Dobutamine associated left ventricular (LV) wall motion analyses exhibit reduced sensitivity for detecting inducible ischemia in individuals with increased LV wall thickness. This study was performed to better understand the mechanism of this reduced sensitivity in the elderly who often manifest increased LV wall thickness and risk factors for coronary artery disease.During dobutamine cardiovascular magnetic resonance (DCMR) stress testing, we assessed rate pressure product (RPP), aortic pulse wave velocity (PWV), LV myocardial oxygen demand  and first pass gadolinium enhanced perfusion defects (PDs) indicative of ischemia in 278 consecutively recruited individuals aged 69 ± 8 years with pre-existing or known risk factors for coronary artery disease. Each variable was assessed independently by personnel blinded to participant identifiers and analyses of other DCMR or hemodynamic variables.Participants were 80% white, 90% hypertensive, 43% diabetic and 55% men. With dobutamine, 60% of the participants who exhibited PDs had no inducible WMA. Among these participants, myocardial oxygen demand was lower than that observed in those who had both wall motion and perfusion abnormalities suggestive of ischemia (p = 0.03). Relative to those with PDs and inducible WMAs, myocardial oxygen demand remained different in these individuals with PDs without an inducible WMA after accounting for LV afterload and contractility (p = 0.02 and 0.03 respectively), but not after accounting for either LV stress related end diastolic volume index (LV preload) or resting concentricity (p = 0.31-0.71).During dobutamine stress testing, elderly patients experience increased LV concentricity and declines in LV preload and myocardial oxygen demand, all of which are associated with an absence of inducible LV WMAs indicative of myocardial ischemia. These findings provide insight as to why dobutamine associated wall motion analyses exhibit reduced sensitivity for identifying inducible ischemia in elderly.(NCT00542503).This study was registered with Clinicaltrials.gov  The presence of inducible left ventricular wall motion abnormalities (LVWMA) observed during dobutamine stress echocardiography (DSE) and dobutamine cardiovascular magnetic resonance (DCMR) is utilized widely to identify myocardial ischemia indicative of coronary artery disease (CAD) and forecast future cardiovascular (CV) events in those unable to exercise -5. DobutIn this study, we sought to understand the mechanism by which myocardial perfusion defects occur without concomitant inducible LVWMA in older individuals undergoing dobutamine stress testing. To accomplish this, we performed DCMR, a procedure which allows simultaneous assessment of wall motion and perfusion, LV concentricity, preload, afterload, and contractility in older individuals who frequently exhibit altered LV remodeling.The study was approved by the Institutional Review Board of Wake Forest Health Sciences, and each participant provided witnessed written informed consent. This study was registered within the United States on Clinicaltrials.gov (NCT00542503) and was performed in accordance with the National Institutes of Health grants R01HL076438 and P30AG21332. In addition, this study complied with the Declaration of Helsinki. The purpose of this initiative was to utilize advanced DCMR techniques to identify rest and stress-induced cardiac and vascular abnormalities in older individuals that are associated with CV disease. In this study, each participant underwent an interview to collect and record information pertinent to CV disease  and then underwent DCMR in which rate pressure product (RPP), aortic pulse wave velocity (PWV), LV myocardial oxygen demand , mass, volumes, concentricity, and the presence of WMA and first pass gadolinium enhanced perfusion defects (PDs) indicative of ischemia were measured and recorded.The study included participants from the rural counties of Central and Western North Carolina that exhibited a >5 years presence of risk factors  for a cardiac event, but no history of myocardial infarction within 6 months of enrollment, no contraindication to intravenous dobutamine or gadolinium based contrast nor the performance of a CMR exam . None of the subjects had angina or symptoms of heart failure in the 12 months prior to enrollment. Recruitment of study participants was achieved through newspaper and television advertisements, or mailings to randomly selected individuals over the age of 55, but <85 years within Forsyth, Davie, and Davidson counties of Northwest North Carolina ,5,11.The DCMR protocol was accomplished according to previously published techniques ,5 with iAccording to previously published techniques ,12, LV vThe LV wall motion at rest, peak dose and in recovery was assessed with a visual scoring system in which 1 = normal wall motion, 2 = hypokinesis, 3 = akinesis, and 4 = dyskinesis. An LV inducible WMA was defined as an increase in score of ≥1  in 1 or more myocardial segments. Segments with an LV wall motion score of 2 or 3 at rest with no worsening of wall motion were considered negative for ischemia.Ten minutes after the administration of gadobenate dimeglumine (Multihance) contrast, late gadolinium enhanced (LGE) inversion recovery images with steady state free precession readout were collected in the same short axis planes used to assess LV volumes. The sequence parameters included a 6 mm thick slice with a 2 mm gap, an 800 msec TR, a 1.7 msec TE, a 40° FA, a 360 × 270 mm FOV, and a 192 × 109 matrix with an inversion time adjusted to null the myocardium. Enhanced  regions were identified.First pass perfusion imaging with gadobenate dimeglumine (0.1 mmol/kg) was performed when 80% MPHRR was achieved. Eighty percent (80%) of the maximum predicted heart rate response for age was selected for this study because  this heaFor each LV myocardial segment, a two-step process was utilized to identify perfusion defects indicative of ischemia. First, regions of first-pass hypo-perfusion were measured as a percentage of the corresponding myocardial wall thickness for that LV myocardial segment in the same imaging plane Figure . The radFurther evaluation was performed to exclude PDs related to prior infarcted territories. The extent of these PDs suspected of ischemia was compared to the extent of infarction as assessed in the LGE images within the same myocardial segments. Participants with PDs that extended beyond the areas of LGE or occurred in a territory or segment that differed from the segmental territory in which the LGE was noted were classified as ischemic. Any PD that matched the area of LGE was not classified as ischemic.According to previously published techniques , PWV wasIn addition to the changes in HR, blood pressure (BP) and the RPP, we also assessed the LV stroke work (SW) and the systolic PVA, a measure indicating the global LV myocardial oxygen demand ,20. The In accordance with the American Heart Association Scientific Statement , the 10 Two hundred seventy-eight (278) consecutive participants were enrolled into the study; the demographic data from the participants are shown in Table According to previously published criteria, 64% of the participants exhibited LV concentricity and 82% had left ventricular hypertrophy. Consistent with previously published data , in the Forty-six participants exhibited a PD indicative of ischemia. Of the 46 subjects with PDs, 18 had corresponding inducible LV WMAs (Group III) . The remOf the 28 patients with perfusion defects consistent with ischemia in Group II, 6 had peri-infarct ischemia (i.e. a PD extending beyond proportion to the region of LGE), 3 had LGE in a different territory and 19 had no LGE. Of the 18 patients in Group III, 9 had periinfarct ischemia, 2 had LGE in a different territory and 7 had no LGE. Compared to the subjects in Group II, those in Group III trended toward larger trans-mural extents of their PDs , somewhat longer duration PDs , and more segments with LGE . Those in Group III did exhibit a greater number of WMAs indicative of ischemia .The cardiac chamber volumes and function, arterial stiffness measures, and hemodynamic parameters of the participants at rest and with stress are shown in Table At rest, those in Group I exhibited a higher LVSV index (LVSVi) and a higher cardiac index compared to those in Groups II and III (p = 0.03 for both indices). No differences between the 3 groups were noted in the LV end-systolic volume index (LVESVi) or the LVEF at rest. Those in Group III possessed the highest concentricity index (p = 0.02) compared to those in Groups I and II with no differences in the LV mass index between the three groups (p = 0.35). With dobutamine, all three groups experienced a similar decrease in the LVEDVi. As expected, individuals in Group III exhibited the lowest stress LVEF and the highest stress LVESVi values relative to those in Groups I and II (p = 0.002 and p = 0.001 respectively). PWV was not different among the groups at rest (p = 0.76) or with stress.(p = 0.14).The indices of myocardial oxygen demand at rest are shown in Figure To determine the factors influencing this lower myocardial oxygen demand between groups II and III, we adjusted the left ventricular PVA and SW for differences in baseline and peak stress LVEDVi (preload), peak stress PWV (afterload), the resting LVEF (contractility), and the LV concentricity as shown in Figure There are three important findings related to this study. First, in older men and women receiving a pharmacologic dobutamine stress test, myocardial oxygen demand often decreases during receipt of intravenous dobutamine despite achieving 80% of the MPHRR for age Figure A. SecondAs shown in Figures To further understand why PDs occurred in the absence of WMA, we examined multiple hemodynamic variables throughout the stress testing procedure. As shown in Table PWV, a measure of arterial stiffening, was mildly elevated at rest across the 3 participant Groups. With stress, PWV remained similar or increased in all 3 Groups with the largest increase occurring in Group III participants. These data indicate that overall, aortic stiffness was elevated in older subjects and remained elevated after receipt of dobutamine. Given the absence of a concomitant increase in SBP in Group III, one possible explanation of the high PWV is that this group did not experience a vasodilator response with dobutamine stress. We have shown that elderly subjects with diabetes and impaired fasting glucose do not experience a normal decrease in afterload with dobutamine and instead experience an increase in arterial stiffness as evidenced by a decrease in aortic distensibility .As shown in Figure Since LV wall motion assessments of ischemia are driven by a supply–demand mismatch, a lower oxygen demand might not be adequate to provoke a WMA and could render the study insensitive for the detection of ischemia. The observation of a lower myocardial oxygen demand in those with increased LV concentricity, leading to hyperdynamic  has been demonstrated by Mirelis, et al. . These iConsistent with findings from other larger population based studies such as the Multi-Ethnic Study of Atherosclerosis, the elderly individuals in our group exhibited a smaller LVEDV and increased LV concentricity . In addiThe results of this study have important implications for the interpretation of dobutamine wall motion stress testing in elderly individuals. As shown in this study, up to 61% of subjects who had ischemia identified by PDs did not experience an inducible WMA. In addition, the presence of these PDs was not associated with failure to achieve target HR during testing, or differences in the SBP response  among all individuals receiving testing. Therefore, inducible ischemia (as defined by an inducible PD) may in fact be present during dobutamine stress in the elderly even though LV WMAs are absent. Other studies have found similar results regarding the lower sensitivity of LVWMA measures in assessing the risks for CAD .Our study does exhibit some limitations. First, we did not perform contrast coronary angiography on the participants. Recently, however, the diagnostic utility and accuracy of CMR perfusion abnormalities have been established in multicenter and multivendor trials ,34,35. SIn conclusion, despite achieving target HR, a subset of elderly patients with risk factors for CAD who undergo dobutamine stress experience perfusion abnormalities indicative of ischemia without a concomitant LV wall motion abnormality. Mechanistically, this occurs in part due to a lower myocardial oxygen demand that appears related to reductions in LV preload and increases in LV concentricity.


