Objectives. The purpose of our study was to identify the suitability of various skeletal muscles as reference regions for calculating the T2 SI ratio for a semiautomated quantification of the extent of myocardial edema with T2-weighted images. Methods. Thirty-four patients with acute myocardial infarction (MI) were enrolled. The extent of myocardial edema was determined by T2 SI ratio map, using 4 different muscles as reference: major and minor pectoralis, serratus anterior, teres minor-infraspinatus, and subscapularis. The size of myocardial edema as visually quantified was used as the standard of truth. The control group consisted of 15 patients with chronic MI. Intra- and interobserver variability were assessed. Results. Due to poor image quality four patients were excluded from the analysis. In acute MI patients, serratus anterior muscle showed the strongest correlation with the visual analysis  and low inter- and intraobserver variability, while the other muscles resulted in a significant interobserver variability. In contrast, the use of other muscles as a reference led to overestimating edema size. Conclusions. In acute MI patients, serratus anterior resulted to be the most reliable and reproducible muscle for measuring the extent of myocardial edema. Myocardial edema has evolved as a novel noninvasive tool for assessing the acuity of heart diseases in experimental –3 and clThe most frequently used CMR sequence for assessing myocardial edema is the segmented Fast Spin Echo technique with a triple inversion recovery preparation, which suppresses the signal from blood flow and fat . Beyond We aimed to identify the suitability of various skeletal muscles as reference regions for calculating the T2 SI ratio using the edematous area measured visually on T2-weighted images as a standard of truth, in patients with acute myocardial infarction.We retrospectively selected 34 consecutive patients presenting with acute, first-time STEMI, who underwent CMR at 1.5 T within 5 days from onset of symptoms (mean time to reperfusion was 337 minutes). Patients were excluded if they were clinically unstable or had severe arrhythmias or known contraindications to CMR. A diagnosis of MI was based on infarct-typical ECG changes combined with a >2-fold elevation of creatine kinase and/or positive troponin T. Infarct localization was performed via coronary angiography which identified the territory of the culprit vessel.The control group consisted of 15 patients who underwent a CMR follow-up 5 months after the acute myocardial infarction (chronic MI). The time between the first and the second CMR scan was 160 ± 25 days. None of the 15 patients had any clinical events between the two CMR studies.Patients gave written informed consent and the study was approved by our internal review board.CMR examinations were performed using a 1.5 T MRI system . Localization was performed by using real-time, breath-hold, and steady state free precession images of true anatomic axes of the heart.The CMR protocol included cine steady state free precession (SSFP) CMR images for left ventricular (LV) function in a short axis orientation from base to apex, for a total of 8 to 10 slices. Cine SSFP images were obtained using the following parameters: repetition time (TR) 3.2 ms, echo time (TE) 1.07 ms, flip angle 65°, slice thickness 10 mm, no interslice gap, matrix 125 × 192, field of view ranging from 340 to 400 mm, and voxel size 1.7 × 1.7 × 10 mm. T2-w images were obtained using a breath-hold, triple inversion recovery sequence  61 ms, inversion time (TI) 170 ms, and flip angle 180°) in a short axis plane  using a body coil in the same slice orientation as the cine SSFP images.42, Circle Cardiovascular Imaging Inc., Calgary, AB, Canada), using cine images of the same cardiac phase for verifying wall thickness and the correct identification of the skeletal muscle. The endocardial and epicardial borders of the LV myocardium were manually traced in each T2-w slice excluding trabeculae and papillary muscles. The T2 SI ratio was calculated by dividing the SI of the myocardium by the SI of skeletal muscle in the same slice [The T2 SI in T2-w images was quantified with certified software , after 4 weeks by the same reader . To test interobserver agreement a second reader  performed the T2 analysis separately in the same 20 patients (10 patients with acute MI and 10 patients with chronic MI).t-tests using PASW Advanced Statistics 19.0.0 . Differences were considered significant if the two-tailed P value was less than 0.05. Pearson correlation coefficient calculations were used to determine the linear relationship between sample observations with a significant correlation occurring when the P value was less than 0.05. Anova analysis was performed to compare edema mass average values. Bland Altman plots [The difference between measurements was assessed with paired an plots  were gent-tests.Chronic patient data were also analyzed using paired We studied 34 patients, four patients were excluded due to poor quality T2-w images, leaving 30 patients  with 168 T2-w images considered suitable for analysis. Detailed patients population characteristics are reported in P value (<0.01) confirming that average values are different. Quantified visually, the edematous area was strongly correlated with the area determined by the T2 SI ratio, when the muscles serratus anterior, the subscapularis, and a combination of major and minor pectoralis muscles were used (P ≤ 0.001), while the serratus anterior showed the strongest correlation (r = 0.799) . There was no significant difference between the extent of T2-w SI measured with the 4 different muscles and the visual analysis, although the serratus anterior showed a tendency to underestimate the edematous area  . The areous area .P = 0.142, P < 0.005, P = 0.389, P = 0.715, P = 0.059 and 0.140, resp., For evaluations using the serratus anterior, the interobserver variability for the edematous area was low and there was no significant difference between readers , muscle serratus anterior was visualized in 95/111 slices (85.6%), muscle subscapularis was visualized in 98/111 slices (88.3%), and a combination of teres minor and infraspinatus muscles was visualized in 95/111 slices (85.6%).The mean size of the T2-w hyperintense area in patients with chronic MI was 1.5 ± 0.6 g using serratus anterior muscle, whereas for the subscapularis muscle, a combination of infraspinatus and teres minor muscles, and a combination of major and minor pectoralis muscles, it was 21.6 ± 5.2 g, 44.5 ± 8.9 g, and 26.7 ± 7.6 g, respectively . An examP = 0.065, P = 0.039, P = 0.580, P = 0.672, Using the muscle serratus anterior as a reference, there was no significant interobserver variability . Furthermore in those patients, evaluation using the serratus anterior muscle as a reference also showed low intra- and interobserver variability. These results and the Bland Altman plots suggest that the serratus anterior is the best available reference muscle when normalizing the myocardial signal intensity for a quantitative analysis of myocardial edema.Clear visibility of the muscle serratus anterior was present in 85–89%  and was mostly limited to the more basal planes. As per our results, however, a combination of the major and minor pectoralis can be used as an alternative to the serratus anterior muscle especially in the more apical planes.While a standardized method for the quantification of myocardial edema appears essential, especially in patients with diffuse edema, most studies do not specify the skeletal muscle used for the T2 SI ratio , 9, 14. z-axis, and thus is expected to be at the same level of homogeneity. Nonetheless, further studies are needed to confirm these findings and better understand the different variables involved in the assessment of edema using skeletal muscle referencing. Finally, with age, the subscapularis and teres minor-infraspinatus muscles tend to undergo atrophy and subsequent fatty replacement [The exact cause of the better performance of the serratus anterior to other muscle groups could be related to B0 field inhomogeneity as well as the location of the muscle. Using the body coil, the isocenter of the magnet has the highest level of magnetic field homogeneity. With increasing distance from the center this homogeneity decreases, which may account for a signal loss in the skeletal muscle, leading to a false high T2 SI ratio. Similarly, there is also an increased B1 inhomogeneity related to the RF pulse in the periphery of the FOV. Furthermore, among the four muscle groups the serratus anterior was the only muscle located at the same level of the LV, along the lacement . This woRecently, T2 mapping has emerged as a novel approach to assess infarct-related edema ; yet theWe used a visual analysis as a standard of truth in evaluating the area of increased T2-w signal intensity, which may be subject to observer bias. Visual analysis has been used as the standard reference for the present study, since myocardial edema cannot be histologically quantified in patients with AMI. An increased amount of free water results in a bright signal on T2-w images which can be visually seen.While detection of focal processes  is more reliable with CMR, recognition of edema in diffuse diseases  remains a major challenge in which visual analysis is of limited support and validation of a reference muscle would provide better standardization and reproducibility of results .The analysis was performed independently by an experienced observer, however, without comparing results during the analysis. Our sample is relatively small and represents patients with acute and chronic myocardial infarction only. Reflecting clinical practice, we analyzed images only in short axis views; thus, our results may be less applicable to long axis images.This study shows that the serratus anterior muscle should be the first choice for quantifying the extent of myocardial edema by calculating the T2 signal intensity ratio with a skeletal muscle reference. This is due to the availability and reliability of the serratus anterior, relative to other muscles groups. However, more studies should be performed. Our findings also demonstrate the need for the standardization of T2 signal evaluation to avoid significant variability among different readers and centers.


