sound of the TMM was measured as 1540 m s(-1) and the attenuation over a frequency range of 2 to 10 MHz was found to be (0.50 +/- 0.01) dB cm(-1) MHz(-1). These results are in excellent agreement with the International Electrotechnical Commission (IEC 60601-2-37) requirements and the previously published properties of biological soft tissue. The temperature stability and uniformity, and suitability of the TTO for the measurement of transducer self-heating were tested and found to be satisfactory. The TTO reached a stable temperature of 37 degrees C in 3 h and the spatial variation in temperature was less than +/- 0.2 degrees C. Lastly, transducer self-heating measurements from a transvaginal transducer exceeded the IEC temperature limit of 43 degrees C in less than 5 min and the temperature reached after 30 min was 47.3 degrees C.

Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X.

AIMS: Endothelial dysfunction and subangiographic atheroma have been reported in patients with cardiac syndrome X (CSX) but little is known regarding chronic inflammation and reduced arterial distensibility as pathogenic mechanisms. We assessed whether markers of inflammation and arterial distensibility differ in CSX patients compared to control subjects. METHODS AND RESULTS: We studied 30 consecutive CSX patients (mean age 57+/-6 years, 25 women) and 30 healthy controls (mean age 54+/-8 years, 25 women). High sensitivity C-reactive protein (hs-CRP) levels were significantly higher in patients with CSX compared to controls (2.6 [1.7-4.5] vs 1.5[0.7-2.7] mg/l, P=0.02). Hs-CRP levels correlated with carotid intima-media thickness (IMT) (Spearman's rho=0.51; P=0.013). CSX patients also had significantly increased mean IMT values than controls (P<0.0001). Arterial stiffness and elastic modulus were also significantly increased in CSX patients compared to control subjects (P=0.04 and P=0.04, respectively). Distensibility tended to be lower in CSX patients than controls although this difference did not reach statistical significance. CONCLUSIONS: This study showed for the first time that compared to control subjects, patients with CSX have higher hs-CRP serum levels, increased mean common carotid artery IMT and increased arterial stiffness. The role of these abnormalities in the pathogenesis of CSX deserves investigation.