Psoriasis vulgaris is a chronic disease with a multifactorial pathogenesis. It affects about 2–4 % of the population all over the world. In course of psoriatic arthritis, joints’ damages are observed. In patients with psoriasis vulgaris and psoriatic arthritis, there is increased morbidity and mortality caused by cardiovascular diseases observed. The aim of the study is to analyze the echocardiography of patients with psoriasis vulgaris and psoriatic arthritis on the basis of the literature available in PubMed database. Abnormalities found in echocardiography of patients with psoriasis include valvular defects (40.7 % of the patients), left ventricle diastolic dysfunction (27.8 %), and left ventricle hypertrophy (11.1 %). Left ventricle’s systolic disorders, increased aorta stiffness index and increased pulmonary artery blood pressure were also observed in this group of patients. Psoriasis is a chronic disease with a multifactorial pathogenesis. Its symptoms may be noticeable on the skin, they also affect joints, and the inflammatory process manifestations are observed outside the skin , 24, 27.The aim of the study is to analyze the echocardiography of patients with psoriasis vulgaris and psoriatic arthritis referring to the available literature. The study is based on the analyzed publications from PubMed database using the search terms “psoriasis” (Mesh) and “echocardiography” (Mesh). We found 27 articles in English language dated between 1991 and 2014 and 3 articles from 1979 to 1986. We identified 17 original studies, which we selected for this review. First works concerning the cardiovascular system disorders in patients with psoriasis were published in the late 1980s. Table Psoriasis is a chronic skin disease. It is one of the most common dermatoses and it is estimated that it occurs in about 2–4 % of the entire population . Many stIn about 5–20 % of patients with psoriasis, there is damage of joints observed . In thisOne of the most important diagnostic methods in heart and vessels diseases is echocardiography, which enables to examine morphological and physiological disorders. Echocardiography is a method allowing to visualize structures of the heart using reflection of ultrasounds of 1.5–10 MHz frequency. Using the Doppler method allows to obtain important data concerning hemodynamic function of the heart. This method is commonly available and non-invasive. It does not require special preparation of the patient and there are no contraindications to perform it. However, the correct assessment of echocardiography results requires experience.Parameters assessed in echocardiography are end-diastolic and end-systolic diameters of the left ventricle  and the left atrial diameter (LAD). In most of the analyzed studies, there were no significant abnormalities in these dimensions of the heart observed in patients with psoriasis vulgaris , 16, 21 The assessment of systolic function of the left ventricle is one of the most important aims of performing echocardiography. It is based on the measurement of left ventricular ejection fraction (LVEF); range of the normal values is within 55–80 %. Systolic function impairment is a base for diagnosing congestive heart failure. In patients with psoriasis vulgaris and psoriatic arthritis, there were no systolic disorders of left ventricle observed by measuring the ejection fraction. LVEF was found to be normal in patients with psoriasis in numerous studies , 21, 39.Echocardiography is also a basic method of diastolic function of the heart assessment. In some patients, there is an isolated diastolic heart insufficiency observed. Diastolic dysfunction may be the first sign of heart diseases as well as metabolic diseases. Diastolic dysfunction is more frequently observed in elderly people. Assessment of diastolic function in echocardiography is based on measuring the mitral inflow parameters, which are isovolumic relaxation time (IVRT), early to late ventricular filling velocities ratio (E/A), early flow deceleration time (DT). There were no significant diastolic function disorders in patients with psoriasis vulgaris and psoriatic arthritis noticed on the basis of the analyzed studies , 15, 21.Echocardiography is also used to measure blood pressure in the pulmonary artery. Value of this parameter is obtained by measuring maximal speed of regurgitation flow through pulmonary valve or tricuspid valve. In a few studies on this subject, the authors observe higher pulmonary artery blood pressure in patients with psoriasis vulgaris and psoriatic arthritis. Gunes et al.  found thValvular defects in patients with psoriasis were analyzed in the oldest described works. In 1986, Pines et al.  studied Aortic stiffness index (ASI) is an echocardiographic parameter used to assess the elastic features of the aorta. An abnormal, increased ASI is observed in patients with hypertension, ischemic heart disease, heart insufficiency, type 2 diabetes, chronic renal insufficiency. ASI is thought to be one of the predictive factors of cardiovascular morbidity and mortality. That is why this parameter is often used during echocardiography of patients with psoriasis. Ardic et al. . The stuTo sum up, despite a number of studies on echocardiography results assessment in patients with psoriasis and psoriatic arthritis, results remain incoherent and sometimes contradictory. Irrefutably, there is a higher prevalence of left ventricle diastolic dysfunction in patients with psoriasis. Subclinical features of left ventricle diastolic function disorders are observed in 8–27 % of patients with psoriasis vulgaris and in 28–63 % patients with psoriatic arthritis. It seems worth noticing that diastolic function disorders are also observed in patients with no standard cardiovascular risk factors. In spite of generally well-preserved left ventricle systolic function, the episodes of systolic disorders were demonstrated using Speckle Tracking Echocardiography. What is more, the aorta elasticity disorders, more frequent occurrence of pulmonary hypertension, mitral and aortal valves insufficiency and left ventricle hypertrophy features with coexistence of hypertension were found in patients with psoriasis. It seems vital to conduct further studies to precisely assess the cardiovascular system function in patients with psoriasis as an increased cardiovascular morbidity and mortality is observed in this group.Although there are no clearly defined indications concerning necessity of performing echocardiographic examination in patients with psoriasis, dermatologists should pay special attention to the possibility of cardiovascular disorders among their patients.


In vivo cardiac diffusion tensor imaging (cDTI) is uniquely capable of interrogating laminar myocardial dynamics non-invasively. A comprehensive dataset of quantative parameters and comparison with subject anthropometrics is required.cDTI was performed at 3T with a diffusion weighted STEAM sequence. Data was acquired from the mid left ventricle in 43 subjects during the systolic and diastolic pauses. Global and regional values were determined for fractional anisotropy (FA), mean diffusivity (MD), helix angle gradient  and the secondary eigenvector angulation (E2A). Regression analysis was performed between global values and subject anthropometrics.All cDTI parameters displayed regional heterogeneity. The RR interval had a significant, but clinically small effect on systolic values for FA, HAg and E2A. Male sex and increasing left ventricular end diastolic volume were associated with increased systolic HAg. Diastolic HAg and systolic E2A were both directly related to left ventricular mass and body surface area. There was an inverse relationship between E2A mobility and both age and ejection fraction.Future interpretations of quantitative cDTI data should take into account anthropometric variations observed with patient age, body surface area and left ventricular measurements. Further work determining the impact of technical factors such as strain and SNR is required. The cardiac musculature has a unique structure with myocytes winding progressively from a left-handed helix in the epicardium, to circumferential in the mid wall, to a right handed-helix in the endocardium –3. The lDiffusion tensor imaging (DTI) is an MRI technique, which enables novel in vivo interrogation of biological tissue structures noninvasively. DTI exploits the fact that tissue components, such as cell walls and collagen, act as natural barriers to diffusion resulting in anisotropy in the measured diffusion. When diffusion sensitizing gradients are applied, the degree of signal attenuation is dependent on the orientation of the gradient, with the greatest attenuation observed when gradients are applied parallel to the long axis of cells i.e. the orientation of greatest diffusion . By measDTI is an established technique in central nervous system imaging –17 but tIn vivo cDTI remains challenging in light of the difficulty of measuring small scale diffusion in the face of myocardial strain and bulk cardiac motion, nonetheless our group has established that the in vivo cDTI STEAM sequence has both good inter and intra-centre reproducibility –28. TherWe prospectively recruited 46 healthy volunteers for cDTI. Subjects were screened and excluded in the event of the following: significant co-morbidities; risk factors for ischaemic heart disease; high blood pressure; or an abnormal ECG. The study was approved by the National Research Ethics Service Committee South East Coast-Surrey, and was conducted in accordance with the principles set out in the declaration of Helsinki, with written informed consent obtained from all volunteers.Images were acquired using a clinical 3T scanner  with an anterior 18 element matrix coil and 8–12 elements of a matrix spine coil. Functional and volumetric data was determined from breath hold, retrospectively gated bSSFP cine acquisition in three long axis planes and contiguous short axes from the atrioventricular ring to the apex . The tim2, slice thickness 8 mm, EPI echo train length = 24 readouts, EPI readout duration = 13 ms, in-plane spatial resolution = 2.8 × 2.8 mm2 interpolated to 1.4 × 1.4 mm2, by zero filling, 3 slices, 4 mm slice gap. For diffusion encoding, the maximum available on axis gradient strength of 45 mT/m was used with a trapezoidal gradient pulse duration of 10 ms, leading to a diffusion sensitivity of b = 350 s/mm2 (assuming a heart rate of 60 beats per minute). When acquiring the reference