The assessment of left ventricular (LV) diastolic function should be an integral part of a routine examination of hypertensive patient; indeed when LV diastolic function is impaired, it is possible to have heart failure even with preserved LV ejection fraction. Left ventricular diastolic dysfunction (LVDD) occurs frequently and is associated to heart disease. Doppler echocardiography is the best tool for early LVDD diagnosis. Hypertension affects LV relaxation and when left ventricular hypertrophy (LVH) occurs, it decreases compliance too, so it is important to calculate Doppler echocardiography parameters, for diastolic function evaluation, in all hypertensive patients. The purpose of our review was to discuss about the strong relationship between LVDD and hypertension, and their relationship with LV systolic function. Furthermore, we aimed to assess the relationship between the arterial stiffness and LV structure and function in hypertensive patients. Left ventricular diastolic dysfunction (LVDD) is an earlier alteration common to many cardiovascular diseases , 2. Any To better understand how LVDD occurs, we have to start from physiopathology of LV diastole. It can be divided into four phases, starting from aortic valve closure. The first phase of diastole is the isovolumic, which does not contribute to ventricular filling. The second of early and rapid filling provides most of ventricular filling, about 60-90%. The third of slow filling, mentioned as diastasis, contributes to only 5% of the total filling. The final atrial booster phase normally accounts for the remaining 5-35%, according to the age, with an increasing contribution in elderly  Fig. 2)Fig. 2).“Isovolumic relaxation time” starts with the closure of the semilunar valves and ends with the opening of the atrioventricular ones. During this phase, there is no change in intraventricular volume , but the geometric configuration of the ventricular cavity changes, followed by a fall in ventricular pressure that becomes lower than atrial pressure. Then atrioventricular valve opens and it begins the second phase of diastole: fast ventricular filling . The iso“Ventricular fast filling time” starts with the opening of the atrioventricular valve, proceeds with increasing speed up to a maximum peak, subsequently decelerates, and ends with the beginning of the third phase. During this phase, the blood which had accumulated in the atrium while the valve was closed is poured rapidly into the ventricle, consequently the atrial pressure falls while the ventricular pressure increases. The contribution of rapid ventricular filling to total diastolic one, in healthy adults, is about 65-80% . “Fast vLVDD is an important predictor of symptoms and clinical outcomes in patients with left ventricular systolic dysfunction (LVSD) , 2, 24. However, patients with LVSD often have variability in PWD-derived indices of LVDD due to increases in LA pressure, so they are preload-dependent , 30. TisIn addition, the diastolic intraventricular pressure gradient (IVPG) can be derived from CMM imaging by mathematical calculations of the spatio-temporal distribution of the early diastolic blood flow velocities into the LV cavity , 35. IVP1. Several studies [1 is highly predictive of adverse events after acute myocardial infarction and in hypertensive cardiomyopathy, severe secondary mitral regurgitation (MR), end-stage renal disease, atrial fibrillation, and cardiomyopathic disorders. The E/E1 ratio is among the most reproducible echocardiographic parameter to estimate pulmonary capillary wedge pressure and is the preferred prognostic parameter in many cardiac conditions. While all Doppler parameters abovementioned estimate LVDD at moment of the performance, left atrial structural and functional remodeling parameters have been proposed as a barometer of diastolic burden over time and as predictor of common cardiovascular outcomes, such as atrial fibrillation, stroke, congestive heart failure, and cardiovascular death [LVDD develops early in most cardiac diseases and leads to the elevation of LV filling pressures. Therefore, echocardiographic measurements of diastolic function provide important prognostic information. E/A ratios  reflect the compensatory increase in the late  filling phase when hypertrophic LV fails to relax normally during diastole. The result is that the E/A ratio on the mitral Doppler pattern decreases or reverses. However, when LV hypertrophy increases and wall fibrosis develops, LV chamber compliance decreases and the E wave again rises. Thus, it becomes difficult to separate E/A ratios that are truly normal from pseudonormal patterns of mitral inflow. Doppler tissue can measure the actual velocity of tissue relaxation of the mitral valve annulus or the posterior wall. Clinical studies have shown the association of short mitral diastolic deceleration time (DDT) with heart failure, death and hospitalizations in patients with acute myocardial infarction  Fig. 3)Fig. 3).  studies  have shoar death , 76.Aortic stiffening is increasingly recognized as an early marker of future cardiovascular disease and mortality among general population and hypertensive patients .Classic risk scores may underestimate the risk of cardiovascular events in specific groups suitable for early prevention, such as asymptomatic hypertensive patients, often being wrongly classified as at low or moderate risk. Arterial stiffness is the most important determinant of increasing systolic and pulse pressures in ageing societies, thus giving a relevant contribution to incidence of stroke and myocardial infarction. Arterial stiffness has a predictive value for cardiovascular events, beyond classical cardiovascular risk factors and gives direct evidence of target organ damage, being itself a “tissue biomarker” . IncreasAlthough LVDD remains poorly understood, it has an important clinical significance. LV diastolic function is influenced by arterial stiffness, changing the different components of its load, modulates LV structure and function. In patients affected by arterial hypertension, the pressure-volume loop shifts to the upper right side, therefore, pulmonary congestion is induced by a significant increase in LV end-diastolic pressure. To preserve LV ejection fraction, the pressure-volume loop shifts right due to a preload increase. Therefore, the LV pressure-volume loop operates on the ascending section of the end-diastolic pressure-volume curve, consequently causing end-diastolic pressure to arise. There is a strong relationship between arterial stiffness and the diastolic properties of the left ventricle. With increasing age, arterial stiffness becomes related to LV hypertrophy and to impaired LV diastolic function , 78, 90.


Reproducibility of myocardial contour determination in cardiac magnetic resonance imaging is important, especially when determining T2* values per myocardial segment as a prognostic factor of heart failure or thalassemia. A method creating a composite image with contrasts optimized for drawing myocardial contours is introduced and compared with the standard method on a single image.A total of 36 short-axis slices from bright-blood multigradient echo (MGE) T2* scans of 21 patients were acquired at eight echo times. Four observers drew free-hand myocardial contours on one manually selected T2* image (method 1) and on one image composed by blending three images acquired at TEs providing optimum contrast-to-noise ratio between the myocardium and its surrounding regions (method 2).P < 0.001) with smaller Coefficient of variance (CoV) of T2* values in the presence of myocardial iron accumulation (9.79 vs. 15.91 %) and in both global myocardial and mid-ventricular septum regions .Myocardial contouring by method 2 met higher interobserver reproducibility than method 1 (The use of contrast-optimized composite images in MGE data analysis improves reproducibility of myocardial contour determination, leading to increased consistency in the calculated T2* values enhancing the diagnostic impact of this measure of iron overload. Myocardial T2* imaging has been adopted in clinical studies for non-invasive longitudinal assessment of myocardial iron deposition , 2. InfeIn myocardial T2* assessment, a single short-axis image that corresponds to a single echo time (TE) of a MGE series is generally selected to draw left ventricular (LV) epicardial and endocardial contours. Commercial software packages available for T2* calculation also rely on single image selection. Examples are the use of the first or second TE of the MGE image series  or a TE The clarity of LV epicardial and endocardial contours depends on the contrast difference between the myocardium and LVBP defining its inner border and between the myocardium with right ventricle blood pool (RVBP), epicardial fat, abdominal fat, stomach, and lung defining its outer border , 6. ReflIn clinical practice, the T2* technique as a measure of myocardial iron accumulation is applied on ROIs covering either mid-ventricular septum  or the eThe standard method for T2* assessment is manually drawing the myocardial contour on one visually selected MGE image. It is likely that contour reproducibility is affected by the choice of which MGE image is used for the tracing. As an alternative, we introduce a contrast-optimized composite image derived from those short-axis MGE images providing maximum contrast-to-noise ratio between LV myocardium and its main surrounding areas  as a new standard image in T2* assessment. The interobserver reproducibility of myocardial contouring in the T2* assessment by this new method is tested by comparing the outcomes to those made by the established manual standard method for global ROI contours as well as those limited to the mid-ventricular septum. Therefore, the purpose of this study is to provide a method for improving reproducibility of myocardial contour and T2* determination in MGE bright blood magnetic resonance imaging.This study was approved by the hospital review board, which waived informed consent since the study was retrospective and involved postprocessing of clinical data. Between February 2009 and May 2011. Twenty-one consecutive patients were examined by MGE cardiac magnetic resonance imaging in a clinical routine, including nine haematology patients  for whom determination of T2* as a measure of myocardial iron content was requested, and twelve patients suspected of cardiomyopathy . No patients were excluded.2 depending on patient size, reconstructed voxel size 1.56 × 1.56 × 10 mm3, 50 % phase resolution sampling, phase encode per cycle 5, or 16–26 cardiac cycles per breath hold, pixel bandwidth 814 Hz, and without enabling parallel imaging. In the analyses described in "Patients were examined by cardiac magnetic resonance at a 1.5 T whole body scanner  using a standard body matrix radio frequency (RF) coil of six elements and a spine matrix coil of 6–24 elements depending on the chosen field of view. A bright blood MGE sequence with a single breath hold was performed at 8 TE , repetition time 200 ms, flip angle 20°, variable field of view (237–400) × 400 mmA custom-written software for myocardial T2* assessment was developed in MATLAB version 7.14 . The software has the option to assess the T2* by manually drawing epicardial and endocardial contours on one subjectively selected TE image of MGE image series , LV myocardium, and standard deviation of air background, respectively.The contrast-optimized composite images were generated first by manual drawing, on the first TE of the MGE image series, a contour of epicardial left ventricular myocardium, LVBP, RVBP, and lung with avoiding blood vessel, and on air background staying clear of any visible artefact Fig. a, b. Theelements . Next, telements :2\documeC corresponds to the composite image, and α, β, γ are the respective short-axis MGE images providing optimum CNR between LV myocardium and LVBP, RVBP, and lung.Images with the highest mean CNR between LV myocardium with LVBP, RVBP, and lung in the MGE image series Fig. c, d werey, K, TE, T2* and C represent signal intensity, a fitting constant, echo time, myocardium transverse relaxation time including the effect of field inhomogeneity, and a constant of offset correction , respectively. For the segmental T2* analysis purposes, the AHA reference point for each slice was defined at the anterior-septal junction of LV and right ventricle [Pixel-wise myocardial T2* was calculated for 4–6 segments per slice according to the American Heart Association (AHA) 16-segment model :4\documeentricle  by the fentricle , 15.For noise determination, the evaluation of SNR of myocardium and an ROI of air background at every TE of all datasets was calculated using Eq. Four observers drew short-axis LV epicardial and endocardial contours by two procedures; method 1: the clinical standard method of drawing on one visually selected MGE image with good contrast  and method 2: our novel procedure of drawing contours on the contrast-optimized composite image. Two observers had more than 3 years cardiovascular imaging experience; the other two had less experience, nonetheless they had profound