images, spoiler gradients are used in place of the diffusion encoding gradients. These gradients introduce a diffusion weighting (135 s/mm2 in this protocol) to the reference images which was accounted for when calculating the diffusion tensor. Localized first and second-order shimming and frequency adjustment were performed with an adjustment box positioned to cover the region of interest. To improve the signal to noise ratio, the acquisition was repeated a minimum of 8 times, with up to 13 repetitions when one or more acquisitions were affected by motion artefacts from breathing or ectopy. Breath-hold duration was 18 cardiac cycles, which was typically 18 s. The order that the diffusion directions were acquired was also rotated to avoid losing data from the same direction at the end of each breath hold. The typical duration of the scan was 45 min.The following sequence parameters were used, as previously described , 26, 27:All cDTI data was analysed by a single observer with in-house custom-built software written in MATLAB . This included a quality control step to reject images visually corrupted by artefacts and rigid co-registration of the remaining images . The RR-Two scalar diffusion parameter maps were calculated from the eigensystems: Fractional Anisotropy (FA) and Mean Diffusivity (MD) . FA is aThe secondary eigenvector (E2A) was taken to represent the mean sheetlet orientation –25. The Global values for FA, MD, HAg and E2A were calculated in systole and diastole. . The myocardium was then divided into 4 segments for each slice and the same segments in each slice were grouped into the conventional LV walls  . Care waVentricular volumes, function, mass, and ejection fraction for all patients were measured for the LV using a semi-automated threshold-based technique . All volume and mass measurements were also indexed to body surface area , 41.Statistical analysis was performed using IBM SPSS Statistics software, version 22. Cohort characteristics are presented as the mean ± SD or median & range, and percentage for categorical data. Variations in parameters between slices were assessed, with no discernible between slice difference for FA, MD and HAg; global and regional data are thus presented from all three slices to reduce parameter variation. However, despite a small interspace gap, there were significant between slice variations in E2A data, therefore global and regional wall E2A data are presented from the mid slice only. Comparison of regional data was conducted with a one-way repeated measures ANOVA, with correction for non-spherical data. Post hoc analysis was performed with paired t-tests with Bonferroni correction, taking the lateral wall as the reference.The following covariates were analysed for association with cDTI measurements: age, gender, body surface area (BSA), ejection fraction (EF), left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), LV mass and maximum LV wall thickness in diastole (MWTd). The association between covariates and global systolic and diastolic quantitative cDTI parameters were assessed with simple linear regression with significance set at <0.05. For helix angle data regression was performed for both HAg and HAG to determine whether normalising the gradient to the local wall thickness eliminates anthropometric associations.The baseline anthropometrics and CMR data of the study population are shown in Table p = 0.007) and anterior (p = 0.017) walls. Global diastolic FA was 0.56 ± 0.04. The lateral wall FA was less than the anterior (p < 0.001), inferior (p < 0.001) and septal walls (p = 0.004).A comparison of regional systolic and diastolic FA values is given in Table 3 mm2/s. There were no regional differences in systolic MD (p = 0.22). Global diastolic MD was 1.11 ± 0.13 × 103 mm2/s. The lateral wall MD was significantly greater than the anterior (p < 0.001) and inferior walls (p = 0.01).Regional systolic and diastolic MD values are shown in Table p = 0.007) and less in the inferior wall (p < 0.001). Global diastolic HAg was 0.68 ± 0.1°. HAg was greater in the anterior wall (p < 0.001) and the septum (p < 0.001) compared to the lateral wall.The helix angle in systole and diastole is depicted in 3D in Fig. p < 0.001; Diastole: apical 23 ± 5° , mid 26 ± 6° , basal 29 ± 6° p < 0.001; Mobility: apical 24 ± 9°, mid 27 ± 8°, basal 29 ± 7°, p=0.006). Regional systolic and diastolic, mid slice E2A values are given in Table p = 0.019). Global diastolic E2A was 26 ± 6°. Regional diastolic E2A was less in the lateral wall compared to the inferior (p < 0.001) and septal walls (p = 0.002). Global E2A mobility was 27 ± 8°. Regionally E2A mobility was greater in the lateral wall compared to the inferior wall (p = 0.009).E2A angles and E2A mobility in both cardiac phases showed significant between slice variation with greatest angulation in the basal slice . No subject characteristics were associated with global diastolic FA.There was a significant relationship between global systolic FA and RR interval with a decrease in FA of 0.013 for every 100 ms increase in RR . RR interval was inversely associated with diastolic MD , with a 100 ms increase in RR interval associated with 0.024 × 103 mm2/s decrease in MD. LV wall thickness was also inversely related to diastolic MD . There were no significant associations between subject anthropometrics and global systolic MD.Diastolic MD was 0.078 × 10p < 0.001), with a 100 ms increase in RR interval accounting for an increase in HA between the endo and epicardium of 3°. There was also a direct relationship between systolic HAg and LV end diastolic volume (EDV) , LV end systolic volume (ESV)  & LV mass . Global diastolic HAg was 0.11°/% greater in male patients, p < 0.001. Global diastolic HAg was also directly related to BSA , LVESV , LV Mass , and maximum wall thickness in diastole (MWTd) .Global systolic HAg was directly related to RR interval , LVEDV , LVMass , MWTd . Global diastolic HAG was inversely related to age , EF  and MWTd .Global systolic and diastolic HAG data were also regressed against subject anthropometrics. Systolic HAG was 0.41°/mm less in male patients, p = 0.011). Systolic E2A was also related to BSA , LV Mass , LVEDV  and MWTd . There were no associations between subject anthropometrics and global diastolic E2A. E2A mobility was inversely related to both age  and ejection fraction .Global systolic E2A was directly related to the RR interval, with an increase in RR of 100 ms associated with an increase in systolic E2A of 1°  [The global systolic (0.47 ± 0.05) and diastolic (0.56 ± 0.04) FA values for this cohort are largely in keeping with previously published data acquired at 3 T with the  ± 0.04) , Tunnicl ± 0.04) . We also ± 0.04) , and our ± 0.04)  and in h ± 0.04) . Regiona ± 0.04) . We sugg ± 0.04)  and regib = 300 s/mm2) [b = 400 s/mm2) [Global phasic results for MD also concur with previous studies adopting this sequence , 42. Reg0 s/mm2) , but sig0 s/mm2) . As MD i0 s/mm2) , cautionThere remains a lack of consensus with regard to optimal helix angle presentation. In this work, we provide descriptive data of the angle by region and transmural layer, in addition to statistical comparison of regional helix angle gradient (HAg), acquired from best-fit, radial transmural projections. The advantage of the latter reduced sensitivity to ROI variation, but this is at the expense of data smoothing. The systolic obliquity of myocyte helices and radial reorientation of sheetlet angles are becoming increasing recognised as important components of LV shortening and myocardial thickening respectively , 45–47. There have been no previous reports relating quantitative measures of cardiac cDTI to patient anthropometrics. This is important to understand, because the complex factors that affect DTI measurements may be affected by simple clinical variables. We observed that, despite applying heart rate correction to the b-value, there was residual heart rate dependent variability within global systolic FA, HAg and E2A measurements. However this effect was clinically small, with variation in parameters over a heart rate range of 60–100 bpm of 14° in epicardial to endocardial helix angle, 0.05 in FA, and 4° in systolic E2A. The reason behind this effect is unclear, but may be related to heart rate dependent changes in strain, or shorter mixing times at faster heart rates.As might be expected global systolic and diastolic HAg is directly related to BSA, LVEDV, LV mass and male gender. Interestingly, many of these correlations persist when helix angle gradient is normalised to the local wall thickness (HAG). This indicates that helix angle has neither a constant range independent of myocardial thickness, nor does it have a constant absolute gradient in degrees/mm.2 accounting for an increase in E2A of 4° and a 1 mm increment in wall thickness accounting for an increase of 2°). With regards to sheetlet mobility: within this healthy population with normal range ejection fractions, an increase in EF of 10% was associated with a decrease in E2A mobility of 5°. Initially this seems somewhat counter intuitive as sheetlet mobility is perceived to be an integral component of LV function. However, increasing age was also associated with decreasing E2A mobility and age related changes in LV function and volumes are well documented, with increasing EF and decreasing cardiac volumes with increasing age [Diastolic E2A conformation was independent of subject characteristics, but in systole increasing BSA, LV mass and LV wall thickness was associated with increasing radial orientation (an increase in LV mass of 50 g or BSA of 0.5 msing age , 41. Thesing age .There are a number of limitations of this work, including the inherently low SNR and spatial resolution of the STEAM diffusion sequence; the possibly of misregistration of slice averages, which could be age or gender dependent; and the potential for strain artefacts. We did not attempt strain correction of our results as we believe that contemporary strain measures are flawed by the assumption that the myocardium behaves like an isotropic jelly. The true impact of strain on quantitative cDTI parameters is a matter of significant debate in this field , 48, 49.Quantitative cDTI parameters display anthropometric variation, most notably HAg which increases with cardiac size. The contribution of technical factors to regional parameter heterogeneity must be taken into consideration when making clinical interpretations at lower b values.