knowledge of short-axis myocardium anatomy.Hand-tracing contours were drawn independently by the observers for each of the two methods using custom-written software described above with an interval of more than 2 weeks between methods. The LV endocardial region was drawn to encompass the entire blood pool with including papillary muscles and LV trabeculae. Optimum settings of window level and width were set by the first author for method 1 and defined automatically for method 2.In method 2, selections of MGE images for maximum CNR between myocardium and its main surroundings were observer independent. Therefore in this study, the first author used the above mentioned semi-automated procedure to generate the composite images.A, B represent the contour regions and ∩, + represent the intersection and addition between regions, respectively [Lacking a gold standard, interobserver segmentation agreement of myocardial contours by the two methods was calculated using the dice similarity coefficient (DSC), which is a simple spatial overlap index that has been used for segmentation validation and shows stronger reflection of differences in location than differences in size , 20. BetThe ability of the contrast-optimized composite image in producing better CNR of myocardium and its main surroundings in one image was assessed by comparing its CNRs to the maximum CNRs between LV myocardium and LVBP, RVBP, and lung assessed on the MGE image series.Myocardial contouring agreement between observers was assessed by the DSC and presented as medians ± median absolute deviations for all observers and observers with experience of more than 3 years and less in cardiovascular imaging. The Paired Wilcoxon test was used to compare the DSC agreement in myocardial contouring by the two methods. T2* value per segment was calculated by using Eq. On each short-axis slice, the minimum segment T2* value was identified to investigate iron deposition in patients with quantification by using method 2. Using this information, short-axis slices containing segments with T2* value <20 and >20 ms were grouped. In these slices' groups, myocardial contouring agreement and segmental T2* reproducibility of the two methods for all observers were also assessed using the Paired Wilcoxon test and Bland–Altman analysis.The T2* quantification on the mid-ventricular septum and global heart regions was performed in this study on seven haematology patients with complete datasets of apical, mid-ventricular, and basal slices. The mid-ventricular septum was defined as the average of T2* values at mid-anterior septum and mid-inferior septum  and the P < 0.05 was considered statistically significant.Variability between observers by using the two methods was presented as the Coefficient of variance (CoV), which is the standard deviation of the differences between observers in each method divided by their general mean and expressed as a percentage. Reliability of the methods as assessed by the observers was tested by using a two-way random intraclass correlation coefficient (ICC), evaluating absolute agreement Statistical analyses were performed using IBM SPSS Statistics software version 20 , n = 12) and at basal 26.95 ms (n = 1).The minimum segmental T2* value per short-axis slice was used to assess  iron deposition in patients. Of the nine haematology patients, seven patients with the complete three slices had the minimum T2* in the range of 10.48–26.33 ms at apical, 8.20–27.97 ms at mid-ventricular, and 7.05–25.65 ms at basal, while two others measured at the mid-ventricular had minimum segmental T2* values of 12.72 and 17.78 ms. For the twelve suspected cardiomyopathy patients, the range of minimum segmental T2* at mid-ventricular was 12.42–36.75 ms  in which on one haematology patient the minimum segmental T2* values <10 ms encountered in apical, mid-ventricular, and basal slices. The minimum segmental T2* values <20 ms was commonly encountered at anterior and inferior segments in apical; at anterior, inferolateral and anterolateral slices in mid-ventricular; and at anterior, anteroseptal and inferolateral in basal slices.The contrast-optimized composite images were produced, as shown in Fig. In method 2, the semi-automatic analysis yielded reproducible improvements of CNR on the composite image as compared with the original MGE images. Beyond the maximum value measured at any MGE image, the composite image increased contrast by an average of 12.08 % between myocardium and LVBP ; 9.74 % between myocardium and RVBP ; and 30.33 % between myocardium and lung . On average, between myocardium and its main surroundings, the contrast improvement was 17.38 %  above maximum CNR at any TE.P < 0.001. Between observers with more than 3 years cardiovascular imaging experience, the improvements also were significant , as were those between observers with less experience in cardiovascular imaging . As expected, the respective dice coefficients were slightly lower for the less experienced observers. On short-axis slices having segments with minimum T2* < 20 and >20 ms, interobserver reproducibility improved similarly when using method 2 compared to method 1 . When myocardial contouring was done by method 1, the most frequently selected MGE images were those of TE 9.28 ms (29.9 %), 7.05 ms (24.3 %), and 4.82 ms (22.9 %). In method 1, reproducibility of contours tended to be less between observers selecting a different image for ROI drawing .The total of 36 short-axis slices yields a set of 36 DSCs of myocardial contours of short-axis images for each method, and the combination of four observers thus adds up to sets of (36 × 6 = 216) DSCs contours. Between all observers, interobserver reproducibility of myocardial contouring improved when using contrast-optimized composite images (method 2) compared to visually selected images (method 1) with DSC of 0.844 ± 0.032 vs. 0.811 ± 0.045, A total of 36 short-axis slices yields two sets of 202 segments of myocardial T2* values between two observers  and the combination of four observers, thus, adding up to two sets of (202 × 6 = 1212) segments of myocardial T2* values for each method. Standard deviations of all T2* values listed in Table In Table T2* analysis of all 16 myocardial segments as assessed by all observers on all 36 short-axis slices of the 21 patients is shown in Table This study shows on average 17 % CNR improvement using the proposed contrast-optimized composite image method 2) over any maximum contrast provided by the single image technique (method 1), providing reproducible T2* values in short-axis slices of the mid-ventricular septum as well as global heart regions. These findings may be beneficial for the use of T2* imaging in the diagnosis of thalassemia and suspected cardiomyopathy patients with borderline myocardial T2* distribution. Iron overload may be heterogeneous with septal T2* values not necessarily representative for the whole left ventricular myocardium [ over anyA recent study by House et al.  on the pEvaluation of the T2* quantification at mid-ventricular septum and global heart regions Table , T2* quaComparing the results using method 2 to other research groups for global heart T2* analysis Table , the intP < 0.001) leading to higher variability (CoV) and lower reliability (ICC) in T2* quantification in this study (Method 1) (data not shown).It was shown in this study that maximum contrast between myocardium and its surrounding borders is not likely to occur on a single MGE image. The observer’s preference in selecting an MGE image having a good contrast also reveals a range of TE values between 4.82 and 9.28 ms. The observer dependent difference in image selection did significantly contribute to the reduction of observers agreement on myocardial contouring  especially for experienced observers getting DSC above 0.85. This demonstrates the consistency of myocardial information acquired by the method [In this study, myocardial contouring was performed by the normal standard method method 1) and by our new method (method 2). In general, both methods showed good interobserver reproducibility with good overlap of myocardial contour drawing. However, even better reproducibility was obtained by method 2(e method . This re and by oP < 0.001). Importantly, in the remaining slices with segments of T2* < 20 ms indicating iron deposition as a result of pathology, the respective values were similar (P < 0.001). These results thus indicate that our newly proposed composite image method not only gives improvement in “normals” but also improves the reproducibility of myocardial contours in the presence of iron deposition as a result of focal pathology.This study documented the minimum segment T2* values in order to provide an indication of the presence of pathology, such as an increased risk of heart failure at T2* < 20 ms . In slicIn this study we thus demonstrated that the use of a contrast-optimized composite image derived from the MGE image series, as a reference image for drawing myocardial contours, leads to higher segmental T2* value reproducibility compared to the use of one visually selected MGE image. The composite image is able to optimize the contrast between the myocardium and its surroundings  on one image with even higher CNR (17 % in this study) than any individual maximum contrast between the myocardium and its surroundings, which are unlikely to be reached at one TE value. An equal weighting factor to generate contrast-optimized composite image Eq.  is used Our novel approach has the limitation that it was done on a small number of patient data for methodological purpose. A validation on a larger patient data base is encouraged to confirm the advantages of our new analysis method in clinical practice. The approach still requires manual drawing of the myocardial and its surrounding contours for composite image formation, which gives an additional task in the clinical routine workflow. Moreover, the ROIs of lung and air background must be carefully positioned to avoid any influence of blood vessels and ghosting artefacts. However, we expect that in the near future standardizing ROI drawing in an automatic manner will minimize this limitation. The MGE MRI protocol of this study did not include parallel imaging acquisition. In the latter case  uneven k-space sampling would make noise estimates tricky. However, in parallel imaging MGE studies the use of relative CNR’s rather than absolute CNR’s Eq.  would beIn conclusion, the proposed contrast-optimized composite method has proven to be effective by providing highly reproducible myocardial contours yielding more accurate T2* measurements not only in the presence of myocardial iron accumulation but also in global heart T2* and mid-ventricular septum T2* analysis. This new method profits from a standardized generation of a composite bright blood T2* MGE image, with on average 17 % improved contrast to noise ratio between LV myocardium and the surrounding tissues. This improves reproducibility of myocardial contour determination, leading to increased consistency in the calculated T2* values enhancing the diagnostic impact of this measure of iron overload.


Patients with dextro-Transposition of the Great Arteries (d-TGA) who have undergone atrial switch palliation and patients with congenitally corrected Transposition of the Great Arteries (ccTGA) have systemic right ventricles which are prone to long term dysfunction and failure. Assessment of right ventricular function by echocardiography has been challenging because of anatomical location and shape. Quantitative echocardiographic measurements have been validated in sub-pulmonary right ventricles, but are understudied in systemic right ventricles. Cardiac MRI (cMRI) is the current gold standard in RV assessment but is time consuming and expensive.27 patients with either d-TGA (n = 15) or ccTGA (n = 12) who had both a cMRI and echocardiogram within 6 months of each other were evaluated. Echocardiographic parameters of RV size including measurements at the base, mid cavity, longitudinal axis, and end diastolic area were compared to volume measurements made by cMRI. Echocardiographic parameters of function including myocardial performance index (MPI), dP/dt and fractional area change (FAC) were compared to cMRI measurements of ejection fraction. Statistical analysis was done using linear regression analysis comparing echocardiographic parameters to cMRI results in all patients in the study and in the subgroups of d-TGA and ccTGA.Echocardiographic measurements of RV size in the longitudinal axis, base, and end diastolic area were predictive of RV end-diastolic volume (RVEDV) as measured by cMRI  in the combined group of d-TGA and ccTGA. MPI, FAC and dP/dt were not predictive of RV ejection fraction (RVEF) by cMRI in the combined group of d-TGA and l-TGA. dP/dt was predictive of RVEF in patients with ccTGA .Echocardiographic measurements of RV size including longitudinal and base measurements, and end diastolic area were predictive of RVEDV as measured by cMRI in patients with systemic right ventricles. dP/dt was predictive of RVEF determined by cMRI in patients with ccTGA.None.