Evolution of extracorporeal life support (ECLS) technology has added a new dimension to the intensive care management of acute cardiac and/or respiratory failure in adult patients who fail conventional treatment. ECLS also complements cardiac surgical and cardiology procedures, implantation of long-term mechanical cardiac assist devices, heart and lung transplantation and cardiopulmonary resuscitation. Available ECLS therapies provide a range of options to the multidisciplinary teams who are involved in the time-critical care of these complex patients. While venovenous extracorporeal membrane oxygenation (ECMO) can provide complete respiratory support, extracorporeal carbon dioxide removal facilitates protective lung ventilation and provides only partial respiratory support. Mechanical circulatory support with venoarterial (VA) ECMO employed in a traditional central/peripheral fashion or in a temporary ventricular assist device configuration may stabilise patients with decompensated cardiac failure who have evidence of end-organ dysfunction, allowing time for recovery, decision-making, and bridging to implantation of a long-term mechanical circulatory support device and occasionally heart transplantation. In highly selected patients with combined severe cardiac and respiratory failure, advanced ECLS can be provided with central VA ECMO, peripheral VA ECMO with timely transition to venovenous ECMO or VA-venous ECMO upon myocardial recovery to avoid upper body hypoxia or by addition of an oxygenator to the temporary ventricular assist device circuit. This article summarises the available ECLS options and provides insights into the principles and practice of these techniques. One should emphasise that, as is common with many emerging therapies, their optimal use is currently not backed by quality evidence. This deficiency needs to be addressed to ensure that the full potential of ECLS can be achieved. Extracorporeal life support (ECLS) is a therapeutic option increasingly used in the management of patients with cardiorespiratory failure that is refractory to maximal conventional treatment ,2. This This review provides a summary of the available ECLS options and cannulation techniques for short-term support of adult patients with cardiorespiratory failure that is refractory to conventional treatment.P = 0.03) [Details about the technology, principles and practice of extracorporeal membrane oxygenation (ECMO) can be found elsewhere ,6. Venov = 0.03) . However = 0.03) .Analysis of 2009 H1N1 pandemic data ,15-18 de2) clearance can still occur with lower blood flows [A number of configurations of VV ECMO can be applied based on individual patient requirements Table . Althougod flows . The bicod flows , but flood flows .2 removal (ECCOR). Refinements in technology [Hypercapnia and respiratory acidosis, although usually well tolerated, is a barrier to implementing ultra-protective ventilation . This bachnology ,23 have chnology , but defchnology .2 is utilised to create a diffusion gradient across the membrane and allows CO2 removal. While ECMO necessitates high blood flow rates (5 to 7 l/minute) to ensure optimal oxygenation, ECCOR allows CO2 removal at much lower blood flow rates (<1 l/minute) due to significant differences in CO2 and oxygen kinetics [ECCOR requires an arterial or venous access cannula, a pump to drain blood during venous access, a membrane lung and a return venous cannula. Heparin-coated wire-reinforced cannulae may be placed percutaneously in a femoral–femoral or a femoral–jugular orientation. Alternatively, a wire-reinforced double-lumen catheter may be inserted under ultrasound guidance via the right internal jugular vein with the drainage port positioned in the intra-hepatic inferior vena cava and the return port in the right atrium ,26. A flkinetics ,23. Alth2 removal in patients with adequate oxygenation and robust haemodynamics. There have been reports of its successful use in patients with ARDS [Various novel ECCOR devices are currently available to facilitate LPV and are reviewed in detail elsewhere ,23. The ith ARDS  and seveith ARDS  and as aith ARDS . Howeverith ARDS . A VV coith ARDS .2 removal at flows between 400 and 600 ml/minute [2 removal only and do not provide any oxygenation benefit. Even though modern low-flow VV ECCOR devices reportedly require a lower degree of anticoagulation, concerns remain over risks of circuit thrombosis. Other emerging technologies such as intravascular gas exchange and respiratory dialysis [Devices such as the Decap™ system  that serve the dual purpose of renal replacement therapy and ECCOR are also available . By combl/minute  using dudialysis  are beyodialysis ,35 with Extracorporeal respiratory support can thus be provided with ECCOR or ECMO depending on the lung pathology, pulmonary compliance and oxygenation and decarboxylation requirements of an individual patient. ECMO and ECCOR can also bridge highly selected patients to lung transplantation.Providing temporary mechanical circulatory support (MCS) support to patients with acute refractory cardiac failure using ECLS techniques is a rapidly evolving area; intervention may be time critical and mortality is higher than ECLS for isolated respiratory failure ,37. The The severity of noncardiac organ system failures can be defined using scoring systems such as the Sequential Organ Failure Assessment score. Severe multiorgan failure  has been considered a contraindication to VV ECMO  and simiFor patients with predominant cardiac failure with preserved pulmonary function, the available MCS devices provide several options Table . CentralLV and aortic root stasis from lack of cardiac ejection and failure of aortic valve opening may result in catastrophic intracardiac and aortic root thrombosis. Increased anticoagulation to minimise this risk may heighten the risk of significant bleeding. Minimally invasive strategies such as percutaneous transseptal left atrial decompression  and subxFemoral VA ECMO is also limited by femoral arterial size, and thus cannula size and the requirement for distal limb perfusion. Given its less invasive nature (compared with thoracic access), peripheral VA ECMO – with attention to optimal LV afterload, minimising LV distension with optimal fluid and inotrope therapy, anticoagulation and pulmonary management – is a viable first-line option for patients with isolated acute cardiac failure refractory to conventional management.The limitations of peripheral VA ECMO have prompted the use of ECMO devices  to facil2 removal and temperature regulation. Upon RV recovery, the graft can be ligated and buried upon decannulation without re-sternotomy.Temporary RV support can be provided with the Centrimag™ ECMO system  through percutaneous femoral venous access to the right atrium and return to the pulmonary artery via a cannulated exteriorised Dacron graft. This strategy is described for temporary support of the RV with insertion of a long-term LVAD but is applicable to other causes of severe isolated RV dysfunction. An oxygenator can be included in the circuit to ensure adequate oxygenation, COPercutaneously inserted LVADs such as TandemHeart™  and Impella™ (Abiomed)  are poteEven though the third-generation, implantable LVADs designed for long-term MCS are a significant improvement on earlier devices , their uThe number of patients with severe combined cardiac and respiratory failure who fail conventional treatment is very small and ECLS in this group is controversial, being considered either heroic or futile. In the setting of pneumonia or sepsis and severe cardiac dysfunction, where feasible, VV ECMO with inotropic support should be the initial perfusion strategy . Septic Upper body hypoxia can occur if myocardial recovery occurs and lung function remains poor. This may be overcome by transition to VV ECMO if myocardial recovery is satisfactory or with the use of VA–venous ECMO, which allows return of oxygenated blood to both arterial and venous sides of the circulation, thereby minimising the risk of upper-body hypoxia. Although peripheral arterial cannulation for VA–venous ECMO is less invasive and is an attractive option, balancing the oxygenation and perfusion needs of an individual patient by regulating the return of oxygenated blood to the underperfused coronary and cerebral circulation may be challenging, and a central configuration may be preferred in this setting. Returning the oxygenated blood in the ascending aorta by cannulating the axillary ,58 or suin extremis[A more invasive, high-risk option in this setting includes use of the Centrimag™ ECMO system (Levitronix LLC) as a temporary LVAD/biventricular assist device with an oxygenator in the circuit. The device can be employed in several configurations Table  to suppo extremis,61 when By providing a range of support options based on the degree of cardiac and respiratory failure Table , ECLS thSeveral other ECLS cannulation strategies merit consideration and further investigation. These strategies are necessitated by inherent limitations of ECLS therapies such as VV ECMO and VA ECMO and also to make some of the support options less invasive. A summary of these therapies is presented in Table 2 removal.Refractory hypoxia and severe pulmonary hypertension may be encountered on VV ECMO and is often terminal. Percutaneous transeptal cannulation of the left atrium to return the oxygenated blood has been proposed as an option to avoid a sternotomy, which needs to be further investigated. Similarly, percutaneous transeptal cannulation of the left atrium for access along with percutaneous right atrial cannulation may assist in venting the left ventricle during VA ECMO. Other emerging less invasive ECLS options include hybrid systems that can provide renal replacement therapy and COECLS therapies are high-risk invasive interventions undertaken in a few specialised centres. Despite the advancements in ECLS technology, the associated complications such as bleeding, thrombosis and infections cannot be underestimated. Apart from the risk profile, the success of ECLS relies heavily on its clinical application. Careful selection of both patients and the ECLS perfusion strategy is the key and not all centres may have the experience or the resources to provide the full complement of ECLS therapies discussed in this paper.The lack of robust evidence is a significant limitation. The complexities in delivering ECLS include resources and cost-effectiveness, staff training, governance and availability of funding for other programmes such as cardiothoracic surgery, long-term mechanical assist devices, and heart and lung transplantation. Such undertaking may be feasible in resource-rich settings, but significant innovation and refinement is required prior to its widespread use. With minimal improvement in outcomes in ARDS over the years, widespread use of VV ECMO and ECCOR may be a reality in years to come. VA ECMO and its use as a temporary VAD for MCS is a complex undertaking and its use will probably be limited to specialised centres.ECLS therapies hold promise and further research is indicated to explore their full potential. Given the small number of patients who receive ECLS for cardiac and/or respiratory support globally, it may not be feasible to generate evidence-based guidelines for all available therapies. However, ongoing refinements in technology, development of minimally invasive techniques, better understanding of the physiological impact of the ECLS circuit  and impARDS: Acute respiratory distress syndrome; CO2: Carbon dioxide; ECCOR: Extracorporeal carbon dioxide removal; ECLS: Extracorporeal life support; ECMO: Extracorporeal membrane oxygenation; LPV: Lung-protective ventilation; LV: Left ventricular; LVAD: Left ventricular assist device; MCS: Mechanical circulatory support; RV: Right ventricular; VA: Venoarterial; VAD: Ventricular assist device; VV: Venovenous.The authors declare that they have no competing interests.