Movement abnormalities in the left ventricle (LV) were shown to be not really frequent in thalassemia major (TM) patients but they were associated with age, myocardial iron overload, LV dilation and dysfunction, and myocardial fibrosis. No data are available about the prevalence and the correlates of right ventricular (RV) wall motion abnormalities. This study investigated the relationship between RV and LV motion abnormalities and between RV motion and function in a large cohort of well-treated TM patients.CMR was performed in 1092 TM patients  enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. Cine images were acquired to evaluate wall motion and to quantify RV volumes and ejection fraction (EF).Abnormal motion of the LV was found in 66 (6%) patients (60 hypokinetic and 6 dyskinetic). Abnormal motion of the RV was found in 35 (3.2%) patients . Abnormal LV motion was not correlated with abnormal RV motion. Seventeen patients showed movement abnormalities in both ventricles. The Table In TM patients movement abnormalities in the right ventricle were less frequent compared to the left ventricle, but were associated with age, sex, RV dilation and dysfunction.The MIOT project receives "no-profit support" from industrial sponsorships (Chiesi Farmaceutici S.p.A. and ApoPharma Inc.). This study was also supported by: "Ministero della Salute, fondi ex art. 12 D.Lgs. 502/92 e s.m.i., ricerca sanitaria finalizzata anno 2006" and "Fondazione L. Giambrone".


Patients with systemic inflammatory diseases are at risk of heart failure due to sustained systemic inflammation leading to diffuse myocardial injury and left ventricular remodelling. Because native T1 and T2 values are raised in the presence of diffuse fibrosis and oedema, T1 and T2 mapping by cardiovascular magnetic resonance (CMR) are emerging as potential tools to assess diffuse myocardial involvement. In this study, we examined native T1 and T2 values in patients with systemic inflammatory diseases.79 patients with a clinical diagnosis of systemic inflammatory disease , rheumatoid arthritis , systemic sclerosis  and Wegener's granulomatosis  underwent CMR study for routine assessment of oedema, function and scar at 3-Tesla. 36 healthy subjects served as controls. Native T1 values were acquired using 3'3'5 MOLLI and measured conservatively within septal myocardium of midventricular short-axis slice (mSAX). T2 values were recorded from T2 maps based on GraSE sequence using equivalent cardiac geometry. We compared regional T2 values between patients and controls, and assessed associations with native T1 values.Patients showed impaired global LV systolic function compared to controls . There were no differences in LV volumes and LV mass between controls and patients' group. Patients showed LGE (SLE: n = 19 (41%); RA: n = 2 (12%); SS:n = 5(56%); WG: n = 4 (57%), which was of non-ischaemic pattern in presentation. Oedema ratio was increased in all systemic inflammatory conditions (p < 0.0001). Native T1 values were significantly raised in patients compared to controls : 1048 ± 26 vs. 1170 ± 52 vs. 1118 ± 52 vs. 1199 ± 81 vs. 1151 ± 57, p < 0.0001). There were no significant regional variations in T2 values between the segments of the mSAX slice in controls with concordant SD between the segments. Patients showed raised native T2 values : 48 ± 3 vs. 58 ± 7 vs. 54 ± 5 vs. 53 ± 3 vs. 57 ± 8, p < 0.001). Patients also showed regional differences in T2 values : SLE: 61 ± 6 vs 54 ± 8; RA: 58 ± 6 vs. 49 ± 3, SS: 59 ± 3 vs 51 ± 3, p < 0.01). There was a linear relationship between native T1 and average T2   comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital National Health Service Foundation Trust. Dr. Rocio Hinojar was supported by the Fundacion Alfonso Martin Escudero.


Heart failure (HF) is characterised by alterations in fatty acid and glucose metabolism. We aimed to determine if myocardial lipid is increased in HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction (EF), and assess whether it is related to cardiac structure and function.1H MR spectroscopy to quantify myocardial lipid/water (%).25 HFrEF due to dilated cardiomyopathy (DCM), 18 HFpEF  and 28 normal volunteers were prospectively recruited. All subjects underwent cardiovascular magnetic (MR) resonance at 3T for the determination of left ventricular (LV) volumes and function, and cardiac As expected DCM patients had significantly increased LV volumes and reduced EF, whilst HFpEF patients had significantly increased LV mass to end-diastolic volume ratio (LV mass/EDV). Importantly, cardiac lipid was increased in both HFrEF and HFpEF when compared to normal controls , with HFpEF group having the highest level of cardiac lipid (Table This is the first study to demonstrate that myocardial steatosis occurs in both HFrEF and HFpEF and is related to parameters of LV remodeling. This suggests that myocardial lipid may play a role in the pathophysiological processes of LV remodeling in both HFrEF and HFpEF. Cardiac lipid accumulation may be a potential therapeutic target in these conditions.N/A.


Delayed left ventricular (LV) lateral wall activation is considered the electrical substrate that characterises patients suitable for cardiac resynchronisation therapy (CRT). Although typically associated with left bundle branch block, delayed LV lateral wall activation may also be present in patients with non-specific intraventricular conduction delay (IVCD). We assessed LV lateral wall activation in a cohort of CRT candidates with IVCD using coronary venous electroanatomical mapping, and investigated whether baseline QRS characteristics on the ECG can identify delayed LV lateral wall activation in this group of patients.Twenty-three consecutive CRT candidates with IVCD underwent intra-procedural coronary venous electroanatomical mapping using EnSite NavX. Electrical activation time was measured in milliseconds from QRS onset and expressed as percentage of QRS duration. LV lateral wall activation was considered delayed if maximal activation time measured at the LV lateral wall (LVLW-AT) exceeded 75 % of the QRS duration. QRS morphology, duration, fragmentation, axis deviation, and left anterior/posterior fascicular block were assessed on baseline ECGs.Delayed LV lateral wall activation occurred in 12/23 patients . In these patients, the latest activated region was consistently located on the basal lateral wall. QRS duration, and prevalence of QRS fragmentation and left/right axis deviation, and left anterior/posterior fascicular block did not differ between patients with and without delayed LV lateral wall activation.Coronary venous electroanatomical mapping can be used at the time of CRT implantation to determine the presence of delayed LV lateral wall activation in patients with IVCD. QRS characteristics on the ECG seem unable to identify delayed LV lateral wall activation in this subgroup of patients. The supposed mechanism of the benefit of cardiac resynchronisation therapy (CRT) is that delayed activation of the left ventricular (LV) lateral wall causes mechanical dysfunction, which can be reverted by paced pre-excitation of this delayed LV region. Left bundle branch block (LBBB) is typically associated with early septal activation and delayed activation of the LV lateral wall –3. Non-sThe objectives of the present study were  to invesTwenty-three consecutive patients referred for CRT device implantation, with LV ejection fraction (LVEF) < 35 %, New York Heart Association (NYHA) functional class II, III or ambulatory IV, and IVCD with QRS duration ≥ 120 ms were enrolled. IVCD was defined as a QRS duration ≥ 120 ms without typical features of LBBB or RBBB, according to accepted criteria . The stuCoronary venous 3D electroanatomical mapping was performed at the time of CRT implantation as described previously . In brieAfter the mapping procedure, the LV lead was positioned in or as close as possible to the region of maximal electrical delay based on current evidence and recommendations , 15.Twelve-lead ECGs were assessed by two experienced clinicians blinded to patient data and mapping results. Any disagreement was reviewed together before achieving consensus. QRS duration was assessed in the lead with the widest QRS. The QRS axis was derived from the automatically computed value on the ECG. Left and right axis deviation, as well as the presence of left anterior and posterior fascicular block, were defined according to AHA/ACC/HRS criteria , excludip < 0.05). Statistical analysis was performed using SPSS version 22.0 (SPSS Inc.) software.Continuous variables are expressed as mean ± standard deviation and were compared using the Mann-Whitney U test. Categorical variables are expressed as observed numbers and percentage values, and were compared using Fisher’s exact test. Statistical significance was accepted at the 95 % confidence interval . Also, baseline characteristics did not differ between the two groups. In patients with delayed LV lateral wall activation, the most delayed lateral region was more frequently located on the ‘basal’ lateral wall than in patients without delayed LV lateral wall activation (p = 0.03).Delayed LV lateral wall activation, defined as maximal LVLW-AT exceeding 75 % of the total QRS duration, occurred in 12/23 (52 %) patients. In Table Figure The ECG characteristics of patients with and without delayed LV lateral wall activation are presented in Table Delayed activation of the LV lateral wall is considered the electrical substrate underlying LV dysfunction amenable to CRT, and may be present in patients without LBBB QRS morphology , 17. TheThe present study demonstrates that coronary venous electroanatomical mapping can be used at the time of CRT implantation to identify IVCD patients with delayed LV lateral wall activation.Detailed 3D LV mapping in patients with IVCD has so far been limited to a single case series recently published by Ploux et al. . The autIn patients with delayed LV lateral wall activation, the region of latest activation was similar to that observed in previous mapping studies of patients with LBBB , 6, 20. Patient selection in CRT has been primarily based on a wide QRS complex . Yet in With respect to the frontal QRS axis, neither left nor right axis deviation was associated with delayed LV lateral wall activation in the present study. Especially the lack of delayed LV lateral wall activation in patients with left axis deviation was remarkable, as this is considered a sign of LV involvement in conduction delay. A possible explanation for this finding is that in heart failure patients, axis deviation may often be the result of a change in the anatomical position of the heart due to for instance LV dilatation, rather than an actual change in the vector of electrical conduction , 23. AltGiven the fact that the presence of myocardial scar and ischaemic cardiomyopathy in a more broader sense have been shown to reduce the likelihood of a favourable response to CRT –26, we hThe present study demonstrates the presence of delayed LV lateral wall activation in approximately 50 % of IVCD patients. Admittedly, the study lacks data on acute haemodynamic response and long-term clinical outcome. Whether delayed LV lateral wall activation is also associated with CRT response in this group of patients needs to be confirmed in subsequent, larger and long-term follow-up studies. The small sample size of this study precludes extrapolating the results in our cohort of IVCD patients to larger populations. Nevertheless, the study population was large enough to demonstrate the feasibility of coronary venous electroanatomical mapping to determine the presence of delayed LV lateral wall activation in CRT candidates with IVCD.Coronary venous electroanatomical mapping can be used at the time of CRT implantation to identify IVCD patients with delayed LV lateral wall activation, who are more likely to benefit from CRT. Baseline QRS characteristics on the ECG seem unable to identify delayed LV lateral wall activation in this subgroup of patients.Frits Prinzen has received research grants from Medtronic, Boston Scientific, EBR Systems, Biological Delivery System Cordis, MSD and Proteus Medical, and is consultant for St. Jude Medical. Harry Crijns has received grant support from St. Jude Medical and Boston Scientific, and honoraria from Medtronic and BiosenseWebster. Kevin Vernooy has received research grants from Medtronic and St. Jude Medical and is consultant for Medtronic. The other authors declare no conflict of interest.


B-type natriuretic peptide (BNP) and the inactive amino-terminal pro-B-type natriuretic peptide (NT-proBNP) have a prognostic value in heart failure and in myocardial infarction. There has been some evidence that BNP and NT-proBNP can be used in the diagnosis of myocardial ischaemia by improving the sensitivity of exercise-stress testing.99mTc-sestamibi single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to diagnose reversible ischaemia, were enrolled. NT-proBNP was determined at rest and one hour after infusion of dipyridamole.To observe the relationship between dipyridamole-induced ischaemia and the secretion of NT-proBNP. Methods: A total of 52 consecutive patients, referred for dipyridamole stress Of the 52 patients, 25 had normal scans, 12 had scans with fixed defects  and 15 had reversible perfusion defects (inducible ischaemia). There was no correlation between ischaemia and resting NT-proBNP, post-stress NT-proBNP and the change in NT-proBNP. There was a correlation between ejection fraction, ventricular volumes and resting NT-proBNP.NT-proBNP does not add to the diagnosis of myocardial ischaemia in dipyridamole stress MPI. The cardiac natriuretic peptides (CNP) have been shown to be of value in the diagnosis, prognosis, treatment and monitoring of heart failure.Myocardial ischaemia can be induced using physical or pharmacological stress. Dipyridamole is often used in the setting of MPI. Dipyridamole has been shown to induce perfusion and regional wall motion abnormalities. The mechanism of this regional redistribution of blood flow is probably multifactorial. A proposed mechanism is due to steal, whereby the normal vessels vasodilate, with resultant enhanced blood flow, leaving relatively reduced pressure and flow across areas of haemodynamically important coronary artery stenoses, inducing ischaemia and regional wall motion abnormalities. Another proposed mechanism is that due to the afterload reduction of dipyridamole, there is a degree of hypotension and reflex tachycardia and this causes or contributes to the myocardial ischaemia.13Dipyridamole-induced myocardial ischaemia has also been shown to increase atrial natriuretic peptide (ANP),in vitro.There are many terms referring to the natriuretic peptides. Pro-BNP (108 AA) is cleaved by a serine protease corin into an inactive protein pro-BNP 1-76 , and into BNP 32, the active hormone, also referred to as BNP. BNP and NT-proBNP can reliably be measured The aim of this study was to observe whether dipyridamole-induced myocardial ischaemia caused a predictable change in NT-proBNP values, and whether these changes could be used to diagnose myocardial ischaemia.Fifty-two consecutive patients referred for dipyridamole stress SPECT MPI at the Nuclear Medicine Department of the Johannesburg Hospital to exclude reversible ischaemia, were enrolled into the study. The study had institutional ethics approval, and informed consent was obtained from the subjects prior to enrolment. The study period was between January and October 2006. The median age was 63 years (40−83); the male-to-female ratio was 26:26.The exclusion criteria were: asthma or severe chronic obstructive pulmonary disease, beta-blocker use, the intake of caffeine in the 24 hours preceding the test, and refusal of consent. There were no adverse reactions to dipyridamole during the time of the study.99mTc-methoxyisobutyl isonitrile (Sestamibi) SPECT MPI protocol was used. On the first day the stress test was performed, with the rest study being done on day two. Dipyridamole and 99mTc sestamibi (740 MBq) were given according to protocol. The patient was allowed to rest and images were acquired between 30 and 60 minutes after the injection of the radiotracer. Imaging was performed using a double-head rotating field-of-view gamma camera  equipped with low-energy, high-resolution, parallel-hole collimators. SPECT images were acquired on a 64 × 64 matrix using the step-and-shoot mode with a total of 180-degree angular range and 20 seconds per image.A two-day Myocardial ischaemia was assessed visually and by means of semi-quantitative scoring of the extent and severity of perfusion abnormality − summed difference score (SDS). This was calculated by subtracting the summed resting score (SRS) from the summed stress score (SSS), using the xeleris multisync work station for processing data, which was fitted with the QGS/QPS and uses a 20-segment model to quantify myocardial perfusion on an arbitrary scale. The sensitivity of the SPECT MPI technique in diagnosing ischaemic heart disease is 91% and the specificity is 81%,An SDS of more than four indicates the presence of myocardial ischaemia. This can be graded: an SDS of 4–8 is mild, 9–12 is moderate and greater than 13 is severe myocardial ischaemia. If there was any doubt about the significance of the myocardial ischaemia, the visual inspection of the MPI study was used to assess the significance of the perfusion defect.The reported timing of blood sampling for NT-proBNP is in subjects undergoing physical stress testing and in some cases where BNP is analysed in conjunction with NT-proBNP. BNP has a half-life of 19 minutes and this forms the rationale for early blood sampling when BNP is the analyte under investigation. NT-proBNP has a half-life of 90 minutes. These differing half-lives have an effect on optimal timing of blood sampling; it cannot be extrapolated that an optimal time for BNP would be optimal for NT-proBNP. A further factor to consider is that even though dipyridamole has a maximal cardiac effect after five minutes of infusion, this effect persists for 10 to 30 minutes after infusion.Blood samples were obtained at rest, 15, 30 and 60 minutes after the infusion of dipyridamole in 15 subjects. The maximal change was observed at 60 minutes. The experiment was repeated on 10 more subjects to confirm this observation, only sampling at 15 and 60 minutes A resting blood sample was obtained before the dipyridamole infusion and the post-stress blood sample was obtained one hour after the infusion in all subjects. The sample was allowed to clot and then centrifuged at 3 000 rpm for 10 minutes. The serum was stored at –70°C and analysed in batches.Roche Diagnostics SA supplied the assay, which is an electrochemiluminesence immunoassay that uses a sandwich technique. The analytical range is 5−35 000 pg/ml; the reference cut-off value based on the manufacturer’s data is 125 pg/ml. Patients with values below this exclude cardiac dysfunction with a high level of certainty, levels above 125 pg/ml may indicate cardiac dysfunction and this is associated with an increased risk of cardiac complications . This value is not corrected for age or gender . The analytical coefficient of variation for the assay was 1.8−2.7%.This was done using SAS Software V9.1 . Spearman correlation coefficient was used to calculate correlations, and the Kruskal−Wallis test was used to calculate differences in NT-proBNP between the groups.Of the group of 52 patients, 25 had a normal scan (no perfusion defects), 12 had a fixed perfusion defect  and 15 had a reversible perfusion defect (inducible ischaemia). Of the 15 patients with reversible defects, five had fixed defects as well The median resting NT-proBNP of all the subjects was 349 pg/ml, with a range of 6−16 334 pg/ml. The median resting NTproBNP in patients with normal scans was 236 pg/ml, for those with fixed defects, 386 pg/ml, and for patients with reversible defects, 330 pg/ml. The highest median resting NT-proBNP result was in the subjects with a fixed perfusion defect, followed by the subjects with reversible ischaemia, and the lowest was seen in the subjects with normal MPI scans. There was a large overlap of values in the different subject groups; these differences are not statistically significant r = 20.58, p < 0.0001), LV end-systolic volume  and LV end-diastolic volume   and resting, post-stress and delta NT-proBNP values This study used a sample population that was made up of the typical patient referred for dipyridamole stress SPECT MPI to assess the presence of reversible myocardial ischaemia. No selection was made on the basis of ventricular function.The subjects in this study population probably had a degree of LV dysfunction, as demonstrated by the median resting NT-proBNP of 349 pg/ml (N cutoff 5 125 pg/ml). The correlation seen between NT-proBNP and LV ejection fraction, LV enddiastolic and LV end-systolic volumes was a reflection of the relationship of NT-proBNP with ventricular function.In the exercise studies, where NT-proBNP increased significantly in individuals with myocardial ischaemia, these individuals were selected and had normal ejection fractions.The mechanism of inducing myocardial ischaemia may also be important. The effect that physical exercise has on CNP has been studied. The effect of pharmacological stress testing has not been investigated to the same extent. There has been one study demonstrating an increase in atrial natriuretic peptide with dipyridamole-induced myocardial ischaemia.24There is a debate as to which marker to use, BNP or NT-proBNP. These markers are secreted in equimolar amounts. The metabolism of NT-proBNP is not fully understood and renal failure is speculated to influence the values. In studies on the use of these markers there is little to choose between them and either can be used.In this study, using SPECT MPI with a sensitivity of 91% to diagnose myocardial ischaemia, there was no correlation between myocardial ischaemia and NT-proBNP – resting values, post-stress values or the change in values. The small number of ischaemic subjects may have limited this study and a larger study may discover statistically significant findings. The question still remains whether NT-proBNP can be used to diagnose myocardial ischaemia in the individual patient presenting with suspected myocardial ischaemia.The median NT-proBNP values were higher in the subjects with fixed defects and inducible defects compared to the subjects with normal perfusion scans. However, there was enormous overlap between the values, making the resting NT-proBNP value useless to predict ischaemia. Apart from the prognostic value of NT-proBNP, it has no value in the diagnosis of myocardial ischaemia in the typical patient referred for dipyridamole stress SPECT MPI.