Growing evidence demonstrates subtle left ventricular myocardial dysfunction in patients with metabolic syndrome (MetS), with central obesity, glucose intolerance and inflammation emerging as important contributors. Whether these results can be translated to the right ventricle (RV) is not yet fully elucidated. Furthermore, although lifestyle intervention favorably impacts MetS components and inflammatory biomarkers, its effect on RV myocardial function remains unknown today.Thirty-nine MetS adults free of diabetes were enrolled in a three month lifestyle intervention program including diet and physical exercise, and compared with forty healthy controls. Blood biochemistry, echocardiography including tissue Doppler imaging (TDI), and vector velocity imaging of the RV free wall to assess global longitudinal strain (GLS) and strain rates (SR) were obtained at baseline and after the intervention.2 = 0.46, P < 0.001). Biological markers of MetS and inflammation as well as RV GLS  and systolic (P = 0.003) and early diastolic (P = 0.01) SR, but not TDI indexes, significantly improved after diet and exercise training, and vector velocity imaging data in MetS following the lifestyle intervention no longer differed from controls.Compared with controls, MetS patients presented similar right atrial and RV morphology but reduced systolic (P = 0.04) and early diastolic (P = 0.02) velocities of the tricuspid annulus. They showed attenuated RV GLS  as well as early diastolic (P = 0.003) and systolic (P < 0.001) SR. Multiple regression analyses revealed log PAI-1 active, (P < 0.001), log adiponectin, (P = 0.01), LV mass indexed (P = 0.004) and central fat (P = 0.03) as independent predictors of RV GLS (RMetS is associated with subtle impairments in both RV free wall diastolic and systolic myocardial function which could be partly related to central-obesity induced changes in pro- and anti-inflammatory cytokines and left ventricular remodeling. The favorable impact of healthy dieting and physical activity on RV free wall mechanics indicates that cellular and sub-cellular alterations responsible for the RV myocardial abnormalities are probably not permanent and modifiable throughout adequate interventional strategies.NCT00917917.American National Institutes of Health database  The metabolic syndrome (MetS) is a cluster of cardio-metabolic risk factors predisposing the development of cardiovascular pathologies . It is aSpeckle tracking echocardiography is a highly sensitive technique used to detect subtle myocardial dysfunction at the preclinical stage of systolic abnormalities ,6]. Rec. Rec6]. Lifestyle intervention based on dietary management and physical activity is a well-established approach to the management of various cardiometabolic diseases, including diabetes, obesity and MetS. Increasing evidence reports favorable and specific effects of lifestyle interventions on central obesity, insulin-resistance, glucose intolerance and inflammation -23]. To. To23]. Accordingly, the aims of the present study were firstly to compare RV free wall mechanics using vector velocity imaging in asymptomatic MetS adults free from type-2 diabetes, with healthy age and gender-matched controls and to evaluate in the MetS group the impact of a lifestyle intervention focused on dietary management and increased physical activity. Furthermore, we also aimed to observe relationships between RV myocardial function and metabolic risk and inflammatory markers as well as their changes consecutive to the life style intervention.This study formed part of the RESOLVE trial . The preBiochemical, clinical and echocardiographic investigations were performed before and after the intervention in MetS, and at baseline only for controls. Participants provided written informed consent. The study was approved by the human ethics committee from the University Hospital of Saint-Etienne, France. The study protocol was registered with the American National Institutes of Health database N°NCT00917917.Anthropometric variables, body composition, blood pressure and routine serum biological analyses plus N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured as previously described . InsulinParticipants were enrolled in a 3-week residential program, before returning home to continue the intervention on their own accord. Throughout the residential program, participants received daily individualized meals, planned by dietitians. Total dietary intake during the intervention was calculated to reach a 500 kcal/day caloric deficit with protein accounting for 15 to 20% and lipids 30-35%. Participants’ physical activity requirements included endurance  and resistance training . Resistance training consisted of 8 free-weight exercises, performed for 3 sets of 10 repetitions. Participants were coached individually and heart rate was monitored by Polar™ S810. Participants also attended information seminars on MetS, nutrition, cooking and exercise, to support the sustainability of their new lifestyle upon returning home. Compliance to the intervention was monitored by a weekly self-reported questionnaire and phone interview conducted by dietitians.Images were obtained by an experienced operator (GW) using a commercially available system  equipped with a 3.5 MHz sector scanning electronic transducer in the left lateral decubitus position. Images at a minimum rate of 60–75 Hz were acquired in cine loops triggered to the QRS complex and saved digitally for subsequent off-line analysis with dedicated software .tri) and the right atrial area were used as surrogates of right atrial pressures . Le. Le26]. ressures ,32]. Th. Thtri) ressures . The pulVelocity vector imaging is a method used to quantify myocardial wall motion through the combination of speckle tracking, tissue-blood border detection and myocardial shape . It is aStatistical analyses were performed using SPSS 20.0 for Windows (SPSS Inc). Statistical significance was set a priori at P < 0.05. Variables are presented as mean ± standard derivation and skewed data were log-transformed. Appropriated unpaired and paired t-tests were used to evaluate the differences between MetS (at baseline and after the lifestyle intervention) and controls and the effect of the lifestyle intervention within the MetS patients, respectively. Mann–Whitney U-test and Wilcoxon test were used for abnormally distributed variables. For categorical variables, a χ2 test was used. Correlations using Pearson’s correlation coefficient or Spearman coefficient of rank correlation for abnormally distributed variables were used to identify associations between RV longitudinal myocardial deformation and clinical as well as biological parameters or their changes after the lifestyle intervention. Multiple stepwise linear regression analyses were performed to assess variables that were independently associated with RV free wall GLS. Biometric, metabolic and inflammatory biomarkers that correlated with RV free wall GLS with a P value <0.05 during the first univariate analysis were entered into the model.For all parameters presented in this section, no significant differences were observed between the whole MetS group (n = 39) and the MetS subgroup (n = 33) involved in the lifestyle intervention program at baseline.All anthropometric, biological and clinical data except height, LDL-cholesterol and NT-proBNP differed significantly between MetS and controls Table . Values,Structure and function of the left ventricle are presented in Table tri as well as isovolumic relaxation time. All these RV parameters, except RV end-diastolic dimensions, tricuspid A and E/A ratio were unaltered by the lifestyle intervention. Differences in tricuspid A and E/A ratio were no longer apparent between MetS and controls after the intervention.Structure and function of the RV are presented in Table Peak and time to peak values of the RV free wall longitudinal strains and strain rates are presented in Table Significant correlations were obtained between RV GLS and markers of central obesity, glucose intolerance and inflammation as well as left ventricular hypertrophy Table . Log PAIWe provide evidence for the first time of non-diabetic MetS patients exhibiting subtle RV free wall systolic and diastolic dysfunction that was significantly improved following a 3-month lifestyle intervention based on healthy dieting and increased physical activity.Currently, a large body of evidence associates MetS with adverse effects on left ventricular myocardial function assessed using tissue deformation imaging tools . HoweverAbdominal obesity, a key component of MetS, is consistently associated with major increases in pro-inflammatory adipocytokines, such as TNF-α, IL-6, hsCRP or PAI-1 active, as well as reduced protective cytokines, such as adiponectin, agreeing with our data -44]. Gr. Gr44]. To the best of our knowledge, no studies have examined the effect on RV myocardial function of non-pharmacological interventional strategies in MetS populations. The other major novel finding from the present study was that a 3-month lifestyle intervention comprising nutrition and exercise training was able to fully restore RV GLS to normal values of age-matched healthy controls. Of note, improvements in RV free wall function were evidenced only using sensitive tools such as vector velocity imaging, as TDI indices were not changed. RV myocardial function enhancements have also been reported with obesity following interventions involving low calorie diet . AgreeinDespite its key role in left ventricular filling, RV function has been insufficiently investigated in cardiometabolic diseases. With prevalence reaching alarming proportions worldwide, MetS is now considered to be the driving force for a cardiovascular disease epidemic. In this context, the present study underlines the necessity for a close clinical RV monitoring in MetS patients even when type 2 diabetes is not associated. Moreover, this study underlines the importance of central obesity and its associated inflammation as independent factors explaining RV mechanical abnormalities, highlighting the need for treatment of central fat and inflammation to decrease or prevent the deleterious impact of MetS on RV function. Finally, the present work emphasizes the importance of lifestyle changes since the RV dysfunction can be corrected even only three months after an exercise and nutrition intervention.tri and right atrial area. Although significant, the differences between the 2 groups in E/Etri were low  and most importantly only one MetS patient out of 39 presented with a ratio greater than 6; a cut-off value proposed by Nagueh et al. ,, did not h et al.  that canz et al.  recentlyIn conclusion, RV myocardial systolic and diastolic abnormalities in MetS patients free of type-2 diabetes were partially accounted for by central adiposity-induced changes in pro- and anti-inflammatory cytokines as well as ventricular interdependence, through direct mechanical interactions between the RV and left ventricular chambers. A lifestyle intervention based on healthy dieting and physical activity was associated with fully restored RV free wall mechanics to healthy control level; indicating probably that cellular and sub-cellular alterations were not permanent but still modifiable throughout adequate interventional strategies. Special attention should be paid to this specific population in clinics, as earlier identification of asymptomatic patients at high risk of evolution to RV failure is of primary importance because it may facilitate timely and more effective intervention.E/Etri: Ratio of peak early filling velocity through the tricuspid valve during diastole to peak early diastolic velocity of the lateral tricuspid annulusHbA1C: Glycated hemoglobinHDL: High-density lipoproteinHOMA-IR: Homeostatic model assessment of insulin resistancehsCRP: High sensitivity C-reactive proteinIL6: Interleukin-6LDL: Low-density lipoproteinMetS: Metabolic syndromeNT-proBNP: N-terminal pro-B-type natriuretic peptidePAI-1 active: Active plasminogen activator inhibitor-1RV: Right ventricleRV GLS: Global longitudinal strain of the right ventricular free wallTAPSE: Tricuspid annular plane systolic excursionTDI: Tissue Doppler imagingTG: TriglyceridesTNF-α: Tumor necrosis factor αThe authors declare that they have no competing interests.PO is the guarantor of the entire manuscript. JS-F contributed to analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content, and takes responsibility for the integrity of the work as a whole. GW contributed to acquisition, analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content, and takes responsibility for the integrity of the work as a whole. EC contributed to analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. AV contributed to analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. FD contributed to study concept and design, acquisition of data, drafting of the manuscript and critical revision of the manuscript for important intellectual content. GN contributed to interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. BL contributed to study concept and design, analysis of data and critical revision of the manuscript for important intellectual content. RC contributed to study concept and design, interpretation of data and critical revision of the manuscript for important intellectual content. DC contributed to study concept and design, to analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. PO contributed to study concept and design, to acquisition, analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.