Liver dysfunction due to heart failure (HF) is often referred to as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI) is a robust scoring system of liver function, and a high score is associated with poor prognosis in advanced HF patients with a heart transplantation and/or ventricular assist device. However, the impact of MELD-XI on the prognosis of HF patients in general remains unclear.n = 289) and Group H . We compared all-cause mortality and echocardiographic findings between the two groups. In the follow-up period (mean 471 days), 104 deaths (62 cardiac deaths and 42 non-cardiac deaths) were observed. The event -free rate was significantly higher in group L than in group H . In the Cox proportional hazard analysis, a high MELD-XI score was found to be an independent predictor of cardiac deaths and all-cause mortality in HF patients. Regarding echocardiographic parameters, right atrial and ventricular areas, inferior vena cava diameter, and systolic pulmonary artery pressure were higher in group H than in group L .We retrospectively analyzed 562 patients who were admitted to our hospital for the treatment of decompensated HF. A MELD-XI score was graded, and patients were divided into two groups based on the median value of MELD-XI score: Group L (MELD-XI <10, The MELD-XI scoring system, a marker of liver function, can identify high-risk patients with right heart volume overload, higher pulmonary arterial pressure and multiple organ failure associated with HF. Liver dysfunction often exists in heart failure (HF) as cardiac or congestive hepatopathy, and is associated with adverse clinical outcomes in advanced HF patients. Therefore, the aim of the present study was to investigate the association of liver function (MELD-XI score) with 1) prognosis  in general HF patients, and 2) cardiac function .n =  289) and Group H . We compared the clinical features and results from several examinations of both groups, such as general laboratory tests and echocardiography, performed upon hospital admission. Hypertension was defined as the recent use of antihypertensive drugs, or a systolic blood pressure ≥140 mmHg, and/or a diastolic pressure ≥90 mmHg. Diabetes was defined as the recent use of insulin or antidiabetic drugs, a fasting blood glucose value of ≥126 mg/dL, and/or a hemoglobinA1c value of ≥6.5%. Dyslipidemia was defined as the recent use of cholesterol-lowering drugs, a triglyceride value of ≥150 mg/dL, a low-density lipoprotein cholesterol value of ≥140 mg/dL, and/or a high-density lipoprotein cholesterol value of <40 mg/dL. Estimated glomerular filtration rate (eGFR) was measured by the Modification of Diet in Renal Disease formula. We retrospectively searched for 621 consecutive patients who were hospitalized at Fukushima Medical University hospital for the treatment of decompensated HF between 2009 and 2012. The diagnosis of decompensated HF was defined based on the Framingham criteria. Echocardiography was performed blindly by an experienced echocardiographer using the standard techniques. Echocardiographic parameters investigated included left ventricular (LV) volume, left ventricular ejection fraction (LVEF), left atrial volume, the ratio of early transmitral flow velocity to mitral annular velocity , inferior vena cava diameter, SPAP, right atrial end systolic area, right ventricular (RV) area, right ventricular fractional area change (RV-FAC), tissue Doppler-derived tricuspid lateral annular systolic velocity , and the ratio of the peak transtricuspid velocity during early diastole to the peak tricuspid valve annular velocity during early diastole , etc.t-test for normally distributed data and the Mann-Whitney U- test for non-normally distributed data, whereas the chi-square test was used for categorical variables. Kaplan-Meier method was used for presenting the event-free rate and the logrank test was used for initial comparisons. Univariate and multivariate Cox proportional hazard analyses were used to analyze predictors of events and adjusting for confounding factors. To prepare for potential confounding, we introduced the following factors, known to affect the risk of worsening heart failure, cardiac death or all-cause mortality in HF patients and parameters of liver function: age, gender, systolic blood pressure, presence of ischemic etiology, atrial fibrillation, anemia, reduced LVEF (<50%), and higher  BNP, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, sodium, C-reactive protein, and MELD-XI score. Univariate parameters with a P-value of <0.10 were included in the multivariate analysis. A value of P < 0.05 was considered significant for all comparisons. These analyses were performed using a statistical software package .Normally distributed data are presented as mean ± SD, non-normally distributed data are presented as median (interquartile range), and categorical variables are expressed as numbers and percentages. Characteristics between the two groups were compared using the independent Student's As shown in n = 50), ventricular fibrillation (n = 12), cancer (n = 12), respiratory failure and/or pneumonia (n = 11), infection/sepsis (n = 6), stroke (n = 5), digestive haemorrhage (n = 3), renal failure (n = 2), and others (n = 3). As shown in P<0.05, respectively).During the follow-up period (mean 471 days), there were 62 cardiac deaths and 42 non-cardiac deaths. Details of cardiac and non-cardiac deaths were as follows: heart failure deaths , aspartate aminotransferase , and MELD-XI  were independent predictors. With respect to non-cardiac death in HF patients (P<0.001). With respect to all-cause mortality in HF patients (P = 0.005), reduced LVEF  and MELD-XI  were independent predictors. In summary, a high MELD-XI score was an independent predictor of cardiac death and all cause mortality.To examine prognostic factors in HF patients, the Cox proportional hazard model was used , , 5. WTo the best of our knowledge, the present study is the first to show the utility of MELD-XI scores for predicting detailed cardiac and non-cardiac deaths in general HF patients with regard to right heart function. It was found that MELD-XI was an independent predictor of cardiac death and all-cause mortality in general HF patients, whose conditions were associated with right heart volume overload and higher pulmonary arterial pressure.HF results in a various abnormal liver functions, such as the elevation of serum bilirubin, alkaline phosphatase, ganma-glutamyl transferase, and alanine aminotransferase. The mechanism possibly responsible for liver dysfunction in HF is considered to be caused by hemodynamic influences: decreased hepatic blood flow originating from low cardiac output and increased hepatic venous pressure with subsequent atrophy of liver cells and edema of the peripheral area, both leading to hepatocellular hypoxia. et al. reported that high total bilirubin is an independent predictor of cardiac events in HF patients. Shinagawa Several limitations remain in the present study. First, it was a retrospective analysis of a single institution. The number of subjects was relatively small. Hence, prospective studies with a larger population are needed. However, diagnosis of HF was accurately made by our experienced cardiologists using the Framingham criteria. Second, we evaluated RV function and SPAP using echocardiography unless we used right heart catheterization. However, this is not routinely performed.A high MELD-XI score was an independent predictor of not only cardiac death but also all-cause mortality in HF patients. HF patients with high MELD-XI scores had 1) poorer nutrition, 2) a greater cholestatic state, and 3) right heart volume overload and higher pulmonary arterial pressure. These mechanisms may in part affect the adverse prognosis of HF patients with high MELD-XI scores.


We aimed to identify the echocardiographic measures associated with survival in a patient population with a high prevalence of co-morbid cardiovascular and pulmonary disease that have significantly elevated estimated pulmonary artery systolic pressures (ePASP).Pulmonary hypertension (PH) is a clinical feature of several cardiopulmonary diseases that are prevalent among elderly. While certain echocardiographic parameters have been shown to be important in the prognosis in specific PH groups, the prognostic relevance of echocardiographic characteristics in a cohort with multiple cardiopulmonary comorbidities is unclear.We retrospectively identified 152 patients with ePASP > 60 mmHg by echocardiography over a five year period (6/2006–11/2011) and followed until 4/2013. Candidate clinical and echocardiographic characteristics suggestive of PH severity were compared between deceased and surviving subpopulations. Cox proportional hazard modeling was used to identify echocardiographic predictors of death adjusted for age and clinical characteristics.This was a predominantly elderly (age 78.8 ± 10.2 years), male (98.7%) cohort with several cardiopulmonary comorbidities. Overall mortality was high . After adjusting for age and clinical characteristics, decreased right ventricular (RV) systolic function assessed by tricuspid annular plane systolic excursion  and increased RV thickness  were independently associated with mortality. In contrast, left ventricular systolic function, left ventricular diastolic parameters, ePASP, or echo-derived pulmonary vascular resistance (PVR) were not associated with increased mortality.In a cohort of patients with PH and high prevalence of cardio-pulmonary comorbidities, RV systolic function and hypertrophy are associated with mortality and may be the most relevant echocardiographic markers for prognosis. Pulmonary hypertension (PH) is associated with several cardiopulmonary diseases that are prevalent among elderly patients –4. MoreoThere may be considerable overlap between the pathophysiologic mechanisms underlying PH in cardiopulmonary diseases. For example, in PH due to left heart disease, impaired left ventricular systolic and diastolic function and/or presence of significant mitral or aortic valvular disease can lead to left atrial hypertension and elevated pulmonary venous pressure. Persistently increased pulmonary venous pressures may lead to remodeling at the level of the pulmonary veins, capillaries, and arteries, ultimately resulting in elevated pulmonary vascular resistance (PVR). Similarly, while PH associated with lung diseases/hypoxia is associated with increased PVR, it is not uncommon to have concomitant left ventricular diastolic dysfunction and elevated left atrial pressure (LAP) in these diseases. An increase in pulmonary artery pressure (PAP) leads to an increased right ventricular (RV) afterload that results in RV hypertrophy. Eventually persistent PH causes RV dysfunction and RV failure –10. SeveHowever, reports of echocardiographic characteristics pertaining to left and right heart structure and function as well as the prognostic impact of these echocardiographically derived parameters related to mortality in a PH cohort with complex cardiopulmonary comorbidities are scant. Also, current survival prediction models for PH have not included any echocardiography derived parameters of biventricular geometry and function . The objThe institutional review board at the Providence VA Medical Center approved the study. The Providence VAMC Institutional Review Board waived the requirement for informed consent for this minimal risk retrospective analysis. The study population was identified from the Providence VA echocardiography database that includes all echocardiograms performed at our institution. In this retrospective study, we identified 160 patients with reported estimated pulmonary artery systolic pressures (ePASP) > 60 mmHg on transthoracic echocardiography over a five year period (6/2006–11/2011). For patients with multiple studies, we included the first study performed and excluded subsequent studies. Eight patients had to be excluded from the final analysis due to missing standard 2D echocardiographic views.Clinical variables  and vital statistics data were retrospectively collected from electronic medical record. The clinical history was abstracted from the problem list in the patient’s electronic medical record and included history of systemic hypertension, chronic obstructive pulmonary disease, pulmonary embolus, pulmonary fibrosis, coronary artery disease, heart failure, and diabetes mellitus. The disposition of the patient at the time of echocardiogram was recorded as inpatient vs. outpatient.RVOT) x 10 + 0.16 in accordance with published guidelines [Routine echocardiographic assessment was performed on all patients, including M-mode, two-dimensional images, and color flow Doppler recording using Philips IE-33 with a 3.5-MHz transducer . All the echocardiograms were reviewed again and all measurements were performed in accordance with the American Society of Echocardiography (ASE) /European Association of Echocardiography guidelines using the Phillips Xcelera Cardiac Reporting system. Heart rate was determined from the echocardiogram during the measurement of tricuspid regurgitant jet velocity. Estimated PA systolic pressure was determined by the sum of the transtricuspid gradient and estimated right atrial pressure based on inferior vena cava dimensions and respiratory variations. Diastolic function and LAP  were assessed using the ASE recommended algorithm using a combination of echocardiographic variables including left atrial volume index , transmitral E-wave acceleration, transmitral E-wave velocity (E), tissue Doppler at the septal and lateral mitral annulus (e’) . Averageidelines . RV funcSince M-Mode of tricuspid annulus was recorded only in a subset of patients (n = 56), we post-processed 2D 4-chamber images using a Java-based imaging software program   to obtaiThe primary outcome measure was defined as all-cause mortality as assessed in April 2013 from the time of the index echocardiogram .Continuous variables were expressed as mean ± standard deviation, and compared using the unpaired Student t-test between the deceased and surviving cohorts. Categorical data were displayed as frequencies and percentages, and comparisons were made using Chi-square tests.The relationship between echocardiographic indices reflecting LVEF, LV diastolic function , RV systolic function , RV hypertrophy (RV thickness), ePASP and PVR; and mortality was investigated using Cox proportional hazards model. Mortality hazard ratios were adjusted for age alone or in a multivariate model containing the following covariates: age, gender, body mass index, systemic hypertension, chronic obstructive pulmonary disease, pulmonary embolus, pulmonary fibrosis, coronary artery disease, heart failure, and diabetes mellitus, inpatient status, heart rate, and significant left-sided valvular disease. For clinical applicability, we studied RV systolic function using ppTAPSE as a continuous variable as well as a categorical variable (≥1.8 vs <1.8 cm). The proportionality of the hazards function assumptions in the Cox model was examined by close observation of the Schoenfeld’s residuals plot over time and tested using the Schoenfeld Test in STATA. This test was not significant (p = 0.56) for ppTAPSE over time; thus, confirmed the proportionality of assumptions. In addition, age-adjusted Kaplan-Meier curves for ppTAPSE were generated and compared using the log-rank test.Given that the main analysis used a novel TAPSE measurement technique (ppTAPSE), a sensitivity analysis was performed using the standard TAPSE recorded at the time of the study (n = 56) in lieu of ppTAPSE to estimate the adjusted hazard ratio of mortality.All statistical tests were two sided. A p value <0.05 was considered statistically significant. All statistical analyses were performed using STATA 10 .From a total of 4,565 individual patient echocardiograms screened, 160 patients (3.5%) met the predefined ePASP search criteria (i.e. ePASP ≥ 60 mm Hg), of which 152 patients had a complete echocardiographic dataset and were included in the analysis. The median follow-up time was 406 days. The clinical baseline characteristics of this cohort are summarized in There were 106 patients (69.7%) who had the primary outcome. The median survival was 129 days . The patients who died at follow-up were more likely to have been inpatients at the time of the echocardiogram acquisition. The prevalence of cardiopulmonary comorbidities did not significantly differ between the groups, with the exception of hypertension, which is more prevalent in patients who were alive compared to those expired. Moreover, surviving patients were more likely to have lower heart rates and were more likely to be on beta-blockers .Patients with ePASP > = 60 mmHg who died were more likely to have reduced ppTAPSE  and increased RV free wall thickness . Also, the deceased patients were more likely to have an increased echo-derived PVR . On the other hand, LVEF, LAP, diastolic function indices, or RV FAC, did not differ between outcome groups.In the current study, we analyzed a cohort of patients with high ePASP who underwent routine echocardiography. In this elderly cohort with prevalent cardio-pulmonary comorbidities, we found that increased RV thickness and decreased RV systolic function as assessed by TAPSE represented the only routine echocardiography-derived marker associated with all-cause mortality.The consequence of elevated pulmonary artery pressures is development of RV hypertrophy and right-sided HF. End-diastolic free wall RV thickness has been shown to be a marker of chronically high ePASP and PVR . RV hypeThe development of RV dysfunction is known to be associated with poor prognosis in patients with Pulmonary Arterial Hypertension , advanceAnother important observation in our study was that not all indices of RV function perform the same in their association with mortality. While the ASE guidelines recommend using at least one index , or RV S) to assess RV systolic function on transthoracic echocardiogram , TAPSE hWe found no significant association between ePASPs and mortality in our study cohort. In fact, a non-significant trend towards higher ePASP in the surviving cohort was observed. Lam et al described a significant relationship between increasing ePASP and mortality  in the general population  as well A significant proportion of our cohort displayed elevated PVR, suggesting pulmonary vascular remodeling that could be associated with the cardiopulmonary comorbidities. Although we observed a significant trend towards higher PVRs in the deceased cohort, echo-derived PVR was not independently associated with death after adjusting for clinical comorbidities. This might reflect limitations to the current echocardiographic estimation of PVR, and/or possible PVR underestimation in the presence of significant RV dysfunction, 29. On First, the limitations of echocardiographic assessments of tricuspid regurgitation in PH patients are well described in the literature . AlthougAlso, since TAPSE recordings were available only in a subset of patients, we processed 2D 4-chamber images using a Java-based imaging software program  to obtain ppTAPSE, that showed very good correlation with original TAPSE; however, this method remains to be validated in other cohorts. Finally, although it is possible that the analysis of RV function using tissue cardiac MR or strain imaging could have provided further prognostic information, the possibility of stratifying the prognosis of PH patients using simple M-mode and tissue Doppler can be easily and widely applied in real world settings.Elevated ePASP in the elderly is associated with a high mortality. In a cohort of patients with high ePASP and high prevalence of co-morbid cardiovascular and pulmonary disease, RV systolic function and hypertrophy are associated with mortality and may be the prognostically most relevant echocardiographic markers.S1 Fig(TIFF)Click here for additional data file.


Right ventricular function has been identified as an important prognostic factor in children with pulmonary arterial hypertension. The aim of the study was to assess the deformation pattern and prognostic value of right ventricular longitudinal strain in children with pulmonary arterial hypertension.We prospectively evaluated 46 children  using conventional and speckle-tracking echocardiography, brain natriuretic peptide levels and clinical status expressed by WHO functional class and 6-min walking test. According to the clinical status after 12 months of follow-up, the pulmonary arterial hypertension patients were divided in two groups: non-worsening (13) and worsening (12).p = 0.0001 and −1.44 ± 0.09 vs −1.09 ± 0.15, p = 0.0001, respectively). There was a more expressed decrease of basal than apical region of right ventricular free wall longitudinal strain/strain rate in pulmonary arterial hypertension patients compared with controls (strain: p = 0.0001 vs p = 0.07 and strain rate: p = 0.0001 vs p = 0.002). Comparing worsening and non-worsening pulmonary arterial hypertension patients there was a significant difference in Mid right ventricular free wall longitudinal strain . In multivariable logistic regression analysis Mid right ventricular free wall longitudinal strain was an independent predictor of worsening in pulmonary arterial hypertension children . In ROC curve analysis a cut-off value of Mid right ventricular free wall longitudinal strain of −18.50 % predicted clinical worsening in pulmonary arterial hypertension children, with a sensitivity and specificity of 91.7 and 30.8 %, respectively .Right ventricular free wall longitudinal strain and strain rate were significantly lower in children with PAH compared with controls (−24.72 ± 3.48 vs −15.60 ± 3.40, Two-dimensional speckle-tracking echocardiography is a complementary non-invasive tool for assessment of right ventricular function in children with severe pulmonary arterial hypertension, allowing also clinical prediction and segmental analysis of right ventricular myocardial performance in these patients. Pulmonary arterial hypertension (PAH) is a rare disease in childhood that is related with significant morbidity and mortality. The most common types of PAH in pediatric population are PAH associated with congenital heart defects (chd-PAH) and idiopathic PAH (IPAH) –4, with There are several clinical, laboratory and echocardiographic parameters that have been shown to be associated with higher risk of death in pediatric pulmonary hypertension, such as: Word Health Organization (WHO) functional class 3/4 , 4, 6, eRV function has been identified as an important prognostic factor in patients with PAH regardless of the causal clinical entity , 10. TheThe aim of this study was to assess the deformation pattern and prognostic value of RV longitudinal strain in children with PAH.This is a prospective clinical observational study. The study group consisted of forty six patients: twenty-five children with PAH and twenty-one age and sex matched healthy children as a control group Table . All chin = 5) or PAH associated with congenital heart defects, with tripartite right ventricle. The associated congenital heart defects in the study population were: ventricular septal defect (n = 12), complete atrioventricular septal defect (n = 5) and truncus arteriosus communis (n = 3), all with pulmonary hypertensive vascular disease . All PAH patients in the present study were on pulmonary vasodilator medication in monotherapy or combined therapy  [The children were scanned with iE33  ultrasound system using an S5-1 transducer, by a single sonographer. At least three consecutive beats were stored in cine-loop format. Frame rate (60 to 100 frames per second), depth and sector width were adjusted in order to obtain accurate speckle-tracking analysis of the RV myocardial deformation..Conventional echocardiographic parameters such as RV-FAC, TAPSE, RV-MPI, S’, RV S/D ratio, pulmonary ejection time (Tej), LV eccentricity index (LV-EI) and mean pulmonary arterial pressure (PAPm) were measured as recommended by current guidelines , 22–24.Speckle-tracking analysis of the RV was performed offline, from the RV-focused 4-chamber view images, using commercially available software . The RV endocardial border has been automatically generated by the software and than manually adjusted if necesarry. A seven-segment model was created according to the software: three at the RV free wall, three at the interventricular septum (IVS) and one at the apex of the RV. Also, speckle-tracking RV longitudinal strain and strain rate curves were automatically generated for every segment  and longitudinal peak systolic strain rate (LpsSR) were measured in the basal, midventricular and apical segments of the RV free wall, IVS and RV apex, respectivelly. RV free wall LpsS and LpsSR were calculated as the average of the three segments, and conventionally are presented as a negative value , 17–20.2) were measured by pulse oximeter. 