Purpose. To evaluate whether the diagnostic performance of Gd-EOB-DTPA-enhanced MRI in evaluating liver function and pathology is improved by considering liver volume (LV). Methods. This retrospective study included 104 patients who underwent Gd-EOB-DTPA-enhanced MRI before liver surgery. For each patient, using the precontrast and hepatobiliary phase images, we calculated the increase rate of the liver-to-spleen signal intensity ratio (LSR), that is, the “ΔLSR,” and the increase rate of the liver-to-muscle signal intensity ratio (LMR), that is, the “ΔLMR.” ΔLSR × LV and ΔLMR × LV were also calculated. The correlation of each MR parameter with liver function data or liver pathology was assessed. The correlation coefficients were compared between ΔLSR (ΔLMR) and ΔLSR (ΔLMR) × LV. Results. The correlation coefficient between ΔLSR (ΔLMR) × LV and cholinesterase was significantly higher than that between ΔLSR (ΔLMR) and cholinesterase. The correlation coefficient between ΔLSR (ΔLMR) × LV and the degree of fibrosis or necroinflammatory activity was significantly lower than that between ΔLSR (ΔLMR) and the degree of fibrosis or necroinflammatory activity. Conclusion. The inclusion of liver volume may improve Gd-EOB-DTPA-based predictions of liver function, but not in predictions of liver pathology. Gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) is a liver-specific agent, and it is widely used to improve both the detection rate of focal liver lesions and the characterization of liver tumors on magnetic resonance imaging (MRI) , 2. As GThe purpose of the present study was to evaluate whether the diagnostic performance of Gd-EOB-DTPA-enhanced MRI in evaluating liver function or fibrosis is improved by considering the LV.This study was approved by the institutional review board of our hospital. The requirements for informed consent were waived for this retrospective study. Referring to the medical data recorded at our hospital, we enrolled 129 consecutive patients who underwent Gd-EOB-DTPA-enhanced MRI and hepatic resection for a liver tumor or liver transplantation between June 2010 and May 2013. Of them, twelve, eight, and five patients were excluded due to a history of splenectomy, a history of right or left lobectomy, and poor image quality derived from respiratory artifacts, respectively. Finally, 104 patients were enrolled in this study. The 104 patients included 69 men and 35 women . The hepatitis C virus antibody was present in 45 cases, the hepatitis B surface antigen in 17 cases, alcoholic hepatitis in five cases, nonalcoholic steatohepatitis in five cases, primary biliary cirrhosis in two cases, autoimmune hepatitis in one case, and primary sclerosing cholangitis in one case. The grading of liver dysfunction was preoperatively evaluated based on the Child-Pugh classification, and 86, seven, and 11 patients were categorized into Grades A, B, and C, respectively. The grading of liver function or severity of liver cirrhosis in patients with chronic liver disease was evaluated according to the Child-Pugh classification [k-space ordering, spectral attenuation with inversion recovery, acquired 133 sections, scan time 17.9 s, and breath-holding.MR imaging was performed on a whole-body 3.0 Tesla (T) scanner . For the Gd-EOB-DTPA-enhanced MRI, axial 3D eTHRIVE  was scanned before and 20 min after an intravenous injection of 0.1 mL/kg  of Gd-EOB-DTPA . The detailed imaging parameters were as follows: 32-channel cardiac phased-array coil, TR/TE/FA = 3 ms/1.4 ms/10°, matrix 252 × 200, FOV 37.5 × 29.8 cm, SENSE factor 1.8, slice thickness = 3 mm, gap = −1.5 mm, linear For the LV measurement, the total of the MR images in the hepatobiliary phase was prepared for each patient. The LV of each patient was semiautomatically measured using the “liver analysis” function of the volume analyzer SYNAPSE VINCENT . A part of liver tumor was not considered as LV.The signal intensity of axial eTHRIVE on Gd-EOB-DTPA-enhanced MRI was measured on the same DICOM viewer. First, two abdominal radiologists with six and 19 years of experience together selected three slices without significant artifacts. On the same slices they measured the signal intensities by placing the largest possible region of interest (ROI) on the liver parenchyma, spleen, and erector spinae muscle, avoiding vessels, tumors, and artifacts in a consensus manner . For theBased on these average values, the liver-to-spleen ratio (LSR) and the liver-to-muscle ratio (LMR) before and after the administration of Gd-EOB-DTPA were recorded for each patient. The same size and shape of ROI were placed at the same position for the images before and after the administration of Gd-EOB-DTPA. As indicators of liver function, the increase rates of the LSR (LMR) in the hepatobiliary phase compared with the precontrast image were calculated using the following equation: (LSR (LMR) on the hepatobiliary phase − LSR (LMR) on the precontrast image)/LSR (LMR) on the precontrast image , 4. We nOne pathologist with 4 years of experience who was unaware of the imaging data reviewed the hematoxylin-eosin-stained glass slides of each patient and referred to the official pathological report to determine the histological findings of the liver parenchyma. When the results were discordant, another experienced pathologist with 17 years of experience was consulted. The degree of liver fibrosis was classified into five groups according to the New Inuyama Classification: F0 (no fibrosis), F1 , F2 (bridging fibrosis), F3 , and F4 (liver cirrhosis) . Similary, z) on a single independent variable (x) was observed, we calculated the correlation coefficient , and we tested the significance of the Rxy, Rxz coefficient by means of the modified t-test, the number of degrees of freedom being f = n − 3, using the following formula (n = sample  number): We used a linear regression analysis to examine the correlations between ΔLSR (ΔLMR) and ΔLSR (ΔLMR) × LV and the laboratory data corresponding to liver function . The correlations of these four parameters with the Child-Pugh score, MELD score, the degree of liver fibrosis, and the grade of necroinflammatory activity were each examined using Spearman's rank correlation test. We also compared the correlation coefficients between ΔLSR and ΔLSR × LV and between ΔLMR and ΔLMR × LV. The statistical significance was evaluated using the following method: when the dependence of a variable (zRxz(see ).p value of <0.05 indicated a significant difference.For all tests, a n = 33), F1 (n = 11), F2 (n = 11), F3 (n = 12), and F4 (n = 37) and A0 (n = 30), A1 (n = 38), A2 (n = 32), and A3 (n = 4). The average LVs ± standard deviation (SD) in F0, F1, F2, F3, and F4 were 1.09 ± 0.24, 1.06 ± 0.26, 1.15 ± 0.17, 1.13 ± 0.26, and 1.06 ± 0.34, respectively. The average LVs ± SD in A0, A1, A2, and A3 were 1.08 ± 0.23, 1.04 ± 0.29, 1.13 ± 0.29, and 1.19 ± 0.30, respectively. The average values and SD of ΔLSR, ΔLSR × LV, ΔLMR, and ΔLMR × LV were 0.53 ± 0.30, 0.59 ± 0.37, 0.64 ± 0.29, and 0.70 ± 0.35, respectively. All four parameters  were significantly correlated with all laboratory data, the grade of fibrosis, and necroinflammatory activity (p < 0.05 in each case).The number of patients in each grade of fibrosis and necroinflammatory activity was as follows: F0 (p < 0.05). The correlation coefficients between ΔLSR × LV and Plt, Alb, LDH, Child-Pugh score, or MELD score tended to be higher than those between ΔLSR and Plt, Alb, LDH, Child-Pugh score, or MELD score. However, the correlation coefficient between ΔLSR × LV and the degree of fibrosis or necroinflammatory activity was significantly lower than that between ΔLSR and the degree of fibrosis or necroinflammatory activity (p < 0.01). The correlation coefficient between ΔLSR × LV and T-bil tended to be lower than that between ΔLSR and T-bil.p < 0.01) (p < 0.05) or necroinflammatory activity (p < 0.01). The correlation coefficient between ΔLMR × LV and T-bil tended to be lower than that between ΔLMR and T-bil. < 0.01) . The cor green test can be improved by considering liver volume [In our study using 3T-MRI, significant correlations between the uptake of Gd-EOB-DTPA and liver function, fibrosis, and necroinflammatory activity were obtained, as reported previously –7. In lir volume –13 and sIn general, liver function data are evaluated with a blood test, which includes a “whole liver” element. Therefore, the consideration of liver volume in the MR parameter could enable the correlation with liver function to be more intensive. We found in the present study that the correlation coefficient between ΔLSR (LMR) × LV and T-bil tended to be lower than that between ΔLSR (LMR) and T-bil, although the difference was only slight. T-bil includes both unconjugated and conjugated bilirubin, and the T-bil value can be affected by a number of factors including prehepatic or posthepatic disorders, hemolysis, and constitutional predisposition. Therefore, considering “liver volume” in the MR parameter might not be effective for the correlation with T-bil.We also found that the correlation coefficients between ΔLSR (LMR) × LV and the degree of fibrosis or necroinflammatory activity were significantly lower than those between ΔLSR (LMR) and the degree of fibrosis or necroinflammatory activity. That is, the consideration of liver volume in addition to the uptake of Gd-EOB-DTPA for setting the MR parameters was not useful. Although this result was beyond the scope of our hypothesis, we propose two plausible reasons why this result was obtained. One is that fibrosis and necroinflammatory activity represent the local state of the liver parenchyma. Therefore, the consideration of “liver volume” might worsen the correlation with liver pathology. Another possible reason is that the LV does not always decrease gradually as the degree of fibrosis progresses. A report on LV change in patients with hepatic fibrosis is available . The LV We obtained a similar result; that is, LV tends to increase with the severity of fibrosis from F0 to F2 but decrease at F3 to F4, which would affect the rank correlation between ΔLSR (LMR) × LV and the degree of fibrosis. It was reported that the LV tends to increase with the aggravation of inflammatory activity (the increase of necroinflammatory activity) . In our  green test results as a laboratory datum corresponding to liver function. Although 80 patients underwent this test preoperatively, the Child-Pugh classification for all of them was Grade A. That is, patients with moderate or severe liver dysfunction were not included. We judged that we should not juxtapose the comparison with ICG test to those with other liver function parameters in our study, because of the difference in patient population. Finally, tumor volumes of small lesions in the liver were not excluded from measured LV for technical difficulty, which may have led to minor overestimation of LV in some patients.Our study had several limitations. First, the trial was a study with a limited patient population, and the number of cases with each degree of fibrosis and necroinflammatory activity was not uniform. Second, we used two organs, the spleen and erector spinae muscle, as signal intensity references of the liver parenchyma. As there may be persistence of contrast enhancement in the spleen and muscle, these organs might be limitations for analyses of LSR and LMR as well as motion artifacts and partial volume effects. Although a T1 map might be preferable for the quantitative analysis of the uptake of Gd-EOB-DTPA, it was difficult to generate such a map with our scanner. Third, we could not evaluate indocyanineWe have demonstrated that the inclusion of liver volume may improve Gd-EOB-DTPA-based predictions of liver function, but not in predictions of liver pathology.


Chagas Heart Disease (CHD) is related to myocardial fibrosis (MF) and has a well-known relationship with sudden cardiac death (SCD). Cardiac magnetic resonance (CMR) can assess MF by late gadolinium enhancement (LGE) sequences. This study seeks to evaluate the presence of scar by LGE as a predictor of adverse outcomes in a CHD cohort.A total of 121 patients with CHD disease  from Ribeirao Preto Clinical Hospital  were included. A CMR was performed at the enrollment from October/2009 to March/2013 in a single 1.5T scanner , including SSFP cines at the vertical and horizontal long axis, and a stack of the short axis. LGE sequences were performed after 10.1 ± 1.5 min gadolinium contrast (0.2 mmol/kg) in the same cine positions, with positive LGE visually assessed and quantified for core and grey zone. All analysis was performed with Mass Research version software . Any death, pacemaker (PC) implant and heart failure hospitalization (HFH) was considered an event during the follow-up. Kaplan-Meier curves, log-rank analysis and Cox regression models were utilized at the statistical analysis.There was scar in 78.5% of the patients, with the lateral, inferolateral and inferior walls as the most common areas of fibrosis. The ones with positive LGE had lower left ventricular (LV) ejection fraction, and higher LV end diastolic volume and LV mass. No difference in other cardiovascular risk factors was noted. After 24.5 ± 13 months of follow-up, 12 events occurred . No events were observed among patients without MF. At the survival analysis, patients with scar had a lower event-free time when compared to the ones without scar .


Urgent cardiac ultrasound examination in the critical care setting is clinically useful. Application of goal-directed echocardiography in this setting is quite distinct from typical exploratory diagnostic comprehensive echocardiography, because the urgent critical care setting mandates a goal-directed approach. Goal-directed echocardiography most frequently aims to rapidly identify and differentiate the cause(s) of hemodynamic instability and/or the cause(s) of acute respiratory failure. Accordingly, this paper highlights 1) indications, 2) an easily memorized differential diagnostic framework for goal-directed echocardiography, 3) clinical questions that must be asked and answered, 4) practical issues to allow optimal image capture, 5) primary echocardiographic views, 6) key issues addressed in each view, and 7) interpretation of findings within the differential diagnostic framework. The most frequent indications for goal-directed echocardiography include 1) the spectrum of hemodynamic instability, shock, and pulseless electrical activity arrest and 2) acute respiratory failure. The differential diagnostic categories for hemodynamic instability can be remembered using the mnemonic ‘SHOCK’  combinations/other kinds of shock). RESP-F  can be used for acute respiratory failure. The goals of goal-directed echocardiography in the unstable patient are: assessing global ventricular systolic function, identifying marked right ventricular and left ventricular enlargement, assessing intravascular volume, and the presence of a pericardial effusion. In an urgent or emergent setting, it is recommended to go directly to the best view, which is frequently the subcostal or apical view. The five views are the subcostal four-chamber view, subcostal inferior vena cava view, parasternal long axis view, parasternal short axis view, and the apical four chamber view. Always interpret goal-directed echocardiographic findings in the context of clinically available hemodynamic information. When goal-directed echocardiography is insufficient or when additional abnormalities are appreciated, order a comprehensive echocardiogram. Goal-directed echocardiography and comprehensive echocardiography are not to be used in conflict with each other. Important guidelines have recently been published for the use of echocardiography in the critical care setting –6 and a Goal-directed echocardiography is different from the comprehensive echocardiograms performed by fully trained, experienced, and certified cardiac sonographers, cardiologist echocardiographers, and advanced critical care echocardiographers –5,9. ComIn conducting goal-directed echocardiography, the most technically difficult patients are imaged in the most challenging situations; hence, diagnostic shortcomings are exaggerated in this population because of, for example, lung interference, mechanical ventilation, positioning limitations, and the urgency to acquire the information for immediate treatment. Current research suggests that training internists and residents with limited previous ultrasound skills is feasible and can result in accurate assessments when using goal-directed echocardiography ,17–19. IThe issues of how goal-directed echocardiography is different from conventional echocardiography and when goal-directed echocardiography alone is sufficient are the subject of careful discussion in the recent publication by Spencer and colleagues . The AmeAn expert round table led by the European Society of Intensive Care Medicine has recently developed an international consensus statement on guidelines for training and accreditation which have been widely adopted . EarlierWhile cardiologists and cardiac sonographers are generally the most highly trained and experienced operators, there are emerging important roles for different kinds of providers. Goal-directed echocardiography is often performed by physicians who are not trained in acquisition and interpretation of comprehensive echocardiograms and who come from diverse backgrounds and different clinical experiences. For these physicians guidelines for goal-directed echocardiography training in the ICU are much more focused and are currently in development ,15,19,23Application of ultrasonography by intensivists and other clinicians is increasing and widespread use is inevitable ,24,25. TGoal-directed echocardiography has now become a reliable tool and can be performed within minutes  and is uGoal-directed echocardiography can be combined with thoracic ultrasound imaging  and imprThe goal of goal-directed echocardiography is to identify the cause (mnemonic SHOCK) of hemodynamic instability, shock, or PEA arrest and to expedite directed therapies ,32–34. TA structured approach to accomplishing the goals of goal-directed echocardiography involves specifically asking and addressing key practical questions, as follows. First, does the LV appear significantly dilated or not? Does the LV function appear ‘significantly’ impaired or not? Second, is the RV dilated or not? Third, is there evidence of hypovolemia  and collapsing >50% with spontaneous respiration). In the more severe cases of hypovolemia, and in a non-mechanically ventilated patient, an IVC diameter of ≤1 cm usually indicates preload responsiveness . Fourth,Goal-directed echocardiography should note the presence of additional abnormalities but the diagnostic pursuit of these additional findings is accomplished by a comprehensive echocardiographic examination. Specifically, the presence of significant valvular abnormalities, wall motion abnormalities, LV aneurysm, RV hypertrophy, cardiac masses, thrombus, diastolic dysfunction, or a dilated ascending aorta with potential dissection should be pursued with a comprehensive echocardiographic examination, when recognized .Use a low-frequency transducer for adequate penetration to image cardiac structures. Transducers with a higher frequency have better resolution at the expense of deeper tissue penetration. Transducers with a lower frequency have better penetration at the expense of higher resolution. The ‘footprint’ or size of the low-frequency transducer head is designed to be small enough to better fit between the intercostal spaces.Depth is increased to 20 to 24 cm to identify pericardial effusion and the incidental finding of pleural effusion. Decrease ‘depth’ to 14 to 16 cm for a full screen cardiac image. Continually adjust the ‘focus’ control to the anatomy imaged for better resolution. Gain should be adjusted to see endocardial borders clearly  view . This view is also used for presence of pericardial effusion. Incidental findings of clot/thrombus in the main pulmonary artery may be noted.Some authors caution about the use of A-4 views since off-axis views lead to erroneous interpretation of the LV and, particularly, RV size and function . This viGoal-directed echocardiography should always be interpreted in the context of clinically available hemodynamic and other clinically relevant information. Accordingly, a goal-directed echocardiography is not an anatomic investigation; it is a physiologic study or hemodynamic assessment Table . Full inSeptic or distributive shock that is less severe or in the earlier stages may show a hyperdynamic LV and a smaller to normal size IVC with >50% collapsibility because septic shock is often initially associated with a degree of hypovolemia. More severe distributive shock may demonstrate impaired LV function .Hypovolemic shock may demonstrate small ventricles, sometimes ‘near cavity obliteration’, due to a small and hyperdynamic LV, and a small IVC with wide respiratory variation which collapses >50% on inspiration in a spontaneously breathing patient ,52,53. IObstructive shock due to tamponade (evidence of hemodynamic compromise) may be observed in the A-4 view Figure A and theIn the subcostal view, where you often image the largest amount of pericardial fluid accumulation, measure maximal echocardiographic-free space in diastole for potential pericardial ‘tap’ . It is bObstructive shock due to acute pulmonary embolism will demonstrate a dilated RV Figure C and an The sensitivity of these findings to diagnose pulmonary embolism is 29% with goal-directed echocardiography and 51% with a comprehensive echocardiographic examination ,63. A paCardiogenic shock will demonstrate a dilated LV  must be considered as a treatable and potentially very responsive cause. Ventricular dysfunction leading to heart failure is important in the differential diagnosis of acute respiratory failure and may be manifested in a goal-directed echocardiographic examination by the same findings that characterize cardiogenic shock.The role of goal-directed echocardiography in the critical care setting is continually evolving and becoming accepted as a beneficial modality in the treatment, care, and monitoring of the critically ill patient. It is time to work together as an interdisciplinary group to utilize this modality to the highest level of quality and accuracy for the benefit of our patients. Proper training is essential for the benefit and accurate diagnosis of patients. Poor training may encourage adverse consequences.Diagnosis and treatment of critically ill patients will likely continue to improve with the use of goal-directed echocardiography with hand carried and portable ultrasound equipment.


Quantitative MR myocardial strain analysis is typically performed using rectilinear or Cartesian grid tagging, and regional contractility is visually assessed by the deformation of the grid1. However, it is difficult to visually isolate circumferential and radial components of displacement and strain from parallel straight lines on short axis images. This study evaluates the potential of a polar coordinate tagging system2 for quantification of circumferential myocardial displacement in a variety of clinical conditions.33 subjects including 12 patients with congenital heart disease (CHD), 11 with cardiomyopathy (CM) and 10 healthy volunteers (HV) underwent cardiac SSFP cine and myocardial tagging in the mid-ventricular short axis plane with grid tags (line separation 5-7 mm), circular tags (5 mm separation) and radial tags . Visual assessment of circumferential and radial displacement was performed by two observers for each of the six mid short axis segments. Scores were assigned for: overall tag quality , strain , confidence in the findings  and ease of interpretation . Quantitative analysis of global and segmental circumferential strain was performed using a semi-automated tool previously described3.Healthy volunteers Figure  had the Polar tagging has advantages for the visual and quantitative assessment of myocardial strain. Compared to rectilinear tagging, radial tags are easier to interpret for isolation of circumferential and radial components of myocardial motion. Overall tag quality, strain, confidence in assessment and ease of interpretation of the image were highest in healthy volunteers, second highest CHD patients and lowest in CM patients.n/a.