19 controls and 23 PAH patients were able to perform 6MWT.6MWT was done corresponding to the American Thoracic Society for adults . ChildreThe functional class was established according to WHO class system .All blood samples were taken on the day of echocardiographic examination. The samples were centrifugated, and plasma was stored at −70 °C until analysis was performed. BNP was assayed on an automatic immunoassay analyzer .All PAH children were evaluated after 12 months for the occurence of the primary end point, clinical worsening. Clinical worsening was defined as increase in WHO functional class.p-value of < 0.05 was considered statistically significant.Statistical analysis was performed using SPSS version 20 (IBM SPSS STATISTICS 20). Data were labelled as nominal or quantitative variables. Nominal variables were expressed as numbers or percentages. Quantitative variables were tested for normality of distribution using Kolmogorov-Smirnov test and were expressed by mean ± standard deviation or median and percentiles , whenever appropriate. Differences between the mean or median between two groups were analysed using the t-test, Mann-Whitney test or chi-test when appropriate. Differences between three groups with normally distributed variables were analysed using ANOVA test with Bonferroni posthoc processing. Multivariate analysis was carried out using logistic regressions. We use as dependent variable the groups of PAH children (worsening and non-worsening). The covariates were Mid RV free wall LpsS, Mid RV free wall LpsSR, Apical RV free wall LpsS, BNP and LV EI. Receiver-operating characteristic curves were constructed, and areas under curve were calculated. Sensitivities and specificities were determined for the ability to identify worsening PAH children. Intraobserver reliability was assessed after reexamination by the same examiner 2 weeks after the initial examination, by intraclass correlation coefficient. A Twenty-five consecutive children with PAH and twenty-one age and sex matched normal children were studied. The main clinical characteristics of the study groups are presented in Table The conventional echocardiographic parameters of the two groups are compared in Table RV free wall LpsS and LpsSR were significantly lower in PAH patients than in controls  presented clinical worsening with augmentation of the WHO functional class.Table Figure We performed a multivariable logistic regression analysis, considering the worsening versus non-worsening PAH children as dependent variables and the BNP, LV-EI, Mid RV free wall LpsS, Apical RV free wall LpsS and Mid RV free wall LpsSR, as covariates. After controlling for these covariates, multivariate analysis showed that Mid RV free wall LpsS was an independent predictor of worsening in PAH children Table .Table 5Mp = 0.001, Fig. In ROC curve analysis, a cut-off value of Mid RV free wall LpsS of −18.50 % predicted clinical worsening in PAH children, with a sensitivity and specificity of 91.7 and 30.8 %, respectively. , conventional echocardiographic parameters are largely used in clinical practice even in children, they have some intrinsic limitations [RV function is an important prognostic factor in PAH , howeveritations –17. Thesdeterioration pattern of regional longitudinal deformation of RV: there is an initial decrease of strain/strain rate in the basal region followed by the mid/apical region 2) Mid RV free wall LpsS has predictive value in PAH children.The present study has some important findings: 1) children with PAH seem to have a speckle-tracking echocardiography has been recently introduced for assessment of myocardial performance. Several previous reports have shown its accuracy and feasibility to assess RV function in adults [Two-dimensional (2D) n adults , 19, 27.n adults , 20, 21.normal children, comparable with those reported in the literature [We found an average value of −24.72 ± 3.48 for RV free wall LpsS and −1.51 ± 0.23 for LpsSR in terature , 29. Theterature . Also, wFurthermore, our results show that RV free wall longitudinal strain indices (LpsS and LpsSR) are significantly lower in children with severe PAH compared with normal controls. However, it is important to underline that myocardial deformation is influenced by loading condition. Simon et al. revealed that, RV longitudinal strain can be decreased in both PAH patients with RV dysfunction and in PAH patients with preserved RV function. However, in the first situation RV strain was found to be much lower than in the second one , 32. On The RV has a complex anatomy, and can be divided in three distinct parts: smooth inlet portion, trabeculated apical portion and outlet portion. The RV free wall is composed by longitudinal fibers in the subendocardial layer, more developed in healthy subjects, and circumferential fibers in the superficial layer . This exWe found a non–homogeneous decrease of the longitudinal strain indices in different segments of RV free wall in PAH patients, with loss of the base-to-apex gradient compared with normal controls. Consistent with the prior studies on pulmonary hypertension , our stuFurthermore, we found a significant decrease of Mid and Apical RV free wall strain indices in worsening group as compared to non-worsening group. Mauritz et al. reported that in RV the longitudinal shortening reduction starts at the basal level and continue to decrease in other regions until a lower limit is reached. Also, they suggested that a further reduction of RV function is due to loss of transverse shortening with leftward septal displacement .pattern of regional longitudinal deformation of RV free wall myocardium in PAH children. There is an initial decrease of strain in the basal region; a further decrease in mid and apical region precedes clinical worsening in PAH children. However, these findings have to be validated in larger studies.In conclusion, our findings suggest a deterioration The predictive value of RV LpsS has been evaluated in adult patients with PAH. Haeck et al. demonstrated that RV global longitudinal strain ≥ −19 % is associated with a 3-fold risk of all-cause mortality . In a stcut-off value of −18.50 % is associated with clinical worsening in these patients. According to our study, Shehata et al. demonstrated by MRI, in a study conducted on PAH patients, that regional  longitudinal free wall deformation can already be affected at the time that RV function is still normal, implying that regional deformation could detect early RV dysfunction in PAH [However, the predictive value of RV regional deformation in PAH children was not studied so far. We found that Mid RV free wall strain indices are significantly lower in worsening group as compared to non-worsening group. Furthermore, we showed that Mid RV free wall LpsS is an independent predictor of worsening in PAH children and a n in PAH . AccordiThe limitation of the study is that we did not compare our results with those obtained by magnetic resonance imaging (MRI), which is considered the “gold standard” method in RV function assessment. However, previous studies have validated the use of speckle-tracking derived strain against sonomicrometry  and magnTwo-dimensional speckle-tracking echocardiography is a complementary non-invasive tool for assessment of right ventricular function in children with severe pulmonary arterial hypertension, allowing clinical prediction and segmental analysis of right ventricular myocardial deformation in these patients.2, oxygen saturation; sRV pressure, systolic right ventricular pressure; TAPSE, tricuspid annular plane systolic excursion; Tej, pulmonary ejection time; TR, tricuspid regurgitation; WHO, World Health Organization6MWD, 6-min walk distance; BNP, brain natriuretic peptide; chd, congenital heart defects; chd-PAH, pulmonary arterial hypertension associated with congenital heart defect; FAC, fractional area change; IVS, interventricular septum; LpsS, longitudinal peak systolic strain; LpsSR, longitudinal peak systolic strain rate; LV-EF, left ventricular ejection fraction; LV-EI, left ventricular eccentricity index; MPI, myocardial performance index; PAH, pulmonary arterial hypertension; PAPm, mean pulmonary arteial pressure; RA, right atrium; RV, right ventricle; S/D ratio, systolic/diastolic ratio; S’, tricuspid annular systolic velocity; SpO


Cardiac imaging in obese adults poses significant technical challenges, yet the prognostic value of diffuse myocardial fibrosis in obese adults quantified with cardiovascular magnetic resonance (CMR) extracellular volume fraction (ECV) measures is unknown. This issue is important because obesity increases the risks of death and hospitalization for heart failure (HHF). Myocardial fibrosis measured in obese adults with ECV may indicate vulnerability to death and HHF.We enrolled 480 consecutive obese patients with a BMI >30 referred for cardiovascular magnetic resonance (CMR) without amyloidosis, stress cardiomyopathy, or hypertrophic cardiomyopathy. We quantified myocardial fibrosis with CMR ECV measures in noninfarcted myocardium. Patient data, BMI, hematocrit, were collected on the day of CMR, and we tracked outcomes prospectively.Median BMI was 35 (IQR 32-41), and median ECV was 27.7% . BMI and ECV were not related (p=0.90). Over a median 1.5 years (IQR 0.9-2.5yrs), 27 HHF events and 28 deaths occurred after CMR in 50 individuals. Adjusting for age, gender, renal function, myocardial infarction size, ejection fraction, hospitalization status, and heart failure stage, ECV in obese adults was associated with HHF (HR1.92 95%CI 1.40-2.65 for every 5% increase in ECV (ECV range: 16.6-45.8), death (HR 2.50 95%CI 1.59-3.95) or both (HR1.97 95%CI 1.44-2.70). ECV improved the classification of obese adults at risk and improved model discrimination for the composite outcome: e.g., HHF or death .Despite the challenges of cardiac imaging in obese adults, diffuse myocardial fibrosis quantified by ECV is associated with HHF, death, or both. Myocardial fibrosis may represent a principal marker of cardiac vulnerability that improves risk stratification even in the setting of obesity. Since myocardial fibrosis can be reversible, myocardial fibrosis and the fibroblast that regulates it may be attractive therapeutic targets in obese patients.Dr. Schelbert was supported by a grant from The Pittsburgh Foundation,Grant M2009-0068, and an American Heart Association Scientist Development grant (09SDG2180083) including a T. Franklin Williams Scholarship Award; funding provided by: Atlantic Philanthropies, Inc., the John A. Hartford Foundation, the Association of Specialty Professors, and the AHA. Dr. Wong was supported by a grant K12 HS19461-01 from the AHRQ. Dr. Shroff's research was supported by the McGinnis Endowed Chair funds. This work was also supported by Grant Number UL1 RR024153 from the National Center for Research Resources (NCRR), NIH.