Nearly 4% of patients with pulmonary embolism develop CTEPH. PEA offers a cure with excellent outcome. By use of cardiovascular magnetic resonance (CMR) combined with hemodynamic measurements pulmonary arterial elastance (Ei), end-systolic (ESVi), and stroke (SVi) volumes were indexed for body surface area. Ea-pulm_i was calculated as pulmonary artery mean pressure (mPAP)/SVi, and Ees-RV_i as mPAP/ESVi.Sixty-five patients  underwent CMR pre- and post-PEA. Ejection fraction (EF), end-diastolic . Ees-RV_i was depressed before and after PEA . EF improved from 25 ± 12% to 46 ± 10%, p =0.0001, because ventriculo-arterial coupling was restored . EDVi and ESVi mproved significantly .mPAP decreased from 47 ± 12 to 25 ± 9 mmHg, p =0.0001. ERV function is largely determined by afterload and returns to normal once afterload is normalized. This is paralleled by a significant improvement of CMR indices of right ventricular remodelling. Chronic thromboembolic pulmonary hypertension (CTEPH) is an important and frequent cause of pulmonary hypertension. The WHO has therefore acknowledged it as an independent entity in the renewed Dana Point Classification . Estimat-5, respectively, in a surgically treated cohort [The changes found in the pulmonary vasculature in CTEPH are a consequence of incomplete thrombus resolution, remodelling of the thrombus, and neoangiogenesis . In lated cohort . This ind cohort .Deterioration of RV function can be readily assessed by cardiovascular magnetic resonance (CMR), which has emerged as the gold standard for evaluating RV function as it allows full coverage of the complex geometry of the RV -14. Thisa-pulm,, the effective pulmonary artery elastance, is a well-validated measure of arterial load; Ees-RV characterizes the effective right ventricular elastance and is a measure of contractiliy. Their ratio Ees-RV/Ea-pulm describes ventriculo-arterial coupling, which should have a value close to 1.0 in order to achieve sufficient energy transfer from the RV to the pulmonary vasculature [For a more in-depth understanding of this process it is important to consider arterial load and ventricular performance independently as well as their coupling. Eculature -19.Traditionally, these parameters have been derived from conductance catheter measurements or simultaneously acquired CMR volumetric and right heart catheter (RHC) data . Both meIn this study of 65 patients who underwent PEA for CTEPH, we combined cine-cardiac CMR data and hemodynamic data available from routine right heart catheterization to study RV adaption to pressure overload and reverse remodelling of the RV before and after surgery.et al. report longitudinal data from CTEPH patients, which show reduced RV volumes after PEA, which are sustained after 12 month. The hemodynamic improvement, they found was paralleled by improved RV volumes and function. However the authors did not link hemodynamic data and CMR measurements.Although we are not aware of any study directly comparing CMR to Echo with respect to their accuracy of reflecting right ventricular remodelling in terms of volumes and mass, we are convinced that CMR is superior to Echo in this setting. While there are well validated echocardiographic indices of right ventricular function  volumetric evaluation of the RV is difficult with echo. Geometric assumptions on which left ventricular volumetric quantification is based, are not valid for the triangular shaped RV. In that respect CMR evaluation of the RV yields additional information not available from echo. D'Armini CTEPH is an excellent setting to study these changes as it behaves like an on/off phenomenon of PH before and after surgery and is therefore the only entity of pulmonary hypertension, that allows to study potential reversal of CMR and hemodynamic indices of RV remodelling.In this paper we try to establish a link between remodelling and the possible physiological bases for the volumetric changes observed by combining hemodynamic data and CMR indices.We retrospectivley defined a two year period during which we screened all 159 patients who were referred to and underwent PEA.Of these Sixty-five consecutive patients completed CMR as part of their perioperative routine workup and were enrolled in this study.Indication for CMR was at the discretion of both the attending thoracic surgeon and cardiologist and was based on the need for further evaluation of right ventricular function.2, incompatible metallic implants, known intolerance to gadolinium, and claustrophobia or the unability to lie supine for the duration of the protocol because of dyspnea.Contraindications for CMR and exclusion criteria were renal failure with a glomerular filtration rate below 30 ml/min/1.73 mThe primary diagnosis of CTEPH was based on right heart catheter measurements, perfusion/ventilation scintigraphy and pulmonary angiography findings. All patients gave written informed consent. The study was approved by the ethics committee of the University of Gießen, Germany.Elastance describes the change in pressure for a given change in volume. Hence, effective arterial elastance of the pulmonary artery can be approximated by the following formula ,20,22:1\mated by 2\documena-pulm is a reliable measure of the load faced by the right ventricle during systole and accounts for pulmonary vascular resistance, compliance, and impedance, and thus also includes the pulsatile components of arterial load [Eial load ,20.es-RV characterizes the chamber elastance at end-systole and can be approximated by [Similarly, Emated by ,204\docua-pulm/Ees-RV. Uncoupling describes the situation in which Ees-RV cannot compensate the disproportionate rise of Ea-pulm, and rapid deterioration of RV function ensues [a-pulm_i and Ees-RV_i as well as Ea-pulm/Ees-RV_i were indexed for body surface area (BSA).In order to provide sufficient energy transfer from the ventricle to the arterial system these properties should be equivalent. The ratio of these parameters, the ventriculo-arterial coupling, is defined as En ensues . Ea-pulmVolumetric measurements of right ventricular function were performed in a standard fashion by cine CMR covering the RV in short-axis slices from base to apex. Typical sequence parameters were TE 1.5 ms, TR 38.8 ms, 13 segments, 1.6 × 2.2 mm in-plane resolution, flip angle 70°, bandwidth 930 Hz/px, slice thickness 8 mm, interslice gap 2 mm.i, ESVi, RVMASSi, SVi). Median time between preoperative CMR and surgery was 1 day (IQR 1- 3). Median time between postoperative CMR and surgery was 12 days (IQR 11-12).Endocardial and epicardial contours were drawn on the RV to determine end-diastolic (EDV), end-systolic (ESV) and stroke (SV) volumes as well as RV myocardial mass (RVMASS) and ejection fraction (EF) using CAAS Software . Trabeculations were excluded from the myocardium. All volumetric parameters were normalized for BSA  and median time between postoperative RHC and postoperative CMR was 11 days (IQR 10 - 11). Patients were not under therapy with vasoactive agents during postoperative RHC measurements.The Shapiro-Wilk test was used to test the data for normality. Metric values are presented as means ± SD, and counts are presented as absolute frequencies and percentages. Student’s t-test for paired data was used to test for significant differences between pre- and postoperative values. A chi-square test was used to compare count variables. An alpha error less than 0.05 was accepted as significant. All tests were computed using STATA11 .2, the majority of patients was NYHA class III, 6 minute walking distance was 386 ± 116 before surgery and 399 ± 120 after surgery .Of the sixty-five consecutive patients enrolled in the study, 28 were female, the mean age was 56.7 ± 16 years, and the mean BSA was 1.96 mes-RV_i after surgery, with only marginally changed absolute values . Consequently, there was marked ventriculo-arterial uncoupling Ea-pulm/Ees-RV_i before PEA, which significantly improved to near normal values after surgery  compare Figure There was a lower, but not significantly lower right ventricular elastance Ei and ESVi) significantly decreased after PEA . Conversely, SVi improved significantly after PEA . RVMASSi was increased before PEA and decreased significantly afterwards but was not clinically relevant . Ea_pulm_i was well correlated with mPAP  preoperatively and postoperatively Ea_pulm_i vs. mPAP  compare Figure The ejection fraction EF was severely depressed before PEA and significantly improved afterwards . Right ventricular volumes ; however, only 3 patients of this cohort had CTEPH and ejection fraction as well as stroke volumes were much lower in our cohort, hence Ea-pulm_i higher (RVEF 37% as compared to our 25% and 35.5 ml/m2 as compared to our 22 ml/m2 ). Kühne et al. reported a similar Ea-pulm of 2.7 in a series of 6 patients with an mPAP of 56 mmHg, which was derived from simultaneously measured pressure-volume curves [et al. found an Ea-pulm  of 0.75, which is lower than our values by the same degree, as mPAP in their study group was lower and stroke volumes were higher [i and greater volumes.We found markedly increased pulmonary arterial load E55 ± 9 ml, a normae curves . This vaes in the face of rising afterload, which has been intensively studied in the systemic circulation. This is frequently observed in hypertensive heart disease, where Ees compensates for increasing loading conditions until Ea increases disproportionately and Ees cannot rise accordingly [et al. found increasing Ees-RV in the initial period after the first embolism, which later decreased with rising afterload and reached levels below the initial value [es-RV_i values reported here are in good agreement with other studies [es-RV_i did not improve immediately after surgery. However, it is important to note that ESVi decreased dramatically after PEA and that the computation of Ees-RV_i is based on a much smaller ESVi. It is therefore essential to study Ees-RV_i in relation to Ea-pulm_i.The contractile state of the RV was depressed before and after PEA, with a trend towards lower values after surgery and only marginally changed absolute values. It is a typical response of the heart to increase Eordingly -29. In aal value . Ees-RV_ studies ,31. Surpa-pulm_i/Ees-RV_i was markedly increased before PEA, indicating severe uncoupling. However, RV afterload dropped by 70% after PEA, and thus ventriculo-arterial coupling was restored despite the fact that contractile properties were still compromised, reflecting sufficient energy transfer from the RV to the pulmonary arterial system. The most efficient energy transfer was found to be at an Ea/Ees ratio of 0.6 to 1.2 for the left ventricle [et al. reported an Ea/Ees ratio of 0.52 for controls and 0.91 for PH patients  [et al. reported an Ea/Ees ratio of 0.37 for controls and 1.26 for PH patients [The effective ventriculo-arterial coupling between pulmonary arterial vasculature and RV expressed as the ratio Eentricle ,32-34; finverse) , Sanz etpatients . Hence, et al., who showed in an animal model of pulmonary arterial embolism that levosimendan is superior to dobutamine in improving ventriculo-arterial coupling because it not only increases Ees (as dobutamine does) but sufficiently lowers Ea. Although contractility was more enhanced under dobutamine treatment, ventriculo-arterial coupling was better under levosimendan because afterload was nearly half the value found under dobutamine [Essentially, PEA reverses the increased RV afterload like an on/off phenomenon in these CETPH patients. Our data show that the RV function is largely afterload dependent and that it can return to normal once normal pulmonary arterial afterload decreases and ventriculo-arterial coupling of the RV is restored. This is in good agreement with data of Kerbaul butamine ,35.a-pulm_i/Ees-RV_i ratio and the ejection fraction showed a curvilinear relationship, with a steep decline of the ejection fraction in the early phase of uncoupling (compare Figure The Ei decreased by 40% while RV-EF almost doubled. This has been described previously [Hemodynamic changes were paralleled by reverse remodelling of RV volumes and an improvement in the ejection fraction. ESVeviously ,36; howeThe inferences made in this study are based on surrogate markers and not on the gold standard of conductance catheters. However, these markers have been thoroughly validated in previous studies ,22,30. TIn this paper we have looked at remodelling in terms of changed RV-volumes, mass and ejection fraction and a possible physiological basis for these changes. These findings do not allow to make inferences to histological remodelling. With the advent and further improvement of T1 Mapping techniques, we might be able to correlate our findings with interstitial remodelling in the future.By combining readily available data from routine RHC measurements and CMR volumetric data in CTEPH patients, we were able to quantify RV contractile properties and pulmonary arterial afterload. We demonstrated that RV function is largely determined by afterload and returns to normal once ventriculo-arterial coupling and effective pulmonary arterial elastance are restored by PEA.This makes CMR in combination with simple RHC measurements an ideal tool to study RV properties in the follow up of PH patients in the clinical and study setting.